2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5df,Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. Antibodies against NGF show analgesic effects in painful knee OA, but clinical development was stopped because of side effects in the joints. Knowledge about the biologic effects of NGF on joint tissues is limited. Therefore, we explored the effects of repeated intra-articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Naïve 10- to 15-week-old male wildtype C57BL/6 mice were injected with NGF (50 or 500 ng) or vehicle IA twice a week for four weeks, and effects on knee swelling, knee hyperalgesia, joint histopathology, and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. Na Compared with vehicle, repeated IA injections of NGF caused dose-dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up-regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up-regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis.31:T94d, Objective Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. Antibodies against NGF show analgesic effects in painful knee OA, but clinical development was stopped because of side effects in the joints. Knowledge about the biologic effects of NGF on joint tissues is limited. Therefore, we explored the effects of repeated intra‐articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Methods Naïve 10‐ to 15‐week‐old male wildtype C57BL/6 mice were injected with NGF (50 or 500 ng) or vehicle IA twice a week for four weeks, and effects on knee swelling, knee hyperalgesia, joint histopathology, and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. Na V 1.8‐tdTomato reporter mice were used to assess joint innervation. Dorsal root ganglia (DRGs) of mice underwent bulk RNAseq after three IA injections of NGF or vehicle. Results Compared with vehicle, repeated IA injections of NGF caused dose‐dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up‐regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up‐regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. Conclusion In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Controlled Animal Study: study design Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Controlled Animal Study (study design). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/study_design/Controlled%20Animal%20Study\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Study Designs\",\"item\":\"https://www.reachrx.ai/hub/tag/study_design\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Controlled Animal Study\",\"item\":\"https://www.reachrx.ai/hub/tag/study_design/Controlled%20Animal%20Study\"}]}}"}}]],["$","$L2f",null,{"title":"Controlled Animal Study: Research & Clinical Takeaways","description":"Browse Controlled Animal Study research papers with clear, practical takeaways for your clinical practice.","papers":[{"doi":"10.1038/s41398-026-04435-2","pmid":null,"title":"Sodium butyrate rescues long-term neurodevelopmental deficits following perinatal methadone exposure","journal_title":"Translational Psychiatry","journal_issn":"2158-3188","published_at":"2026-09-10T00:00:00.000Z","url":"https://doi.org/10.1038/s41398-026-04435-2","source_score":34,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-09-16T06:22:51.900Z","updated_at":"2026-09-16T06:22:51.900Z","tags":[{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"age_group","value":"infant","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"age_group","value":"neonate","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"condition","value":"Neonatal Opioid Withdrawal Syndrome","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"condition","value":"Neurodevelopmental Deficits","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"condition","value":"Prenatal Opioid Exposure","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"generic","value":"methadone","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"generic","value":"sodium butyrate","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"modality","value":"Opioid Agonist","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"modality","value":"Short-Chain Fatty Acid Supplement","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"sample_size","value":"n=26","value_numeric":26},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"warning","value":"Findings are in a rat model; clinical applicability to human prenatal opioid exposure requires cautious interpretation.","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"warning","value":"Sample size refers to 26 pregnant rat dams; offspring counts are not separately reported in the abstract, making the effective N for behavioral/neurological outcomes unclear.","value_numeric":null},{"paper_doi":"10.1038/s41398-026-04435-2","tag_type":"warning","value":"Study design tag reflects a controlled preclinical animal experiment — no randomization of human subjects was involved.","value_numeric":null}],"summaries":{"what_studied":"A 2×2 rat model study tested whether prenatal sodium butyrate (NaB, via drinking water) could prevent long-term neurodevelopmental deficits caused by perinatal methadone exposure (via mini-osmotic pump in 26 pregnant dams), with assessments spanning offspring infancy, adolescence, and adulthood.","key_result":"Perinatal methadone disrupted maternal gut microbiota butyrate production and reduced fecal butyric acid; NaB reversed methadone-induced infant gut barrier permeability increases, partially rescued adolescent anxiety-like behavior and adult working spatial memory and attentional deficits, and partially reversed methadone-induced hippocampal hypomyelination.","limitations":"Preclinical rat model only — direct translation to human neonates is uncertain. Small number of dams (n=26) limits statistical power. Mechanisms mediating NaB rescue were not fully characterized beyond the microbiota-gut-brain axis.","practice_takeaway":"While not yet ready for clinical use, these findings position maternal or perinatal sodium butyrate supplementation as a candidate intervention worth evaluating in human trials for prenatal opioid-exposed infants. Clinicians managing neonatal opioid withdrawal syndrome (NOWS) should watch for emerging translational data on gut-brain axis therapies."}},{"doi":"10.1111/ejn.70669","pmid":"42708183","title":"Hyperdopaminergic States Bias Explorations–Exploitation Trade‐Off in Foraging and Impair Survival","journal_title":"European Journal of Neuroscience","journal_issn":"0953-816X","published_at":"2026-09-08T00:00:00.000Z","url":"https://doi.org/10.1111/ejn.70669","source_score":29,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-10T06:20:09.514Z","updated_at":"2026-09-10T06:20:09.514Z","tags":[{"paper_doi":"10.1111/ejn.70669","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"condition","value":"Foraging Behavior Impairment","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"condition","value":"Hyperdopaminergic State","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"generic","value":"alpha-methyl-p-tyrosine","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"generic","value":"amphetamine","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"modality","value":"Dopamine Synthesis Inhibitor","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"modality","value":"Dopamine Transporter Modulation","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"modality","value":"Thermogenetics","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"sample_size","value":"n=48","value_numeric":48},{"paper_doi":"10.1111/ejn.70669","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"warning","value":"Level of evidence set to 5 (animal study); translational relevance to human dopaminergic conditions is inferential.","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"warning","value":"Sample sizes vary widely across experiments (n=12 to n=100); the value reported is representative of the primary survival assay. Total N across all experiments is not consolidated in the paper.","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"warning","value":"Study conducted entirely in male Drosophila melanogaster; authors explicitly caution against generalizing to females.","value_numeric":null},{"paper_doi":"10.1111/ejn.70669","tag_type":"warning","value":"The study design tag 'Controlled Animal Study' is used as no single canonical label (e.g., RCT) applies to this multi-method invertebrate genetics study.","value_numeric":null}],"summaries":{"what_studied":"This study examined how hyperdopaminergic states—induced via the *Drosophila* DAT-null mutant *fumin* (DATfmn), amphetamine, and thermogenetic neuronal activation—affect foraging strategy, food consumption, and survival under energetic scarcity versus abundance. The foraging paradigm used a single sucrose-filled capillary as the sole food source.","key_result":"In free-feeding conditions, DATfmn flies showed normal consumption and survival. In food-scarce foraging, most DATfmn flies died by Day 5 (vs. controls that survived well), driven by reduced meal frequency—not meal size—and excessive exploration away from the known food source. Amphetamine impaired survival only when given in the post-learning phase (Days 4–8), not during the learning phase (Days 1–3), dissociating learning deficits from exploration–exploitation bias as the cause.","limitations":"- Only male flies aged 1–5 days were used; results may not generalize to females or other ages.\n- The DATfmn mutation causes chronic developmental dopamine dysregulation, making it difficult to fully separate acute dopaminergic effects from lifelong compensatory changes.\n- Blinding was not used, which introduces potential observer bias, though authors note effects were large and obvious.","practice_takeaway":"These findings reinforce that elevated baseline dopamine—relevant to conditions like stimulant use, ADHD pharmacotherapy, or genetic dopamine transporter variants—can shift behavior toward excessive exploration and energy expenditure, which may be maladaptive in resource-limited contexts. Clinicians managing patients with hyperdopaminergic states should consider the environmental context when evaluating behavioral outcomes."}},{"doi":"10.1016/j.immuni.2026.07.023","pmid":"42648284","title":"T cell fate is dictated by different antigen-presenting cells in response to dietary versus gut epithelial self-antigen","journal_title":"Immunity","journal_issn":"1074-7613","published_at":"2026-08-26T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13519990/","source_score":22,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-03T06:19:56.209Z","updated_at":"2026-09-03T06:19:56.209Z","tags":[{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"condition","value":"Food Tolerance","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"condition","value":"Gut Autoimmunity","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"condition","value":"Intestinal Inflammation","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"generic","value":"ovalbumin","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"modality","value":"Antigen Presentation / T Cell Immunology","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"warning","value":"Study design is classified as a controlled animal study rather than a randomized controlled trial; level of evidence reflects preclinical work.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the mechanistic novelty of distinguishing dietary vs. epithelial APC pathways, not a clinical trial outcome.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.023","tag_type":"warning","value":"This is a mouse study using a model antigen (OVA); direct translation to human gut autoimmunity or food allergy is speculative at this stage.","value_numeric":null}],"summaries":{"what_studied":"This study compared CD4+ T cell fate decisions in mice exposed to ovalbumin (OVA) via dietary intake versus gut epithelial expression (secreted, cytosolic, or transmembrane forms), examining how antigen origin and presenting cell context shape immune outcomes — including after reovirus or helminth infection.","key_result":"BATF3+ APCs were required for CD4+ T cell proliferation only with cytosolic epithelial OVA, but drove Treg differentiation across all epithelial OVA models; in contrast, RORγt+MHC II+ APCs were exclusively required for Treg induction by dietary OVA — and these distinct APC dependencies correlated with differential susceptibility to gut pathology.","limitations":"All experiments used OVA as a model antigen in engineered mouse systems, which may not fully replicate the complexity of human food antigens or gut autoimmune disease; helminth and reovirus infection models may not capture all clinically relevant inflammatory triggers.","practice_takeaway":"The cellular pathway driving gut immune tolerance differs depending on whether antigen comes from food or the epithelium itself — a distinction that may help predict which patients are prone to dietary intolerance versus gut autoimmunity and could inform antigen-specific therapeutic targeting."}},{"doi":"10.1016/j.exer.2026.111192","pmid":"42556773","title":"C1q dependency of retinal ganglion cell death in blast-mediated traumatic brain injury","journal_title":"Experimental Eye Research","journal_issn":"0014-4835","published_at":"2026-08-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.exer.2026.111192","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-14T13:24:55.547Z","updated_at":"2026-08-14T13:24:55.547Z","tags":[{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"condition","value":"Glaucoma","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"condition","value":"Retinal Ganglion Cell Degeneration","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"condition","value":"Traumatic Brain Injury","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"generic","value":"C1qa knockout (genetic model)","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"modality","value":"Complement Inhibition","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"warning","value":"Publication date (2026-08-06) is recent; this paper has not yet been subject to broad post-publication peer scrutiny.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"warning","value":"Sex of mice is not explicitly reported in the abstract; the 'mixed' sex tag is uncertain.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the mechanistic novelty of C1q's role in blast-TBI RGC death, but this is a preclinical mouse study — no human clinical data are presented. Clinicians should interpret translational implications cautiously.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111192","tag_type":"warning","value":"The study uses genetic knockout rather than a pharmacological C1q inhibitor, so direct therapeutic applicability cannot yet be assumed.","value_numeric":null}],"summaries":{"key_result":"C1qa knockout mice showed no significant RGC soma or optic nerve axon loss relative to sham controls at either 5 or 16 weeks after bTBI, indicating that C1q deletion confers robust and persistent neuroprotection of RGCs.","what_studied":"This study tested whether complement factor C1q drives retinal ganglion cell (RGC) death in a mouse model of blast-mediated traumatic brain injury (bTBI), comparing RGC soma and optic nerve axon survival in C1qa knockout (B6.C1qako) vs. wild-type C57BL/6J mice at 5 and 16 weeks post-blast exposure.","limitations":"Pre-clinical mouse model only — direct translation to human bTBI is uncertain. The study does not assess functional visual outcomes (e.g., electroretinography, visual acuity). Only C1qa was knocked out; the broader complement cascade and other neuroinflammatory mediators were not fully characterized.","practice_takeaway":"C1q-mediated complement signaling appears to be a key driver of RGC neurodegeneration after blast TBI, paralleling its role in glaucoma. Targeting C1q may represent a viable neuroprotective strategy for blast-related vision loss, though clinical validation is still needed."}},{"doi":"10.3389/fimmu.2026.1813722","pmid":null,"title":"Sucrose-free low-fat diet induces metabolic dysfunction through gut dysbiosis and colonic inflammation in mice","journal_title":"Frontiers in Immunology","journal_issn":"1664-3224","published_at":"2026-07-21T00:00:00.000Z","url":"https://doi.org/10.3389/fimmu.2026.1813722","source_score":190,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-23T13:33:26.063Z","updated_at":"2026-07-23T13:33:26.063Z","tags":[{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"condition","value":"Colonic Inflammation","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"condition","value":"Gut Dysbiosis","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"condition","value":"Hepatic Steatosis","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"condition","value":"Insulin Resistance","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"condition","value":"Metabolic Dysfunction","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"sample_size","value":"n=12","value_numeric":12},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"warning","value":"Extremely small group size (n=6/group, total n=12) is a major limitation; findings should be considered hypothesis-generating only.","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"warning","value":"Sex of mice is not explicitly stated in the abstract; the 'mixed' sex tag is uncertain.","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"warning","value":"Study is in mice only — direct clinical translation to human dietary recommendations is not supported by this data alone.","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1813722","tag_type":"warning","value":"The paper is dated 2026-07-21, which is very recent; it has not yet been subject to broad peer citation or replication.","value_numeric":null}],"summaries":{"what_studied":"This mouse study compared a sucrose-free low-fat diet (SF-LFD) to a sucrose-containing low-fat control diet (C-LFD) over 16 weeks (n=6/group), examining effects on metabolic homeostasis, gut microbiota (16S rRNA), colonic histology, and liver pathology.","key_result":"Despite no change in body or liver weight, SF-LFD impaired glucose tolerance and insulin sensitivity, elevated C-peptide, incretins, ghrelin, and resistin, depleted SCFA-producing gut commensals (e.g., *Lactobacillus murinus*, Lachnospiraceae), enriched pro-inflammatory taxa (e.g., *Helicobacter ganmani*, *Alistipes* spp.), and drove colonic inflammation (CD3⁺ T-cell and F4/80⁺ macrophage infiltration, upregulated *Il1b*, *Il6*, *Ccl2*, *Rorγt*, *Tbx21*) plus hepatic microvesicular steatosis with lobular inflammation.","limitations":"- Very small group size (n=6/group) limits statistical power and generalizability.\n- Mouse model only; translation to human low-fat dietary guidelines is uncertain.\n- No mechanistic intervention (e.g., germ-free or antibiotic arm) to confirm causality between dysbiosis and metabolic dysfunction.","practice_takeaway":"Blanket sucrose elimination within a low-fat diet framework may not be metabolically neutral — it can disrupt gut microbiota and trigger gut and liver inflammation even without weight gain. Clinicians advising low-fat, sugar-restricted diets should be aware this preclinical evidence signals a potential unintended metabolic risk."}},{"doi":"10.1152/ajplung.00090.2026","pmid":"42397154","title":"Inhibition of thrombospondin-1 signaling prevents experimental bronchopulmonary dysplasia","journal_title":"American Journal of Physiology-Lung Cellular and Molecular Physiology","journal_issn":"1040-0605","published_at":"2026-07-03T00:00:00.000Z","url":"https://doi.org/10.1152/ajplung.00090.2026","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-09T13:25:15.175Z","updated_at":"2026-08-09T13:25:15.175Z","tags":[{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"age_group","value":"neonate","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"condition","value":"Bronchopulmonary Dysplasia","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"condition","value":"Pulmonary Hypertension","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"generic","value":"LSKL peptide","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"generic","value":"soluble CD47 receptor ligand trap","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"modality","value":"Ligand Trap","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"modality","value":"Peptide Inhibitor","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"warning","value":"LSKL and sCD47r were administered on different schedules and doses — direct efficacy comparisons should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"warning","value":"Study design is labeled 'Controlled Animal Study'; no standard RCT or human observational design applies — level of evidence set to 5 (animal/mechanistic study).","value_numeric":null},{"paper_doi":"10.1152/ajplung.00090.2026","tag_type":"warning","value":"Study is entirely preclinical (neonatal rat model); no human data are presented. Clinical applicability is speculative at this stage.","value_numeric":null}],"summaries":{"what_studied":"In a neonatal rat model of hyperoxia-intermittent hypoxia (H-IH)-induced BPD (PND 1–21), this study compared two TSP-1 inhibition strategies: LSKL (blocks TSP-1-mediated TGF-β1 activation only; 20 mg/kg/day SQ) vs. soluble CD47 receptor ligand trap (sCD47r; global TSP-1 signaling blockade; 3 mg/kg every 3 days).","key_result":"Both LSKL and sCD47r equally prevented H-IH-induced rises in active TGF-β1, macrophage influx, alveolar and pulmonary vascular hypoplasia, and pulmonary hypertension; only sCD47r additionally increased lung NO content and signaling, suggesting TGF-β1 pathway blockade alone is sufficient for the structural and hemodynamic benefits.","limitations":"- Rat model only; findings may not directly translate to human neonates with BPD.\n- Pharmacologic dosing and schedule (daily LSKL vs. every-3-day sCD47r) differ, making strict dose-equivalence comparisons difficult.\n- Mechanistic endpoints are biochemical/histologic; no long-term outcomes or safety data are provided.","practice_takeaway":"Targeting TSP-1–mediated TGF-β1 activation with LSKL peptide prevented experimental BPD as effectively as global TSP-1 blockade, identifying TGF-β1 activation as a key actionable node. Clinicians should watch for translational trials testing TSP-1/TGF-β1 pathway inhibitors in premature infants at risk for BPD."}},{"doi":"10.1152/ajprenal.00125.2026","pmid":"42390335","title":"Blood pressure responses to dietary salt in renin-deficient Dahl salt-sensitive rats","journal_title":"American Journal of Physiology-Renal Physiology","journal_issn":"1931-857X","published_at":"2026-07-02T00:00:00.000Z","url":"https://doi.org/10.1152/ajprenal.00125.2026","source_score":6,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-03T06:19:59.736Z","updated_at":"2026-09-03T06:19:59.736Z","tags":[{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"condition","value":"Salt-Sensitive Hypertension","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"modality","value":"Dietary Salt Intervention","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"warning","value":"Sex of animals is not explicitly stated in the abstract; the 'mixed' sex tag is assumed — verify in full text.","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"warning","value":"Study design tag 'Controlled Animal Study' is used as there is no standard canonical label that perfectly captures a genetic knockout animal experiment; no RCT or human cohort involved.","value_numeric":null},{"paper_doi":"10.1152/ajprenal.00125.2026","tag_type":"warning","value":"This is a preclinical animal study (rat model); clinical applicability to human salt-sensitive hypertension requires further validation.","value_numeric":null}],"summaries":{"what_studied":"This study examined the role of renin in blood pressure regulation in Dahl salt-sensitive (SS) rats, comparing wild-type (SSWT) to renin-knockout (SSren-/-) rats under salt-deficient (0.01% NaCl), normal-salt (0.4% NaCl), and high-salt (4% NaCl) diets over 10 days, measuring mean arterial pressure, GFR, urine output, and electrolytes.","key_result":"A 10-day high-salt diet caused a rapid rise in blood pressure and **100% mortality** in SSren-/- rats; salt-deficient diet significantly reduced blood pressure, plasma Na+, and Cl- in SSren-/- rats. In SSWT rats, a salt-deficient diet robustly activated all circulating RAAS components, while a high-salt diet significantly decreased the aldosterone-to-Ang II ratio.","limitations":"- Animal model only (Dahl SS rats); direct translation to human salt-sensitive hypertension is uncertain.\n- Short dietary intervention period (10 days) limits insight into chronic adaptations.\n- Complete renin knockout is an extreme genetic model that may not reflect partial RAAS impairment seen clinically.","practice_takeaway":"Intact RAAS signaling — specifically renin — appears essential for survival under high dietary salt loads in a salt-sensitive model, reinforcing caution when using renin-suppressing therapies in patients with salt-sensitive hypertension. Clinicians should be mindful that blunted renin responses may severely limit adaptive capacity to dietary sodium changes."}},{"doi":"10.1097/fbp.0000000000000886","pmid":"42348457","title":"Teneurin C-terminal associated peptide-1 attenuates chronic stress in male rats","journal_title":"Behavioural Pharmacology","journal_issn":"0955-8810","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1097/fbp.0000000000000886","source_score":30,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:02.235Z","updated_at":"2026-08-04T18:18:02.235Z","tags":[{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"condition","value":"Anxiety","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"condition","value":"Chronic Stress","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"generic","value":"CP-154,526","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"generic","value":"TCAP-1","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"modality","value":"CRF1 Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"modality","value":"Neuropeptide","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"sample_size","value":"n=28","value_numeric":28},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"warning","value":"All five authors are employees or consultants of Protagenic Therapeutics, the sponsor — high conflict-of-interest risk.","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"warning","value":"Sample sizes are small (n=6–8 per group) and no power analysis was performed, increasing risk of false-positive findings.","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"warning","value":"Study conducted exclusively in male rats; results may not generalize to females or humans.","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"warning","value":"TCAP-1 and CP-154,526 are not approved drugs; findings are preclinical only.","value_numeric":null},{"paper_doi":"10.1097/fbp.0000000000000886","tag_type":"warning","value":"The study design is a controlled animal experiment, not a randomized controlled trial — level of evidence is accordingly low.","value_numeric":null}],"summaries":{"what_studied":"This study tested whether TCAP-1 (250 nmol/kg, s.c., days 12–13) could reduce physiological and behavioral markers of chronic stress in male Sprague-Dawley rats using a 14-day chronic unpredictable stress (CUS) model, compared to the CRF1 receptor antagonist CP-154,526 (20 mg/kg, s.c., given for 2 days or all 14 days).","key_result":"TCAP-1 reduced plasma corticosterone by **56.4%** vs. saline controls (P=0.029) and increased open-field center time by **282%** (P=0.031). CP-154,526 showed no significant effect on either endpoint under either dosing regimen.","limitations":"- Only male rats were studied; female data are absent, limiting generalizability.\n- Small group sizes (n=6–8) with no a priori power analysis; experimenters were not blinded to treatment.\n- All authors are employees or consultants of Protagenic Therapeutics (the sponsor), creating a conflict of interest.","practice_takeaway":"TCAP-1 is still preclinical, but its efficacy in a chronic stress model — where CRF1 antagonists have repeatedly failed both in rodents and in human trials — supports continued development as a potential anxiolytic with a distinct upstream mechanism. Clinicians should watch for early-phase human trials of this neuropeptide."}},{"doi":"10.1002/art.70239","pmid":"42257519","title":"Homocitrullinated Peptides Drive Pro‐Inflammatory T‐Cell Responses in a Humanized Mouse Model of Rheumatoid Arthritis","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-06-08T00:00:00.000Z","url":"https://doi.org/10.1101/2025.10.30.685402","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:26.931Z","updated_at":"2026-06-12T13:24:26.931Z","tags":[{"paper_doi":"10.1002/art.70239","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"generic","value":"HomoCitJED","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"modality","value":"Peptide Immunization","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"sample_size","value":"n=15","value_numeric":15},{"paper_doi":"10.1002/art.70239","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"warning","value":"Sample size range (n=6–15) is reported across groups; exact per-group N for each outcome is not always specified, which may affect interpretation of statistical comparisons.","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"warning","value":"Study design tag 'Controlled Animal Study' is used as the closest standard label; this is a mouse immunization experiment, not a clinical trial or observational human study.","value_numeric":null},{"paper_doi":"10.1002/art.70239","tag_type":"warning","value":"This paper was originally posted as a preprint on bioRxiv (October 2025) and is listed as published in Arthritis & Rheumatology (June 2026); peer-review status at time of final publication should be confirmed.","value_numeric":null}],"summaries":{"what_studied":"This study investigated whether a homocitrullinated peptide (HomoCitJED) can drive pro-inflammatory T-cell responses in HLA-DR4-transgenic (DR4tg) mice — a humanized model expressing the strongest RA genetic risk factor — compared to PBS-injected controls, with T-cell analysis at 10 days post-immunization.","key_result":"HomoCitJED immunization produced >7-fold expansion of Th1, Th17, and hybrid Th1/Th17 CD4+ cells in draining lymph nodes (p<0.0087), elevated IL-17A+, TNF-α+IL-17A+, and IFN-γ+IL-17A+ CD4+ T cells (p<0.0207), a 6-fold increase in CD25+ CD8+ T cells, and upregulation of exhaustion markers LAG-3, Tim-3, and PD-1 on both CD4+ and CD8+ T cells — consistent with a dysregulated, co-activated/exhausted T-cell state.","limitations":"- Animal model only (DR4tg mice); human translation is uncertain.\n- Small group sizes (n=6–15 per group) limit statistical power.\n- Single time point (10 days) does not capture chronic or longitudinal T-cell dynamics.","practice_takeaway":"Homocitrullinated peptides can independently drive Th1/Th17 and Tc1/Tc17 T-cell dysregulation in an HLA-DR4 context, suggesting homocitrullination-specific immunity as a potential therapeutic target in RA. Clinicians should watch for emerging immunomodulatory strategies aimed at this antigen class."}},{"doi":"10.1186/s12974-026-03890-4","pmid":"42237180","title":"Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury","journal_title":"Journal of Neuroinflammation","journal_issn":"1742-2094","published_at":"2026-06-03T00:00:00.000Z","url":"https://doi.org/10.1186/s12974-026-03890-4","source_score":50,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-14T13:34:55.782Z","updated_at":"2026-06-14T13:34:55.782Z","tags":[{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"condition","value":"Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"condition","value":"Post-Traumatic Epilepsy","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"condition","value":"Traumatic Brain Injury","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"generic","value":"SB-3CT","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"generic","value":"TAK-242","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"modality","value":"MMP-9 Inhibitor","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"modality","value":"TLR4 Inhibitor","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"sample_size","value":"n=100","value_numeric":100},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"warning","value":"Sample sizes are small (n = 6–10 rats, 3–4 mice per group), which may limit generalizability. The total N listed in the tag is approximate as exact total animal numbers are not aggregated in the abstract.","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"warning","value":"Study design is labeled 'Controlled Animal Study' rather than a standard RCT label given the preclinical nature; level of evidence set to 5 accordingly.","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"warning","value":"The paradoxical pro-excitatory effect of TLR4 inhibition in healthy (sham) animals is not fully mechanistically explained and represents an important safety consideration for translational studies.","value_numeric":null},{"paper_doi":"10.1186/s12974-026-03890-4","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novelty of the TLR4–MMP-9 axis identification and early intervention data, but findings are preclinical only — no human data are presented.","value_numeric":null}],"summaries":{"what_studied":"This study examined how neuronal TLR4 signaling and downstream MMP-9 activity regulate dentate gyrus (DG) circuit function in rat and mouse models of lateral fluid percussion injury (FPI), measuring synaptic inputs to dentate granule cells (DGCs), in vivo LTP, and spatial memory (Barnes maze) at 1 week and 1 month post-injury.","key_result":"Neuronal TLR4 drove post-TBI increases in excitatory input frequency to DGCs via MMP-9, while TLR4-mediated decreases in inhibitory input frequency were MMP-9-independent. Systemic TLR4 inhibition (TAK-242) or MMP-9 inhibition (SB-3CT) given within 24 h of injury reduced network hyperexcitability, rescued in vivo DG LTP (normalized slope ~140–141% vs. ~110% in untreated FPI at 180 min post-TBS), and attenuated spatial memory deficits at 1 month. Paradoxically, TLR4 inhibition in uninjured sham animals increased excitatory and inhibitory input frequency and augmented network excitability without changing MMP-9 levels.","limitations":"Studies used acute pharmacological inhibition and conditional genetic deletion, so long-term effects of sustained TLR4 or MMP-9 blockade are unknown. Small group sizes (n = 6–10 rats, 3–4 mice per group) limit statistical power. The paradoxical pro-excitatory effect of TLR4 inhibition in healthy animals raises concerns about off-target or context-dependent risks not fully resolved.","practice_takeaway":"Early post-TBI inhibition of the TLR4–MMP-9 axis (within 24 h) is a candidate therapeutic strategy to reduce hippocampal hyperexcitability and cognitive deficits. Clinicians and researchers should note that TLR4 blockade may have opposite effects in the uninjured brain, warranting careful patient selection and timing in any translational application."}},{"doi":"10.1038/s41593-026-02301-4","pmid":"42225897","title":"Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks","journal_title":"Nature Neuroscience","journal_issn":"1097-6256","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1038/s41593-026-02301-4","source_score":109,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-11T13:42:53.826Z","updated_at":"2026-06-11T13:42:53.826Z","tags":[{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"condition","value":"Treatment-Resistant Depression","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"modality","value":"Deep Brain Stimulation","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Full page text was not extractable from the PDF; sample sizes, exact statistical results, and stimulation parameters could not be confirmed and are not included in the summary.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Level of evidence set to 5 (animal/experimental study) given the preclinical macaque model design.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Study was conducted in macaques — generalizability to human clinical DBS practice should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This study examined the anatomical and functional effects of subcallosal anterior cingulate cortex deep brain stimulation (SCC-DBS) in macaques, modeling the white matter-targeted approach used in treatment-resistant depression in humans. Outcomes included white matter microstructure (fractional anisotropy), cellular changes (myelination, oligodendrocytes), and brain-wide functional connectivity.","key_result":"SCC-DBS selectively increased fractional anisotropy in the cingulum bundle, associated with increased myelinated oligodendrocytes and greater myelination in the mid-cingulum. Functional connectivity was also altered brain-wide, with notable changes in interactions between the SCC and the default mode network.","limitations":"- Animal model only (macaques); direct translation to human DBS outcomes is uncertain.\n- Full text pages were not extractable, so sample sizes, stimulation parameters, and statistical details could not be verified from the source.\n- Causal link between white matter remodeling and clinical antidepressant efficacy remains inferred, not directly tested.","practice_takeaway":"SCC-DBS may work partly by remodeling white matter and reshaping default mode network connectivity — not just by acute neuromodulation. Clinicians should consider that structural brain changes may be part of DBS's therapeutic mechanism in depression."}},{"doi":"10.1111/nan.70082","pmid":"42189000","title":"Early Regional Microglial Remodelling in the Hippocampus of the\n App\n ^{\n NL‐G‐F\n}\n Alzheimer's Model","journal_title":"Neuropathology and Applied Neurobiology","journal_issn":"0305-1846","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1111/nan.70082","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-06T13:22:55.485Z","updated_at":"2026-06-06T13:22:55.485Z","tags":[{"paper_doi":"10.1111/nan.70082","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"generic","value":"Iba1","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"modality","value":"Neuroimaging / Morphometric Analysis","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"warning","value":"Iba1 is a microglial marker protein, not a therapeutic drug — tagged under 'generic' for indexing purposes but should be interpreted as an immunohistochemical label.","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"warning","value":"No sample size (number of mice per group) is reported in the abstract or results excerpt; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1111/nan.70082","tag_type":"warning","value":"Study design is classified as a controlled animal study; no randomization or blinding details are described in the available text.","value_numeric":null}],"summaries":{"what_studied":"This study examined microglial morphology in 2-month-old AppNL-G-F Alzheimer's model mice versus wildtype controls, focusing on the dorsal CA1 apical hippocampal field before local amyloid plaque deposition, using high-resolution confocal microscopy and 3D automated morphometric analysis.","key_result":"Microglial density and total Iba1 coverage were unchanged, but Sholl analysis showed significant genotype-dependent reductions in process intersections, total process length, and individual-cell territorial coverage — indicating early surveillance arbor contraction before local amyloid deposition.","limitations":"- Single brain region (dorsal CA1) and single early timepoint (2 months) limit generalizability across disease stages and other brain areas.\n- Study is purely morphological; functional consequences of the observed structural changes are not assessed.\n- Mouse model findings may not fully translate to human Alzheimer's disease pathogenesis."}},{"doi":"10.1523/jneurosci.0077-26.2026","pmid":"42150875","title":"Pronounced Neuroplasticity in the Primary Visual Cortex of the Thirteen-lined Ground Squirrel During Hibernation","journal_title":"The Journal of Neuroscience","journal_issn":"0270-6474","published_at":"2026-05-18T00:00:00.000Z","url":"https://doi.org/10.1523/jneurosci.0077-26.2026","source_score":36,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-22T13:22:29.263Z","updated_at":"2026-05-22T13:22:29.263Z","tags":[{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"condition","value":"Hibernation-Related Neuroplasticity","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"condition","value":"Neurodegeneration","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"condition","value":"Stroke Recovery","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"modality","value":"Neuroanatomical Morphology Assessment","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"warning","value":"Sample sizes per group are not reported in the abstract, so a sample_size tag could not be assigned.","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"warning","value":"The study design tag 'Controlled Animal Study' is used as the closest standard label — no formal randomization or blinding protocol is described in the abstract.","value_numeric":null},{"paper_doi":"10.1523/jneurosci.0077-26.2026","tag_type":"warning","value":"This is a basic science animal study with no human subjects; clinical applicability is speculative and framed as a future translational model.","value_numeric":null}],"summaries":{"what_studied":"Hibernation-related neuroplasticity in the primary visual cortex (V1) of thirteen-lined ground squirrels (*Ictidomys tridecemlineatus*) was examined by comparing neuronal morphology (Golgi-stained tissue) in male and female squirrels during torpor, inter-torpor arousal, and non-hibernating states, with follow-up at 6 months post-hibernation.","key_result":"V1 layer 2/3 pyramidal neurons showed significant reductions in dendritic length, number, and complexity during torpor; these changes fully reversed during inter-torpor arousal, with dendritic arbors growing an average of 0.75 mm (65%) in ~1.5 hours. No lasting morphological differences were found 6 months after hibernation, and layer 4 spiny stellate neurons showed no neuroplastic changes.","limitations":"Study is conducted in a non-human animal model (ground squirrel), limiting direct clinical translation; only male and female squirrels were included without separate sex-stratified analyses reported; morphological assessment is limited to Golgi staining without functional or electrophysiological readouts.","practice_takeaway":"While not yet clinically applicable, the rapid and reversible magnitude of V1 dendritic remodeling in this model (~65% growth in ~1.5 hours) positions ground squirrel V1 as a potentially powerful translational platform for studying neuroplasticity relevant to stroke recovery and neurodegeneration. Clinicians and translational researchers should watch for future studies leveraging this model for neuroplasticity-promoting therapies."}},{"doi":"10.1016/j.healun.2026.05.005","pmid":"42134713","title":"Optimized Cellular Perfusate Increases Lung Viability Ex Vivo and Extends the Duration of Ex Vivo Lung Perfusion","journal_title":"The Journal of Heart and Lung Transplantation","journal_issn":"1053-2498","published_at":"2026-05-14T00:00:00.000Z","url":"https://doi.org/10.1016/j.healun.2026.05.005","source_score":2,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-05-21T13:20:57.997Z","updated_at":"2026-05-21T13:20:57.997Z","tags":[{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"brand","value":"OCS (TransMedics)","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"condition","value":"Ex Vivo Lung Perfusion","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"condition","value":"Graft Preservation","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"condition","value":"Lung Transplantation","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"generic","value":"DEVOL solution","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"modality","value":"Perfusate / Organ Preservation Solution","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"sample_size","value":"n=10","value_numeric":10},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"warning","value":"DEVOL solution is novel and not commercially available; individual component contributions remain under investigation.","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"warning","value":"Study design is best classified as a controlled animal experiment; 'Randomized Controlled Trial' label does not apply here.","value_numeric":null},{"paper_doi":"10.1016/j.healun.2026.05.005","tag_type":"warning","value":"Study is preclinical (porcine model only, n=5 per group); findings may not translate directly to human transplantation.","value_numeric":null}],"summaries":{"what_studied":"This study compared a novel optimized cellular perfusate (DEVOL solution) vs. standard TransMedics OCS perfusate in a porcine ex vivo lung perfusion (EVLP) model (n=5 per group), evaluating physiological parameters, biomarkers, histology, and transcriptomics during extended perfusion.","key_result":"DEVOL perfusate more than tripled median lung perfusion survival time compared to standard OCS perfusate (36 vs. 12 hours), with reduced edema and lower endothelial injury markers (PECAM-1, syndecan-1); transient early rises in PVR and IL-10, and sustained IL-17 elevations were noted without evidence of increased tissue injury.","limitations":"Small sample size (n=5 per group) in a porcine—not human—model limits generalizability; mechanisms underlying late graft failure remain incompletely defined; individual DEVOL component contributions have not yet been isolated.","practice_takeaway":"DEVOL perfusate shows promise for extending EVLP beyond the current 10–12 hour clinical limit to potentially multi-day preservation, which could expand the donor lung utilization window. Human studies are needed before clinical adoption."}},{"doi":"10.1113/jp290431","pmid":"42113966","title":"Δ\n ⁹\n Tetrahydrocannabinol and cannabis extracts differentially improve adipoinsular dysfunction in diet‐induced obesity","journal_title":"The Journal of Physiology","journal_issn":"0022-3751","published_at":"2026-05-11T00:00:00.000Z","url":"https://doi.org/10.1113/jp290431","source_score":57,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:36.091Z","updated_at":"2026-05-18T13:25:36.091Z","tags":[{"paper_doi":"10.1113/jp290431","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Diet-Induced Obesity","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Insulin Resistance","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"generic","value":"tetrahydrocannabinol","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"modality","value":"Cannabinoid","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"sample_size","value":"n=not explicitly stated (multiple mouse cohorts + 3T3-L1 cells)","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Cannabis extract composition (beyond THC content) was not detailed in the abstract, making it difficult to attribute effects to specific non-THC constituents (e.g., CBD, terpenes).","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Study used only male mice — sex-based differences in cannabinoid metabolism and metabolic disease are well documented, limiting generalizability.","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"The study design is preclinical (animal + in vitro); the impact_flag 'limited_evidence' reflects the gap between mouse/cell data and human clinical applicability.","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Total sample size (number of mice per group) was not reported in the abstract; the sample_size tag could not be populated with a precise integer.","value_numeric":null}],"summaries":{"what_studied":"Chronic (30-day) daily administration of THC (5 mg/kg) or THC-matched cannabis extracts in male mice with diet-induced obesity (high-fat/sucrose diet for 60 days), evaluating effects on body weight, fat mass, glucose homeostasis, adipoinsular axis, and cellular bioenergetics in 3T3-L1 adipocytes.","key_result":"Both THC and cannabis extracts reduced body weight and fat mass in obese mice and reversed DIO-associated adipokine dysregulation; however, only cannabis extracts — not THC alone — normalized glucose clearance to levels seen in lean mice.","limitations":"Study was conducted exclusively in male mice, limiting generalizability to females and humans. All findings are preclinical (mouse model and cell culture), so clinical translation is uncertain. THC dose (5 mg/kg) may not map directly to human cannabis consumption patterns.","practice_takeaway":"Chronic cannabinoid exposure — particularly whole cannabis extracts — shows preclinical promise for improving obesity-related metabolic dysfunction and glucose homeostasis, but human clinical evidence is not yet available. Clinicians should not recommend cannabis for obesity or diabetes management based on these findings alone."}},{"doi":"10.1186/s13293-026-00911-y","pmid":"42071257","title":"Reproductive history differentially shapes the neural response of middle-aged hAPOEɛ4 female rats to estradiol therapy after a metabolic challenge","journal_title":"Biology of Sex Differences","journal_issn":"2042-6410","published_at":"2026-05-03T00:00:00.000Z","url":"https://doi.org/10.1186/s13293-026-00911-y","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-10T13:20:49.391Z","updated_at":"2026-05-10T13:20:49.391Z","tags":[{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"condition","value":"Metabolic Dysregulation","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"condition","value":"Neuroinflammation","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"generic","value":"estradiol","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"modality","value":"Estrogen Therapy","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"warning","value":"Sample sizes per subgroup (e.g., nulliparous vs. primiparous × genotype × diet × treatment) are not reported in the abstract/results excerpt — subgroup power may be limited.","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"warning","value":"Study design label 'Controlled Animal Study' is used as the closest standard label; this is a factorial preclinical experiment, not a traditional RCT.","value_numeric":null},{"paper_doi":"10.1186/s13293-026-00911-y","tag_type":"warning","value":"This is a preclinical rat study; findings are mechanistic and hypothesis-generating, not directly applicable to clinical practice without human trial replication.","value_numeric":null}],"summaries":{"what_studied":"This study examined how prior parity (nulliparous vs. primiparous) and APOE genotype (wildtype vs. humanized APOEɛ4) influence brain and metabolic responses to estradiol (E2) therapy in middle-aged female rats (10 months) fed a Western or standard diet for 2 months, with daily E2 or vehicle injections in month 2.","key_result":"E2 reduced Western diet-induced weight gain more strongly in WT than hAPOEɛ4 rats. Primiparous hAPOEɛ4 females on a Western diet showed increased hippocampal inflammatory cytokines with E2, reduced neurogenesis, and impaired contextual fear memory linked to higher weight. Parity boosted neurogenesis and reduced hippocampal cytokines in WT rats on a standard diet.","limitations":"Animal model only (rat), limiting direct translation to human clinical decisions. Study uses a single parity level (primiparous only) and one E2 dose/route, which may not capture the full range of reproductive or hormonal variation. Fear conditioning outcomes may not fully represent complex human memory deficits seen in AD.","practice_takeaway":"When counseling midlife women with the APOEɛ4 allele about hormone therapy, clinicians should factor in both reproductive history (prior pregnancies) and metabolic status — this rat model suggests E2 may carry greater inflammatory and cognitive risks in parous APOEɛ4 carriers with diet-driven weight gain. These findings reinforce the need for personalized, genotype- and parity-informed approaches to menopausal hormone therapy decisions."}},{"doi":"10.1016/j.exer.2026.111037","pmid":"42061597","title":"Vasoactive intestinal peptide attenuates form-deprivation myopia in guinea pigs by suppressing the Wnt/β-catenin pathway along the retina-choroid-scleral axis","journal_title":"Experimental Eye Research","journal_issn":"0014-4835","published_at":"2026-04-28T00:00:00.000Z","url":"https://doi.org/10.1016/j.exer.2026.111037","source_score":2,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-19T13:22:48.809Z","updated_at":"2026-05-19T13:22:48.809Z","tags":[{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"condition","value":"Form-Deprivation Myopia","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"condition","value":"Myopia","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"generic","value":"vasoactive intestinal peptide","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"modality","value":"Vasoactive Intestinal Peptide","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"sample_size","value":"n=99","value_numeric":99},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"warning","value":"Optimal dose identified as 100 pmol intravitreal in this model; dose translation to humans would require additional studies.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"warning","value":"Study is entirely preclinical (guinea pig model and in vitro scleral fibroblasts); no human data. Clinical relevance is speculative at this stage.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111037","tag_type":"warning","value":"The 'pediatric' age group tag reflects the 3-week-old guinea pig developmental stage, which is used as an approximate analog to young/juvenile eyes; direct age equivalence to humans is uncertain.","value_numeric":null}],"summaries":{"what_studied":"Intravitreal vasoactive intestinal peptide (VIP) was evaluated across six doses (0.1–10,000 pmol) in 99 guinea pigs (3 weeks old) with monocular form-deprivation myopia (FDM), measuring refraction and axial length over 4 weeks to identify the optimal dose and assess Wnt/β-catenin pathway modulation along the retina-choroid-scleral axis.","key_result":"VIP (optimal dose: 100 pmol intravitreal) suppressed form-deprivation–induced aberrant activation of scleral Wnt/β-catenin signaling, reduced myopic refractive error and axial elongation in a dose-dependent manner, and partially restored collagen fibril organization in myopic sclera.","limitations":"Animal model only (guinea pigs); intravitreal delivery route may limit clinical translation; mechanistic data from scleral fibroblasts are in vitro and may not fully reflect in vivo complexity.","practice_takeaway":"These findings are preclinical and not yet ready for clinical application, but VIP and Wnt/β-catenin signaling represent potential therapeutic targets worth monitoring as myopia control research matures."}},{"doi":"10.1002/art.70168","pmid":"41940477","title":"Nerve Growth Factor is Sufficient to Cause Multiple Osteoarthritis‐Relevant Pathologic Features in Naïve Murine Knee Joints","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-04-06T00:00:00.000Z","url":"https://doi.org/10.1002/art.70168","source_score":17,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1002/art.70168","days":"7","issn":"2326-5191","rank":"3","field":"Clinical Medicine","score":"17","category":"Rheumatology","categories":["Rheumatology"],"_categories":["Rheumatology"]},"pubmed":{"doi":"10.1002/art.70168","title":"Nerve Growth Factor is Sufficient to Cause Multiple Osteoarthritis-Relevant Pathologic Features in Naïve Murine Knee Joints.","journal":"Arthritis & rheumatology (Hoboken, N.J.)","methods":"","results":"Compared with vehicle, repeated IA injections of NGF caused dose-dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up-regulation of axonal growth pathways in the DRGs. 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Rheumatology"],"reference-count":62,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,5,10]]},"references-count":62,"short-container-title":["Arthritis & Rheumatology"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1002/art.70168","is_oa":true,"title":"NERVE GROWTH FACTOR IS SUFFICIENT TO CAUSE MULTIPLE OSTEOARTHRITIS-RELEVANT PATHOLOGICAL FEATURES IN NAÏVE MURINE KNEE JOINTS","updated":"2026-04-07T15:15:44+00:00","published_date":"2025-06-26","best_oa_location":{"url":"https://doi.org/10.1002/art.70168","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1002/art.70168"}}},"created_at":"2026-05-12T13:18:10.502Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1002/art.70168","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"generic","value":"nerve growth factor","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"modality","value":"Nerve Growth Factor","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sample_size","value":"n=not explicitly stated (multiple cohorts of male C57BL/6 mice)","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Sample size (total N) was not explicitly reported in the abstract; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Study used only male mice; findings may not apply to female biology or human OA populations without further validation.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"The 'practice_changing' impact flag is used cautiously — this is a preclinical animal study, but the mechanistic findings directly inform the clinical controversy around anti-NGF joint side effects.","value_numeric":null}],"summaries":{"what_studied":"Repeated intra-articular (IA) injections of NGF (50 or 500 ng, twice weekly for 4 weeks) into naïve murine knee joints were evaluated for effects on pain sensitization, joint innervation, synovial histopathology, bone, and cartilage using histology, scRNAseq, reporter mice, and bulk DRG RNAseq.","key_result":"NGF caused dose-dependent knee swelling, hyperalgesia, synovial pathology, increased medial subchondral bone mineral density, and medial preosteophytes — but no overt cartilage damage. Nociceptor sprouting in the medial synovium was preceded by upregulation of axonal growth pathways in dorsal root ganglia; scRNAseq implicated lining fibroblasts as key drivers of neuronal sprouting, synovial fibrosis, and ossification.","limitations":"- Animal model only (naïve male C57BL/6 mice); direct translation to human OA pathogenesis is uncertain.\n- Only male mice studied, limiting generalizability to female sex.\n- No cartilage damage was observed, which differs from the full OA phenotype seen in humans.","practice_takeaway":"NGF drives multiple OA-relevant joint changes — including nociceptor sprouting, synovial fibrosis, and subchondral bone remodeling — independent of cartilage damage, supporting its role early in OA pathogenesis. Clinicians should note that while anti-NGF therapies reduce pain, their joint side effects may reflect on-target biological activity of NGF in joint tissues."}}],"initialOffset":18,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"study_design","value":"Controlled Animal Study"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Study Designs","href":"/hub/tag/study_design"},{"name":"Controlled Animal Study"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"study_design","hub_tag_value":"Controlled Animal Study"}}}]]

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