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:T5bc,Cerebrospinal fluid (CSF) flow dynamics play a critical role in clearing pathological proteins from the brain, which may potentially influence the progression of neurodegenerative diseases. We aimed to investigate the alterations of CSF flow dynamics in patients with Parkinson's disease (PD). We employed the multiple low b-values diffusion magnetic resonance imaging combined with CSF-based spatial statistics to evaluate changes of CSF pseudo-diffusivity within ventricles, sulci, and cisterns in PD. We assessed the relationships between CSF pseudo-diffusivity and other indirect markers of glymphatic system, including the diffusion-tensor imaging along the perivascular space (DTI-ALPS) index, the volume of the choroid plexus and perivascular spaces. We explored the association between CSF pseudo-diffusivity and the integrity of the locus coeruleus (LC). A total of 44 patients and 48 healthy controls participated in the study. PD patients showed significantly reduced CSF pseudo-diffusivity within the ventricles and sulci, with no significant changes within the cisterns. Lower CSF pseudo-diffusivity was correlated with lower DTI-ALPS index. Furthermore, decreased CSF pseudo-diffusivity was correlated with LC degeneration. These findings suggested that PD exhibit reduced CSF flow dynamics within the ventricles and sulci. Furthermore, LC-norepinephrine system dysfunction may represent a potential mechanism and target for modulating CSF flow dynamics.31:T626,Parkinson's disease (PD) is the fastest growing neurodegenerative disorder. The current lack of efficient early diagnostic tools necessitates novel approaches to biomarker discovery. We propose an untargeted metabolomics approach using non-invasive exhaled breath analysis. Breath samples, collected from 73 PD patients, encompassing both genetic (LRRK2: n = 12, GBA1: n = 35, PRKN: n = 6) and idiopathic PD (n = 20), 4 unaffected LRRK2 pathogenic variant carriers, and 90 controls underwent extreme-resolution FT-ICR-MS analysis. Findings were compared with metabolomics data from blood plasma. Biostatistical analyses identified discernible metabolic patterns in both biofluids, enabling differentiation of PD patients from healthy controls (OOB error < 1%). Metabolomic breath profiling of PD patients yielded 7 significant metabolites putatively identified as tricosanoic acid, docosanamide, eicosanoic acid, homophytanic acid, nonadecyl-MG, stearic acid, and palmitic acid in PD patients, irrespective of the genetic status. Five of these metabolites were also found in unaffected carriers of pathogenic variants in LRRK2 when compared to controls. Most of the proposed structures are intermediates in fatty acid metabolism, introducing new candidate biomarkers for breath analysis in PD, although their identities require MS/MS confirmation. Breath analysis effectively distinguishes between PD patients and healthy controls and can identify metabolites that could serve as noninvasive biomarkers for PD, potentially including its presymptomatic stage.32:T7eb,Abstract Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder. The current lack of efficient early diagnostic tools necessitates novel approaches to biomarker discovery. We propose an untargeted metabolomics approach using non-invasive exhaled breath analysis. Breath samples, collected from 73 PD patients, encompassing both genetic ( LRRK2 : n = 12, GBA1 : n = 35, PRKN : n = 6) and idiopathic PD (n = 20), 4 unaffected LRRK2 pathogenic variant carriers, and 90 controls underwent extreme-resolution FT-ICR-MS analysis. Findings were compared with metabolomics data from blood plasma. Biostatistical analyses identified discernible metabolic patterns in both biofluids, enabling differentiation of PD patients from healthy controls (OOB error < 1%). Metabolomic breath profiling of PD patients yielded 7 significant metabolites putatively identified as tricosanoic acid, docosanamide, eicosanoic acid, homophytanic acid, nonadecyl-MG, stearic acid, and palmitic acid in PD patients, irrespective of the genetic status. Five of these metabolites were also found in unaffected carriers of pathogenic variants in LRRK2 when compared to controls. Most of the proposed structures are intermediates in fatty acid metabolism, introducing new candidate biomarkers for breath analysis in PD, although their identities require MS/MS confirmation. Breath analysis effectively distinguishes between PD patients and healthy controls and can identify metabolites that could serve as noninvasive biomarkers for PD, potentially including its presymptomatic stage. 33:T733,Children with certain underlying conditions are at higher risk for severe influenza-related complications. In the United States, annual influenza vaccination is recommended for all children aged 6 months and older, yet vaccine effectiveness (VE) in children with underlying conditions remains less understood. We assessed VE against laboratory-confirmed influenza in children with and without underlying conditions presenting to emergency departments or admitted to hospitals. We enrolled US children aged 6 months to 17 years at 7 pediatric medical centers within the New Vaccine Surveillance Network during 5 influenza seasons (2015-2020). Influenza status was confirmed by molecular testing and vaccination status was verified using state immunization registries or from health care clinicians. Underlying conditions were abstracted from medical records or self-reported by parents/guardians. VE was estimated by comparing the odds of vaccination among influenza-positive cases vs controls, adjusting for age, site, and calendar time. Of the 15 875 children included, 2821 (18%) tested positive for influenza. Overall, VE against influenza-associated emergency department visits or hospitalizations was 43% (95% CI: 35%-50%) for children with underlying conditions and 53% (95% CI: 47%-59%) for those without, and there was significant effect measure modification by the presence of underlying conditions (P = .04). VE was lowest among children with respiratory conditions (31%, 95% CI: 19%-42%). Influenza vaccination provided protection in both children with and children without underlying conditions. Efforts to improve influenza vaccination coverage and to initiate early treatment for influenza, particularly in populations at increased risk for severe influenza, are essential to reducing influenza-associated complications.34:T9d9, OBJECTIVE Children with certain underlying conditions are at higher risk for severe influenza-related complications. In the United States, annual influenza vaccination is recommended for all children aged 6 months and older, yet vaccine effectiveness (VE) in children with underlying conditions remains less understood. We assessed VE against laboratory-confirmed influenza in children with and without underlying conditions presenting to emergency departments or admitted to hospitals. METHODS We enrolled US children aged 6 months to 17 years at 7 pediatric medical centers within the New Vaccine Surveillance Network during 5 influenza seasons (2015–2020). Influenza status was confirmed by molecular testing and vaccination status was verified using state immunization registries or from health care clinicians. Underlying conditions were abstracted from medical records or self-reported by parents/guardians. VE was estimated by comparing the odds of vaccination among influenza-positive cases vs controls, adjusting for age, site, and calendar time. RESULTS Of the 15 875 children included, 2821 (18%) tested positive for influenza. Overall, VE against influenza-associated emergency department visits or hospitalizations was 43% (95% CI: 35%-50%) for children with underlying conditions and 53% (95% CI: 47%-59%) for those without, and there was significant effect measure modification by the presence of underlying conditions (P = .04). VE was lowest among children with respiratory conditions (31%, 95% CI: 19%-42%). CONCLUSION Influenza vaccination provided protection in both children with and children without underlying conditions. Efforts to improve influenza vaccination coverage and to initiate early treatment for influenza, particularly in populations at increased risk for severe influenza, are essential to reducing influenza-associated complications. 35:T660,This study was designed to identify genes for further study as modifiers of the severity of cardiomyopathy in DMD-related Duchenne Muscular Dystrophy (DMD). We evaluated genome sequencing results in a well-phenotyped DMD cohort with severe cardiomyopathy against those with less severe cardiomyopathy. Using combined annotation-dependent depletion variant annotation to look at variant burden, we created a difference between group mean (DBGM) summative C-Scores by gene. We completed analyses on three groups. For each analysis, we normalized DBGM summative C-Score and determined which genes had a value > three standard deviations from the mean in all three analyses. There were 54 DMD males in this analysis. 18 individuals (33%) had severe cardiomyopathy and 36 individuals (67%) had less severe cardiomyopathy. Nine genes were identified as possible cardiomyopathy severity modifiers: ANKLE1, ESRRA, FRAS1, GEMIN4, GXYLT1, MTCH2, PKD1L2, PRSS2 and QRFPR. DBGM summative C-Scores in well-phenotyped groups are a feasible exploratory method to identify genetic targets for additional study. There is preliminary evidence from this and other studies suggesting further evaluation of ESRRA, GEMIN4, and MTCH2 as modifiers of cardiomyopathy severity could advance understanding of DMD cardiomyopathy progression. This article identifies possible genetic modifiers of DMD cardiomyopathy severity via a novel method of looking at variant burden between groups. This adds to the existing literature by providing new evidence for modifier pathway targets for possible therapeutic targets or drug repurposing in a rare genetic disorder.36:Te89,Abstract Background This study was designed to identify genes for further study as modifiers of the severity of cardiomyopathy in DMD- related Duchenne Muscular Dystrophy (DMD). Methods We evaluated genome sequencing results in a well-phenotyped DMD cohort with severe cardiomyopathy against those with less severe cardiomyopathy. Using combined annotation-dependent depletion variant annotation to look at variant burden, we created a difference between group mean (DBGM) summative C-Scores by gene. We completed analyses on three groups. For each analysis, we normalized DBGM summative C-Score and determined which genes had a value > three standard deviations from the mean in all three analyses. Results There were 54 DMD males in this analysis. 18 individuals (33%) had severe cardiomyopathy and 36 individuals (67%) had less severe cardiomyopathy. Nine genes were identified as possible cardiomyopathy severity modifiers: ANKLE1 , ESRRA , FRAS1 , GEMIN4 , GXYLT1 , MTCH2 , PKD1L2 , PRSS2 and QRFPR . Conclusion DBGM summative C-Scores in well-phenotyped groups are a feasible exploratory method to identify genetic targets for additional study. There is preliminary evidence from this and other studies suggesting further evaluation of ESRRA , GEMIN4 , and MTCH2 as modifiers of cardiomyopathy severity could advance understanding of DMD cardiomyopathy progression. Impact

This article identifies possible genetic modifiers of DMD cardiomyopathy severity via a novel method of looking at variant burden between groups. This adds to the existing literature by providing new evidence for modifier pathway targets for possible therapeutic targets or drug repurposing in a rare genetic disorder.

37:T884,Innovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear. To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC. HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025. The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models. A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non-industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor. In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure.38:Tc9f, Importance Innovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear. Objective To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC. Design and Setting HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025. Main Outcomes and Measures The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models. Results A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non–industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor. Conclusions and Relevance In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure. 39:Tbc7,During the 2024-2025 respiratory syncytial virus (RSV) season in the US, nirsevimab and maternal RSV vaccination became widely available to prevent severe RSV disease in infants. Assessments of the real-world effectiveness and impact of both products are needed to inform RSV prevention policy. To estimate nirsevimab and maternal RSV vaccine effectiveness against medically attended RSV-associated acute respiratory illness (ARI) and to estimate the impact of these products on RSV-associated hospitalizations during 2024-2025. Population-based surveillance for medically attended ARI was conducted among children younger than 2 years with systematic molecular testing for RSV. Children were enrolled at 7 US pediatric medical centers from October 1, 2024, through April 30, 2025. A test-negative case-control design was used to estimate maternal RSV vaccine and nirsevimab effectiveness. To estimate maternal RSV vaccine effectiveness, the exposure was maternal RSV vaccination among newborns and infants younger than 6 months at medical encounters; to estimate nirsevimab effectiveness, the exposure was nirsevimab receipt among newborns and infants younger than 8 months as of October 1, 2024, or born after that date. The primary outcome was medically attended RSV-associated ARI and RSV-associated hospitalization. Immunization effectiveness was calculated as (1 - adjusted odds ratio) × 100%. To estimate population-level impact of RSV prevention products, relative rate reductions were estimated by comparing observed RSV-associated hospitalization rates during 2024-2025 to (1) observed rates in 2017-2020 or (2) counterfactual 2024-2025 rates estimated by a difference-in-differences approach; estimates from both approaches are presented as ranges. Overall, 5029 children younger than 2 years with medically attended ARI were enrolled during October 2024 to April 2025. Median (IQR) age was 10 months (5-16 months), and 2176 children (43.3%) were female. Among newborns and infants younger than 6 months, maternal RSV vaccine effectiveness was 64% (95% CI, 37%-79%) against any medically attended RSV-associated ARI and 70% (95% CI, 37%-86%) against RSV-associated hospitalization. Nirsevimab effectiveness was 81% (95% CI, 71%-87%) against RSV-associated hospitalization, and nirsevimab remained 77% (95% CI, 42%-92%) effective against RSV-associated hospitalization at 130 to 210 days after receipt. RSV-associated hospitalizations were reduced by 41% to 51% among newborns and infants aged 0 to 11 months, with the highest reduction of 56% to 63% in those aged 0 to 2 months. According to the results of this population-based surveillance study, during 2024-2025, both maternal RSV vaccine and nirsevimab were estimated to be effective at protecting infants from RSV-associated hospitalizations in their first RSV season, and RSV-associated hospitalization rates in newborns and infants aged 0 to 11 months were reduced by up to half compared to seasons before these products were introduced.3a:T109e, Importance During the 2024-2025 respiratory syncytial virus (RSV) season in the US, nirsevimab and maternal RSV vaccination became widely available to prevent severe RSV disease in infants. Assessments of the real-world effectiveness and impact of both products are needed to inform RSV prevention policy. Objectives To estimate nirsevimab and maternal RSV vaccine effectiveness against medically attended RSV-associated acute respiratory illness (ARI) and to estimate the impact of these products on RSV-associated hospitalizations during 2024-2025. Design, Setting, and Participants Population-based surveillance for medically attended ARI was conducted among children younger than 2 years with systematic molecular testing for RSV. Children were enrolled at 7 US pediatric medical centers from October 1, 2024, through April 30, 2025. A test-negative case-control design was used to estimate maternal RSV vaccine and nirsevimab effectiveness. Exposures To estimate maternal RSV vaccine effectiveness, the exposure was maternal RSV vaccination among newborns and infants younger than 6 months at medical encounters; to estimate nirsevimab effectiveness, the exposure was nirsevimab receipt among newborns and infants younger than 8 months as of October 1, 2024, or born after that date. Main Outcomes and Measures The primary outcome was medically attended RSV-associated ARI and RSV-associated hospitalization. Immunization effectiveness was calculated as (1 − adjusted odds ratio) × 100%. To estimate population-level impact of RSV prevention products, relative rate reductions were estimated by comparing observed RSV-associated hospitalization rates during 2024-2025 to (1) observed rates in 2017-2020 or (2) counterfactual 2024-2025 rates estimated by a difference-in-differences approach; estimates from both approaches are presented as ranges. Results Overall, 5029 children younger than 2 years with medically attended ARI were enrolled during October 2024 to April 2025. Median (IQR) age was 10 months (5-16 months), and 2176 children (43.3%) were female. Among newborns and infants younger than 6 months, maternal RSV vaccine effectiveness was 64% (95% CI, 37%-79%) against any medically attended RSV-associated ARI and 70% (95% CI, 37%-86%) against RSV-associated hospitalization. Nirsevimab effectiveness was 81% (95% CI, 71%-87%) against RSV-associated hospitalization, and nirsevimab remained 77% (95% CI, 42%-92%) effective against RSV-associated hospitalization at 130 to 210 days after receipt. RSV-associated hospitalizations were reduced by 41% to 51% among newborns and infants aged 0 to 11 months, with the highest reduction of 56% to 63% in those aged 0 to 2 months. Conclusions and Relevance According to the results of this population-based surveillance study, during 2024-2025, both maternal RSV vaccine and nirsevimab were estimated to be effective at protecting infants from RSV-associated hospitalizations in their first RSV season, and RSV-associated hospitalization rates in newborns and infants aged 0 to 11 months were reduced by up to half compared to seasons before these products were introduced. 3b:T4ba,Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.3c:T6c5,Abstract Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls ( n = 35), acutely infected individuals ( n = 54), convalescent controls ( n = 24) and patients with LC ( n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls ( n = 20) and patients with LC ( n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease. 3d:Tb7a,Parkinson's disease is a progressive neurodegenerative disorder characterized by motor dysfunction, dopaminergic neuronal loss in the substantia nigra and abnormal accumulation of α-synuclein Lewy bodies. Research suggests that the cerebrovascular system plays a role in fluid dynamics, waste clearance and removal of abnormal proteins. Imaging studies show that this waste clearance system, known as the glymphatic system, is disrupted in Parkinson's disease, highlighting its involvement in the disease. This immunohistochemical human brain tissue study quantified changes in the cerebrovascular system (perivascular space, string vessels, pericytes, aquaporin-4 and astrocytes) in Parkinson's disease (n = 18) cases with variable disease durations (median = 14 years, range = 19 years) compared with age- and post-mortem-matched (P > 0.05) control cases (n = 7). Analysis was carried out in brain regions variably affected by cell loss (substantia nigra) and protein deposition (substantia nigra and medial temporal cortex). The occipital cortex was included because this region is not affected by cell loss or protein deposition. Group differences were analysed, and the relationship with protein deposition (Lewy body stage, amyloid score and neurofibrillary tangle score) was assessed. Although total astrocyte density did not change (P > 0.05), Parkinson's disease cases exhibited reduced aquaporin-4 in astrocytic endfeet and enlargement of the arteriolar and venular perivascular space. Significant changes in the capillary network were also observed, with increased presence of string vessels (P < 0.001) and pericyte loss (P < 0.001), changes likely to impact blood flow and its regulation. The increased presence of string vessels was significantly correlated with disease duration (P < 0.05), especially in the occipital cortex. The occipital cortex demonstrated the greatest decreases in pericytes (P < 0.001) and aquaporin-4 mislocalization (P < 0.05), and changes in pericyte density were also significant in the substantia nigra. In contrast, these changes were not significant in the medial temporal cortex despite protein deposition in this region. Although no Lewy pathology was detected in the occipital cortex, there was a positive relationship between Lewy body stage and perivascular space size (ρ = 0.6, P < 0.05). These findings reveal progressive, region-specific alterations in the cellular components of the glymphatic system and vascular integrity in Parkinson's disease. Notably, the correlation between increased presence of string vessels and disease duration, even in a region unaffected by protein deposition, suggests that vascular changes might play an important role in disease progression. These results emphasize the need for further investigation into the interplay between regional vascular changes and Parkinson's disease progression, which might offer new insights for therapeutic strategies.3e:Tc60,Abstract Parkinson's disease is a progressive neurodegenerative disorder characterized by motor dysfunction, dopaminergic neuronal loss in the substantia nigra and abnormal accumulation of α-synuclein Lewy bodies. Research suggests that the cerebrovascular system plays a role in fluid dynamics, waste clearance and removal of abnormal proteins. Imaging studies show that this waste clearance system, known as the glymphatic system, is disrupted in Parkinson's disease, highlighting its involvement in the disease. This immunohistochemical human brain tissue study quantified changes in the cerebrovascular system (perivascular space, string vessels, pericytes, aquaporin-4 and astrocytes) in Parkinson's disease (n = 18) cases with variable disease durations (median = 14 years, range = 19 years) compared with age- and post-mortem-matched (P > 0.05) control cases (n = 7). Analysis was carried out in brain regions variably affected by cell loss (substantia nigra) and protein deposition (substantia nigra and medial temporal cortex). The occipital cortex was included because this region is not affected by cell loss or protein deposition. Group differences were analysed, and the relationship with protein deposition (Lewy body stage, amyloid score and neurofibrillary tangle score) was assessed. Although total astrocyte density did not change (P > 0.05), Parkinson's disease cases exhibited reduced aquaporin-4 in astrocytic endfeet and enlargement of the arteriolar and venular perivascular space. Significant changes in the capillary network were also observed, with increased presence of string vessels (P < 0.001) and pericyte loss (P < 0.001), changes likely to impact blood flow and its regulation. The increased presence of string vessels was significantly correlated with disease duration (P < 0.05), especially in the occipital cortex. The occipital cortex demonstrated the greatest decreases in pericytes (P < 0.001) and aquaporin-4 mislocalization (P < 0.05), and changes in pericyte density were also significant in the substantia nigra. In contrast, these changes were not significant in the medial temporal cortex despite protein deposition in this region. Although no Lewy pathology was detected in the occipital cortex, there was a positive relationship between Lewy body stage and perivascular space size (ρ = 0.6, P < 0.05). These findings reveal progressive, region-specific alterations in the cellular components of the glymphatic system and vascular integrity in Parkinson's disease. Notably, the correlation between increased presence of string vessels and disease duration, even in a region unaffected by protein deposition, suggests that vascular changes might play an important role in disease progression. These results emphasize the need for further investigation into the interplay between regional vascular changes and Parkinson's disease progression, which might offer new insights for therapeutic strategies.3f:T5b0,Postacute sequelae of SARS-CoV-2 infection, also known as long COVID (LC), is a complex and heterogenous condition affecting millions worldwide with a poorly understood underlying pathology. Although metabolic dysregulations have been described in LC, it remains unclear whether circulating immune cells exhibit immunometabolic alterations. We conducted a detailed clinical, immunologic, and mitochondrial analysis on 27 patients with LC and 27 who recovered from COVID-19 and were healthy. Symptom burden and severity were assessed and quantified via a digital platform with the modified COVID-19 Yorkshire Rehabilitation Scale. Mitochondrial function of circulating immune cell populations (lymphocytes and monocytes) was analyzed by measuring mitochondrial mass and mitochondrial membrane potential. Production of 11 cytokines after whole blood stimulation with bacterial and viral agonists was measured by multiplex immunoassay. Relationships between mitochondrial and immune parameters with LC symptoms were investigated. Patients with LC exhibited significant symptom burden, with worsening across all symptom domains as compared with their health state before SARS-CoV-2 infection. They also had a decreased mitochondrial membrane potential of CD56 Symptom severity in LC is associated with immune cell mitochondrial dysfunction and altered cytokine responses, highlighting potential disease biomarkers and targets for future therapeutic strategies.40:T9d3,Abstract Background Postacute sequelae of SARS-CoV-2 infection, also known as long COVID (LC), is a complex and heterogenous condition affecting millions worldwide with a poorly understood underlying pathology. Although metabolic dysregulations have been described in LC, it remains unclear whether circulating immune cells exhibit immunometabolic alterations. Methods We conducted a detailed clinical, immunologic, and mitochondrial analysis on 27 patients with LC and 27 who recovered from COVID-19 and were healthy. Symptom burden and severity were assessed and quantified via a digital platform with the modified COVID-19 Yorkshire Rehabilitation Scale. Mitochondrial function of circulating immune cell populations (lymphocytes and monocytes) was analyzed by measuring mitochondrial mass and mitochondrial membrane potential. Production of 11 cytokines after whole blood stimulation with bacterial and viral agonists was measured by multiplex immunoassay. Relationships between mitochondrial and immune parameters with LC symptoms were investigated. Results Patients with LC exhibited significant symptom burden, with worsening across all symptom domains as compared with their health state before SARS-CoV-2 infection. They also had a decreased mitochondrial membrane potential of CD56bright natural killer cells, particularly in patients experiencing dizziness, whereas reduced mitochondrial membrane potential in CD4+ lymphocytes was found in patients with worsening breathlessness. Upon LPS stimulation, patients with LC demonstrated significantly lower IFN-γ production. In response to viral ligand R848, impaired IFN-β and IL-10 responses were associated with worsening cough and executive functions. Conclusions Symptom severity in LC is associated with immune cell mitochondrial dysfunction and altered cytokine responses, highlighting potential disease biomarkers and targets for future therapeutic strategies. 41:T767,Pediatric anxiety disorders are common and predict adult psychopathology, yet current treatments, such as cognitive-behavioral therapy (CBT), produce lasting remission in less than 50% of affected youths. To support the search for improved, mechanistically grounded interventions, this study evaluated neural efficiency, defined as similarity in functional connectivity between a threat task and rest, as a potential biomarker. The study evaluated neural efficiency in relation to anxiety diagnosis and treatment response. The authors compared 103 youths with an anxiety disorder diagnosis (mean age, 12.5 years [SD=2.91], 62% female) to 103 youths with no psychiatric diagnosis (mean age, 13.4 years [SD=2.58], 53% female). Participants completed functional MRI while resting and during a dot-probe task with threatening faces. Neural efficiency was calculated as partial correlations between intrinsic and task-related functional connectivity patterns across the whole brain. Four-month test-retest reliability as well as relationships with anxiety and response to exposure-based CBT were examined. Neural efficiency demonstrated satisfactory test-retest reliability (intraclass correlation coefficient=0.65) in healthy youths over a period of 11 to 18 weeks. Neural efficiency was significantly negatively related to anxiety as both a diagnostic category (t=2.62, d=0.29) and a symptom dimension (r=-0.18). Although it did not change after CBT, lower neural efficiency at baseline was significantly associated with poorer treatment response in a subset of 80 anxious youths who underwent CBT (β=-11.88, χ Neural efficiency, measured as network reconfiguration between rest and task, holds promise as a biomarker in pediatric anxiety. Its association with CBT response suggests that it might aid in patient stratification and offer a target for interventions aimed at enhancing CBT efficacy.42:T441,Giant cell arteritis (GCA) is a large-vessel vasculitis, potentially causing complications such as blindness and strokes. This study aims to gain insights into the pathogenesis of GCA by identifying specific DNA methylation signatures in the arterial tissue of patients with this vasculitis. DNA methylation profiling was analyzed in 79 temporal artery biopsy samples (69 patients with GCA and 10 controls) by performing an epigenome-wide association study (EWAS). Differential analysis was performed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs). Lastly, we compared our findings with previous transcriptomics and epigenomics studies on GCA-affected arteries. EWAS identified 3,644 DMPs (P Our study identified GCA-specific DNA methylation signatures in arterial tissue, revealing disrupted inflammatory and vascular pathways and suggesting the involvement of exhausted T cells in this condition. These findings offer new insights into GCA pathogenesis and provide new potential targets for the treatment of this debilitating disease.43:Taaf, Objective Giant cell arteritis (GCA) is a large‐vessel vasculitis, potentially causing complications such as blindness and strokes. This study aims to gain insights into the pathogenesis of GCA by identifying specific DNA methylation signatures in the arterial tissue of patients with this vasculitis. Methods DNA methylation profiling was analyzed in 79 temporal artery biopsy samples (69 patients with GCA and 10 controls) by performing an epigenome‐wide association study (EWAS). Differential analysis was performed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs). Lastly, we compared our findings with previous transcriptomics and epigenomics studies on GCA‐affected arteries. Results EWAS identified 3,644 DMPs ( P adj < 0.05, |Δβ| > 0.3), indicating a profound alteration within GCA‐affected arterial tissue. These DMPs were annotated to 1,517 potentially dysregulated genes. A total of 282 additional genes were identified by annotation of significant DMRs. Pathway enrichment analysis revealed a significant alteration of inflammatory mechanisms, such as interleukin‐2 and interleukin‐7, as well as pathways related to vascular remodeling. Omics study comparison revealed 37 genes consistently affected across datasets, many of them linked to immune signaling and T cell regulation. Notably, markers of exhausted T cells, including SLAMF6 and HAVCR2 , were present among them. Conclusion Our study identified GCA‐specific DNA methylation signatures in arterial tissue, revealing disrupted inflammatory and vascular pathways and suggesting the involvement of exhausted T cells in this condition. These findings offer new insights into GCA pathogenesis and provide new potential targets for the treatment of this debilitating disease. 44:T52f,A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.45:Tbc1,The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.46:Tef1,ImportanceThe gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.ObjectiveTo characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.Design, Setting, and ParticipantsThis single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment−naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021.Main Outcomes and MeasuresFecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups.ResultsA total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P &lt; .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P &lt; .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.Conclusions and RelevanceThe findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. 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approach. Of 15,875 enrolled, 2,821 (18%) tested positive; vaccination status was registry/clinician verified, and underlying conditions were from records or parent/guardian report.","key_result":"Vaccine effectiveness against influenza-associated ED visits or hospitalizations was 43% (95% CI 35%–50%) in children with underlying conditions and 53% (95% CI 47%–59%) in those without, with a significant difference by underlying condition status (P=.04); VE was lowest in children with respiratory conditions at 31% (95% CI 19%–42%).","limitations":"Underlying conditions were obtained from medical records or parent/guardian self-report. Findings reflect ED and inpatient encounters at 7 centers during 2015–2020 and may not represent outpatient illness or other settings.","practice_takeaway":"Vaccinate all eligible children, including those with chronic conditions; expect meaningful protection against ED visits and hospitalizations, though protection may be lower in children with respiratory comorbidities. For high-risk children with suspected influenza, prioritize early treatment."}},{"doi":"10.1038/s41390-025-04683-w","pmid":"41501410","title":"Variant burden and severity of cardiomyopathy in patients with DMD-related Duchenne muscular dystrophy","journal_title":"Pediatric Research","journal_issn":"0031-3998","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.1038/s41390-025-04683-w","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-12","doi":"10.1038/s41390-025-04683-w","days":"7","issn":"0031-3998","rank":"10","field":"Clinical Medicine","score":"19","category":"Pediatrics","categories":["Pediatrics"],"_categories":["Pediatrics"]},"pubmed":{"doi":"10.1038/s41390-025-04683-w","title":"Variant burden and severity of cardiomyopathy in patients with DMD-related Duchenne muscular dystrophy.","journal":"Pediatric research","methods":"","results":"There were 54 DMD males in this analysis. 18 individuals (33%) had severe cardiomyopathy and 36 individuals (67%) had less severe cardiomyopathy. Nine genes were identified as possible cardiomyopathy severity modifiers: ANKLE1, ESRRA, FRAS1, GEMIN4, GXYLT1, MTCH2, PKD1L2, PRSS2 and QRFPR.","abstract":"$35","keywords":[],"pubmed_id":"41501410","conclusions":"DBGM summative C-Scores in well-phenotyped groups are a feasible exploratory method to identify genetic targets for additional study. There is preliminary evidence from this and other studies suggesting further evaluation of ESRRA, GEMIN4, and MTCH2 as modifiers of cardiomyopathy severity could advance understanding of DMD cardiomyopathy progression.","publication_date":"2026-01-08T00:00:00"},"crossref":{"DOI":"10.1038/s41390-025-04683-w","URL":"https://doi.org/10.1038/s41390-025-04683-w","ISSN":["0031-3998","1530-0447"],"link":[{"URL":"https://www.nature.com/articles/s41390-025-04683-w.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41390-025-04683-w","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41390-025-04683-w.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Variant burden and severity of cardiomyopathy in patients with DMD-related Duchenne muscular dystrophy"],"author":[{"given":"Gabrielle C.","family":"Geddes","sequence":"first","affiliation":[]},{"given":"Stephanie M.","family":"Ware","sequence":"additional","affiliation":[]},{"given":"Tae-Hwi","family":"Schwantes-An","sequence":"additional","affiliation":[]},{"given":"Marco A.","family":"Abreu","sequence":"additional","affiliation":[]},{"given":"John J.","family":"Parent","sequence":"additional","affiliation":[]},{"given":"Conner C.","family":"Earl","sequence":"additional","affiliation":[]},{"given":"Jonathan H.","family":"Soslow","sequence":"additional","affiliation":[]},{"given":"Larry W.","family":"Markham","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,1,7]]},"member":"297","prefix":"10.1038","source":"Crossref","volume":null,"created":{"date-time":"2026-01-07T10:23:14Z","timestamp":1767781394000,"date-parts":[[2026,1,7]]},"indexed":{"date-time":"2026-01-08T00:04:32Z","timestamp":1767830672516,"date-parts":[[2026,1,8]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000,"date-parts":[[2026,1,7]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000,"date-parts":[[2026,1,7]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$36","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.nature.com/articles/s41390-025-04683-w"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"30 May 2025"},{"name":"revised","group":{"name":"ArticleHistory","label":"Article History"},"label":"Revised","order":2,"value":"8 October 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":3,"value":"20 November 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":4,"value":"7 January 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":1,"value":"J.S. has worked as a consultant for: Boerhinger Ingelheim, Capricor, Dyne, Fibrogen, Immunoforge, Sardocor and Sarepta. 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HNSCC trials on ClinicalTrials.gov (2000–2024) comparing early‑terminated/withdrawn trials with matched completed trials to identify characteristics linked to failure; data were analyzed June–August 2025. A total of 692 matched trials were included (346 failures; 346 completed controls).","key_result":"Top reasons for failure were strategic decisions (102/346; 29.5%) and poor recruitment (90/346; 26.0%). Strategic decisions predominated in phase 1, industry‑sponsored, and immunotherapy/targeted therapy trials, whereas poor recruitment was more common in later‑phase, non‑industry, and chemotherapy/radiation/chemoradiation/combination/supportive‑care trials; failure rates increased over time, higher enrollment protected against failure, and industry funding was an independent risk factor.","practice_takeaway":"Plan for robust accrual and anticipate sponsor‑driven strategic stops, especially in phase 1 and immunotherapy/targeted therapy trials. 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Median (IQR) age was 10 months (5-16 months), and 2176 children (43.3%) were female. Among newborns and infants younger than 6 months, maternal RSV vaccine effectiveness was 64% (95% CI, 37%-79%) against any medically attended RSV-associated ARI and 70% (95% CI, 37%-86%) against RSV-associated hospitalization. Nirsevimab effectiveness was 81% (95% CI, 71%-87%) against RSV-associated hospitalization, and nirsevimab remained 77% (95% CI, 42%-92%) effective against RSV-associated hospitalization at 130 to 210 days after receipt. 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Persistence beyond 180 days after infection was evaluated against convalescent controls.","key_result":"Long COVID showed persistent immune activation >180 days after infection versus convalescent controls, with upregulated JAK-STAT, interleukin-6, complement, metabolism, and T cell exhaustion pathways; similar patterns were seen in the second cohort.","limitations":"Long COVID sample sizes were small (n=28 and n=18). The abstract reports no quantitative effect sizes or clinical outcomes and focuses on mechanistic profiling.","practice_takeaway":"Patients with Long COVID can exhibit ongoing inflammatory and immune-exhaustion pathway activation beyond 180 days after infection; the findings suggest candidate biomarkers but do not support any specific treatment changes."}},{"doi":"10.1111/irv.70191","pmid":"41290396","title":"COVID‐19 Vaccine Effectiveness Against Hospitalization in Older Adults, VEBIS Hospital Network, Europe, September 2024–May 2025","journal_title":"Influenza and Other Respiratory Viruses","journal_issn":"1750-2640","published_at":"2025-11-26T00:00:00.000Z","url":"https://doi.org/10.1111/irv.70191","source_score":51,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-11-26","doi":"10.1111/irv.70191","days":"14","issn":"1750-2640","rank":"6","field":"Clinical Medicine","score":"51","category":"Infectious Diseases","categories":["Infectious Diseases"],"_categories":["Infectious Diseases"]},"pubmed":{"doi":"10.1111/irv.70191","title":"COVID-19 Vaccine Effectiveness Against Hospitalization in Older Adults, VEBIS Hospital Network, Europe, September 2024-May 2025.","journal":"Influenza and other respiratory viruses","methods":"","results":"","abstract":"We estimated COVID-19 vaccine effectiveness (VE) against PCR-confirmed SARS-CoV-2 hospitalization in patients ≥ 60 years with severe acute respiratory infection, using a multicenter, test-negative, case-control study across seven sites in six European countries between September 2024 and May 2025. We included 352 cases (115 vaccinated; 33%) and 9980 controls (5024 vaccinated; 50%). VE was 42% (95% CI: 15; 61) 14-59 days post-vaccination, 32% (95% CI: -1; 54) at 60-119 days, and 36% (95% CI: 2; 60) at 120-179 days, and no effect thereafter. Among adults aged 60-79 and ≥ 80 years, we observed moderate VE against COVID-19 hospitalization for up to 2 and 4 months, respectively.","keywords":["case–control study","elderly","severe acute respiratory infection (SARI)","test‐negative design","vaccine effectiveness"],"pubmed_id":"41290396","conclusions":"","publication_date":"2025-11-26T00:00:00"},"crossref":{"DOI":"10.1111/irv.70191","URL":"https://doi.org/10.1111/irv.70191","ISSN":["1750-2640","1750-2659"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/irv.70191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"11","score":1,"title":["COVID‐19 Vaccine Effectiveness Against Hospitalization in Older Adults, VEBIS Hospital Network, Europe, September 2024–May 2025"],"author":[{"given":"Madelyn","family":"Rojas‐Castro","sequence":"first","affiliation":[{"name":"Epiconcept Paris France"}]},{"given":"Nuno","family":"Verdasca","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department National Health Institute Doutor Ricardo Jorge Lisbon Portugal"}]},{"given":"Susana","family":"Monge","sequence":"additional","affiliation":[{"name":"National Centre of Epidemiology, CIBERINFEC Institute of Health Carlos III Madrid Spain"}]},{"given":"Laurane","family":"De Mot","sequence":"additional","affiliation":[{"name":"Scientific Directorate of Epidemiology of Infectious Diseases, Sciensano Brussels Belgium"}]},{"given":"Camino","family":"Trobajo‐Sanmartín","sequence":"additional","affiliation":[{"name":"Instituto de Salud Pública de Navarra – IdiSNA – CIBERESP Pamplona Spain"}]},{"given":"Róisín","family":"Duffy","sequence":"additional","affiliation":[{"name":"Health Service Executive‐Health Protection Surveillance Centre (HPSC) Dublin Ireland"}]},{"given":"Gergő","family":"Túri","sequence":"additional","affiliation":[{"name":"National Laboratory for Health Security, Epidemiology and Surveillance Centre Semmelweis University Budapest Hungary"}]},{"given":"Monika","family":"Kuliese","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Lithuanian University of Health Sciences Kaunas Lithuania"}]},{"given":"Ralf","family":"Duerrwald","sequence":"additional","affiliation":[{"name":"National Reference Centre for Influenza Robert Koch Institute Berlin Germany"}]},{"given":"Maria‐Louise","family":"Borg","sequence":"additional","affiliation":[{"name":"Infectious Disease Prevention and Control Unit (IDCU) Msida Malta"}]},{"given":"Odette","family":"Popovici","sequence":"additional","affiliation":[{"name":"National Institute of Public Health (INSP/NIPH) ‐ National Centre for Surveillance and Control of Communicable Diseases Bucharest Romania"}]},{"given":"Verónica","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Epidemiology National Institute of Health Doctor Ricardo Jorge Lisbon Portugal"}]},{"given":"Zvjezdana Lovrić","family":"Makarić","sequence":"additional","affiliation":[{"name":"Divison for Epidemiology of Communicable Diseases Croatian Institute of Public Health Zagreb Croatia"}]},{"given":"Odile","family":"Launay","sequence":"additional","affiliation":[{"name":"INSERM CIC 1417, F‐CRIN, I‐REIVAC Network, Assistance Publique‐Hôpitaux de Paris Hôpital Cochin Paris Paris France"}]},{"given":"Diogo F. 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We included 352 cases (115 vaccinated; 33%) and 9980 controls (5024 vaccinated; 50%). VE was 42% (95% CI: 15; 61) 14–59 days post‐vaccination, 32% (95% CI: −1; 54) at 60–119 days, and 36% (95% CI: 2; 60) at 120–179 days, and no effect thereafter. Among adults aged 60–79 and ≥ 80 years, we observed moderate VE against COVID‐19 hospitalization for up to 2 and 4 months, respectively.","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1111/irv.70191"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2025-07-29"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2025-10-22"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2025-11-25"}],"deposited":{"date-time":"2025-11-26T06:05:58Z","timestamp":1764137158000,"date-parts":[[2025,11,26]]},"issn-type":[{"type":"print","value":"1750-2640"},{"type":"electronic","value":"1750-2659"}],"published":{"date-parts":[[2025,11]]},"publisher":"Wiley","reference":[{"DOI":null,"key":"e_1_2_15_2_1","year":"2024","issue":null,"author":"World Health Organization (WHO)","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_15_3_1","year":"2024","issue":null,"author":"European Medicines Agency (EMA)","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_15_4_1","year":"2024","issue":null,"author":"European Centre for Disease Prevention and Control (ECDC)","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"e_1_2_15_5_1","year":"2024","issue":null,"author":"Mahase E","volume":"386","first-page":null,"unstructured":null,"article-title":"Covid‐19: Are We Seeing a Summer Wave?","journal-title":"BMJ","doi-asserted-by":null},{"DOI":null,"key":"e_1_2_15_6_1","year":"2025","issue":null,"author":"European Centre for Disease Prevention and Control (ECDC)","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.vaccine.2025.126966","key":"e_1_2_15_7_1","year":"2025","issue":null,"author":"Moore M.","volume":"54","first-page":null,"unstructured":null,"article-title":"Durability of COVID‐19 Vaccine and Infection Induced Immunity: A Systematic Review and Meta‐Regression Analysis","journal-title":"Vaccine","doi-asserted-by":"crossref"},{"DOI":null,"key":"e_1_2_15_8_1","year":"2024","issue":null,"author":"European Centre for Disease Prevention and Control (ECDC)","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1002/sim.7273","key":"e_1_2_15_9_1","year":"2017","issue":"14","author":"Puhr R.","volume":"36","first-page":"2302","unstructured":null,"article-title":"Firth's Logistic Regression With Rare Events: Accurate Effect Estimates and Predictions?","journal-title":"Statistics in Medicine","doi-asserted-by":"crossref"},{"DOI":null,"key":"e_1_2_15_10_1","year":"2023","issue":null,"author":"Heinze G","volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1111/irv.13360","key":"e_1_2_15_11_1","year":"2024","issue":"8","author":"Antunes L.","volume":"18","first-page":null,"unstructured":null,"article-title":"Early COVID‐19 XBB.1.5 Vaccine Effectiveness Against Hospitalisation Among Adults Targeted for Vaccination, VEBIS Hospital Network, Europe, October 2023–January 2024","journal-title":"Influenza and Other Respiratory Viruses","doi-asserted-by":"crossref"},{"DOI":"10.1111/irv.70081","key":"e_1_2_15_12_1","year":"2025","issue":"3","author":"Antunes L.","volume":"19","first-page":null,"unstructured":null,"article-title":"Effectiveness of the XBB.1.5 COVID‐19 Vaccines Against SARS‐CoV‐2 Hospitalisation Among Adults Aged ≥ 65 Years During the BA.2.86/JN.1 Predominant Period, VEBIS Hospital Study, Europe, November 2023 to May 2024","journal-title":"Influenza and Other Respiratory Viruses","doi-asserted-by":"crossref"},{"DOI":"10.15585/mmwr.mm7406a1","key":"e_1_2_15_13_1","year":"2025","issue":"6","author":"Link‐Gelles R.","volume":"74","first-page":"73","unstructured":null,"article-title":"Interim Estimates of 2024–2025 COVID‐19 Vaccine Effectiveness Among Adults Aged ≥18 Years — VISION and IVY Networks, September 2024–January 2025","journal-title":"MMWR. 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Group differences and correlations with Lewy body stage, amyloid score, and neurofibrillary tangle score were assessed.","key_result":"Parkinson’s disease showed reduced aquaporin‑4 in astrocytic endfeet, enlarged arteriolar and venular perivascular spaces, more string vessels (P < 0.001), and pericyte loss (P < 0.001), with unchanged total astrocyte density (P > 0.05). String vessels correlated with disease duration (P < 0.05); the occipital cortex had the greatest pericyte decreases (P < 0.001) and aquaporin‑4 mislocalization (P < 0.05), changes were not significant in medial temporal cortex, and perivascular space size correlated with Lewy body stage (ρ = 0.6, P < 0.05).","limitations":"Small sample with 18 Parkinson’s disease and 7 control cases and a post-mortem, cross-sectional design. 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Early-stage melanoma showed higher alpha diversity than late-stage (Inverse Simpson 14.6 [IQR 9.8–23.0] vs 10.8 [7.2–16.8]; P=.003), and in the stage III adjuvant cohort recurrence occurred in 30.3%, with α-diversity differing by recurrence (P=.008) but no microbial taxa predicting recurrence on adjusted analyses.","limitations":"Single-site case-control design with controls sampled in 2021–2022 vs cases in 2015–2019. Functional pathways were inferred from 16S rRNA data rather than directly measured.","practice_takeaway":"Gut microbiota profiles differ between controls and melanoma and between early- and late-stage disease, but specific taxonomic signals attenuate after adjustment and did not predict adjuvant recurrence. 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