bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small fiber pathology in fibromyalgia syndrome
Authors: Sommer Claudia , Üçeyler Nurcan 
Published: December 2024

Abstract
About 50% of women with fibromyalgia syndrome have reduced skin innervation. This finding is consistent in patient cohorts from different regions of the world. Small fiber function may also be affected, as shown by various studies using different methods, such as quantitative sensory testing or special small fiber neurophysiology such as C-fiber microneurography. Microneurography in particular has shown increased spontaneous activity, mechanosensitivity, and enhanced activity-induced slowing in C fibers of patients with fibromyalgia. Generalized reduction of skin innervation, ie, proximally and distally, was associated with higher symptom severity and more pronounced central nervous system changes as seen in magnetic resonance tomography. The question whether peripheral or central nervous system changes come first, or whether both are signs of an underlying pathology, has not been resolved yet. For clinical practice, it is important to note that reduced skin innervation in fibromyalgia must not be confused with small fiber neuropathy, which is a separate entity with different characteristics and pathophysiology. Further prospective research is warranted to transfer these findings in the peripheral nervous system into clinical fibromyalgia patient management.
Applying evidence-based cross-disciplinary concepts helps to explain the heterogeneity in pain, function, and biological measures in individuals with knee pain with/at risk of osteoarthritis
Authors: Mickle Angela M. , Tanner Jared J. , Holmes Udell , Rashid Ahmed , Barolette Olivier , Addison Brittany , Sambuco Nicola , Garvan Cynthia , Lai Song , Seubert Christoph , Schmidt Siegfried , Staud Roland , Edberg Jeffrey C. , Redden David , Goodin Burel R. , Price Catherine C. , Fillingim Roger B. , Sibille Kimberly T. 
Published: December 2024

Abstract

Introduction:
Factors contributing to individual differences in knee osteoarthritis remain elusive. Dispositional traits and socioeconomic status are independent predictors of mental and physical health, although significant variability remains. Dispositional traits serve as the biological interface for life experiences.

Objectives:
We investigate group differences based on dispositional traits and poverty status, specific to (1) pain intensity and functional limitations and (2) biological measures, a clinical composite and brain age.

Methods:
Adults aged 45 to 85 years with knee pain associated with chronic musculoskeletal pain provided information on demographics, socioeconomic and psychosocial factors, pain, and physical function. Kellgren–Lawrence scores were determined from knee radiographs, the clinical composite from fasting blood draws, and brain age from MRI data.

Results:
One hundred seventy-three individuals participated in the study. Of those, 117 had protective dispositional traits (81 above poverty/36 in poverty), and 56 had vulnerable dispositional traits (24 above poverty/32 in poverty). With sex, study site, Kellgren–Lawrence score, and age/or image quality as covariates, significant group differences were observed across clinical pain (P < 0.001), functional limitations (P ≤ 0.001), and brain age (P ≤ 0.002) measures. Although not significant, the clinical composite measure aligned with the other outcome measures and demonstrated the hormesis inverted U pattern.

Conclusions:
Groups based on dispositional traits and socioeconomic status explain differing clinical outcomes. Consistent with the allostatic load and hormesis inverted U models, one group was in an adaptive health status, 2 groups were showing signs of developing load, and the fourth group showing signs of overload, at risk of worse health outcomes.
APHIX: Analysis Pipeline for HIV-1 Isoform eXploration Using Long-read RNA Sequencing Data
Authors: Albert Jessica L , Gallardo Christian M , Torbett Bruce E 
Published: December 2024

AbstractHIV-1 uses 4 major splice donors and 8 major splice acceptors as well as dozens of minor, cryptic, and uncharacterized splice sites to produce over one hundred distinct transcript isoforms from a single 9.2 kb genome. As a result, existing bioinformatic pipelines struggle to accurately analyze spliced HIV sequences due to the complex nature of HIV alternative splicing compared to human mRNA splicing. Previous approaches to identify HIV isoforms from long-read sequencing data used pipelines that are not publicly available, are convoluted to operate, or are locked into a specific HIV strain, which limits their wide adoption to other experimental designs or systems. To address this gap, we have developed a bioinformatic pipeline calledAPHIXthat fully automates spliced isoform assignment, splice site usage quantification, and non-coding exon detection. APHIX takes a FASTQ/A of long-read transcripts and a HIV genome reference sequence and fully automates HIV isoform analysis. APHIX calculates splice site usage counts and percentages for each donor and acceptor site and their pairwise combinations, accurately assigns isoforms, and automatically identifies transcripts containing non-coding exons. APHIX is compatible with long-reads sequences generated from multiple platforms and library preps, including direct DNA and RNA sequencing. APHIX can also be adapted to multiple HIV-1 clades and strains by providing the appropriate reference sequence during bioinformatic processing. Overall, APHIX enables comprehensive processing of spliced sequences with reproducible results in a manner that is faster and easier to run compared to other methods.
Liver Radioembolization: Predicting Lung Shunt Fraction with Contrast-Enhanced CT, Eliminating the Need for 99mTc-MAA
Authors: Mehadji Brahim , Marx Talia , Carter Adrianna , Goldman Roger , Vu Catherine , Roncali Emilie 
Published: December 2024

1.AbstractAccurate estimation of the Lung Shunt Fraction (LSF) is a standard of care in yttrium-90 (90Y) radioembolization treatment planning to prevent excessive lung irradiation due to arterio-venous shunting in the liver. LSF is assessed using99mTc macroaggregated albumin (99mTc-MAA) imaging, but this approach adds risk, complexity, and expense to the treatment planning. This study investigates the potential of Contrast-Enhanced Computed Tomography (CECT) as a non-invasive alternative for LSF estimation.MethodsWe developed a novel metric to estimate the LSF from differences between CECT phases, based on the premise that LSF results from tumor angiogenesis and arterio-venous shunting that create excessive local opacity in the CECT arterial phase. Hypervascular volumes were identified by subtracting the portal phase from the arterial phase and contouring the corresponding regions using an density threshold. The perfused volume corresponded to the lobe and to the volume injected with99mTc-MAA.We conducted a retrospective analysis involving 30 liver cancer patients who underwent 4-phase liver CECT and99mTc-MAA imaging prior to90Y radioembolization to study several markers based on the subtraction images. The patient cohort included several types of liver tumors (primary or metastatic), predominantly hepatocellular carcinoma. Correlations between the hypervascular-to-perfused volume ratio from CECT and LSF values from standard-of-care99mTc-MAA planar imaging were assessed.ResultsThe strongest correlation was obtained between the hypervascular-to-perfused volume ratio from CECT and LSF values from99mTc-MAA planar gamma imaging (R²=0.95). The best correlation was demonstrated when the hypervascular volume was corrected by the hypoxic volume and then normalized by the perfused volume. In contrast, the tumor volume did not show a strong correlation with LSF (R²=0.38). Moreover, the predictive power of the hypervascular-to-perfused volume ratio on LSF demonstrated a 1-sigma uncertainty of 3%.ConclusionCECT-based LSF estimation shows promise as a non-invasive alternative to99mTc-MAA imaging in90Y treatment planning. Further validation with prospective studies on larger cohorts is necessary to confirm the accuracy and safety of this approach.
A STUDY TO ASSESS THE KNOWLEDGE AND ATTITUDE REGARDING OPTIONAL VACCINES AND BARRIERS TO USE AMONG MOTHERS OF UNDER FIVE CHILDREN IN KHEDA GUJARAT
Authors: Parmar Sherin , Dave Shlok , Vankar Sneha , Selot Srusti , Dabhi Sejal , Nagar Kailash 
Published: December 2024

ABSTRACTIntroductionVaccination is a straightforward and reliable method to safeguard oneself from dangerous diseases before encountering them. Vaccination remains one of the most effective public health interventions in human history, significantly reducing the burden of infectious diseases and saving countless lives worldwide.AimTo determine knowledge and attitude regarding optional vaccines and barriers to use among mothers of under five children in Kheda districtMethodologyThe non-experimental Descriptive Survey Research design used for this study. The study was conducted on 384 mothers of under five children from selected areas of Kheda district by systematic random sampling technique. A knowledge questionnaire tool, Likert attitude scale and barrier questionnaire was used for data collection.Result240 (63%) of mothers have low knowledge, 123 (32%) have moderate knowledge, and 21 (5%) have good knowledge regarding optional vaccination. When 1 (0.3%) mother have Unfavourable attitude, 275 (71.6%) have moderate attitude, and 108 (28.1%) have favourable attitude towards optional vaccination. The mean score of attitude is 8.7083. The Correlation-Coefficient (r) of knowledge and attitude is 0.76.ConclusionThe study highlights the disparity between knowledge and attitude regarding optional vaccination among mothers of under five children. Although the majority lack adequate knowledge, a considerable number still maintain a moderate attitude. This emphasizes the need for targeted interventions to improve understanding and promote positive attitudes toward optional vaccination.
Subtypes of Older Adults Starting Long-Term Care in Japan: Unsupervised Machine Learning Approach
Authors: Hamasaki Yoko , Iwagami Masao , Komiyama Jun , Ito Yuji , Taniguchi Yuta , Inokuchi Ryota , Watanabe Taeko , Goto Tadahiro , Kuroda Naoaki , Suzuki Ai , Yoshie Satoru , Ishizaki Tatsuro , Iijima Katsuya , Tamiya Nanako 
Published: December 2024

AbstractObjectivesThe older population requiring long-term care (LTC) exhibits heterogeneity in physical and cognitive functions; however, an established classification is lacking. We aimed to identify distinct subgroups of older adults with LTC needs using unsupervised machine learning and to examine differences in their prognoses.DesignRetrospective cohort study.Setting and participantsUsing survey data for care-need certification (linked to LTC and medical insurance claims) in City A, Japan, we identified community-dwelling adults aged ≥ 65 years who started LTC. Data from City B were used for validation of clustering.MethodsWe applied latent class analysis to group the participants in City A, based on all 74 items (38 on physical functions, 9 on cognitive functions, 15 on behavioral problems, and 12 on medical procedures) in the Japanese standardized care-needs certification survey. Then, we examined the association between the identified subtypes and four outcomes, including death, hospitalization, nursing home admission, and care-need level deterioration, using regression models.ResultsAmong 3,841 participants in City A (median age, 83 years; 59.3% female), five subtypes were identified: (i) mild physical, (ii) mild cognitive, (iii) moderate physical, (iv) moderate multicomponent, and (v) severe multicomponent. The results of clustering were replicated in City B. Compared with the mild physical subtype, the severe multicomponent subtype showed the highest risk of death (adjusted hazard ratio [aHR] 2.56; 95% confidence interval [CI] 2.02–3.24), and nursing home admission (aHR 5.91; 95% CI 4.57–7.63). The moderate physical subtype showed a higher risk of hospitalization (aHR 1.32; 95% CI 1.16–1.49), and the moderate multicomponent subtype was more likely to experience care-need deterioration (adjusted odds ratio 1.67; 95% CI 1.26–2.22).Conclusions and ImplicationsThis study identified five subtypes of older adults who started LTC. These findings inform individualized care decisions and tailored planning of medical and LTC services.
Immune Cell Exhaustion and Apoptotic Markers in Major Depressive Disorder: Effects of in Vitro Cannabidiol Administration
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Tunvirachaisakul Chavit , Sughondhabirom Atapol , Li Jing , Zhang Yingqian , Maes Michael 
Published: December 2024

AbstractBackgroundImmune dysregulation is a component of Major Depressive Disorder (MDD). Cannabidiol (CBD) has immunomodulatory and putative antidepressant effects. The relationship between apoptotic and exhaustion immune markers and the clinical features of MDD and the effects of CBD on these markers are still unknown.ObjectivesTo assess pro-apoptotic (CD95) and T cell exhaustion (TIM-3) markers on immune cells in patients with MDD, as well as the impact of in vitro CBD administration on these markers.MethodsWe recruited healthy controls and MDD patients and evaluated the immunophenotypes of T/B lymphocytes using flow cytometry in unstimulated and anti-CD3/CD28 stimulated conditions. We evaluated the immune profiles of M1 macrophages, T helper (Th)17 cells, immune-inflammatory response system (IRS), T cell proliferation, and immune-related neurotoxicity (IRN). We investigated the in vitro effects of CBD on immune cell subsets at concentrations of 0.1 µg/mL, 1 µg/mL, and 10.0 µg/mL.ResultsThe stimulated CD3+CD95+ cell percentages were substantially correlated with the number of depressive episodes, recurrence of illness, and suicidal behaviors. The stimulated CD8+TIM-3+ cell percentages were substantially and inversely associated with the M1, IRS, CIRS, T cell growth, and IRN immune profiles. TIM-3+ bearing CD3+, CD4+ and CD8+,cells were significantly suppressed by lower CBD concentrations (0.1 – 1 µg/mL). TIM-3+ and all CD95+ bearing cells, with the exception of CD3+CD95+, were suppressed by the higher CBD concentrations.DiscussionAberrations in immune checkpoint molecular processes impact the features of MDD. CBD significantly impacts apoptotic and exhaustion processes thereby possibly interfering with immune homeostasis.
Sex hormone-binding globulin, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause
Authors: Goedecke Julia H. , Kufe Clement Nyuyki , Masemola Maphoko , Lichaba Mamosilo , Seipone Ikanyeng D. , Mendham Amy E , Gibson Hylton , Hawley James , Selva David M. , Magodoro Itai , Kengne Andre Pascal , Chikowore Tinashe , Crowther Nigel J. , Norris Shane A , Karpe Fredrik , Olsson Tommy , Storbeck Karl-Heinz , Micklesfield Lisa K. 
Published: December 2024

AbstractObjectivesSex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. We investigated whether these associations differ by HIV and menopausal status in Black South African women living with (WLWH) and without HIV (WLWOH).DesignCross-sectional observational.MethodsEighty one premenopausal (57 WLWOH, 24 WLWH) and 280 postmenopausal (236 WLWOH, 44 WLWH) women from the Middle-Aged Soweto Cohort (MASC) completed the following measures: circulating SHBG and sex hormones, body composition (dual energy x-ray absorptiometry), oral glucose tolerance test to estimate insulin sensitivity (Matsuda index), secretion (insulinogenic index, IGI) and clearance, and beta-cell function (disposition index, DI). Dysglycaemia was defined as either impaired fasting or postprandial glucose or T2D.ResultsSHBG was higher and total and free testosterone were lower in postmenopausal WLWH than WLWOH (all p<0.023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance and DI and inversely with HOMA-IR (all p<0.011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (p=0.043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (p=0.021), and positively associated with HOMA-IR in premenopausal and not post-menopausal women (p=0.015 for interaction).ConclusionsWe show for the first time that midlife African WLWH have higher SHBG and lower total and free testosterone than WLWOH, which corresponded to their higher beta-cell function, suggesting a putative protective effect of SHBG on T2D risk in WLWH.Significance statementThis study in midlife Black African women suggest that higher sex hormone binding protein (SHBG) and lower free testosterone in women living with HIV (WLWH) may be associated with reduced risk of type 2 diabetes (T2D) compared to women living without HIV. Further, this study provides a putative mechanism underlying the lower prevalence of T2D in WLWH and obesity compared to women living with obesity but without HIV. However, longitudinal studies are required to understand the clinical implications of these findings.
No one-size-fits-all approach: Retrospective analysis of efficacy and safety of serum concentrations of continuously administered vancomycin in critically ill adults reveals different target serum concentrations depending on disease severity
Authors: Viertel Katrin , van Meegen Carmen , Herbrandt Swetlana , Annecke Thorsten , Mattner Frauke 
Published: December 2024

AbstractBackgroundVancomycin is frequently monitored, but target levels for continuous infusion of vancomycin (CIV) are based on expert opinion. Rarely have vancomycin concentrations been correlated with therapeutic efficacy or safety of CIV.ObjectivesAssociations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.MethodsA retrospective, single-centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010-2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (</≥90mL/min/1.73m²) and Simplified Acute Physiology Score (SAPS) II (≤/>36). Failure and toxicity of vancomycin serum concentrations were assessed using primary (mortality, acute kidney injury (AKI)) and secondary (clinical and microbiological failure) endpoints. Predictors of outcome parameters were identified using logistic and Cox regression. Concentrations were compared by bivariate comparisons, post-hoc tests following analysis of variance for the regression models and desirability of outcome ranking. Concentration cut-offs were determined by receiver-operating characteristic and classification and regression tree analyses.Results922 patients were included. Higher vancomycin concentrations (first 72h average; specifically >25mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS>36, concentrations <20mg/L (i.e. 15-20mg/L or <17mg/L) correlated with the best treatment outcome, for SAPS≤36 concentrations >19mg/L (i.e. 20-25mg/L or 19-28mg/L).ConclusionRetrospective analyses of vancomycin serum concentrations during CIV suggest that ICU patients’ disease severity should be considered when selecting a target concentration. The target concentration might be sought inversely related to SAPS, which should be confirmed in future prospective controlled trials.
Early effectiveness of the BNT162b2 KP.2 vaccine against COVID-19 in the US Veterans Affairs Healthcare System
Authors: Appaneal Haley J. , Lopes Vrishali V. , Puzniak Laura , Zasowski Evan J. , Jodar Luis , McLaughlin John M. , Caffrey Aisling R. 
Published: December 2024

ABSTRACTWe conducted a test-negative case-control study within the US Veterans Affairs Healthcare System to estimate early vaccine effectiveness (VE) of the BNT162b2 KP.2 vaccine (Pfizer 2024-2025 formulation) against COVID-19 outcomes. Among 44,598 acute respiratory infections between September 5 and November 30, 2024, VE was 68% (42-82%), 57% (46-65%), and 56% (36-69%) against COVID-19-associated hospitalizations, emergency department and urgent care visits, and outpatient visits, respectively. Uptake of updated COVID-19 vaccines remains low.
Clonal expansion from standing genetic variation underpins the evolution of an emerging plant pathogen in Australia
Authors: Sparks Adam H. , Adorada Dante L. , Colombi Elena , Kelly Lisa A. , Young Anthony , Knight Noel L. , Vaghefi Niloofar 
Published: December 2024

AbstractPathogens can evolve rapidly, leading to the emergence of novel strains that can overcome commercially deployed host plant resistance. Understanding the genetic and phenotypic diversity and population dynamics of plant pathogens is crucial to inform breeding programs targeting resistance. Tan spot, otherwise known as bacterial wilt, caused byCurtobacterium flaccumfacienspv.flaccumfaciens, is a destructive disease of mungbean in Australia. Since the 1990s, several mungbean cultivars with partial resistance to tan spot have been released; however, cultivars initially rated as moderately resistant were later rated as moderately susceptible to tan spot. This study investigated the genetic and phenotypic diversity and temporal evolutionary dynamics ofC. flaccumfacienspv.flaccumfaciensin Australian mungbean fields. Whole-genome sequencing of 119 isolates collected from mungbean and other legumes (1986–2019) enabled analyses of pathogen evolution in Australia and in a global context. Results revealed that clonal expansion from standing genetic variation, rather than introduction of novel genotypes, has driven the evolution of this pathogen in Australia since the 1980s. Glasshouse trials confirmed the role of a plasmid in pathogenicity ofC. flaccumfacienspv.flaccumfaciensbut found no significant differences in aggressiveness between clonal lineages. This study underscores the importance of understanding pathogen diversity and aggressiveness to guide breeding programs for effective and durable disease resistance and highlights the need for further studies on the competitive fitness of isolates and characterisation of private alleles linked to dominant clonal lineages.SignificanceTan spot is an increasingly significant pathogen affecting beans and mungbean worldwide, with a broad host range and quarantine importance in many countries underscoring the need for effective breeding strategies to manage the disease. Our research provides insights into genetic and phenotypic diversity of this important plant pathogen and temporal changes in its population structure in Australia, which are crucial for developing informed breeding strategies and managing the spread and impact of the disease. This work also underscores the critical need for robust, validated screening protocols and selection of aggressive, locally representative isolates for resistance breeding to ensure accurate assessment of resistance in crops for effective and durable resistance.