bluuebunny/crossref_metadata_2025 huggingface dataset:
“Biceps femoris calcific tendinitis as a rare cause of lateral knee pain; a case report”
Authors: Karki Shivaji , Pokhrel Sushil , Khadka Karuna
Published: February 2025

Introduction:

Calcific tendinitis is a common cause of periarticular pain, though it rarely affects the distal biceps femoris tendon, leading to lateral knee pain. This case report highlights a rare instance of biceps femoris calcific tendinitis and its successful conservative management.

Case presentation:

A 40-year-old female presented with a one-week history of sharp lateral knee pain, which worsened with movement but persisted at rest. There was no history of trauma or systemic illness. On examination, tenderness was localized to the lateral knee, specifically over the fibular head and biceps femoris tendon. Blood tests were unremarkable. Radiographs and ultrasound revealed multifocal calcifications at the fibular head. Although MRI was recommended, it was not feasible in this resource-limited setting. The patient was initially treated conservatively with NSAIDs and physiotherapy but did not respond. She subsequently underwent ultrasound-guided barbotage and corticosteroid injection, resulting in complete resolution of symptoms within one week.

Discussion:

Calcific tendinitis is caused by the deposition of calcium hydroxyapatite crystals in periarticular tendons, leading to inflammation and pain. Biceps femoris calcific tendinitis is rare, and diagnosis can be made using cost-effective imaging modalities such as radiography and ultrasound. Conservative management, including NSAIDs, physiotherapy, and ultrasound-guided barbotage, is the preferred first-line treatment. In this case, the combination of barbotage and physiotherapy led to complete symptom relief.

Conclusion:

Biceps femoris calcific tendinitis, though rare, should be considered in cases of lateral knee pain. Early diagnosis and conservative treatment can result in rapid symptom relief.
Acute spontaneous hemorrhagic cholecystitis with systemic lupus erythematosus and antiphospholipid antibody syndrome: a case report and literature review
Authors: Abdul–Hafez Hamza A , Abudeyak Yazan , Ali Abd-Alkarim , Barakat Mohammed A. , Abdallah Yazan N. , Alawneh Mahmoud
Published: February 2025

Introduction and importance:

Hemorrhagic cholecystitis (HC) is a rare and serious complication of acute cholecystitis, characterized by intraluminal or extraluminal bleeding within the gallbladder. While commonly associated to gallstones, HC may also arise from coagulopathies, anticoagulant therapy, and autoimmune conditions such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). However, HC in patients with SLE or APS is rarely reported in the literature.

Case presentation:

A 59-year-old female with a history of SLE and APS, on corticosteroids, hydroxychloroquine, methotrexate, and warfarin, presented with acute right upper quadrant pain, vomiting, hematemesis, and melena. Clinical examination revealed right upper quadrant tenderness and positive Murphy’s sign. Imaging studies, including ultrasound and computed tomography, confirmed a distended gallbladder with intraluminal hyperdense content and surrounding inflammation. An urgent open cholecystectomy was performed, revealing clotted blood within the gallbladder. The patient recovered uneventfully and was discharged in stable condition.

Clinical discussion:

HC is an uncommon but critical condition that requires prompt recognition and intervention. In this case, the coexistence of autoimmune diseases and anticoagulant therapy likely predisposed the patient to HC. Imaging played an essential role in diagnosis, and open cholecystectomy provided definitive management.

Conclusion:

HC should be considered in patients with SLE, APS, or coagulopathies presenting with acute abdominal symptoms. Early recognition and multidisciplinary management are essential to prevent life-threatening outcomes.
Reducing Unnecessary Penicillin Allergy Labels in the Pediatric Surgical Population
Authors: Hefel Ann M. , Wang Laura A. , Bauer Maureen , Tong Suhong , Tan Gee Mei
Published: February 2025

Background:

Up to 10% of children report having a penicillin allergy; however many of these are misdiagnoses or the allergy resolves over time. Having an unnecessary penicillin allergy label increases risk of adverse clinical outcomes and increased health care costs.

Local Problem:

At our local pediatric surgical center, the percentage of patients with a penicillin allergy label was 7%.

Methods:

A pre/postimplementation design was used.

Interventions:

Pediatric surgical patients with a penicillin allergy label were identified and risk-stratified to undergo a single-dose oral provocation test (OPT) to amoxicillin.

Results:

Forty-two patients underwent an OPT. The percentage of patients with a penicillin allergy label decreased to 6.4% after 6 months (P = .045). Median wait time for an allergy evaluation decreased from 102 to 42 days (P < .0001).

Conclusions:

This quality improvement project decreased penicillin allergy labeling rates in pediatric surgical patients, improved access to penicillin allergy evaluation, and had no adverse outcomes.
Impact of Personalized Nursing Care on Bowel Preparation for Colonoscopy
Authors: Lu Lijuan , Huang Hua
Published: February 2025

Background:

Effective bowel preparation is critical for successful colonoscopy, yet inadequate preparation frequently impairs outcomes.

Purpose:

This study evaluated personalized nursing care (PNC) against standard care in improving bowel preparation quality for colonoscopy.

Methods:

A prospective, 2-phase, single-center trial was conducted from July 2023 to July 2024. In phase 1, patients received standard care; in phase 2, personalized preparations were used.

Results:

Among 1057 patients, PNC significantly improved bowel preparation quality (P < .001). Adequate preparation was achieved by 79% of the PNC group vs 64.3% of the control group. Adherence to bowel preparation was higher in the PNC group (84.0% vs 70.4%, P < .001), as were polyp detection rates (38.2% vs 28.1%, P = .003). Patient satisfaction increased with PNC interventions.

Conclusion:

PNC enhances colonoscopy preparation, boosting clinical effectiveness and patient satisfaction and advocating for its integration into routine protocols.
Personalized Auditory Rhythmic Cues to Optimize Gait in Older Adults and People With Parkinson Disease
Authors: Harrison Elinor C. , Tueth Lauren E. , Haussler Allison M. , Rawson Kerri S. , Earhart Gammon M.
Published: February 2025

Background and Purpose:

Gait dysfunction in people with Parkinson disease (PwPD) is common and debilitating. Internal cues (ie, mental singing) may provide a useful alternative to external cueing (ie, listening to music) to improve walking for PwPD. In this study, we individually tailored cues to each participant by allowing them to choose their own cue song and by selecting the cue rate that elicited the longest strides.

Methods:

Fifty-six participants (28 controls and 28 PwPD) performed walking trials in a single-session, cross-sectional study. Initially, uncued trials were compared with cued conditions in which participants walked to music or while they mentally sang at 4 randomized cue rates (90%, 100%, 110%, and 120% of uncued walking cadence). Participants chose their songs from a curated catalog. Cues were optimized according to longest stride lengths as measured by APDM wearable sensors. Repeated measures Analysis of Variance assessed differences between gait characteristics (velocity, cadence, and stride length) and gait variabilities (coefficients of variations) across conditions and groups.

Results:

Both cue types improved velocity, cadence, and stride length as compared to uncued walking. Internal cues were most beneficial to gait variability. The majority of participants exhibited the longest strides and fastest velocities at the highest cue rate of 120%, though a cue rate of 110% was most beneficial to gait variability.

Discussion and Conclusions:

This study shows how internal and external cues personalized by song choice and cue rate may be tailored to individuals. The information gained may help tailor cues to optimize gait performance for older adults and PwPD.

Video Abstract available

for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A518).
Drug resistance testing at regimen failure in individuals diagnosed with HIV-1 between 2010 and 2018 in Israel
Authors: Wagner Tali , Levy Itzchak , Wieder-Finesod Anat , Wax Marina , Gozlan Yael , Elbirt Daniel , Kedem Eynat , Olshtain-Pops Karen , Elinav Hila , Chowers Michal , Istomin Valery , Smolyakov Rozalia , Matus Natasha , Girshengorn Shirley , Marom Rotem , Turner Dan , Mor Orna
Published: February 2025

Objective:

Assess virological failures, analyze the results of resistance testing (RET), and investigate factors associated with acquired drug resistance mutations (aDRM).

Design:

A retrospective longitudinal cohort study.

Methods:

Virological failures (viral load >50 copies/ml) from a cohort of 1130 individuals, diagnosed with HIV-1 in 2010–2018 and followed up until 2020, were included. Demographic, clinical, and virological data were collected. A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM.

Results:

Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010–2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4+ levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes (P = 0.039). Diagnoses with CD4+ cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51–7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11–0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13–0.86, P = 0.022) had a significant and persistent relative effect on aDRM.

Conclusion:

The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4+ cell counts and AIDS is associated with detection of aDRM.
Discrepancies in Temporal Artery Biopsy Positivity Rate Among White and Black Patients Suspected of Having Giant Cell Arteritis
Authors: Vachhani Raj , Li Peng , Tavakoli Mehdi , Kline Lanning , Gaffo Angelo
Published: February 2025

Objective

Our hypothesis is that biopsy-positive giant cell arteritis (GCA) is infrequent among Black patients. To evaluate this, we compared the temporal artery biopsy (TAB) positivity rates among White and Black patients.

Methods

This is a case-control study review from all patients who underwent TAB at our institution from 2012 until 2021. The main study outcome was the TAB positivity rate. The main independent variable was race/ethnicity. Clinical and demographic features of patients undergoing TAB were compared between those with positive and negative biopsies with t tests, Wilcoxon rank sum test, χ2 test, or Fisher exact test where appropriate. A multiple logistic regression with Firth correction was performed with factors found to be significant in bivariate analysis to evaluate for independent associations with a positive biopsy.

Results

Three hundred eighty-five patients who underwent TAB for suspected GCA were included (290 White, 95 Black). Mean sedimentation rate was higher in Black patients, but otherwise, both groups had similar demographic and clinical characteristics. Positivity rate of TAB in White patients was 20.3% and 8.4% in Black patients. White race was associated with higher likelihood of TAB positivity compared with Black race (odds ratio, 3.47). Patients with positive TAB were more likely to have jaw claudication, constitutional symptoms, and higher inflammatory markers. Other factors significant in the logistic regression model included age, and inversely with decreased visual acuity.

Conclusions

Our study results support the hypothesis that there is a discrepancy in the frequency of biopsy-confirmed GCA in patients referred for TAB, with Black patients having lower rates than their White counterparts.
Immunogenicity of virus-like particle vaccine candidates against SARS-CoV-2 infection
Authors: Nguyen Hai Trong , Garg Ravendra , Kroeker Andrea , Gerdts Volker , Falzarano Darryl , Liu Qiang
Published: February 2025

SARS-CoV-2 variants could become more virulent and transmissible due primarily to the mutations of the viral spike protein, rendering currently approved vaccines less effective. More effective vaccines are needed as vaccination is by far the best strategy against this virus. We have produced two SARS-CoV-2 virus-like particles (VLPs) using a baculovirus BacMam expression platform and examined their immunogenicity in mice. VLP1 contains the spike protein from the Wuhan strain whereas VLP2 contains that of an Omicron variant. Mice immunized with VLP1 and boosted with VLP2 developed significantly higher antibodies in the sera, and more IFNγ secreting cells than the control group. Furthermore, both VLPs induced virus neutralization antibodies against the ancestral Wuhan and an Omicron variant. In conclusion, our study warrants further development of VLPs as effective vaccines against emerging variants of SARS-CoV-2.
Genome description of a potentially novel species of Brevibacterium sp. strain IMA_C3 isolated from an integrated mangrove aquaculture pond
Authors: . Yash , Ghosh Anwesha , Dey Ajanta , Sinha Milon , Bera Nimai , Chakraborty Sabyasachi , Bhadury Punyasloke
Published: February 2025

Brevibacterium sp. IMA_C3, a Gram-positive bacterium was isolated from an integrated mangrove aquaculture pond located near Sundarbans mangrove. The bacterium was isolated from the mangrove leaf litter and grown on Luria-Bertani medium of salinity 20. The 16S rRNA-based phylogeny showed 99.67% identity with Brevibacterium linens AE038-8 from INSDC DNA databases (GenBank/DDBJ/ENA). Whole genome was sequenced using long read sequencing chemistry on Oxford Nanopore MinION platform and annotation was performed against RefSeq and GTDB databases. The genome is approximately 4.1 Mb in size with a G+C content of 64.59 %. The genome of the isolated bacterium comprises of functional genes for complex carbon utilisation, nitrogen, phosphate metabolism and metal transporter. The genome also encodes for secondary metabolites such as ε-Poly-L-lysine, ectoine, terpene, and phenazine that could be potentially explored to control viral infections in indigenous shrimp populations within integrative mangrove aquaculture systems.
Genome Report: First whole genome assembly ofPython regius(ball python), a model of extreme physiological and metabolic plasticity
Authors: Hunt Dakota R. , Allen Holly , Martin Thomas G. , Feghali Sophia N. , Chuong Edward B. , Leinwand Leslie A.
Published: February 2025

The study of nontraditional model organisms, particularly those exhibiting extreme phenotypes, offers unique insights into adaptive mechanisms of stress response and survival. Snakes, with their remarkable physiological, metabolic, and morphological adaptations, serve as powerful models for investigating these processes. Pythons are a unique model organism that have been studied for their extreme metabolic and physiological plasticity. To date, the Burmese python (Python bivittatus) is the only member of thePythonidaefamily to have been sequenced. The low contiguity of this genome and rising challenges in obtaining Burmese pythons for study prompted us to sequence, assemble, and annotate the genome of the closely related ball python (Python regius). Using a hybrid sequencing approach, we generated a 1.45 Gb genome assembly with a contig N50 greater than 18 Mb and a BUSCO score of 98%, representing the highest quality genome to date for a member of thePythonidaefamily. This assembly provides a valuable resource for studying snake-specific traits and evolutionary biology. Furthermore, it enables exploration of the molecular mechanisms underlying the remarkable cardiac and muscular adaptations in pythons, such as their ability to rapidly remodel organs following feeding and resist muscular atrophy during prolonged fasting. These insights have potential applications in human health, particularly in the development of therapies targeting cardiac hypertrophy and muscular atrophy.
Estimating recombination using only the allele frequency spectrum
Authors: Hahn Matthew W. , Mishra Sarthak R.
Published: February 2025

Standard methods for estimating the population recombination parameter,ρ, are dependent on sampling individual genotypes and calculating various types of disequilibria. However, recent machine learning (ML) approaches to estimating recombination have used pooled sequencing data, which does not sample individual genotypes and cannot be used to calculate disequilibria beyond the length of a single sequence read. Motivated by these results, this study examines the “black box” of such ML methods to understand what signals are being used to infer recombination rates. We find that it is indeed possible to estimate recombination solely using the allele frequency spectrum, and we provide a genealogical interpretation of these results. We further show that even a simplified representation of the allele frequency spectrum can be used to estimate recombination. We demonstrate the accuracy of such inferences using both simulations and data from humans. These results offer a new way to understand the effects of recombination on patterns of sequence data, as well as providing an example of how the internal workings of ML methods can give insight into biological processes.

Article Summary

Machine learning methods are becoming more common, offering powerful approaches to study the natural world. We investigated a popular machine learning method to see how it worked, discovering that it was exploiting data (the allele frequency spectrum) to estimate genetic recombination rates that had not been considered before. Our study demonstrates that this approach is indeed quite powerful, opening up new avenues of research. The work also demonstrates that looking inside machine learning models can sometimes teach us novel things about nature.
Sialidases derived from Gardnerella vaginalis remodel the sperm glycocalyx and impair sperm function
Authors: Dohadwala Sarah , Shah Purna , Farrell Maura , Politch Joseph , Marathe Jai , Costello Catherine E , Anderson Deborah J
Published: February 2025

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiome, affects approximately 29 percent of women worldwide (up to 50% in some regions) and is associated with several adverse health outcomes including preterm birth and increased incidence of sexually transmitted infection (STI). BV-associated bacteria, such asGardnerella vaginalisandPrevotella timonensis,damage the vaginal mucosa through the activity of sialidase enzymes that remodel the epithelial glycocalyx and degrade mucin glycoproteins. This damage creates an inflammatory environment which likely contributes to adverse health outcomes. However, whether BV-associated glycolytic enzymes also damage sperm during their transit through the reproductive tract has not yet been determined. Here, we show that sialidase-mediated glycocalyx remodeling of human sperm increases sperm susceptibility to damage within the female reproductive tract. In particular, we report that desialylated human sperm demonstrate increased susceptibility to complement lysis and agglutination, as well as decreased sperm transit through cervical mucus. Our results demonstrate a mechanism by which BV-associated sialidases may affect sperm survival and function and potentially contribute to adverse reproductive outcomes such as preterm birth and infertility.

Significance statement

Sperm surface glycans are crucial for reproductive and immune processes in the female reproductive tract. We found that sialidases derived from BV-associated bacteria remodel the sperm glycocalyx resulting in aberrant agglutination, mucus trapping, and complement-mediated cytolysis of sperm. These results implicate glycolytic damage to sperm as a potential mechanism for BV-associated adverse reproductive outcomes.

Classification:Biological Sciences, Immunology and Inflammation,
Loss of a major venom toxin gene in a Western Diamondback rattlesnake population
Authors: Dowell Noah L. , Cahill Elizabeth , Carroll Sean B.
Published: February 2025

The biochemical complexity and evolutionary diversity of snake venom composition reflects adaptation to the diversity of prey in their diets. However, the genetic mechanisms underlying the evolutionary diversity of venoms are not well understood. Here, we explored the potential extent of and genetic basis for venom protein variation in the widely-distributed Western Diamondback rattlesnake (Crotalus atrox). As in many rattlesnake venoms, metalloproteinases (SVMPs) are the major component ofC. atroxvenom, with three proteins belonging to three distinct major structural SVMP classes, MDC4, MAD3a, and MPO1, constituting the most abundant SVMPs. We found that while most venom proteins, including MDC4 and MAD3a, vary little among individuals, the MPO1 protein is completely absent from some animals, most commonly those from the western part of the species’ geographic range. This distribution correlates with the previous finding of two distinct lineages withinC. atroxand indicates that different ecological factors have shaped venom composition across the species’ range. We further show that the loss of MPO1 expression is not due to transcriptional down-regulation, but to several independent inactivating mutations at the locus, including whole gene deletion. The recurrent inactivation of a major toxin gene within aC. atroxpopulation may reflect relaxed selection on the maintenance ofMPO1function, but we also raise the possibility that the loss of venom components may be favored if there is a cost to producing a less effective toxin in protein-rich venoms.
Impact of intestinal parasitic infections on gut epithelial barrier and inflammation among foreign-born persons living with HIV
Authors: Reimer-McAtee Melissa , Serpa Jose , McAtee Casey , Ortega Emma , Somasunderam Anoma , Arduino Roberto , Mejia Rojelio , Utay Netanya S.
Published: February 2025

Systemic inflammation is a major driver of comorbidities in people with HIV (PWH). Increased levels of biomarkers of enterocyte turnover, microbial translocation, and systemic inflammation have been shown to predict morbidity and mortality in PWH on antiretroviral therapy (ART). We conducted a prospective cohort study of foreign-born PWH with undetectable HIV RNA (<20 copies/mL) with and without intestinal parasitic coinfection. Biomarkers of enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), microbial translocation (soluble CD14), and systemic inflammation (soluble CD163) were measured. Stool parasite quantitative PCR (qPCR) testing andStrongyloides stercoralisrecombinant IgG ELISA (StrongyIgG) were utilized to diagnose parasitic infection. Of the 52 participants, 14 (27%) tested positive for infection withStrongyloides stercoralisbyStrongyIgG, and 7 (16%) of the 45 participants who provided stool samples tested positive for a parasitic infection (not includingBlastocystis) by stool qPCR. The median sCD14 level in PWH with (+)StrongyIgG was significantly higher than PWH with (-)StrongyIgG (1.69 ug/ml versus 1.48 ug/ml, p=0.03). The median sCD163 in PWH with parasitic infections by qPCR was not significantly different from sCD163 in PWH negative for parasitic infections. I-FABP levels did not differ significantly between groups. Participants with both HIV and intestinal parasite infections had increased levels of sCD14, a marker of microbial translocation that is an independent predictor of mortality in PWH, compared to PWH without parasitic infections. These findings raise concern about the long-term sequelae of intestinal parasitic infections in PWH.
Abnormal Blood Pressure Dipping Pattern in Smokers
Authors: Arslan Muhammed Ömer , Acar Tijen , Doğan Yunus , Koç Şahbender , Güneş İbrahim Sefa
Published: February 2025

Aim

Hypertension with non-dipper or reverse dipper patterns has worse outcomes. Smokers have some risk factors for abnormal dipping. There are conflicting results about the association between smoking and blood pressure (BP) dipping patterns, thus we aimed to examine it in essential hypertension.

Methods

178 essential hypertension patients (ages 30-83) completed Fagerström Nicotine Dependence Test (FNDT) and our custom Patient Data Collection Test (PDCT). We analyzed these data with the ambulatory BP measurements (ABPM) and performed logistic regression analysis.

Results

Abnormal dipping patterns were significantly more frequent among patients with a history of smoking (75,0%) than those without history of smoking (47,4%), (p<0,001). Among smokers, abnormal dipping patients had significantly higher FNDT Scores (5 (0-10) versus 2 (0-9), p=0,046), longer smoking years (25 (6-50) versus 20 (5-50), p=0,017), and more smoking exposure in terms of pack.years (25 (3-135) versus 15 (1-75), p=0,023). Patients with history of smoking had significantly higher nocturnal systolic (128,10±15,54 versus 120,56±12,84 mmHg, p=0,001), nocturnal diastolic (80,82±12,60 versus 76,44±10,89 mmHg, p=0,016), and 24-hour mean systolic (133,15±13,52 versus 127,90±12,03 mmHg, p=0,008) BP values; and more blunted systolic and diastolic dipping ratios than non-smokers. Patients with a history of smoking were 3,484 (1,693-7,171 CI:0,95 p=0,001) times more likely to have abnormal dipping. Smoking was also associated with diabetes mellitus, dyslipidemia, and metabolic syndrome.

Conclusion

Smoking was associated with abnormal dipping patterns; higher nocturnal systolic, diastolic, and 24-hour systolic BP values; and lower systolic and diastolic dipping rates. FNDT score and smoking exposure parameters were significantly higher in abnormal dipping.
Developing a Data Note reporting guideline for qualitative health and social care research datasets (the DeNOTE study): A study protocol
Authors: Long Hannah A. , Toomey Elaine , Stevenson Fiona , Brooks Joanna M. , Stewart Andrew J. , French David P.
Published: February 2025

Background

Data Note articles provide concise descriptions of research datasets, detailing how and why the data were created and facilitating reuse of the data. Additionally, Data Notes are typically believed to have the added value of increasing research transparency and making the data comply with the FAIR principles (i.e., Findable, Accessible, Interoperable, and Reusable). However, existing guidelines and templates for Data Note articles are designed for quantitative research datasets and there are no equivalents for qualitative research datasets.

Aim

To develop a novel reporting guideline for Data Note articles describing qualitative health and social care datasets (i.e., the DeNOTE reporting guideline).

Methods

Our plans to develop the DeNOTE reporting guideline have been registered on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. In summary, the DeNOTE study consists of (a) a rapid scoping exercise of existing literature, resources, and expert knowledge to identify and synthesise ‘items’ or ‘statements’ of a reporting guideline that are relevant to a Data Note article describing qualitative health and social care data, (b) an online questionnaire with expert participants to rate their agreement with items identified in (a) and to propose new or amended items, (c) an online workshop with participants to further co-develop the reporting items, with the aim to reach consensus on the items, (d) eliciting feedback from participants on the draft reporting guideline, and (e) finalising the DeNOTE reporting guideline.

Conclusion

Our goal is to produce a novel reporting guideline to support researchers when producing a Data Note article describing qualitative health and social care research data. In the process, we will produce tailored open research infrastructure to better support qualitative researchers engaging in open research practices.
Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer’s disease in cognitively normal individuals
Authors: Hüls Anke , Liu Jiaqi , Konwar Chaini , Conneely Karen N. , Levey Allan I. , Lah James J. , Wingo Aliza P. , Wingo Thomas S.
Published: February 2025

INTRODUCTION

Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are reliable predictors of future AD risk. We investigated whether pre-clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants.

METHODS

We profiled blood-based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS; N=495) and ADNI (N=122). Their CSF Aβ42, tTau, and pTau levels were quantified using Elecsys immunoassays. We conducted epigenome-wide association studies to assess associations between DNAm and CSF biomarkers of AD.

RESULTS

In EHBS, no loci were Bonferroni-significant after adjusting for confounding factors. In ADNI, two loci were significant, but they were not replicated in EHBS. There was little agreement between the top loci from EHBS and ADNI.

DISCUSSION

Our study showed little evidence of an association between differential blood-based DNAm and pre-clinical AD CSF biomarkers.
Effectiveness of Social Networks in Enhancing the Uptake of Artemisinin-based Combination Therapy (ACT) in Malaria-Prone Zones of Kenya
Authors: Nyongesa Florence Nelima , Gathiaka John Kamau , Mwabu Germano
Published: February 2025

Introduction

Malaria remains a critical health challenge in Kenya, particularly among children under five years who are highly vulnerable to its complications. Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria. However, their uptake varies due to socio-economic inequalities, geographic disparities, and the influence of social networks. Understanding how social interactions, particularly those mediated by religious affiliations, impact ACT uptake can inform strategies to improve malaria treatment outcomes in malaria-prone regions.

Methods

This study utilized data from the Kenya Malaria Indicator Survey (KMIS) 2020, employing a cross-sectional design and stratified two-stage cluster sampling. Data on malaria prevalence, treatment-seeking behavior, and ACT usage were analyzed using descriptive statistics and logistic regression. The analysis focused on socio-demographic factors, geographic differences, and the role of social networks mediated through religious affiliations.

Results

ACT uptake among children under five was 52%. Male children were less likely to receive ACTs, with probabilities 6.3% lower in rural areas and 3.1% lower in urban areas. Younger children in rural areas, particularly those aged one, had a 5.7% higher likelihood of ACT usage, while uptake declined with age. Caregivers’ education significantly enhanced ACT uptake in rural areas, increasing the likelihood by 25%. Rural Muslim households were 17.2% more likely to use ACTs, while urban Christian households showed modest improvements. Wealth disparities also affected uptake, with wealthier urban households less likely to use ACTs.

Conclusion

The study highlights the critical role of social networks, particularly religious affiliations, in shaping ACT uptake in malaria-prone zones of Kenya. Addressing barriers to access through these networks offers a promising avenue for increasing ACT utilization and improving health outcomes. Leveraging community-driven approaches and religious institutions could enhance equitable malaria treatment coverage across vulnerable populations.
The burden of rheumatic heart disease and issues affecting the provision of care in Malawi: A scoping review
Authors: Blennerhassett E , Brady Bates O , O’Connor M , Gondwe H , Msimuko L , Ledwidge M , Mbakaya B , Gallagher J
Published: February 2025

Background

Rheumatic heart disease (RHD) is an autoimmune sequela of group A streptococcal (GAS) pharyngitis. Single or recurrent episodes of acute rheumatic fever (ARF), a complication arising 2-3 weeks after GAS infection, can cause damage to the valves of the heart and RHD. This trajectory towards severe disease is now rare in high-income countries. The appropriate use of antibiotics has contributed to this decline in RHD prevalence, but socio-economic factors have also had a profound impact. In Malawi, as in many low-income countries, RHD continues to pose a significant challenge. Limited access to healthcare and poor education likely contribute to the disease burden, and actionable solutions are needed to eradicate RHD in these communities.

Aim

To determine the present burden of GAS, ARF and RHD in Malawi, the issues affecting the provision of care and the solutions that have been proposed.

Design and setting

A scoping review encompassing four electronic databases from which relevant articles were drawn.

Method

A systematic search of ‘PubMed’, ‘EMBASE’, ‘Cochrane Library’ and ‘Clinicaltrials.gov’ was conducted to identify research related to the study objectives. Supplemental grey literature and internet searches were carried out and collaboration with experts in the field ensured a comprehensive review of the available data. The selected articles spanned from 2008 to October 2024 and addressed one or more of the diseases of interest. A scoping review was carried out according to the Arksey and O’Malley procedure.

Results

This scoping review includes thirty papers, which focus primarily on RHD burden, screening, treatment, and barriers to care in Malawi. There was significantly less research on ARF and GAS infections. A wide variety of study designs were employed (mostly descriptive, cross-sectional and retrospective studies) and the number of participants varied significantly across the different studies. Two government reports were also included. The primary findings included a shift in the focus of research towards solutions to the high burden of RHD in Malawi.

Conclusion

The significant morbidity and mortality associated with RHD are a major concern in the communities and healthcare systems of Malawi. As in many low-income countries, resource mobilisation and improved education are areas requiring attention. To address the high burden of disease in the country, ongoing research is largely focused on establishing a sufficiently large and appropriately trained workforce to diagnose and monitor RHD using the resources available within the constraints of the country’s socioeconomic context.
Dysregulated Immune Proteins in Plasma in the UK Biobank Predict Multiple Myeloma 12 years Before Clinical Diagnosis
Authors: Fieggen Josh , Thakur Anshul , Butler Christopher C , Ramasamy Karthik , Thakurta Anjan , Clifton David A. , Clifton Lei
Published: February 2025

High-throughput proteomics has emerged as a potentially rich data source to improve capacity to forecast disease. This study explores the utility of plasma proteomics for identifying novel predictors of Multiple myeloma (MM), combining machine learning with statistical approaches. Utilising data from the UK Biobank, including proteomic profiles of over 50k participants, we applied an “extreme gradient boosting” (XGBoost) algorithm with SHapley Additive exPlanation (SHAP) feature-importance measures to identify key proteomic biomarkers to predict onset of MM. At least seven of the top 10 identified proteins are related to immune function and activation of lymphoid cells; two are validated MM targets with approved therapies. The top 10 proteins along with key clinical predictors were further analysed using Cox proportional hazards models to assess their contribution to incident MM risk. 10 proteomic biomarkers ranked by SHAP value substantially outperformed traditional clinical predictors. This superior performance was maintained over the 12-year follow-up period, demonstrating the predictive ability of these proteomic biomarkers for early detection of MM. The demonstration of the dysregulated expression of proteins in serum from healthy individuals, if confirmed in prospective cohorts and independent datasets, could lead to novel approaches to screening for MM and precursor conditions.
Brain size dependent speciation and extinction rates in birds and the cognitive buffer hypothesis
Authors: Oyston Jack W. , May Michael R. , Felice Ryan N
Published: February 2025

Both brain and body size vary greatly across birds, with both traits hypothesized to play a key role in diversification patterns across the group. Larger brains facilitate the evolution of greater behavioural plasticity, which could facilitate diversification in two ways, either by driving increased speciation (behavioural drive) or by making lineages more resilient to extinction (cognitive buffer). Here, we model brain size dependent diversification dynamics from published endocranial volume data for a sample of 2291 extant and fossil bird taxa, jointly modelling speciation rate, extinction rate and fossilisation rate separately for perching birds and other groups. We find that increasing relative brain size primarily increases diversification rate through decreasing extinction rate, supporting the cognitive buffer hypothesis and suggesting that larger brains in birds promote diversification by making species more resilient to extinction. Although speciation and extinction are dependent on relative brain size in both perching birds and other groups, this dependence is non-linear. In perching birds, the highest diversification rates are found over a narrow range of relative brain sizes, in contrast to other bird groups which show lower diversification rates over a broader range of relative brain sizes.

Significance

The potential for speciation and extinction are thought to be shaped by key phenotypic traits. In birds, brain size is one important trait hypothesized to have an impact on diversification. Testing this hypothesis requires the evolution of brain size, speciation rate, and extinction rate to be jointly modelled across the bird phylogeny. The inclusion of information on past diversity has been shown to be important in inferring diversification patterns, and so we include not only data from a broad sample of living birds but also information from the fossil record. Our study reveals patterns of brain size dependent diversification in birds which are consistent with the cognitive buffer hypothesis, with higher relative brain sizes being associated with lower extinction rates.
Effectivein vivoRNA base editingviaengineered cytidine deaminase APOBECs fused with PUF proteins
Authors: Han Wenjian , Yuan Bo , Fan Xiaojuan , Li Weike , Yuan Yiting , Zhang Yuefang , Wang Shu , Shan Shifang , Hafner Markus , Wang Zefeng , Qiu Zilong
Published: February 2025

Base editing stands at the forefront of genetic engineering, heralding precise genetic modifications with broad implications. While CRISPR-based DNA and RNA base editing systems capitalize on sgRNA-guided specificity and diverse deaminase functionalities, the pursuit of efficient C-to-U RNA editing has been hampered by the inherent constraints of cytidine deaminases. Here, we report an RNA base editing platform by refining cytidine deaminases, termed professional APOBECs (ProAPOBECs), through systematic enhancements and AI-driven protein engineering. ProAPOBECs demonstrate unprecedented catalytic versatility, particularly fused with RNA-recognizing Pumilio and FBF (PUF) proteins. We present the first effective use of RNA base editing in the brain with ProAPOBECs in Mef2c mutant mice, a model for autism. The AAV-mediated RNA base editing via ProAPOBEC not only corrects genetic mutation in mRNAs but significantly alleviates autistic-like behaviors in the mice. This work introduces a pioneering collection of RNA base editing instruments, emphasizing their therapeutic potential in combatting genetic disorders.
Chimeric Antigen Receptors Discriminate Between Tau and Distinct Amyloid-Beta Species
Authors: Siebrand Cynthia J. , Bergo Nicholas J. , Lee Suckwon , Andersen Julie K. , Walton Chaska C.
Published: February 2025

Abstract/Summary

The lack of a definitive cure for Alzheimer’s disease (AD) is fueling the search for innovative therapeutic strategies. Having revolutionized cancer immunotherapy, immune cell engineering with chimeric antigen receptors (CAR) is being explored to target AD. Whether CARs can recognize distinct amyloid-β (Aβ) species and tau neurofibrillary tangles (NFTs)—hallmark pathologies of AD—remains unclear. To investigate this, we engineered CARs based on AD antibodies targeting tau (E2814), Aβ (Lecanemab and Aducanumab), and truncated pyroglutamate form of Aβ (Aβp3-42; Donanemab and Remternetug). To evaluate CAR function, we established the murine DO11.10 hybridoma T-cell line as a practical and scalable testing platform. Our findings demonstrate that CARs can detect and discriminate between tau preformed fibrils (PFFs), Aβ1-42, and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques.
Non-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia Virus
Authors: Dalla Rosa Ilaria , Way Michael
Published: February 2025

Vaccinia virus is a large enveloped DNA virus, which, like all poxviruses, replicates in the cytoplasm of infected cells. Vaccinia was historically thought to encode all the proteins required for its replication. However, recent findings have shown that nuclear host proteins are redirected to the cytoplasm to facilitate viral replication. Among these, topoisomerase 2α (TOP2A) and 2β (TOP2B), which mediate nuclear transcription, DNA replication, and chromosome segregation are the most abundant host proteins associated with nascent viral genomes. Here, we investigate the mechanisms driving TOP2A and TOP2B cytoplasmic translocation and their role in viral replication. We found that early viral protein synthesis induces the cytosolic relocalization of both isoforms, which are subsequently recruited to viral factories by an interaction of their C-terminal domains with the viral ligase, A50. TOP2A promotes replication by interacting with the vaccinia DNA replication machinery. In contrast, TOP2B suppresses replication by enhancing the formation of double-stranded RNA and antiviral granules, containing components of the tRNA splicing ligase complex. Our analysis provides new insights into host-pathogen interactions during poxvirus infection and the role of topoisomerase 2 outside of the nucleus.
Multiplexing Light-Inducible Recombinases to Control Cell Fate, Boolean Logic, and Cell Patterning in Mammalian Cells
Authors: Tous Cristina , Kinstlinger Ian S. , Rice Maya E. L. , Deng Jenny , Wong Wilson W.
Published: February 2025

Light-inducible regulatory proteins are powerful tools to interrogate fundamental mechanisms driving cellular behavior. In particular, genetically encoded photosensory domains fused to split proteins can tightly modulate protein activity and gene expression. While light-inducible split protein systems have performed well individually, few multichromatic and orthogonal gene regulation systems exist in mammalian cells. The design space for multichromatic circuits is limited by the small number of orthogonally addressable optogenetic switches and the types of effectors that can be actuated by them. We developed a library of red light-inducible recombinases and directed patterned myogenesis in a mesenchymal fibroblast-like cell line. To address the limited number of light-inducible domains (LIDs) responding to unique excitation spectra, we multiplexed light-inducible recombinases with our ‘Boolean Logic and Arithmetic through DNA Excision’ (BLADE) platform. Multiplexed optogenetic tools will be transformative for understanding the role of multiple interacting genes and their spatial context in endogenous signaling networks.
Kohn-Sham-Proca equations for ultrafast exciton dynamics
Authors: Dewhurst J. K. , Gill D. , Shallcross S. , Sharma S.
Published: February 2025

A longstanding problem in time-dependent density functional theory has been the absence of a functional able to capture excitonic physics under laser pump conditions. Here we introduce a scheme of coupled Kohn-Sham and Proca equations in a pump-probe setup that we show (i) produces linear-response excitonic effects in the weak pump regime in excellent agreement with experiment, but also (ii) captures excitonic physics in the highly nonlinear regime of ultrafast strong laser pumping. In particular ”bleaching” (i.e., reduction) of the excitonic weight and the appearance of excitonic side bands is demonstrated. The approach is a procedural functional—the Kohn-Sham and Proca equations are simultaneously time propagated—allowing the straightforward inclusion of, for example, lattice and spin degrees of freedom into excitonic physics. The functional is shown to have universal applicability to a wide range of materials, and we also establish a relation between the parameters used in the functional and the exciton Bohr radii of the materials.

Published by the American Physical Society
2025
Theoretical bounds on dark Higgs mass in a self-interacting dark matter model with
U(1)′
Authors: Li Song , Yang Jin Min , Zhang Mengchao , Zhu Rui
Published: February 2025

Motivated by the null results of current dark matter searches and the small-scale problems, we study a dark sector charged by a spontaneous broken gauge U(1)′. To explore the parameter space of this model, in addition to the consideration of the small-scale data, we also consider the theoretical bounds on the dark Higgs mass, with the upper bound coming from the tree-level perturbative unitarity and the lower bound from the one-loop Linde-Weinberg bound. We deeply examine the dependence of the Linde-Weinberg bound on gauge choice and energy scale, and present a Linde-Weinberg bound that is gauge and scale independent. Combining the theoretical and observational constraints, we obtain the following ranges for the parameter space: the dark matter mass is 10–500 GeV, the mediator (dark photon) mass is 0.5–5 MeV, the dark Higgs mass is 0.05–50 MeV, and the dark fine-structure constant is 0.001–0.4. We conclude that the dark Higgs in this model cannot be ignored in the phenomenological study of the dark sector.

Published by the American Physical Society
2025