bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of doravirine-based regimens in clinical practice in Europe: a real-life retrospective observational study
Authors: Rami Agathe , Pozniak Anton L. , Assoumou Lambert , Movahedi Roya , Lacombe Karine , Raffi François , Fox Julie , Levi Laura , Melnyk Tetiana , Roberts Debbie , Fletcher Carl , Molina Jean-Michel 
Published: February 2025

Objectives:
We evaluated antiviral effectiveness and safety of doravirine (DOR)-based regimens in people with HIV (PWH) in routine clinical practice.

Design:
A retrospective, noninterventional study across 16 sites in five European countries [United Kingdom (UK), France, Spain, Belgium, Netherlands].

Methods:
The study was conducted in both treatment-experienced and treatment-naive PWH who either switched to, or initiated DOR-containing antiretroviral therapy (ART). The primary endpoints were virological success (defined as the percentage of participants with HIV RNA <50 copies/ml, using FDA Snapshot method) and virological failure (FDA Snapshot, HIV RNA ≥50 copies/ml) at 48 weeks after initiation of DOR regimen.

Results:
Between August 2017 and February 2022, 394 participants were enrolled, 63 naive and 331 treatment-experienced. 75.4% were men, with a median age of 45 years, and 92.2% received DOR in combination with tenofovir disoproxil fumarate and lamivudine or emtricitabine. The proportion of participants with virological success at week 48 after initiation of DOR regimen was 90.6% [95% confidence interval (CI) 87.3–93.3] overall, 87.3% (95% CI 76.5–94.4) in the ART-naive group, and 91.2% (95% CI 87.7–94.1) in the switch group. The proportion of participants with virological failure was 3.3% (95% CI 1.8–5.6) overall, 1.6% (95% CI 0–8.5) in the ART-naive group and 3.6% (95% CI 1.9–6.2) in the switch group. Of the 394 included participants, two (0.5%) were lost to follow-up and 13 (3.3%) discontinued the DOR regimen, four (1%) due to adverse events.

Conclusion:
Our results show high levels of efficacy and low levels of side effects in DOR-containing regimens in both treatment-naive and treatment-experienced PWH.
The effect of a social network-based intervention on adherence to HIV pre-exposure prophylaxis and HIV viral suppression among Kenyan fishermen
Authors: Sheira Lila A. , Kwena Zachary A. , Ayieko Benard , Charlebois Edwin D. , Agot Kawango , Gutin Sarah A. , Lewis-Kulzer Jayne , Olugo Phoebe , Gandhi Monica , Bukusi Elizabeth A. , Thirumurthy Harsha , Adede Daniel , Moody James , Camlin Carol S. 
Published: February 2025

Objective:
Social networks may play a vital role in shaping health behaviors, including engagement in HIV prevention and treatment. We evaluated the impact of an HIV status-neutral, social-network-based HIV self-testing and linkage intervention on pre-exposure prophylaxis (PrEP) adherence and HIV viral suppression among men working alongside Lake Victoria, Kenya.

Design:
Cluster-randomized controlled trial.

Methods:
After a census of fishermen, distinct social networks with highly socially-connected men were identified, “promoters” per network were recruited, and networks were randomized to study arms. Promoters distributed HIV self-tests kits to fishermen in their network and encouraged linkage and retention in prevention and care (intervention) or distributed vouchers redeemable for routine HIV testing (control). We report the tertiary outcomes of a) PrEP adherence, measured via a urine tenofovir assay among PrEP users, and b) viral load among PLHIV. We conducted a logistic regression to evaluate the intervention's association with PrEP adherence and viral suppression.

Results:
Of 733 baselined, 339 linked to clinics: 62 initiated PrEP, 25 were already on PrEP, and 166 were living with HIV. Urine tenofovir was detected among 12 of 70 participants who gave urine samples (14% control vs. 19% intervention), and 43 of 166 participants on antiretroviral therapy had detectable viral loads (40.2% control vs. 35.7% intervention). There were no significant differences by arm in urine tenofovir levels nor viral suppression.

Conclusions:
A social network-based, status-neutral intervention that increased men's testing and linkage was not associated with PrEP adherence nor viral suppression. An adequately-powered study is necessary to evaluate whether social-network-based interventions can improve these outcomes.
Incisional Hernia Risk Reduction for Living Kidney Donors: Kidney Extraction Site Matters
Authors: Punukollu Rachana , Arias Sandra , Ohara Stephanie , Nica Alexandru , Briggs Logan G , Cosentino Christopher , Frasco Peter , Andrews Paul , Nguyen Michelle , Mao Shennen , Heimbach Julie , Jadlowiec Caroline 
Published: February 2025

Background:
Although most transplant centers preferentially offer minimally invasive approaches to donor nephrectomies, there remains less standardization specific to the kidney extraction site. This study aimed to evaluate incisional hernia occurrence in living kidney donors based on kidney extraction site location.

Study Design:
This was a retrospective study of all donors who underwent minimally invasive living donor nephrectomies at the Mayo Clinic Arizona between 2011 and 2023 with a 2-year external validation cohort from Mayo Clinic Florida and Mayo Clinic Minnesota. The cohort was divided into two groups based on the kidney extraction site type: midline infraumbilical and Pfannenstiel.

Results:
In the primary cohort, incisional hernia occurrence was observed in 1.2% of donors with an infraumbilical midline kidney extraction site compared to 0.1% with a Pfannenstiel extraction site (p=0.04). Donors with an infraumbilical midline kidney extraction site were more likely to be male (50.8% vs. 23.3%, p<0.0001), have a higher BMI (mean 27.2 vs. 26 kg/m2, p<0.0001), and have current or former tobacco use (p=0.002). There were no differences in incisional hernia occurrence when comparing minimally invasive surgical techniques (p=0.52). In the external validation cohort, hernia occurrence was observed in 4.5% of donors with a midline incision compared to 0.0% with a Pfannenstiel incision (p=0.09). Using combined data from the three sites, use of a Pfannenstiel incision as the extraction site was associated with a significantly lower odds of developing a hernia compared to the infraumbilical midline incision (OR 0.06; 95% CI 0.008, 0.456).

Conclusions:
Although the risk of hernia in living kidney donors is generally low, use of a Pfannenstiel incision for kidney extraction appears to offer an additional incremental reduction in risk.
A STUDY ON ASSESSMENT OF MEDICATION ADHERENCE IN HEMODIALYSIS PATIENTS
Authors: Gahrouei Razieh Bahrami , Ranganathan Srinivasan 
Published: February 2025

AbstractBackgroundMedication adherence is a crucial factor in managing chronic diseases such as chronic kidney disease (CKD), particularly in hemodialysis patients who require complex and lifelong medication regimens. Non-adherence in this population is associated with increased morbidity, hospitalizations, and reduced treatment efficacy. This study aims to assess medication adherence levels, identify key demographic and clinical factors influencing compliance, and evaluate the impact of counseling interventions on adherence behavior.MethodsA six-month prospective observational study was conducted at BGS Global Hospital, Bangalore, involving 89 hemodialysis patients (61 males, 28 females). The Morisky Green Levine Scale (MGLS)was used to assess medication adherence before and after structured counseling sessions. Participants were stratified by gender and age groups (18–35, 35–60, and 60–80 years) to analyze adherence patterns. Health-related quality of life (KDQOL) was also evaluated to determine the impact of adherence on patient well-being. Statistical significance was assessed using p-values, with a threshold of p < 0.05 considered significant.ResultsPre-counseling adherence assessments revealed that only 3.37% of participants were highly adherent, while 80.89% had medium adherence and 15.73% exhibited low adherence. Gender analysis showed that males had slightly higher adherence rates before counseling (4.91%) compared to females (0%), while females had a greater proportion of medium adherence (85.71%). Post-counseling, adherence improved significantly, with high adherence increasing to 39.3% in males and 39.2% in females. Age-based analysis indicated that the 35–60 age group demonstrated the highest adherence rates both before and after counseling, while younger patients(18–35 years) had lower baseline adherence but showed significant improvement post-intervention. KDQOL assessments revealed that improved adherence was associated with better quality-of-life scores, particularly among males(p = 0.217 before counseling, 0.256 after)and females(p = 0.060 before, 0.071 after).ConclusionThe findings demonstrate that structured counseling interventions significantly improve medication adherence among hemodialysis patients across gender and age groups. Given the chronic nature of hemodialysis treatment, integrating adherence-enhancing strategies into routine patient care is essential to optimize treatment outcomes and improve quality of life. Future research should focus on tailored adherence interventions, incorporating behavioral strategies, digital health tools, and long-term monitoring approaches to sustain adherence improvements over time.
Incorporating Hierarchical Information into Multiple Instance Learning for Patient Phenotype Prediction with scRNA-seq Data
Authors: Do Chau , Lähdesmäki Harri 
Published: February 2025

AbstractMultiple Instance Learning (MIL) provides a structured approach to patient phenotype prediction with single-cell RNA-sequencing (scRNA-seq) data. However, existing MIL methods tend to overlook the hierarchical structure inherent in scRNA-seq data, especially the biological groupings of cells, or cell types. This limitation may lead to suboptimal performance and poor interpretability at higher levels of cellular division. To address this gap, we present a novel approach to incorporate hierarchical information into the attentionbased MIL framework. Specifically, our model applies the attention-based aggregation mechanism over both cells and cell types, thus enforcing a hierarchical structure on the flow of information throughout the model. Across extensive experiments, our proposed approach consistently outperforms existing models and demonstrates robustness in data-constrained scenarios. Moreover, ablation test results show that simply applying the attention mechanism on cell types instead of cells leads to improved performance, underscoring the benefits of incorporating the hierarchical groupings. By identifying the critical cell types that are most relevant for prediction, we show that our model is capable of capturing biologically meaningful associations, thus facilitating biological discoveries.
Craft: A Machine Learning Approach to Dengue Subtyping
Authors: van Zyl Daniel J. , Dunaiski Marcel , Tegally Houriiyah , Baxter Cheryl ,   The INFORM Africa research study group, de Oliveira Tulio , Xavier Joicymara S. 
Published: February 2025

AbstractMotivationThe dengue virus poses a major global health threat, with nearly 390 million infections annually. A recently proposed hierarchical dengue nomenclature system enhances spatial resolution by defining major and minor lineages within genotypes, aiding efforts to track viral evolution. While current subtyping tools – Genome Detective, GLUE, and NextClade – rely on computationally intensive sequence alignment and phylogenetic inference, machine learning presents a promising alternative for achieving accurate and rapid classification.ResultsWe present Craft (ChaosRandomForest), a machine learning framework for dengue subtyping. We demonstrate that Craft is capable of faster classification speeds while matching or surpassing the accuracy of existing tools. Craft achieves 99.5% accuracy on a hold-out test set and processes over 140 000 sequences per minute. Notably, Craft maintains remarkably high accuracy even when classifying sequence segments as short as 700 nucleotides.Contactdanielvanzyl@sun.ac.zaSupplementary informationA supplemental table acknowledging the authors of the GISAID dengue sequences is available atBioinformaticsonline.
Lineage plasticity of the integrated stress response is a hallmark of cancer evolution
Authors: Diao Shiqi , Zou Jia Yi , Wang Shuo , Ghaddar Nour , Chan Jason E. , Kim Hyungdong , Poulain Nicolas , Koumenis Constantinos , Hatzoglou Maria , Walter Peter , Sonenberg Nahum , Le Quesne John , Tammela Tuomas , Koromilas Antonis E. 
Published: February 2025

ABSTRACTThe link between the “stress phenotype”-a well-established hallmark of cancer-and its role in tumor progression and intratumor heterogeneity remains poorly defined. The integrated stress response (ISR) is a key adaptive pathway that enables tumor survival under oncogenic stress. While ISR has been implicated in promoting tumor growth, its precise role in driving tumor evolution and heterogeneity has not been elucidated. In this study, using a genetically engineered mouse models, we demonstrate that ISR activation—indicated by elevated levels of phosphorylated eIF2 (p-eIF2) and ATF4—is essential for the emergence of dedifferentiated, therapy-resistant cell states. ISR, through the coordinated actions of ATF4 and MYC, facilitates the development of tumor cell populations characterized by high plasticity, stemness, and an epithelial-mesenchymal transition (EMT)-prone phenotype. This process is driven by ISR-mediated expression of genes that maintain mitochondrial integrity and function, critical for sustaining tumor progression. Importantly, genetic, or pharmacological inhibition of the p-eIF2–ATF4 signaling axis leads to mitochondrial dysfunction and significantly impairs tumor growth in mouse models of lung adenocarcinoma (LUAD). Moreover, ISR-driven dedifferentiation is associated with poor prognosis and therapy resistance in advanced human LUAD, underscoring ISR inhibition as a promising therapeutic strategy to disrupt tumor evolution and counteract disease progression.
Six-Minute Knee MRI: A Comparison of Novel Approaches for Accelerated Imaging
Authors: Goyal Ananya , MacKay James , Petterson Matthew , van der Heijden Rianne , Stevens Kathryn , Yoon Min , Liang Tie , Chaudhari Akshay , Kogan Feliks 
Published: February 2025

AbstractBackgroundAccelerated knee MRI protocols using deep learning (DL)-based reconstruction, 3D acquisitions, and parallel imaging can significantly reduce scan times. These methods enhance patient throughput and comfort while maintaining diagnostic quality. However, their clinical efficacy and diagnostic performance across various knee pathologies requires systematic evaluation.PurposeTo evaluate the diagnostic performance and image quality of four accelerated knee MRI protocols (∼6 minutes) compared with the standard conventional 2D FSE protocol (∼15–30 minutes).Materials and MethodsThis prospective study enrolled adults with symptomatic knee pain between May 2021 and March 2022. All participants underwent five knee MRI protocols: a conventional 2D fast spin echo (FSE) protocol, a 2D FSE protocol with DL reconstruction, a 3D Cube protocol, a 3D quantitative double-echo steady-state (qDESS) protocol, and a thin-slice 2D FSE protocol. Five radiologists evaluated pathologies in joint tissues. Inter-reader and inter-method agreements were assessed using Gwet’s AC, with sensitivity and specificity calculated. Image diagnostic quality was evaluated using a Likert scale, and the Friedman was test used (p<0.05 indicative of statistically significant difference).ResultsA total of 32 participants were evaluated (14 men, aged 47±16 years). Of 160 total scans, 12 were excluded due to motion artifacts. Across pathologies, the 3D qDESS protocol had the highest inter-reader agreement for menisci (0.86) and cartilage (0.48), with sensitivities of 95% and 83%, respectively. The 2D DL protocol showed strong performance for bone marrow (sensitivity: 78%). Lastly, for effusion, both the 2D DL and 3D Cube protocols exhibited high inter-reader agreement (0.89 and 0.87, respectively). Diagnostic image quality scores exceeded were diagnostically acceptable in 95% of evaluations for menisci, bone marrow, and ligaments.ConclusionThe 2D DL, 3D Cube, and 3D qDESS protocols matched the diagnostic performance of the conventional protocol while reducing scan times to six minutes, improving workflow and patient experience.
Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures
Authors: Kang Moonil , Ang Ting Fang Alvin , Devine Sherral A. , Sherva Richard , Mukherjee Shubhabrata , Trittschuh Emily H. , Gibbons Laura E. , Scollard Phoebe , Lee Michael , Choi Seo-Eun , Klinedinst Brandon , Nakano Connie , Dumitrescu Logan C. , Hohman Timothy J. , Cuccaro Michael L. , Saykin Andrew J. , Kukull Walter A. , Bennett David A. , Wang Li-San , Mayeux Richard P. , Haines Jonathan L. , Pericak-Vance Margaret A. , Schellenberg Gerard D. , Crane Paul K. , Au Rhoda , Lunetta Kathryn L. , Mez Jesse , Farrer Lindsay A. 
Published: February 2025

AbstractBackgroundGenome-wide association studies (GWAS) have identified over 1,000 blood pressure (BP) loci and over 80 loci for Alzheimer’s disease (AD). Considering BP is an AD risk factor, identifying pleiotropy in BP and cognitive performance measures may indicate mechanistic links between BP and AD.MethodsGenome-wide scans for pleiotropy in BP variables—systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP)—and co-calibrated scores for cognitive domains (executive function, language, and memory) were performed using generalized linear mixed models and 116,075 longitudinal measures from 25,726 participants of clinic-based and prospective cohorts. GWAS was conducted using PLACO to estimate each SNP’s main effect and interaction with age, and their joint effect on pleiotropy. Effects of genome-wide significant (GWS) pleiotropic SNPs on cognition as direct or mediated through BP were evaluated using Mendelian randomization. Potential contribution of genes in top-ranked pleiotropic loci to cognitive resilience was assessed by comparing their expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms.ResultsPleiotropy GWAS identified GWS associations withAPOEand 11 novel loci. In the total sample, pleiotropy was identified for SBP and language withJPH2(PJoint=6.09×10-9) andGATA3(PG×Age=1.42×10-8), MAP and executive function withPAX2(PG×Age=4.22×10-8), MAP and language withLOC105371656(PG×Age=1.75×10-8), and DBP and language withSUFU(PG=2.10×10-8). In prospective cohorts, pleiotropy was found for SBP and language withRTN4(PG×Age=1.49×10-8), DBP and executive function withULK2(PJoint=2.85×10-8), PP and memory withSORBS2(PG=2.33×10-8), and DBP and memory withLOC100128993(PG×Age=2.81×10-8). In clinic-based cohorts, pleiotropy was observed for PP and language withADAMTS3(PG=2.37×10-8) and SBP and memory withLINC02946(PG×Age=3.47×10-8). Five GWS pleiotropic loci influence cognition directly, and genes at six pleiotropic loci were differentially expressed between pathologically confirmed AD cases with and without clinical symptoms.ConclusionOur results provide insight into the underlying mechanisms of high BP and AD. Ongoing efforts to harmonize BP and cognitive measures across several cohorts will improve the power of discovering, replicating, and generalizing novel associations with pleiotropic loci.
Identifying Priority Countries for Scaling Up Small-Quantity Lipid-Based Nutrient Supplements
Authors: Noori Navideh , Stewart Christine P. , McDonald Christine M. , Wessells K. Ryan , Root Elisabeth D. , Dewey Kathryn G. 
Published: February 2025

AbstractIntroductionUndernutrition is a cause of nearly half of all deaths among children under-5. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to prevent child wasting, stunting, anemia and mortality among children 6-23 months of age in low- and middle-income countries (LMICs). Scaling up effective preventive interventions is urgent given the current global food insecurity and nutrition crisis.MethodTo prioritize SQ-LNS scale-up activities, we identified countries with the highest burdens of wasting, stunting, and all-cause mortality among children 6-23 months of age at the national level using the most recent national survey data including the Demographic and Health Survey (DHS) and Multiple Indicator Cluster Surveys (MICS), as well as the Lives Saved Tool (LiST) in LMICs. National-level estimates informed a care cascade model to assess the potential impact of SQ-LNS on all-cause mortality, stunting, and wasting. We also conducted a sub-national level analysis among the 20 highest burden countries with the most recent available survey data to identify the highest burden regions.ResultsOur analysis identified the top 20 countries with the highest burden of the three outcomes as: Niger, South Sudan, Yemen, Sudan, Somalia, Democratic Republic of Congo, Eritrea, Nigeria, Central African Republic, Guinea, Equatorial Guinea, Chad, Papua New Guinea, Benin, Mali, Angola, Pakistan, Timor-Leste, Sierra Leone and Côte d’Ivoire, although for some countries the survey data were collected > 10 years ago. Some of these countries also ranked high in population estimates of acute food insecurity. The care cascade model demonstrates that a large number of cases of stunting and wasting and deaths could be potentially averted if SQ-LNS is provided.ConclusionMost of the top 20 countries are in Sub-Saharan Africa, with a few in South and Southeast Asia. This geographical concentration underscores the urgent need for targeted interventions in these regions to prevent child malnutrition.What is already known on this topicIt is known that SQ-LNS reduces child wasting, stunting, anemia and mortality among children 6-23 months of age in LMICs. However, survey reports generally estimate stunting, wasting, and mortality rates among all children under 5 years of age, and not specifically for the 6-23 months old age group.What this study addsBy estimating the burden of stunting, wasting and all-cause mortality for the specific age group of 6-23 months old at the national and sub-national level, we identified high burden countries and regions where SQ-LNS will be most impactful. No other study has focused on this age group even though it is a particularly vulnerable period for undernutrition.How this study might affect research, practice or policyOur analysis could help decision-makers and funders to determine where scale-up of SQ-LNS should be prioritized.
Context-dependent hierarchical categorization of human faces: Behavioral and EEG/MEG evidence
Authors: Wang Xuena , Han Shihui 
Published: February 2025

AbstractSocial categorization of faces provides a key cognitive basis of human behavior and may occur along various dimensions of facial attributes. The present study investigated a potential hierarchical structure of social categorization of faces based on a superordinate (Species) versus a subordinate (Race) level of abstraction of facial attributes. We recorded behavioral performances in a face classification task and found faster responses to the same set of Asian faces when presented alternately with dog faces (a species context) relative to Black faces (a race context). In addition, using a repetition suppression (RS) paradigm, we recorded electroencephalography (EEG) and magnetoencephalography (MEG) signals to Asian faces in the species and race contexts, respectively. Our analyses of the RS effects on EEG/MEG signals to Asian faces revealed that dynamic neural encoding of similarity of Asian faces occurred in the right fusiform gyrus at 140-200 ms and in the left temporoparietal junction at 317-413 ms after stimulus onset in the species context but only in the left temporoparietal junction at 317-413 ms in the race context. These behavioral and EEG/MEG findings unravel the neurocognitive mechanisms of context-dependent social categorization of faces by highlighting its hierarchically organized structure based on different levels of facial attributes.