bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Antiretroviral Therapy Scale-Up in Mozambique and Estimated Averted HIV Infections and Related Deaths, 2004–2023
Authors: Chilundo Sónia , Gaspar Irénio , Keating Ryan , Fortmann Joshua , Filimão Dércio , Nguimfack Alexandre , Pereira Isabel , Alfredo Charity , Gudo Paula Samo , Langa António , Dirlikov Emilio , Greenberg Seth , Pathmanathan Ishani , Couto Aleny 
Published: November 2024

IntroductionMozambique is a HIV high-burden country. In 2004, Mozambique had an estimated HIV prevalence of 15.6% and 1.5 million people living with HIV (PLHIV). During same year the country started antiretroviral therapy (ART) scale-up supported by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). We describe the ART scale-up and estimate averted HIV infections and HIV-related deaths.MethodsWe analyzed PEPFAR Monitoring, Evaluation, and Reporting program data from fiscal year 2004 to 2023. Before October 2018, PLHIV on ART were defined as clients with ≤90 days since last missed visit; in October 2018, this changed to ≤28 days. Viral load suppression (VLS) rate was calculated as PLHIV at PEPFAR-supported sites with VLS (<1,000 viral copies/mL) among those tested in previous 12 months. We used the 2024 United Nations Programme on HIV/AIDS (UNAIDS) Spectrum AIDS Impact Model and Goals Age Structured Model (ASM) to estimate HIV infections and HIV-related deaths averted.ResultsBy September 2023, 2.1 million PLHIV in Mozambique were receiving PEPFAR-supported ART (1.4 million women [66%]; 1.9 million aged ≥15 years [95%]), a 650-fold increase from 3,226 in March 2004. The VLS rate increased from 62% (78,808/126,212) in 2017 to 94% (1,235,626/1,318,544) in 2023. During 2004–2023, ART scale-up helped avert an estimated 1.6 million HIV infections, including over 350,000 infections among HIV-exposed infants, and 1,070,295 HIV-related deaths.ConclusionThe over 20 years of Mozambique’s scaled up ART effort has greatly expanded effective treatment and averted many new infections and HIV-related deaths. While progress has been impressive, gaps remain toward ending HIV as a public health threat.
Factors influencing healthcare providers’ knowledge and skills retention following helping mothers survive and helping babies survive training in Tanzania: A mixed methods cross-sectional study
Authors: Mwilike Beatrice Erastus , Rimoy Martha , Mabada Lucy , Komba Nicodem , Mwanga Feddy , Gosse Rashid , Ambikile Joel 
Published: November 2024

AbstractThe Tanzanian Midwives Association (TAMA), in collaboration with development partners, implemented a project (50,000 Happy Birthdays)from 2018 to 2020 to improve providers’ knowledge and skills in saving lives at birth. The project was implemented under two training modules namelyHelping Mothers Survive(HMS) andHelping Babies Survive(HBS). Through a mixed-methods cross-sectional design, knowledge retention was assessed by comparing follow-up and post-test knowledge scores among healthcare providers in the selected health facilities in Tanga, Geita, and Katavi regions. Four knowledge areas were evaluated using a written test and five skills areas were assessed using skills observation checklists for each. Quantitative data was analyzed using IBM SPSS version 25 by performing descriptive analysis,t-test and One-Way ANOVA with the level of significance determined at p< 0.05. Qualitative analysis was conducted through a thematic analysis approach and themes were generated to describe the factors influencing retention. 210 respondents participated in the study with more than half holding diploma (n=116; 55.2%) and working in urban area (n=123; 58.6%). There was a statistically significant drop in mean knowledge scores for controlling bleeding after birth (t=15.404,p<0.001), in helping babies breathe (t=8.580,p<0.001), and in essential care for small babies (t=19.620,p<0.001). Working in a rural area had a statistical significant higher drop in mean knowledge scores for managing pre-eclampsia (F=4.491,p=0.035) and for helping babies breathe (F=5.005,p=0.026). Education level also showed a significant difference in the mean knowledge score for managing pre-eclampsia (F=4.850,p=0.003).There was poor knowledge retention following receiving training on HMS and HBS. The level of professional education and residential area significantly influenced knowledge retention. Frequent refresher training and other relevant training among healthcare workers may be helpful in knowledge retention regarding maternal and neonatal care, with much emphasis on providers working in rural areas and those with lower level of professional education.
Healthy Dietary Patterns and Lower Atherosclerosis in High-Risk Individuals
Authors: Cherian Laurel , Agarwal Puja , Agrawal Sonal , James Bryan D. , Yang Dixon , Wagner Maude , Leurgans Sue , Bennett David , Aggarwal Neelum , Schneider Julie 
Published: November 2024

AbstractBackgroundThis study investigates associations between diet patterns and the risk of intracranial atherosclerosis (ICAD) in individuals with preexisting hypertension (HTN) or myocardial infarction (MI).Method676 autopsied participants (mean age at death =91.1±6.1, 71% women) of a longitudinal clinical neuropathological cohort study, with complete dietary and neuropathology data, were included. Diet scores were computed (median interval to death = 5.9 (3.0, 8.7 years). HTN and MI history was self-reported. Large vessel atherosclerosis was evaluated at the circle of Willis, and severity of intracranial atherosclerosis was assessed based on number of atherosclerotic plaques, extent of vessel involvement, and degree of vessel occlusion to create a 4-level grading system (0-3). All regression models were adjusted for age, sex, education, caloric intake, and APOE4.ResultsOf the 676 subjects, 361 (53%) had mild, 142 (21%) had moderate, and 29 (5%) had severe atherosclerosis. There was no direct relationship between diet and atherosclerosis. The relationship between ICAD and MI (OR = 1.38, 95% CI = 0.95, 2.00) showed a nonsignificant trend. HTN (OR = 1.598, 95% CI = 1.15, 2.18) was positively associated with intracranial atherosclerosis. The association of diet with intracranial atherosclerosis differed by history of MI (MIND (p=0.007), MedDiet (p=0.006)). The association between ICAD and the MIND diet also differed by whether HTN was reported (β=-0.212, SE= 0.111, p=0.055) as did the relationship between ICAD and the MedDiet (β = -0.077, SE= 0.035, p=0.029). In stratified analysis, among individuals with preexisting MI (N=130), those with a better diet had lower odds of intracranial atherosclerosis (MedDiet: OR = 0.88, 95% CI = 0.81, 0.96; MIND: OR = 0.69, 95% CI = 0.53, 0.90).ConclusionA healthy dietary pattern is associated with lower odds of severe intracranial large vessel atherosclerosis in high-risk older adults. In-vivo studies of dietary habits and brain health, specifically in those at high vascular risk are needed.
The impact of knowledge, attitudes, and practices on hypertension Control and associated Comorbidities among workers of a beverage company in Bangladesh
Authors: Saleh Abu Sayeed Md. , Rahman Monjur , Mashreky S M Saidur Rahman 
Published: November 2024

AbstractHypertension is well known globally as a major health issue because of its high magnitude and further complications of cardiovascular and kidney diseases. Bangladesh has witnessed a gradual epidemiological transition where communicable diseases especially the chronic ones are dominating including the rural area where people have least access to the health care services. As is evident from aforementioned complications, hypertension if not well managed, equally has dire consequences hence calls early diagnosis and intervention. Consequently, hypertension prevalence in low-income countries rises due to certain lifestyle aspects; for instance, Afghanistan. In regard to this, Knowledge, Attitude, and Practice (KAP) questionnaires facilitate in assessing gaps in the approach toward managing hypertension. The same issues are seen in Benin: China, Egypt: Ethiopia, Ghana: India: Iran, Lebanon, Malaysia: and Mongolia where the government acknowledges that solutions should be specific to increase awareness, act on lifestyle factors and therapy compliance. Thus, management of hypertension must address general approaches to reducing the burden of hypertension and its effects on the affected individuals and healthcare facilities across the world.
Investigating immune amnesia after measles virus infection in two West African countries: A study protocol Short Title - Investigating immune amnesia in two West African countries
Authors: Fouth Tchos Karine , Ridzon Renée , Haidara Mory Cherif , Dabitao Djeneba , Akpa Esther , Camara Daouda , Vallée David , Coulibaly Mariam , Camara Sekou , Aboulhab Jamila , Diakité Mahamadou , Diarra Bassirou , Diarra Samba , Dicko Ilo , Francis Alyson , Kolié Cécé Francis , Koropogui Michel , Lim Caeul , Samaké Seydou , Hunsberger Sally , Sidibé Moussa , Chen Ray Y. , Konate Issa , Doumbia Seydou , Beavogui Abdoul Habib , Shaw-Saliba Kathryn 
Published: November 2024

Abstract“Investigation of Immune Amnesia Following Measles Infection in Select African Regions” (ClinicalTrials.govIdentifier:NCT06153979) is a prospective, observational, longitudinal study being conducted in two West African countries, Guinea, and Mali. The overall goal is to investigate the impact of measles virus (MeV) infection on pre-existing immunity, vaccine response, and susceptibility to subsequent illness. A total of 256 children aged 1 to 15 years are being enrolled into one of two study arms: those with acute MeV infection (cases) and without (controls). Acute MeV is confirmed by RT-PCR testing on upper respiratory specimens or IgM detection on blood samples at screening. Blood samples are collected at multiple time points at screening (Day 0), at an optional visit to repeat IgM serology for inconclusive or negative Day 0 results (Day 7-10), and during follow-up visits on Day 14, Week 13, and Week 52. These blood samples will be tested to evaluate both humoral and cellular immune responses to endemic pathogens to measure variations in antibody diversity and antibody secreting cells (ASCs). To explore how recent MeV infection may affect the child’s ability to respond to a controlled immune stimulus, all participants will receive rabies vaccine pre-exposure prophylaxis (PrEP) using Verorab inactivated rabies vaccine. Three doses of 0.5 ml of VERORAB vaccine are administered on Days 0, 7, and 28. Biological samples will be collected after vaccination to assess if the rabies vaccine response differs: 1) between cases and controls, and 2) based on the timing of the rabies vaccination after acute measles infection. In addition, the study team will collect information on healthcare encounters during the year-long follow-up will be collected to determine if there is a difference in the number of encounters by study group. The findings of this study will further the understanding of the MeV immune amnesia phenotype.
From protection of sacrificial self to critical turning points and growth: Nurses’ experiences on the frontline during the COVID-19 pandemic
Authors: Creedon Sinéad , Trace Anna 
Published: November 2024

AbstractThe mental health and wellbeing of nurses has been a concern, long before the arrival of the COVID-19 pandemic. Working on the frontline under such challenging circumstances, for extended periods of time, has resulted in negative psychological responses. The current study aims to examine nurses’ resilience in acute hospitals in Ireland, during a period of adversity (pandemic), to explore it’s impact on their personal and professional identity, and their perception of meaningful supports and coping. An interpretative phenomenological analysis was carried out to gain insight into how nurses adapted to the changing work environment during the pandemic. Online semi-structured interviews were carried out with six experienced female nurses, who were redeployed to the frontline from their own roles. Three experiential themes representing the nurses’ journey were generated: Protection of Sacrificial Self; The Fortifying Effect of Us, and Critical Turning Points & Growth. Nurses made significant sacrifices and had to find ways to detach to cope. They revitalized themselves by creating a sense of ‘us’ to help them face a harsh climate against others, which enabled critical turning points and growth. This study has strongly highlighted the emotional effects on nurses due to feeling isolated, undervalued, and excluded during redeployment to the frontline. It has also featured how well nurses coped while faced with an existential crisis and has given voice to all nurses who faced this pandemic despite exposure to risk of burnout and threats to their mental health and wellbeing. This study has further enriched our understanding of personal growth and trauma in adverse work conditions by including an exploration of what sacrificial commitment adds to our understanding of physical and moral courage. Future provision of supports for nurses must be ongoing both during and after crisis events.
Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways
Authors: Wyatt Rachael A. , Jamaluddin Aqfan , Mistry Vinesh , Quinn Caitlin , Gorvin Caroline M. 
Published: November 2024

AbstractThe melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R. Variants in MRAP2 have also been identified in overweight and obese individuals. However, functional studies that have only measured the effect of MRAP2 variants on MC4R-mediated cAMP signaling have produced inconsistent findings and most do not reduce MC4R function. Here we investigated the effect of twelve of these previously reported MRAP2 variants and showed that all variants that have been identified in overweight or obese individuals impair MC4R function. When expressed at equal concentrations, seven MRAP2 variants impaired MC4R-mediated cAMP signaling, while nine variants impaired IP3 signaling. Four mutations in the MRAP2 C-terminus affected internalization. MRAP2 variants had no effect on total or cell surface expression of either the MRAP2 or MC4R proteins. Structural models predicted that MRAP2 interacts with MC4R transmembrane helices 5 and 6, and mutations in two MRAP2 residues in putative contact sites impaired the ability of MRAP2 to facilitate MC4R signaling. In summary, our studies demonstrate that human MRAP2 variants associated with obesity impair multiple MC4R signaling pathways and that both Gs-cAMP and Gq-IP3 pathways should be assessed to determine variant pathogenicity.
Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth
Authors: Funk Amy L. , Katerji Meghri , Afifi Marwa , Nyswaner Katherine , Woodroofe Carolyn C. , Edwards Zoe C. , Lindberg Eric , Bergman Knickole L. , Gough Nancy R. , Rubin Maxine R. , Karpińska Kamila , Trotter Eleanor W. , Dash Sweta , Ries Amy L. , James Amy , Robinson Christina M. , Difilippantonio Simone , Karim Baktiar O. , Chang Ting-Chia , Chen Li , Xu Xin , Doroshow James H. , Ahel Ivan , Marusiak Anna A. , Swenson Rolf E. , Cappell Steven D. , Brognard John 
Published: November 2024

AbstractThe worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded byMAP3K13) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplifiedMAP3K13. A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules. Inhibition of LZK catalytic activity suppressed tumor growth in HNSCC PDX models with amplifiedMAP3K13. We found that the kinase activity of LZK stabilized c-MYC and that LZK stabilized gain-of-function (GOF) p53 through a kinase-independent mechanism. Therefore, we designed proteolysis-targeting chimeras (PROTACs) and demonstrate that our lead PROTAC promotes LZK degradation and suppresses expression of GOF p53 and c-MYC leading to impaired viability of HNSCC cell lines. This research provides a strong basis for development of therapeutics targeting LZK in HNSCCs with amplification of the gene.One Sentence SummaryThis study establishes the kinase LZK as a therapeutic target for HNSCC through regulation of c-MYC expression.
Enhanced encephalitic tropism of bovine H5N1 compared to the Vietnam H5N1 isolate in mice
Authors: Goldin Kerry , van Tol Sarah , Johnson Randall C. , Mukesh Reshma Koolaparambil , Gallogly Shane , Schulz Jonathan E. , Prado-Smith Jessica , Saturday Greg , Yinda Kwe Claude , Munster Vincent J. , de Wit Emmie , van Doremalen Neeltje 
Published: November 2024

AbstractIn recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease.Significance statementThe rise in HPAI H5N1 infections among mammals, including humans in the USA, highlights an emerging One Health concern. Understanding the phenotypic changes of HPAI H5N1 and associated increase in infection of mammalian hosts is critical. In this study, we investigated the tissue tropism in mice of a bovine HPAI H5N1 strain isolated in 2024 and compared it to a strain isolated from a human patient in 2004. Our findings reveal that the bovine isolate exhibits enhanced neurotropism, unlike the respiratory-restricted replication observed with the HPAI H5N1 isolate from 2004. This difference in tissue tropism, accompanied by distinct cytokine responses in the brain, underscores the potential for altered disease outcomes in other mammalian hosts.
Boltz-1: Democratizing Biomolecular Interaction Modeling
Authors: Wohlwend Jeremy , Corso Gabriele , Passaro Saro , Reveiz Mateo , Leidal Ken , Swiderski Wojtek , Portnoi Tally , Chinn Itamar , Silterra Jacob , Jaakkola Tommi , Barzilay Regina 
Published: November 2024

AbstractUnderstanding biomolecular interactions is fundamental to advancing fields like drug discovery and protein design. In this paper, we introduce Boltz-1, an open-source deep learning model incorporating innovations in model architecture, speed optimization, and data processing achieving AlphaFold3-level accuracy in predicting the 3D structures of biomolecular complexes. Boltz-1 demonstrates a performance on-par with state-of-the-art commercial models on a range of diverse benchmarks, setting a new benchmark for commercially accessible tools in structural biology. By releasing the training and inference code, model weights, datasets, and benchmarks under the MIT open license, we aim to foster global collaboration, accelerate discoveries, and provide a robust platform for advancing biomolecular modeling.
Critical assessment of nanopore sequencing for the detection of multiple forms of DNA modifications
Authors: Kong Yimeng , Zhang Yanchun , Mead Edward A. , Chen Hao , Loo Christian E. , Fan Yu , Ni Mi , Zhang Xue-Song , Kohli Rahul M. , Fang Gang 
Published: November 2024

AbstractWhile nanopore sequencing is increasingly used for mapping DNA modifications, it is important to recognize false positive calls as they can mislead biological interpretations. To assist biologists and methods developers, we describe a framework for rigorous evaluation that highlights the use of false discovery rate with rationally designed negative controls capturing both general background and confounding modifications. Our critical assessment across multiple forms of DNA modifications highlights that while nanopore sequencing performs reliably for high-abundance modifications, including 5-methylcytosine (5mC) at CpG sites in mammalian cells and 5-hydroxymethylcytosine (5hmC) in mammalian brain cells, it makes a significant proportion of false positive detections for low-abundance modifications, such as 5mC at CpH sites, 5hmC and N6-methyldeoxyadenine (6mA) in most mammal cell types. This study highlights the urgent need to incorporate this framework in future methods development and biological studies, and advocates prioritizing nanopore sequencing for mapping abundant over rare modifications in biomedical applications.
The RNA binding protein LIN28A mediates chromatin dynamics during neuronal differentiation
Authors: Piscitelli Silvia , Cascone Emanuela , D’Ambrosio Chiara , Divisato Giuseppina , De Lisio Laura , Leoni Guido , Matassa Danilo Swann , Lanzuolo Chiara , Rosti Valentina , Zizolfi Maria Chiara , Matuozzo Monica , di Patrizio Soldateschi Emanuele , Maiuri Paolo , Scaloni Andrea , Passaro Fabiana , Parisi Silvia 
Published: November 2024

AbstractThe transition of embryonic stem cells (ESCs) from pluripotency to lineage commitment is regulated by multiple mechanisms, including chromatin dynamics and both transcriptional and post-transcriptional processes. Recent advances have highlighted that these mechanisms often interact, forming intricate multi-layered regulatory networks that require detailed characterization. In this study, we demonstrate that the RNA-binding protein LIN28A plays a pivotal role in neuronal differentiation by mediating RNA-dependent interactions with the Polycomb repressive complex 2 (PRC2). This interaction facilitates the eviction of PRC2 from chromatin, thereby activating a neuronal lineage-specific transcriptional program. Proteomic analyses revealed that the LIN28A interactome undergoes substantial remodeling during differentiation, corresponding to changes in LIN28A localization. In ESCs, LIN28A is predominantly nuclear and interacts with several components of the PRC2 complex in an RNA-dependent manner, assisting in chromatin dynamics. Our findings show that in the absence of LIN28A, PRC2 remains associated with chromatin, impairing the expression of genes critical for neuronal differentiation in ESCs. Chromatin immunoprecipitation sequencing (ChIP-seq) further confirmed that loss of LIN28A results in preferential PRC2 occupancy at the promoters of differentiation-associated genes. This study uncovers a novel role for LIN28A in epigenetic remodeling, which is essential for the proper differentiation of ESCs into the neuronal lineage.