bluuebunny/crossref_metadata_2025_split huggingface dataset:
“They provide the right kind of support.”A qualitative study of preferences for differentiated service delivery location among recipients of antiretroviral therapy at Lighthouse Trust in Lilongwe Malawi
Authors: Orii Lisa , Wilson Kate S. , Huwa Jacqueline , Kiruthu-Kamamia Christine , Sande Odala , Thawani Agness , Berner-Rodoreda Astrid , Viola Evelyn , Tweya Hannock , Tembo Petros , Masambuka Wapu , Anderson Richard , Feldacker Caryl 
Published: December 2023

AbstractDifferentiated service delivery (DSD) models for antiretroviral therapy (ART) allow stable recipients of care (RoC) to receive multi-month ART drug refills and complete rapid reviews in community sites. As DSD options expand across sub-Saharan Africa, RoC’s preferences and perspectives on community-versus clinic-based care models warrants attention. We describe the factors that influence RoC choice of ART delivery approaches at Lighthouse Trust (LT) clinics and community-based DSD sites in Lilongwe, Malawi. We conducted eight focus group discussions (FGDs) among LT RoC in the Nurse-led Community-based ART Program (NCAP) (n=4) and in clinic settings (n=4) to explore opinions, preferences, and perceptions about ART service delivery. FGDs were conducted and recorded in Chichewa and then translated and transcribed into English for analysis. Data was analyzed using thematic analysis and findings discussed with the LT and NCAP teams to jointly reflect on the findings. Sixty-three participants took part in the qualitative study. Results were largely similar across care locations. In both NCAP and clinic FGDs, RoC appreciated the convenience of integrating their appointment visits at their chosen care location into their daily lives, though some RoC traveled far to access LT’s high quality of care. RoC were satisfied with the quality of the care they received at their location of choice. Privacy protection was an important consideration for choosing care models. At LT clinics, RoC highlighted the importance of physical separation between LT’s HIV-specific service site and other service sites. In NCAP, RoC expressed that their choice of care model was reinforced by the sense of mutual support that they received through the peer support model. At LT, RoC in both clinic and NCAP care models expressed satisfaction with their chosen care model and preferred that choice over alternative options and locations. Overall, LT RoC appreciated the quality of care, the respectful provider-to-patient interactions, and the attention to privacy at community and clinic sites. These findings suggest continued emphasis on offering choices to RoC on where and how they receive ART delivery approaches may support ongoing engagement in care.
Mathematical modelling to estimate the impact of maternal and perinatal healthcare services and interventions on health in sub-Saharan Africa: A scoping review
Authors: Collins Joseph H , Cambiano Valentina , Phillips Andrew N. , Colbourn Tim 
Published: December 2023

AbstractMathematical modelling is a commonly utilised tool to predict the impact of policy on health outcomes globally. Given the persistently high levels of maternal and perinatal morbidity and mortality in sub-Saharan Africa, mathematical modelling is a potentially valuable tool to guide strategic planning for health and improve outcomes. The aim of this scoping review was to explore how modelling has been used to evaluate the delivery of maternal and/or perinatal healthcare interventions or services and predict their impact on health-related outcomes in the region. A search across three databases was conducted in November 2023 which returned 8660 potentially relevant studies, from which 60 were included in the final review. Characteristics of these studies, the interventions which were evaluated, the models utilised, and the analyses conducted were extracted and summarised. Findings suggest that the popularity of modelling within this field is increasing over time with most studies published after 2015 and that population-based, deterministic, linear models were most frequently utilised, with the Lives Saved Tool being applied in over half of the reviewed studies (n=34, 57%). Much less frequently (n=6) models utilising system-thinking approaches, such as individual-based modelling or systems dynamics modelling, were developed and applied. Models were most applied to estimate the impact of interventions or services on maternal or neonatal mortality outcomes with morbidity-related outcomes and stillbirth reported on much less often. Going forward, given that healthcare delivery systems have long been identified as complex adaptive systems, modellers may consider the advantages of applying systems-thinking approaches to evaluate the impact of maternal and perinatal health policy. Such approaches allow for a more realistic and explicit representation of the systems- and individual-level factors which impact the effectiveness of interventions delivered within health systems.
Effects of early childhood education on early childhood development in Bangladesh
Authors: Khanam Shimlin Jahan , Alam Md Badsha , Khan Md Nuruzzaman 
Published: December 2023

AbstractBackgroundEarly childhood education is considered as vital for the early childhood development (ECD) instead of scarcity of the relevant literature. This study aims to investigate the relationship between early childhood education and the early childhood development index (ECDI) in Bangladesh.MethodsWe analyzed data from 9,420 children (aged 3 and 4) extracted from the Multiple Indicator Cluster Survey conducted in 2019. The outcome variable considered was the Early Childhood Development Index, a composite index generated based on the responses to 10 items and categorized as children either developmentally on track (coded as 1) or not (coded as 0). Four domains of ECDI—physical, learning, emotional, and social well-being— were also considered as outcome variable. Attendance of the early childhood education program was the major exposure variable. The association between explanatory and outcome variables was determined using a multilevel logistic regression model, adjusting for potential covariates.ResultsOnly one in every five children in Bangladesh was found to be enrolled in early childhood education. Non-participation in early childhood education was associated with a 44% lower likelihood (aOR, 0.56, 95% CI, 0.47-0.66) of positive ECDI compared to participation in early childhood education. Additionally, non-attendance of early childhood education, compared to attendance, was associated with lower odds in literacy-numeracy (aOR, 0.25, 95% CI, 0.21-0.28) and learning (aOR, 0.59, 95% CI, 0.45-0.77) domains of ECDI.ConclusionThe findings provide evidence of the importance of early childhood education programs in ensuring early childhood development. This indicates the necessity of strengthening early childhood education programs in Bangladesh to ensure the overall well-being of children.
Salivary Biomarkers as Pioneering Indicators for Diagnosis and Severity Stratification of Pediatric Long COVID
Authors: Tyrkalska Sylwia D. , Pérez-Sanz Fernando , Franco-Martínez Lorena , Peres-Rubio Camila , Tvarijonaviciute Asta , Martínez-Subiela Silvia , Méndez-Hernández María , González-Aumatell Alba , Carreras-Abad Clara , Domènech-Marçal Èlia , Cerón José J. , Cayuela María L. , Mulero Victoriano , Candel Sergio 
Published: December 2023

ABSTRACTLong COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection. Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms post-acute infection. In this study, we examined 105 saliva samples (49 from children with long COVID and 56 controls), revealing significant alterations in salivary biomarkers. Pediatric long COVID exhibited increased oxidant biomarkers, decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms. This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unraveling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals.
Implementation and Evaluation of a Home-Based Pre-Exposure Prophylaxis Monitoring Option: A Protocol for a Randomized Controlled Trial
Authors: Cannon Chase A. , Holzhauer Kate , Golden Matthew 
Published: December 2023

AbstractBackgroundHIV prevention is a public health priority. Despite progress in recent years, PrEP use remains suboptimal especially among groups disproportionately impacted by new HIV diagnoses such as gender and sexual minorities of color. Multiple barriers including lack of PrEP providers and challenges with attending quarterly monitoring visits contribute to low PrEP uptake and retention. Home-based PrEP (HB-PrEP) services could reduce stigma, increase convenience, expand health system capacity for PrEP care, and improve PrEP retention.ObjectiveHOT4PrEP (Home Option Testing for PrEP) is a hybrid randomized controlled trial (RCT) that aims to examine whether HB-PrEP care is acceptable to PrEP users, feasible to implement into a sexual health clinic setting, and impacts PrEP retention over time.MethodsThe RCT will recruit approximately 450 persons currently taking or soon to initiate PrEP at the Sexual Health Clinic in Seattle, WA and randomize them to continue standard of care or have the option to use HB-PrEP for two of three tri-annual PrEP follow-up visits. Participants in the intervention arm will be sent home kits containing gonorrhea and chlamydia swabs and Tasso devices for blood self-collection. The primary outcome is PrEP retention between groups at 20 months; secondary outcomes include user satisfaction/acceptability, feasibility, self-reported PrEP adherence, and STI incidence. Interviews with PrEP users and clinic staff will elucidate barriers and facilitators of implementation.ResultsThe HOT4PrEP RCT began enrolling in March 2022, was on hold during the height of the US mpox epidemic, then resumed in December 2022. From the first 100 enrollees, median age is 34 years and most are cisgender gay men (89%) with at least some college education (91%). Among those randomized to the HB-PrEP option, 65% have opted at least once to self-collect samples at home and 84% have successfully returned test kits for HIV/STI testing. Primary PrEP retention and qualitative analyses are ongoing.ConclusionsImplementation of HB-PrEP into a high-volume sexual health clinic seems to be feasible and acceptable to early RCT enrollees. This strategy has the potential to address individual and systemic barriers associated with initiating and persisting on PrEP such as increasing sexual health agency and expanding clinical capacity to serve greater numbers of PrEP users.Trial Registration:ClinicalTrials.govNCT05856942
Investigating the Effects of Artificial Baroreflex Stimulation on Pain Perception: A Comparative Study in Healthy Participants and Individuals with Chronic Low Back Pain
Authors: Venezia Alessandra , Jones Harriet-Fawsitt , Hohenschurz-Schmidt David , Mancini Matteo , Howard Matthew , Makovac Elena 
Published: December 2023

AbstractThe autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, whereupon acute pain triggers ANS responses, while resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by “top-down” processes occurring in the brain, brainstem, and spinal cord, known asdescending modulation. By employing the Conditioned Pain Modulation (CPM) paradigm, our previous study revealed a connection between reduced low-frequency heart rate variability (HRV) and CPM. Chronic pain patients often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and HRV regulation, may play a significant role in this relationship, but their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In this study, we combined artificialbaroreceptor stimulationin both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. 22 patients with chronic low back pain (CLBP) and 29 healthy controls (HC) took part in this study. We identified a relationship between baroreflex functioning and perception of pressure pain, finding differential modulation of pressure pain between diagnostic groups. Specifically, HC participants perceived less pain in response to baroreflex activation, whereas CLBP patients exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex efficiency in both patients and controls. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the autonomic nervous system and descending pain modulation.
The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality
Authors: Mutz Julian , Wong Win Lee Edwin , Powell Timothy R. , Young Allan H. , Dawe Gavin S. , Lewis Cathryn M. 
Published: December 2023

ABSTRACTBackgroundLithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality.MethodsThe UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use, and duration of the first prescription period) and telomere length, frailty, metabolomic age, pulse rate and all-cause mortality.Results591 individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β= −0.022, 95% CI −0.081 to 0.037,p= 0.47), the total duration of use (β= −0.005, 95% CI −0.023 to 0.013,p= 0.57) or the duration of the first prescription period (β= −0.018, 95% CI −0.051 to 0.015,p= 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or metabolomic age. However, a higher prescription count or a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict mortality.ConclusionsWe observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by duration of use.
The gut-microbiome in adult Attention-deficit/hyperactivity disorder - A Meta-analysis
Authors: Jakobi Babette , Vlaming Priscilla , Mulder Danique , Ribases Marta , Richarte Vanesa , Ramos-Quiroga Josep Antoni , Tendolkar Indira , van Eijndhoven Philip , Vrijsen Janna N. , Buitelaar Jan , Franke Barbara , Hoogman Martine , Bloemendaal Mirjam , Arias-Vasquez Alejandro 
Published: December 2023

AbstractAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (NADHD=312, NNoADHD=305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g.,Ruminococcus_torques_group(LogOdds=0.17, pfdr=4.42×10−2), which was more abundant in adults with ADHD, andEubacterium_xylanophilum_group(LogOdds= −0.12,pfdr=6.9 x 10−3), which was less abundant in ADHD.Ruminococcus_torques_groupwas further associated with hyperactivity/impulsivity symptoms andEisenbergiellawith inattention and hyperactivity/impulsivity (pfdr<0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties.
Single cell AI-based detection of DNA mismatch repair deficiency in 1,988 colorectal cancers reveals prognostic and predictive value in the SCOT trial
Authors: Nowak Marta , Jabbar Faiz , Rodewald Ann-Katrin , Gneo Luciana , Tomasevic Tijana , Harkin Andrea , Iveson Tim , Saunders Mark , Kerr Rachel , Oein Karin , Maka Noori , Hay Jennifer , Edwards Joanne , Tomlinson Ian , Sansom Owen , Kelly Caroline , Easton Alistair , Domingo Enric ,   TransSCOT group, Koelzer Viktor H , Church David N 
Published: December 2023

SUMMARYTesting for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRC). Automation of this would facilitate precision medicine, particularly if it provided information on likely aetiology. We developed AIMMer, anAI-based method for determination ofMMRprotein expression at single cell level in routine pathology samples. We applied it to over 2,000 colorectal cancers (CRC) from the SCOT clinical trial, which compared 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy (FOLFOX or CAPOX). Benchmarking of AIMMeR against pathologist ground truth MMR calls revealed AUROC of 0.98, and positive predictive value (PPV) greater than 95% for the commonest pa[ern of somatic MMRd, and for retained MMR expression. Analysis of CRC recurrence confirmed the prognostic value of MMRd in oxaliplatin-treated patients. While MMRd did not predict differential benefit from chemotherapy duration, it correlated with difference in clinical outcome by chemotherapy regimen (PInteraction=0.04). AIMMeR holds promise to reduce pathologist workflow and streamline clinical diagnostics in CRC.
Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice
Authors: Zeisler Zachary R , Heslin Kelsey A , Stoll Frederic M , Hof Patrick R , Clem Roger L , Rudebeck Peter H 
Published: December 2023

Short abstractThe basolateral amygdala (BLA) projects to the frontal cortex (FC) in both rodents and primates, but the comparative organization of single-neuron BLA-FC projections is unknown. Using a barcoded connectomic approach, we found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens are similarly organized in mice and macaques, BLA-FC connections differ.
On the necessity to include multiple types of evidence when predicting molecular function of proteins
Authors: de Crécy-Lagard Valérie , Swairjo Manal A. 
Published: December 2023

AbstractMachine learning-based platforms are currently revolutionizing many fields of molecular biology including structure prediction for monomers or complexes, predicting the consequences of mutations, or predicting the functions of proteins. However, these platforms use training sets based on currently available knowledge and, in essence, are not built to discover novelty. Hence, claims of discovering novel functions for protein families using artificial intelligence should be carefully dissected, as the dangers of overpredictions are real as we show in a detailed analysis of the prediction made by Kim et al1on the function of the YciO protein in the model organismEscherichia coli.
The Developmental Transcription Factor TBX3 Physically Engages with the Wnt/β-catenin Transcriptional Complex in Human Colorectal Cancer Cells to Regulate Metastasis Genes
Authors: Jauregi-Miguel Amaia , Söderholm Simon , Weiss Tamina , Nordin Anna , Ghezzi Valeria , Brütsch Salome M. , Pagella Pierfrancesco , van de Grift Yorick , Zambanini Gianluca , Ulisse Jacopo , Mattia Alessandro , Deviatiiarov Ruslan , Faustini Elena , Moparthi Lavanya , Lottersberger Francisca , Koch Stefan , Moor Andreas E. , Sun Xiao-Feng , von Castelmur Eleonore , Sheng Guojun , Cantù Claudio 
Published: December 2023

AbstractWnt signaling orchestrates gene expression in a plethora of processes during development and adult cell homeostasis via the action of nuclear β-catenin. Furthermore, neoplasia of the colorectal epithelium begins with aberrant Wnt/β-catenin signaling. Yet, little is known about how β-catenin generates context-specific transcriptional outcomes. We have previously identified the developmental transcription factor TBX3 as a tissue-specific component of the Wnt/β-catenin nuclear complex during mouse forelimb development. In this study, we show that TBX3 is present and functionally active in human colorectal cancers. TBX3’s genomic binding pattern suggests a regulatory role that broadly coincides with that of Wnt/β-catenin. Moreover, proteomics proximity labelling indicated that, during Wnt pathway activation, TBX3 is vicinal to several protein partners, including the transcription factors TCF/LEF and chromatin remodeling complexes which are usually found at Wnt responsive elements. Sequence and structure analysis revealed that TBX3 possesses an exposed Asp-Pro-Phe (NPF) motif predicted by AlphaFold2 Multimer to mediate direct interactions with several Wnt-activated TBX3 partners. Deletion of NPF abrogates TBX3 proximity to these partners and its ability to modulate Wnt-dependent transcription. TBX3 emerges as a key modulator of the oncogenic activity of Wnt/β-catenin in colorectal cancer, and its mechanism of action exposes a novel druggable protein-interaction surface.