bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Supply Management at First-level Public Health Facilities: Case of Pyay District, Myanmar
Authors: Hlaing Thein , Lat Tun Win 
Published: January 2024

AbstractBackgroundFirst-level public health facilities (PHFs) serve as primary providers of essential medicines, necessitating critical attention to drug availability and quality assurance. This study aimed to examine the status of functional areas within the drug supply chain management framework and assess the overall capability maturity at first-level PHFs.MethodsThe cross-sectional study was conducted among 183 drug store sites from six townships of Pyay District. Only situational analysis was exercised to determine the existing situations. The overall capability maturity was determined according to the definitions of levels of the Capability Maturity Module Tool.ResultsThe study encompassed 6 Maternal and Child Health Centers, 43 Rural Health Centers, and 134 Sub-rural Health Centers. In terms of drug supply management training, 58.47% lacked formal training, with 23.5% not undergoing performance reviews. Drug forecasting predominantly relied on a pen-paper system (91.6%) and factors like patient load (87.39%), drug consumption (85.71%), and disease prevalence (64.71%). Store site analysis revealed that 65.03% exhibited marginal capability, lacking standardized drugstores and employing unstandardized procedures. Storage practices varied, with 48.69% storing drugs conveniently and others categorizing them by drug type (32.79%) or using the first-expired-first-out system (40.98%). Approximately 42.69% reported having expired drugs. Concerning transportation costs, 37.16% incurred expenses exceeding 20,000 Kyats per time, with management staff often covering the costs. Waste management methods included burial pits (49.18%), incineration (62.84%), and sharp pits (55.19%). A majority (78.14%) used safety boxes, and 57.38% implemented a color-coded system for waste bins. The logistics management information system was entirely paper-based (100%), with key challenges attributed to insufficient training (62.84%), capacity issues (19.13%), and staffing concerns (38.25%). On average, assessments of drug quality conditions and physical damages scored 46.51% and 48.20%, respectively.ConclusionThe study revealed that the overall supply chain maturity at first-level public health facilities is at a marginal capability level (36.35%). While some basic drug supply chain management procedures were in place, they were not consistently followed, and many systems remain manual. The findings underscored significant inconsistencies in the management functions of supplied drugs, with poor adherence to Standard Operating Procedure (SOP) guidelines.
Proteome-scale tagging and functional screening in mammalian cells by ORFtag
Authors: Nemčko Filip , Himmelsbach Moritz , Loubiere Vincent , Yelagandula Ramesh , Pagani Michaela , Fasching Nina , Brennecke Julius , Elling Ulrich , Stark Alexander , Ameres Stefan L. 
Published: January 2024

AbstractDetermining protein function in a systematic manner is a key goal of modern biology, but remains challenging with current approaches. Here, we present ORFtag, a versatile, cost-effective and highly efficient method for the massively-parallel tagging and functional interrogation of proteins at proteome scale. Using mouse embryonic stem cells, we showcase ORFtag’s utility through screens for transcriptional activators, repressors and post-transcriptional regulators. Each screen finds known and novel regulators, including long ORFs not accessible to other methods, revealing that Zfp574 is a highly selective transcriptional activator and that oncogenic fusions frequently function as transactivators.
Increased positive selection in highly recombining genes does not necessarily reflect an evolutionary advantage of recombination
Authors: Joseph Julien 
Published: January 2024

AbstractIt is commonly thought that the long-term advantage of meiotic recombination is to dissipate genetic linkage, allowing natural selection to act independently on different loci. It is thus theoretically expected that genes with higher recombination rates evolve under more effective selection. On the other hand, recombination is often associated with GC-biased gene conversion (gBGC), which theoretically interferes with selection by promoting the fixation of deleterious GC alleles. To test these predictions, several studies assessed whether selection was more effective in highly recombining genes (due to dissipation of genetic linkage) or less effective (due to gBGC), assuming a fixed distribution of fitness effects (DFE) for all genes. In this study, I directly derive the DFE from a gene’s evolutionary history (shaped by mutation, selection, drift and gBGC) under empirical fitness landscapes. I show that genes that have experienced high levels of gBGC are less fit and thus have more opportunities for beneficial mutations. Only a small decrease in the genome-wide intensity of gBGC leads to the fixation of these beneficial mutations, particularly in highly recombining genes. This results in increased positive selection in highly recombining genes that is not caused by more effective selection. Additionally, I show that the death of a recombination hotspot can lead to a higherdN/dSthan its birth, but with substitution patterns biased towards AT, and only at selected positions. This shows that controlling for a substitution bias towards GC is therefore not sufficient to rule out the contribution of gBGC to signatures of accelerated evolution. Finally, although gBGC does not affect the fixation probability of GC-conservative mutations, I show that by altering the DFE, gBGC can also significantly affect non-synonymous GC-conservative substitution patterns.
The human complement factor B-C3b complex: Investigation of the interaction using C3b bound to thiol-Sepharose
Authors: Williams Samantha , Pondman Kirsten , Varghese Praveen M. , Aiyan Ahmad Al , Kishore Uday , Sim Robert B. 
Published: January 2024

AbstractFactor B, a serine protease proenzyme and part of the complement system, binds to other complement proteins such as C3b and properdin. While it is known to be activated by factor D, other interactions that interfere with the binding between Factor B and C3b are less well-understood. We attached C3b to a thiol Sepharose via its free SH group and conducted a competition assay employing125I-labelled factor B to study competitive binding. Two anti-C3d monoclonal antibodies (F49b and 4C2) were found to partially inhibit the binding of Factor B to C3b. The inhibitory effects of these monoclonal antibodies were found to be dose-dependent. 4C2 was found to have a maximum inhibition of 50%, while the maximum inhibition by F49b was ∼40%. In contrast, two anti-C3c monoclonal antibodies (F39b and F20b) were able to enhance the formation of the factor B-C3b complex in a dose-dependent manner. Competition binding studies with isolated C3 fragments further supported the involvement of the C3d region in factor B binding, as C3d inhibited the binding of factor B to C3b completely. Furthermore, additional competition binding studies conducted with each of the three domains of factor B (Ba, vWF and SP) demonstrated that each domain independently inhibited the binding of intact factor B to C3b by ∼50%.
VPAC2 receptor signaling promotes pancreatic cancer cell growth and decreases the immunogenicity of the tumor microenvironment
Authors: Passang Tenzin , Wang Shuhua , Zhang Hanwen , Zeng Fanyuan , Hsu Po-Chih , Wang Wenxi , Li Jian Ming , Liu Yuan , Ravindranathan Sruthi , Lesinski Gregory B. , Waller Edmund K. 
Published: January 2024

AbstractIdentifying mechanisms underlying tumor growth and immune resistance is needed to treat pancreatic ductal adenocarcinoma (PDAC) effectively. The complexity of the tumor microenvironment (TME) suggests that the crosstalk between cells in the TME could drive drug resistance and relapse in PDAC. We have previously determined that vasoactive intestinal peptide (VIP) is overexpressed in PDAC and that VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to anti-PD1 therapy. In this study, we show that pancreatic cancer cells engage in autocrine signaling of VIP through VIP-receptor 2 (VPAC2), and that high co-expression of VIP with VPAC2 leads to reduced relapse-free survival in PDAC patients. Mechanistically, we identified piwi-like RNA-mediated gene silencing2 (Piwil2) as a tumor-cell intrinsic protein downstream of VPAC2 that regulates cancer cell growth. In addition, we discovered TGFβ-1 as a potential tumor-extrinsic inhibitor of T cell function induced by VPAC2 signaling.In vivo, knock out and knockdown of VPAC2 on PDAC cells led to reduced tumor growth rate and increased sensitivity to anti-PD-1 therapy in various mouse models of PDAC that were T-cell dependent. Overall, these findings emphasize the implications of VIP/VPAC2 signaling in the PDAC tumor microenvironment and further support the rationale for developing VPAC2-specific antagonists.SignificanceThe autocrine VIP signaling via VPAC2 promotes cancer cell growth and dampens T cell function in pancreatic ductal adenocarcinoma and thus represents a potential therapeutic target in PDAC.
Advancing the Application of pXRF for Biological Samples
Authors: Brandis K.J. , Francis R. , Zawada K.J.A. , Hasselerharm C.D. , Ramp D. 
Published: January 2024

AbstractPoint 1: Portable x-ray fluorescent (pXRF) technology provides significant opportunities for rapid, non-destructive data collection in a range of fields of study. However, there are sources of variation and sample assumptions that may influence the data obtained, particularly in biological samples.Point 2: We used representative species for four taxa (fish, mammals, birds, reptiles) to test the precision of replicate scans, and the impact of sample thickness, sample state, scan location and scan time on data obtained from a pXRF.Point 3: We detected significant differences in concentration data due to sample state, scanning time and scanning location for all taxa. Infinite thickness assumptions were met for fish, reptile and mammal representatives at all body locations when samples were thawed, but not dried. Infinite thickness was not met for feathers. Scan time results found in most cases the 40, 60 and 80 second beam times were equivalent. Concentration data across replicate scans were highly correlated.Point 4: The opportunities for the use of pXRF in biological studies are wide-ranging. These findings highlight the considerations required when scanning biological samples to ensure the required data are suitably collected, while maintaining minimal radiation exposure to live animals.
Changes in surface temperatures reveal the thermal challenge associated with catastrophic moult in captive Gentoo penguins
Authors: Lewden Agnès , du Fretay Tristan Halna , Stier Antoine 
Published: January 2024

AbstractOnce a year, penguins undergo a catastrophic moult replacing their entire plumage during a fasting period on land or on sea-ice during which time individuals can lose 45% of their body mass. In penguins, new feather synthesis precedes the loss of old feathers leading to an accumulation of two feathers layers (double coat) before the old plumage is shed. We hypothesize that the combination of the high metabolism required for new feathers synthesis and the potentially high thermal insulation linked to the double coat could lead to a thermal challenge requiring additional peripheral circulation to thermal windows to dissipate extra-heat. To test this hypothesis, we measured the surface temperature of different body regions of captive Gentoo penguins (Pygoscelis papua) throughout the moult under constant environmental conditions.The surface temperature of the main body trunk decreased during the initial stages of the moult, therefore suggesting a higher thermal insulation. On the opposite, the periorbital region, a potential proxy of core temperature in birds, increased during these same early moulting stages. The surface temperature of bill, flipper and foot (thermal windows) tended to initially increase during the moult period, highlighting the likely need for extra heat dissipation in moulting penguins. These results raise questions regarding the thermoregulatory capacities of wild penguins during the challenging period of moulting on land in the current context of global warming.
Evaluation of HIV Viral Load Surveillance System, National Perspective in Tanzania
Authors: Torokaa Peter Richard , Urio Loveness John , Mwakalobo Ambwene , Magesa Alex Sifaeli , Allan James , Osima David J. , Shao Focus Medard , Mziray Joseph , Barnabas Yulitha , Joachim Agricola , Majigo Mtebe 
Published: January 2024

AbstractBackgroundHuman immunodeficiency virus (HIV) infection is still a global public health problem. The number of HIV-positive individuals was estimated to be 38.0 million worldwide in 2020, with 2.78 million being children and adolescents aged 0 to 19 years. We aimed to assess the usefulness and system attributes of the HIV Viral Load (HVL) surveillance system in Tanzania and determine whether it meets its objectives.MethodologyThis was a descriptive cross-sectional analysis conducted to describe the attributes and usefulness of the HVL surveillance system. From January through December 2022, we consistently captured HVL data, which we extracted and analysed. The system description, case definition, and eligibility criteria were obtained from the system guidelines. We used Updated Guidelines for Evaluating Public Health Surveillance Systems from the Centre for Disease Control and Prevention (CDC) to evaluate system attributes. We observed the data entry to determine the simplicity and time spent entering data into the system. Turnaround time were determined from the sample collected at the spoke to the result returned to the clients.ResultsThe HVL surveillance system is implemented by 90.6% (4314/4764) of facilities in the country. The overall national data completeness was 97.4%. The system’s sensitivity was 84.4%, with a predictive value positive (PVP) of 52% and a national data accuracy of 97%. Of eight data clerks interviewed, 100% (8/8) said the system was simple to use.ConclusionThe system’s overall performance achieved its goals was satisfactory. The system was representable, simple, flexible, and sensitive. Turnaround time was at a median of 13 days.
Why didn’t people get vaccinated against COVID-19? Results from a nationwide survey among Mexican adults
Authors: Wrzecionkowska Dagmara , Stephens Christopher R. , Gutiérrez Reyes Juan Pablo 
Published: January 2024

AbstractObjectiveTo explore the reasons for not getting vaccinated against COVID-19.Material and methodsIn October 2021, a nationwide structured telephone survey (disproportionate stratified sampling) was conducted regarding COVID-19 pandemics, including vaccination experience. To examine associations between inoculation and other characteristics, the chi-square test and logistic regression analysis were applied.ResultsOut of 3 126 adults, 68% reported complete vaccination and 21% only the first dose, while 11% remained unvaccinated. Non-vaccination was associated with being younger, male, without a partner, low socioeconomic level, and no previous diagnosis of hypertension, obesity or diabetes. Furthermore, the non-vaccinated were less likely to have tested for COVID-19, and more likely to consider COVID-19 as low severe and not real compared with the vaccinated. Using logistic regression models: place of residence, marital status, educational level, age, BMI, testing for COVID-19, and the perception of COVID-19 (severe and real) were significant predictors of non-vaccination. The predominant reasons for not getting vaccinated were: 63% “external barriers” (e.g., not being able to attend an appointment), and 37% “internal motives” (e.g., “vaccine does not work”).ConclusionsThe causes of non-vaccination against COVID-19 are related to both social and geographical determinants. Addressing external barriers is necessary in order to promote equity in vaccination. Reviewing the results in the context of earlier studies on the willingness to vaccinate, the gap between intention and vaccination is notable.
Factors associated with human papillomavirus (HPV) virus load variations in genital infections in young women
Authors: Tessandier Nicolas , Boué Vanina , Kamyia Tsukushi , Supplisson Olivier , Murall Carmen Lia , Reyné Bastien , Selinger Christian , Bernat Claire , Grasset Sophie , Groc Soraya , Rahmoun Massilva , Bonneau Marine , Foulongne Vincent , Graf Christelle , Tribout Vincent , Prétet Jean-Luc , Reynes Jacques , Segondy Michel , Bravo Ignacio G , Boulle Nathalie , Alizon Samuel 
Published: January 2024

AbstractHuman papillomaviruses (HPVs) are the most oncogenic viruses known to humans, with 12 high-risk (HR) genotypes causing nearly all cervical cancers. Cytology is commonly used to screen for cervical lesions but is currently being replaced by testing for high-risk HPV (HR HPV). Although HR HPV screening has a higher sensitivity, its specificity is limited, and it is currently advised to repeat the first screening 4 to 6 months later. To increase the sensitivity of the screening triage, other biomarkers have been suggested, including HPV viral load. Indeed, since 1999, several independent studies have found an association between HR HPV viral load in cervical samples and the severity of cervical disease. Here, we further explore the determinants of variations in HPV viral load in genital infections in young adult women.We analysed samples collected in the PAPCLEAR clinical cohort for participants who were infected by HPV genotypes for which we quantified virus load using qPCR targeting 13 genotypes. We developed a Bayesian statistical model estimating the effect of covariates of interest on the HPV viral load. To analyse precisely the viral load difference between HPV genotypes, phylogenetic distances between HPVs were also integrated in the Bayesian model.Our results fail to identify an effect of anti-HPV vaccination, co-infections by multiple HPVs or tobacco smoking on the detected viral load. On the opposite, swabs contained significantly more viral copies than cervical smears. Our results also highlight that most of the viral load variance could be explained at the genotype level (80%) rather than at the individual level (20%). Our model reveals important differences in viral load detected between the different genotypes tested, with HPV16 being the highest and HPV18 the lowest. The impact of phylogenetic signal on viral load was also estimated to be low, except for a cluster comprised of HPV53, HPV66 and HPV56. These results contribute to identifying the main drivers of HPV viral load detected and could help design needed future screening policies.
Clonal hematopoiesis of indeterminate potential-associated non-small cell lung cancer risk is potentiated by small particulate matter air pollution among non-smokers: a novel somatic variant–environment interaction
Authors: Vlasschaert Caitlyn , Buttigieg Marco , Pershad Yash , Lanktree Matthew , Aldrich Melinda C. , Rauh Michael J. , Bick Alexander G. 
Published: January 2024

AbstractSmall particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC) among non-smoking individuals. Inhaled PM2.5recruits pro-inflammatory macrophages to the air-lung interface, which promotes malignant lung epithelial cell growth and progression to overt cancer. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, exacerbates PM2.5-associated NSCLC in non-smokers using genetic, environmental, and phenotypic data from 413,901 individuals in the UK Biobank. Among non-smokers, PM2.5is not associated with NSCLC and not associated with prevalence of CHIP, but CHIP is associated with a doubling of NSCLC risk (hazard ratio (HR) 2.01, 95% confidence interval (CI): 1.34-3.00). Moreover, CHIP-associated NSCLC risk is exacerbated in the setting of above-median PM2.5levels (HR 2.70, 95% CI: 1.60–4.55). PM2.5× CHIP is also associated with significantly greater markers of systemic inflammation (CRP, IL-6, and IL-1β) than expected. Altogether, these results suggest CHIP and PM2.5form a novel gene × environment interaction promoting NSCLC tumorigenesis in non-smokers.
Temporal mismatches in flight activity patterns between Pipistrellus kuhlii and Prays oleae in olive farms: Implications for biocontrol services potential
Authors: Herrera José M. , Carvalho Ana , Barreiro Sílvia , Jiménez‐Navarro Gerardo , Melguizo‐Ruiz Nereida , Beja Pedro , Moreira Francisco , Vasconcelos Sasha , Morgado Rui , Silva Bruno 
Published: January 2024

Abstract

Biocontrol services are widely recognized to provide key incentives for bat conservation. However, we have virtually no information on whether and how disruptions in bat‐mediated biocontrol services are driven by mismatches between the temporal activity patterns of insectivorous bats and insect pests.

We investigated the temporal relationship between the nightly activity patterns of the common pipistrelle bat (Pipistrellus kuhlii) and the olive fruit moth (Prays oleae). Temporal mismatches between species pairs were estimated as the time difference (expressed as a percentage of the night) at which P. kuhlii and P. oleae reached 50% of their abundance.

The study was carried out during spring, summer, and fall between 2017 and 2019 in 60 olive farms representing increasing levels of structural simplification (as a surrogate of agricultural intensification). Olive farms were classified as exhibiting high (i.e. HIGH olive farms; n = 27), intermediate (MID; n = 18), and low (LOW; n = 15) structural complexity.

Temporal mismatches between the activity levels of P. kuhlii and P. oleae varied between seasons and types of olive farms, being comparatively lower in summer than in spring and fall. Furthermore, summer was the only season in which temporal mismatches between species pairs differed between types of olive farms, with higher temporal mismatches found in LOW than in HIGH and MID olive farms.

Overall, our work demonstrates the existence of temporal mismatches between the nightly activity patterns of P. kuhlii and P. oleae. Furthermore, it demonstrates that the structural simplification of olive farms increases temporal mismatches between species pairs, particularly in summer when bat‐mediated biocontrol services are most needed.

Synthesis and applications. Future research should consider mismatches between the temporal activity patterns of insectivorous bats and insect pests. Otherwise, the actual impact of agricultural intensification on bat‐mediated biocontrol services as well as the economic impact of their loss on the agriculture industry might be underestimated. To enhance biocontrol services, we propose increasing the availability of suitable roosting and foraging sites as well as conserving areas of remnant native woodland and scattered hollow‐bearing trees.