bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale genotyping and meta-analysis ofPIEZO1short tandem repeat alleles suggest a modest association with malaria susceptibility
Authors: Leffler Ellen M. , Band Gavin , Jeffreys Anna E. , Rowlands Kate , Hubbart Christina , Bojang Kalifa A. , Conway David J. , Jallow Muminatou , Sisay-Joof Fatoumatta , D’Alessandro Umberto , Ndila Carolyne M. , Macharia Alexander W. , Marsh Kevin , Williams Thomas N. , Kachala David , Molyneux Malcolm , Nyirongo Vysaul , Taylor Terrie E. , Rockett Kirk A. , Kwiatkowski Dominic P. 
Published: June 2024

AbstractPIEZO1 forms a mechanosensitive ion channel involved in regulating calcium levels in red blood cells. E756del, a deletion allele within a short tandem repeat (STR) inPIEZO1, is common in many African populations and has been proposed to be associated with protection from malarial disease, but epidemiological evidence has been inconsistent. Here, we use Illumina sequencing of amplicons covering thePIEZO1STR to genotype 5,558 severe malaria cases and 8,174 population controls from The Gambia, Kenya, and Malawi. We estimate a modest effect for E756del and meta-analysis with two published studies, for a total of 8,224 cases and 10,103 controls, reveals a consistent protective effect (OR=0.93, 95% CI 0.88-0.99). By comprehensively genotyping the STR, we identify additional, less common alleles, with two (Q745del and E756ins) showing consistent, but also modest, risk effects across studies. Although allele frequency differentiation between African and non-African populations could be consistent with a selective effect, we show that it is not exceptional compared with STR variants genome wide. Thus, our results support a protective effect of E756del against risk of malaria but with a much smaller effect size than initially reported.
GABABreceptors mediate intracellular calcium release in astrocytes of the prefrontal cortex
Authors: Bostel Jennifer , Kürten Alina J. , Beiersdorfer Antonia 
Published: June 2024

AbstractThe prefrontal cortex (PFC) is a cortical brain region whose multifaceted functions are based on a complex interplay between excitatory pyramidal neurons, inhibitory GABAergic interneurons and astrocytes maintaining a fine-tuned excitation/inhibition balance (E/I balance). The regulation of the E/I balance in cortical network is crucial as the disruption leads to impairments in PFC-associated behavior and pathologies. Astrocytes express specific GABA receptors that mediate intracellular Ca2+signaling upon stimulation by γ-aminobutyric acid (GABA), resulting in the release of gliotransmitters directly impacting information processing. However, the signaling pathway leading to GABA-induced Ca2+signaling in astrocytes of the PFC is not well understood. Here we took advantage of GLAST-promoter driven GCaMP6s expression in astrocytes to study GABAergic Ca2+signaling in PFC astrocytes by confocal microscopy. The results show that GABA induces Ca2+signaling via the stimulation of the metabotropic GABABreceptor in astrocytes. GABABreceptor-mediated Ca2+signals greatly depend on intracellular Ca2+stores rather than on extracellular Ca2+. Additionally, antagonists of the PLC/IP3-signaling cascade significantly reduced GABABreceptor-mediated Ca2+signaling in astrocytes, suggesting that astrocytic GABABreceptors in the PFC are coupled to the Gq-GPCR signaling pathway.
The QDIS-7: one scale for measuring the disease-specific quality-of-life impact of different medical conditions
Authors: Fukuhara Shunichi , Green Joseph , Wakita Takafumi , Yamamoto Yosuke , Yamazaki Hajime , Ware John E. 
Published: June 2024

AbstractBackgroundWhen studying health-related quality of life (QOL), disease-specific instruments have the advantage of measuring the unique effects of particular medical conditions. Almost every disease-specific QOL instrument uses its own metric, and measures QOL in its own content areas. The unfortunate result is that scores from different disease-specific QOL instruments cannot be compared. In contrast, the seven-item Quality of Life Disease Impact Scale (QDIS-7) has response choices on only one scale (one metric) and its content is standardized. Thus, the QDIS-7 should allow disease-specific QOL to be compared across different diseases. We therefore tested whether, unlike scores from the traditional mutually-incompatible metrics, those from the single-metric QDIS-7 are comparable across diseases.MethodsResponses to the QDIS-7 questions (regarding global QOL, physical functioning, role functioning, social functioning, vitality, mental health, and health outlook) were used to compute a single score, based on an item-response model. When the QDIS-7 was completed by respondents with different diseases, the content of the question-items was the same, and the only difference was the name of the disease to which the respondents explicitly attributed any impact on their QOL. In an online survey, 2,627 adults who had sought care for headache, low-back pain, asthma, or diabetes, each responded to the QDIS-7 and to a previously-validated disease-specific QOL instrument (“legacy scale”) that was developed to measure QOL in their specific disease. We examined the slopes from four regressions of legacy-scale scores on QDIS-7 scores. Similarity of those slopes would support the hypothesis that the QDIS-7 enables quantitative comparisons of disease-specific QOL across those four different medical conditions.ResultsFor all four groups, the regression-line slopes were nearly the same: 0.12 to 0.14 legacy-scale standard deviations per 1-point difference in QDIS-7 score. Thus, each 10-point difference in QDIS-7 scores is equal to slightly more than one standard-deviation difference in legacy-scale scores, forall fourgroups.ConclusionsThe relationships of score differences on the legacy measures to score differences on the QDIS-7 (i.e., the slopes) were similar across the four groups, which is consistent with the idea that the QDIS-7 enables comparisons of disease-specific QOL across different medical conditions.
Estimating HPV16 genome copy number per infected cell in cervical smears
Authors: Elie Baptiste , Boué Vanina , Paget-Bailly Philippe , Algros Marie-Paule , Baraquin Alice , Prétet Jean-Luc , Alizon Samuel , Tessandier Nicolas , Bravo Ignacio G. 
Published: June 2024

AbstractHuman papillomavirus (HPV) 16 is the most oncogenic biological agents for humans. However, essential quantitative aspects of its infection cycle remain inadequately characterized. Specifically, the proportion of infected cells and the viral copy number per infected cell in cervical smears are not well understood. To address this, we employed a combination of limiting dilution techniques and Bayesian statistics on routine cervical smears to estimate the frequency of infected cells and the viral copy number per cell. Our methodology was initially validated through numerical simulations and cell culture experiments. Subsequently, we analyzed 38 HPV16-positive cervical smears, comprising 26 samples from patients without cytological lesions and 12 from patients with low-grade lesions. Our findings indicated that the substantial variability in viral load across samples predominantly stemmed from differences in the frequency of infected cells. Additionally, the mean number of HPV copies per infected cell was consistently low across all samples, ranging from approximately 2.3 to 100 copies. However, in samples with low-grade lesionMarie-Paule Algross, this number was observed to double on average. These results challenge existing assumptions regarding the biology of HPV genital infections, which are typically asymptomatic or minimally symptomatic.
Improved five year mortality in an RCT of a lung cancer biomarker to select people for screening
Authors:   The Early Diagnosis of Lung Cancer Scotland (ECLS) Team, Sullivan Frank M. , Mair Frances S. , Anderson William , Chew Cindy , Dorward Alistair , Haughney John , Hogarth Fiona , Kendrick Denise , Littleford Roberta , McConnachie Alex , McCowan Colin , McMeekin Nicola , Patel Manish , Rauchhaus Petra , Daly Fergus , Ritchie Lewis , Robertson John , Sarvesvaran Joseph , Sewell Herbert , Taylor Thomas , Treweek Shaun , Vedhara Kavita , Schembri Stuart 
Published: June 2024

AbstractRisk-based early detection should be cost effective and widely accessible. EarlyCDT-Lung is a blood-based autoantibody biomarker which may improve accessibility to Low dose CT screening. We randomized 12 208 individuals aged 50-75 at high risk of developing lung cancer to either the test or to standard clinical care. Outcomes were ascertained from Register of Deaths and Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio of the rate of deaths from all causes and lung cancer. Additional analyses were performed for cases of lung cancer diagnosed within two years of the initial test.After 5 years 326 lung cancers were detected (2.7% of those enrolled). The total number of deaths reported from all causes in the intervention group was 344 compared to 388 in the control group.There were 73 lung cancer deaths in the intervention arm and 90 in the controls (Adjusted HR 0.789 (0.636, 0.978). An analysis of cases of lung cancer detected within 2 years of randomization in the intervention group showed that there were 34 deaths from all causes and 29 from lung cancer. In the control group there were 56 deaths with 49 from lung cancer. In those diagnosed with lung cancer within 2 years of randomization the hazard ratio for all cause mortality was 0.615 (0.401,0.942) and for lung cancer 0.598 (0.378, 0.946).Further large-scale studies of the role of biomarkers to target lung cancer screening, in addition to LDCT, should be undertaken.
Calculating Muscular Driven Speed Estimates forTyrannosaurus
Authors: Boeye Adrian T. , Swann Scott 
Published: June 2024

ABSTRACTTop speed estimates of extinct dinosaurs have been of long-standing interest to gain better understanding of the animals’ lifestyle and ecology.Tyrannosaurus rextop speeds have been examined using a wide range of methods that draw on more traditional biomechanical formulas, computer simulations, and allometric equations based on mass. However, these calculations may be made more precise using input from contemporary research on anatomy and biomechanics that account for mass allometry and scaling. This study builds on existing studies in anatomy, biomechanical data, and established equations for locomotion to calculate a muscular driven range of top speed for several (n=4) specimens that had sufficient data to undertake this work. When properly refined with additional data on muscle mass allometry and scaling, several adult specimens ofT. rexcould confidently be placed in a range of top speed from 7.7 to 10.5 m/s, and possibly up to 10.7 m/s. Additionally, a younger specimen ofT. rexwas analyzed and found to have a higher top speed than the adultT. rexat 6.3 to 14.5 m/s. Although the estimated top speeds in this study are slower than some previous estimates, these results find some support for slow running gaits and reinforce interpretations ofT. rexas an active and effective apex predator. Future work can build upon this study by investigating how muscular driven top speeds may affect ontogenetic niche partitioning and prey species regularly targeted by adultT. rex.
Autonomous bioluminescence emission from transgenic mice
Authors: Kiszka Kamila A. , Dullin Christian , Steffens Heinz , Koenen Tanja , Rothermel Ellen , Alves Frauke , Gregor Carola 
Published: June 2024

AbstractThe bacterial bioluminescence system can be applied to produce autonomous bioluminescence in mammalian cells. Until now, the system has only been stably inserted into cells culturedin vitro. Here we report the generation of an autobioluminescent transgenic mouse line constitutively expressing the genes of the bacterial bioluminescence system, enabling substrate-freein vivoluminescence imaging of a living mammal.
The Mlh1-Pms1 endonuclease uses ATP to preserve DNA discontinuities as strand discrimination signals to facilitate mismatch repair
Authors: Piscitelli Jonathan M. , Witte Scott J. , Sakinejad Yasmine S. , Manhart Carol M. 
Published: June 2024

ABSTRACTIn eukaryotic post-replicative mismatch repair, MutS homologs (MSH) detect mismatches and recruit MLH complexes to nick the newly replicated DNA strand upon activation by the replication processivity clamp, PCNA. This incision enables mismatch removal and DNA repair. Biasing MLH endonuclease activity to the newly replicated DNA strand is crucial for repair. In reconstitutedin vitroassays, PCNA is loaded at pre-existing discontinuities and orients the major MLH endonuclease Mlh1-Pms1/MLH1-PMS2 (yeast/human) to nick the discontinuous strand.In vivo,newly replicated DNA transiently contains discontinuities which are critical for efficient mismatch repair. How these discontinuities are preserved as strand discrimination signals during the window of time where mismatch repair occurs is unknown. Here, we demonstrate that yeast Mlh1-Pms1 uses ATP binding to recognize DNA discontinuities. This complex does not efficiently interact with PCNA, which partially suppresses ATPase activity, and prevents dissociation from the discontinuity. These data suggest that in addition to initiating mismatch repair by nicking newly replicated DNA, Mlh1-Pms1 protects strand discrimination signals, aiding in maintaining its own strand discrimination signposts. Our findings also highlight the significance of Mlh1-Pms1’s ATPase activity for inducing DNA dissociation, as mutant proteins deficient in this function become immobilized on DNA post-incision, explainingin vivophenotypes.GRAPHICAL ABSTRACT
DeepNeo: Deep Learning for neointimal tissue characterization using optical coherence tomography
Authors: Koch Valentin , Holmberg Olle , Blum Edna , Sancar Ece , Aytekin Alp , Seguchi Masaru , Xhepa Erion , Wiebe Jens , Cassese Salvatore , Kufner Sebastian , Kessler Thorsten , Sager Hendrik , Voll Felix , Rheude Tobias , Lenz Tobias , Kastrati Adnan , Schunkert Heribert , Schnabel Julia A. , Joner Michael , Marr Carsten , Nicol Philipp 
Published: June 2024

AbstractAimsThis study aimed to develop a deep-learning algorithm to enable a fully-automated analysis and interpretation of optical coherence tomography (OCT) pull-backs from patients after percutaneous coronary intervention (PCI).Methods and resultsIn 1148 frames from 92 OCTs, neointima was manually classified as homogeneous, heterogenous, neoatherosclerosis, or not analyzable at quadrant level by an experienced expert. Additionally, stent and lumen contours were annotated in 90 frames to enable segmentation of lumen, stent struts and neointima. Annotated frames were used to train “DeepNeo”, a deep learning tool for prediction of neointimal tissue characteristics. Performance of DeepNeo was additionally evaluated in an animal model of neoatherosclerosis, using co-registered histopathology images as the gold-standard. DeepNeo demonstrated excellent classification performance of neointimal tissue with an overall accuracy of 75%, comparable to manual classification accuracy of two clinical experts (75%, 71%). The accurate performance of DeepNeo was confirmed in an animal model of neoatherosclerosis, where an overall accuracy of 87% was achieved. Segmentation of lumen, stent struts and neointima in human pullbacks yielded very good performance with mean Dice overlap scores of 0.99, 0.66 and 0.86.ConclusionDeepNeo is the first deep learning algorithm allowing fully automated segmentation and classification of neointimal tissue, with a performance comparable to human experts. DeepNeo might ultimately help assess vascular healing after percutaneous coronary intervention in a standardized, reliable and time-efficient manner, support therapeutic decisions and improve the detection of patients at risk of future cardiac events.
Selective electron beam sensing through coherent Cherenkov diffraction radiation
Authors: Senes E. , Krupa M. , Mazzoni S. , Lasocha K. , Lefevre T. , Schloegelhofer A. , Wendt M. , Davut C. , Karataev P. , Pakuza C. , Spear B. 
Published: June 2024

We exploit the coherent emission of Cherenkov diffraction radiation (ChDR) by a relativistic electron beam to sense its position even in the presence of other particle beams. ChDR is produced in alumina inserts embedded in the vacuum chamber walls and recorded in a narrow band centered at 30 GHz. This nontrivial solution has been implemented for plasma wakefield accelerators, where the electron beam to be sensed can copropagate with another high-energy proton beam that generates the plasma wakefield. In addition, at variance with most existing position detectors, this method is insensitive to spurious electric charges due to the presence of plasma. We present the overall design of the detector as well as experimental results obtained in the AWAKE facility at CERN.

Published by the American Physical Society
2024
Books by kids for kids: the impact of a collaborative project-based learning international book exchange on pre-service teachers
Authors: Hall Pistorio Kalynn , Hendricks Mary Beth 
Published: June 2024

PurposeThe purpose of this article is to discuss the impact of an international book exchange project done with elementary students from a professional development school partnership on the understanding of project-based learning by pre-service teachers.Design/methodology/approachA collaborative project between a school in Uganda, a university teacher education preparation program in the United States and an elementary school resulted in a book exchange between the schools. The pre-service teachers worked to develop lesson plans related to social studies and language arts for students with and without special education needs. These lessons were then taught to students at an elementary school who are part of the university’s school partnership program. Upon completion of the book exchange, pre-service and in-service teachers reflected on their experiences.FindingsPre-service teachers reported that the project provided them a better understanding of collaborative work and project-based learning during their reflections and said they were more willing to take on large projects after seeing the buy-in and value for students.?Originality/valueWhile pen pal and similar writing exchange programs are not novel, this project sought to explore the impact of having one embedded into a teacher training program on pre-service teacher perceptions of project-based learning and the potential impact to their future teaching practices.
Role of psychological well-being, quality of life and distress tolerance in caregivers of geriatric population: an Indian exploratory study
Authors: Sridhar Abhinaya , Kuriakose Harsha 
Published: June 2024

Purpose
This study aims to gain an understanding of how caring for an ageing population affects caregivers’ psychological well-being, quality of life and ability to tolerate distress. This study provides valuable insights into the challenges faced by family caregivers and underscores the critical need for comprehensive support systems.

Design/methodology/approach
A correlational method and cross-sectional research design was used for the study. For this, a sample of 200 caregivers in the age range of 25–60 years who were taking care of the geriatric population above the age of 70 years for a minimum of one year were chosen. Four questionnaires − Burden Scale for Family Caregivers, Psychological Well-Being Scale, World Health Organization’s Quality of Life Scale-BRIEF version and Distress Tolerance Scale were chosen. Correlation and multivariate regression were calculated using statistical package for social sciences (SPSS) 21 and Jamovi 3.4.1.

Findings
This study found that there is a negative correlation of caregiver burden with psychological well-being, quality of life and distress tolerance. The sub-domains of self-acceptance, psychological health and tolerance levels were most impacted for the caregivers. Through multivariate regression, it was found that the caregiver burden significantly predicted psychological well-being and quality of life.

Research limitations/implications
This study focuses on the English-speaking caregivers which may overlook the diverse linguistic and cultural variations within the broader caregiver community in India and the data collection exclusively targeted family caregivers providing support to geriatric population without chronic illnesses. This restriction could potentially limit the generalizability of the findings to the broader caregiving context.

Practical implications
The implications of this research are that for caregivers, this study underscores the importance of tailored support programmes that address the negative impact of caregiver burden on psychological well-being and quality of life. Health-care professionals can use the findings to incorporate mental health assessments and interventions within caregiving contexts, recognizing the interconnected nature of these variables. Policymakers can use the findings to inform policies related to caregiver support and health-care resource allocation.

Originality/value
In India, the social norm is that children are expected to take care of their parents when they become old. Taking care of elderly parents can be challenging, even emotionally. As a result, this study will focus on how caregivers’ psychological well-being, quality of life and ability to tolerate distress are affected. Consequently, promoting the creation of community support groups and workplace mental health programmes which could give caregivers a forum to voice their concerns.
Environmental factors and host sex influence the skin microbiota structure of Hong Kong newt (Paramesotriton hongkongensis) in a coldspot of chytridiomycosis in subtropical East Asia
Authors: WAN Bowen , CHEN Guoling , POON Emily Shui Kei , FUNG Hon Shing , LAU Anthony , SIN Simon Yung Wa 
Published: June 2024

AbstractChytridiomycosis, an infectious skin disease caused by the chytrid fungi, Batrachochytrium dendrobatidis and B. salamandrivorans, poses a significant threat to amphibian biodiversity worldwide. Antifungal bacteria found on the skin of chytrid‐resistant amphibians could potentially provide defense against chytridiomycosis and lower mortality rates among resistant individuals. The Hong Kong newt (Paramesotriton hongkongensis) is native to East Asia, a region suspected to be the origin of chytrids, and has exhibited asymptomatic infection, suggesting a long‐term coexistence with the chytrids. Therefore, the skin microbiota of this resistant species warrant investigation, along with other factors that can affect the microbiota. Among the 149 newts sampled in their natural habitats in Hong Kong, China, putative antifungal bacteria were found in all individuals. There were 314 amplicon sequence variants distributed over 25 genera of putative antifungal bacteria; abundant ones included Acinetobacter, Flavobacterium, and Novosphingobium spp. The skin microbiota compositions were strongly influenced by the inter‐site geographical distances. Despite inter‐site differences, we identified some core skin microbes across sites that could be vital to P. hongkongensis. The dominant cores included the family Comamonadaceae, family Chitinophagaceae, and class Betaproteobacteria. Moreover, habitat elevation and host sex also exhibited significant effects on skin microbiota compositions. The antifungal bacteria found on these newts offer an important resource for conservation against chytridiomycosis, such as developing probiotic treatments for susceptible species.