bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype and Haplotype Analysis With In Silico Prediction of TMPRSS2 Gene in Jordanian Population
Authors: Abu‐Almfalfal Razan Issam , Jarrar Yazun Bashir , Gharaibeh Munir 
Published: December 2024

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become a global health concern. The entry of the virus into host cells is facilitated by the transmembrane protease serine 2 (TMPRSS2) receptor, and genetic variations in the TMPRSS2 gene may influence disease susceptibility. However, there is a lack of knowledge regarding TMPRSS2 genetic variants and haplotypes in the Jordanian population.AimsThis study aimed to characterize the genotype and haplotype variations in the TMPRSS2 binding domain with SARS‐CoV‐2 among Jordanian volunteers.MethodsThe binding domain of TMPRSS2 with SARS‐CoV‐2 (Exons 9 and 10) was amplified using polymerase chain reaction (PCR) for a random sample of 120 healthy unrelated Jordanian volunteers, followed by Sanger DNA sequencing for the PCR products. The effect of the novel genetic variants on the TMPRSS2 protein structure was predicted using in silico methods.ResultsThe results showed significant (p < 0.05, chi‐square) allele frequencies for known TMPRSS2 variants, with c.888C > T being the most prevalent among Jordanian volunteers. Novel genetic variants, including c.869A > G and c.923T > A, were also identified, with the latter being the most common novel variant. Haplotype analysis showed that the most prevalent TMPRSS2 haplotype is c.911G/1051A/1052T/1010 + 45C/1011 − 38T/1011 − 52C/1011 − 54A. In silico programs predicted that TMPRSS2 c.923T > A and c.1052T > A variants affect transmembrane proteins and catalytic sites.ConclusionsThis research provides information about the gene structure of the TMPRSS2 binding domain in Jordanians. Some of the identified variants, especially c.923T > A, may influence protein function, warranting further in vitro and in vivo investigations. In addition, further clinical research studies are needed to link the identified TMPRSS2 variants with COVID‐19 susceptibility and severity among Jordanians.
The probability of pregnancy in 100 episodes of sexual intercourse: A measure of male contraceptive performance
Authors: Amory John K. 
Published: December 2024

AbstractBackgroundAccurately judging the efficacy of contraceptives is vital for preventing unintended pregnancy. The Pearl index and life table analysis describe female contraceptive performance. However, they are not ideal for quantifying male contraceptive efficacy given differences between male and female methods. In particular, male contraceptives like condoms are used “on demand” rather than long‐term like female contraceptives. Additionally, the number of episodes of sexual intercourse, a key determinant of risk, is not considered. Lastly, men can father concurrent pregnancies in more than one woman. For these reasons, a male‐specific measure may provide a more accurate measure of male contraceptive efficacy.Objectives and MethodsAs each episode of heterosexual intercourse within a fertile couple is associated with an approximately 3% risk of pregnancy, the chance of an unintended pregnancy with a given number of episodes of sexual intercourse can be modeled with and without contraceptives of various effectiveness.ResultsSuch modeling demonstrates that unintended pregnancy is strongly associated with both the number of episodes of sexual intercourse and the efficacy of the method. Based on these models, I propose a novel metric for male contraceptive efficacy called the Probability of Pregnancy100, defined as the percent chance of an unintended pregnancy occurring with 100 episodes of intercourse. Probability of Pregnancy100 should be easy for men to understand and is applicable to men with multiple sexual partners or men using “on‐demand” contraceptives.Discussion and conclusionsThe prevention of unintended pregnancy by a male contraceptive is strongly influenced by both method efficacy and sexual frequency. Probability of Pregnancy100 may offer a better measure of male contraceptive efficacy compared to the Pearl index and life table analysis as it takes sexual frequency into account; however, Probability of Pregnancy100 will need to be tested prospectively in male contraceptive studies alongside the Pearl index and life table analysis to determine its utility compared to these existing measures of contraceptive efficacy.
The mixed blessing of leader mindfulness: The competing lens of dyadic affective and cognitive conflicts in investigating follower creativity
Authors: Liu Beini , Dust Scott , Xu Minya , Zhang Xinyu 
Published: December 2024

AbstractSocial scientists and practitioners alike, so far, assume that leader mindfulness is inherently beneficial while paying limited attention to its potential drawbacks. Drawing upon social information processing theory, we contend that leader mindfulness is a mixed blessing as it relates to follower creativity. Using two multi‐wave, multi‐source field studies, our findings indicate a negative relationship between leader mindfulness and leader–follower dyadic affective conflict, which in turn increases follower creativity. However, leader mindfulness has a negative relationship with leader–follower dyadic cognitive conflict, resulting in decreased follower creativity. Further, perceived leaders' organizational embodiment strengthens the positive indirect effect of leader mindfulness on follower creativity through leader–follower dyadic affective conflict, whereasperceived leaders' organizational embodiment does not moderate the indirect effect through leader–follower dyadic cognitive conflict. Theoretical and practical insights regarding leader mindfulness and follower creativity are discussed.
From Circum Red Sea Sources to the Levant Basin Sink: An Integrated Provenance Study of Oligocene–Miocene Siliciclastic Sediments From Deep‐Sea Boreholes
Authors: Glazer Adar , Avigad Dov , Morag Navot 
Published: December 2024

ABSTRACTThe Levant Basin of the Eastern Mediterranean accumulated voluminous siliciclastic sediments during the Oligocene–Miocene. The deep‐sea section has attracted significant interest as it contains world‐class hydrocarbon reservoirs (‘Tamar Sands Play’). Our recent sandstone provenance study revealed that the hydrocarbon‐bearing, lower Miocene ‘Tamar Sands’ were recycled from older quartz‐rich sandstones that covered the Arabian flank of the Red Sea Rift. However, sandstones constitute just a third of the thickness of the Oligocene–Miocene siliciclastic section in the Levant Basin, with the rest being mainly composed of shales. Unravelling the provenance of the shale fraction is therefore essential for a comprehensive reconstruction of the Oligocene–Miocene source‐to‐sink system of the Levant Basin. In the present study, we examined the mineralogy and Sr‐Nd isotopes of clay samples retrieved from deep‐sea boreholes that penetrated the Oligocene–Miocene siliciclastic section. The isotopic composition of most clay fractions resembles that of Nile Delta sediments, indicating that unlike the ‘Tamar Sands’, their dominant provenance lay in NE Africa. Our investigations show that they were derived from Neoproterozoic basement rocks of the Arabian‐Nubian Shield and Tertiary continental flood basalts. The absence of chlorite and serpentine negates detrital contribution from the Arabia‐Eurasia suture in the north. Compilation of the available thermochronology data and major geologic events shows that the accumulation of the siliciclastic section in the Levant Basin coalesced with uplift of the continental areas around the Red Sea. The marked switch to shale deposition recognised in the basin during the late early Miocene signifies the downfall of the ‘quartzose’ Arabian sediment transport system, when it was partially captured by the evolving Dead Sea Transform valley. Our study highlights the strength of coupling sand and clay provenance investigations in source‐to‐sink studies of sedimentary basins.
Origin stories: how does learned migratory behaviour arise in populations?
Authors: Fugate Janey , Wallace Cody , Aikens Ellen O. , Jesmer Brett , Kauffman Matthew 
Published: December 2024

ABSTRACTAlthough decades of research have deepened our understanding of the proximate triggers and ultimate drivers of migrations for a range of taxa, how populations establish migrations remains a mystery. However, recent studies have begun to illuminate the interplay between genetically inherited and learned migrations, opening the door to the evaluation of how migration may be learned, established, and maintained. Nevertheless, for migratory species where the role of learning is evident, we lack a comprehensive framework for understanding how populations learn specific routes and refine migratory movements over time (i.e., their origins). This review draws on advances in behavioural and movement ecology to offer a comprehensive framework for how populations could transition from resident to migratory by connecting cognitive research on fine‐scale perceptual cues and movement decisions with literature on learning and cultural transmission, to the emergent pattern of migration. We synthesize the multiple cognitive mechanisms and processes that allow a population to respond to seasonal resource limitation, then encode spatial and environmental information about resource availability in memory and engage in social learning to navigate their landscapes and track resources better. A rise in global reintroduction efforts, along with human‐induced rapid shifts in environmental cues and changing landscapes make evaluating the origins of this threatened behaviour more urgent than ever.
Single‐Cell RNA Sequencing Reveals the Tumor Heterogeneity and Immunosuppressive Microenvironment in Urothelial Carcinoma
Authors: Lyu Tianqi , Wu Kerong , Zhou Yincong , Kong Tong , Li Lin , Wang Kaizhe , Fu Pan , Wei Pengyao , Chen Ming , Zheng Jianping 
Published: December 2024

ABSTRACTUrothelial carcinoma (UC) can arise from either the lower urinary tract or the upper tract; they represent different disease entities and require different clinical treatment strategies. A full understanding of the cellular characteristics in UC may guide the development of novel therapies. Here, we performed single‐cell transcriptome analysis from four patients with UC of the bladder (UCB), five patients with UC of the ureter (UCU), and four patients with UC of the renal pelvis (UCRP) to develop a comprehensive cell atlas of UC. We found the rare epithelial cell subtype EP9 with epithelial‐to‐mesenchymal transition (EMT) and cancer stem cell (CSC) features, and specifically expressed SOX6, which was associated with poor prognosis. We also found that ACKR1+ endothelial cells and inflammatory cancer‐associated fibroblasts (iCAFs) were more enriched in UCU, which may promote pathogenesis. While ESM1+ endothelial cells may more actively participate in UCB and UCRP tumorigenesis by promoting angiogenesis. Additionally, CD8 + effector T cells were more enriched in UCU and UCRP patients, while Tregs were mainly enriched in UCB tumors. C1QC+ macrophages and LAMP3+ dendritic cells were more enriched in UCB, which is closely related to the formation of the heterogeneous immunosuppressive microenvironment. Furthermore, we found strong interactions between iCAFs, EP9, and Endo_ESM1, and different degrees of activation of the FGF‐FGFR3 axis and immune checkpoint pathway were observed in different UC subtypes. Our study elucidated the cellular heterogeneity and the components of the microenvironment in UC arising from the upper and lower urinary tracts and provided novel therapeutic targets.
Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant
Authors: Morais Sara , Leal Loureiro José , Brandão Eva , Sequeiros Jorge , Stevanin Giovanni , Santos Mariana 
Published: December 2024

ABSTRACTHereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness. To date, over 80 genes have been associated with HSP, but many families remain without a molecular diagnosis.In this study, linkage analysis and whole‐exome sequencing (WES) were performed to identify the causal gene in a HSP family with autosomal recessive inheritance. Multipoint linkage analysis revealed a maximum significant multipoint LOD score of 4.6 on chromosome 4. WES analysis focused on this region led to the identification of a homozygous missense variant in AIMP1 (c.223G>A). Minigene assays showed that the presumed missense variant in AIMP1 caused loss of the exon 3 donor splice site. Ultimately, this led to the use of an alternative splice site within the intron and the insertion of a premature stop codon.The identification of a novel AIMP1 causal variant contributes to the growing list of HSP genes. Furthermore, it shows that, considering also previous reported cases, disruption of AIMP1 causes a spectrum of disorders ranging from intellectual disability to more complex neurodegenerative diseases.
HPSCAN: Human Perception‐Based Scattered Data Clustering
Authors: Hartwig S. , Onzenoodt C. v. , Engel D. , Hermosilla P. , Ropinski T. 
Published: December 2024

AbstractCluster separation is a task typically tackled by widely used clustering techniques, such as k‐means or DBSCAN. However, these algorithms are based on non‐perceptual metrics, and our experiments demonstrate that their output does not reflect human cluster perception. To bridge the gap between human cluster perception and machine‐computed clusters, we propose HPSCAN, a learning strategy that operates directly on scattered data. To learn perceptual cluster separation on such data, we crowdsourced the labeling of bivariate (scatterplot) datasets to 384 human participants. We train our HPSCAN model on these human‐annotated data. Instead of rendering these data as scatterplot images, we used their x and y point coordinates as input to a modified PointNet++ architecture, enabling direct inference on point clouds. In this work, we provide details on how we collected our dataset, report statistics of the resulting annotations, and investigate the perceptual agreement of cluster separation for real‐world data. We also report the training and evaluation protocol for HPSCAN and introduce a novel metric, that measures the accuracy between a clustering technique and a group of human annotators. We explore predicting point‐wise human agreement to detect ambiguities. Finally, we compare our approach to 10 established clustering techniques and demonstrate that HPSCAN is capable of generalizing to unseen and out‐of‐scope data.
Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers
Authors: Pergola Pablo E. , Joy Melanie S. , Garsd Armando , Hasal Steve J. , Khare Atul , Reddy Guru , Gupta Pramod , Finn William F. 
Published: December 2024

ABSTRACTDespite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end‐stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g., many large tablets) and adverse gastrointestinal effects may decrease compliance to labeled dosing instructions, thus decreasing their efficacy. Oxylanthanum carbonate is a new molecule yielding the same phosphate‐binding capacity as lanthanum carbonate, but in a much smaller drug volume and tablet size. It is formulated as small tablets that can be easily swallowed. In a double‐blind dose‐escalation phase 1 study, healthy volunteers (n = 32) were randomly divided into four treatment arms and randomly assigned to receive oxylanthanum carbonate tablets or a placebo over a period of 4 days to evaluate safety, urinary and fecal excretion of phosphorus, and pharmacokinetics. Each treatment arm evaluated a different dose of oxylanthanum carbonate: 500, 1000, 1500, or 2000 mg three times a day (TID). The study drug was well‐tolerated. Oxylanthanum carbonate effectively decreased dietary phosphorus absorption, demonstrated by decreased urinary phosphorus excretion and increased fecal phosphorus excretion. Systemic absorption of oxylanthanum carbonate was minimal, with lanthanum serum concentration values below the level of quantification (0.500 ng/mL) in all subjects receiving 500 mg TID and did not exceed 0.7 ng/mL at other doses. Future studies should evaluate and confirm the ability of oxylanthanum carbonate to reduce pill burden and improve dose administration, patient tolerability, adherence, and treatment outcomes.
Trial Registration: ClinicalTrials.gov identifier: NCT01560884
The impact of novel probiotics isolated from the human gut on the gut microbiota and health
Authors: Caesar Robert 
Published: December 2024

AbstractThe gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short‐chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross‐feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain‐specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.
Anti‐diabetic effects of GLP‐1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review
Authors: Wong Hon Jen , Lin Norman H. Y. , Teo Yao Hao , Yeo Brian S. Y. , Toh Keith Zhi Xian , Teo Yao Neng , Chan Mark Y. , Yeo Leonard L. L. , Poh Kian Keong , Kong William K. F. , Eng Pei Chia , Tan Benjamin Y. Q. , Dalakoti Mayank , Sia Ching‐Hui 
Published: December 2024

AbstractGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are increasingly used for anti‐obesity indications. However, little is known of the comparative effect of GLP‐1 RAs and their glycemic impact across the different routes of administration, diabetic statuses and durations of prescription. PubMed, EMBASE and CENTRAL were searched from inception to 13 February 2024. Only randomised controlled trials were included in this systematic review and meta‐analysis. Adults aged above 18 years old, who were in the overweight/obesity range, with or without type 2 diabetes mellitus (T2DM) were included. Baseline characteristics and changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were obtained. GLP1‐RAs demonstrated an overall reduction in HbA1c of −0.72% (95% confidence interval [CI] −0.79 to −0.65, p < 0.01) and in FPG of −1.00 mmol/L (95% CI −1.16 to −0.84, p < 0.01). HbA1c reduction in pre‐DM patients was −0.44% (95% CI −0.54 to −0.18, p < 0.01). Patients who were followed up for more than a year experienced a smaller reduction of HbA1c. Meta‐regression showed that the GLP‐1 RAs are more efficacious at higher HbA1c and lower body mass index. Overall, GLP‐1 RAs consistently led to a significant reduction in HbA1c at −0.72% and FPG at −1.00 mmol/L. These effects may be equally efficacious in pre‐DM patients with obesity and those at lower BMI. With pre‐DM and obesity being risk factors for metabolic syndrome, these findings may provide newer perspectives in expanding indications for GLP‐1 RA initiation.
Selection for increased sexual bimaturism in the common housefly, Musca domestica
Authors: Petrucci Giovanni , Francuski Ljubinka , Jansen Walter L. , Beukeboom Leo W. 
Published: December 2024

AbstractThe growing demand for insect mass production requires methodologies that allow for easy separation of males and females as the two sexes can have very different economic values. The common housefly, Musca domestica (L.) (Diptera: Muscidae), is one of the candidate species for industrial production. In this species, males typically develop faster and are smaller than females. Exploiting housefly sexual bimaturism (sexual difference in developmental time) could allow the maintenance of colonies with a higher proportion of females, which is favourable in terms of egg yield. Here, we report an artificial selection experiment of breeding early‐emerging males with late‐emerging females for six generations, with the aim to increase the time interval between emergence of males and females. The level of sexual bimaturism was not increased after six generations of selection. The life‐history traits fecundity, egg‐to‐adult survival and hatchability were not affected by the selection procedure. Wing size measurement revealed that early‐ and late‐emerging males did not differ in size, suggesting that developmental time and body size are decoupled in this sex. Still, large females consistently emerged later than small females, suggesting an intricate sex‐specific genetic architecture for size and developmental time in the housefly. Our results are relevant in the context of mass production, providing new insight into the manipulation and maintenance of female‐biased sex ratios in production colonies of the common housefly.