bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making Biological Ageing Clocks Personal
Authors: Pusparum Murih , Thas Olivier , Beck Stephan , Ertaylan Gökhan , Ecker Simone 
Published: February 2024

SummaryBackgroundAge is the most important risk factor for the majority of human diseases. Addressing the impact of age-related diseases has become a priority in healthcare practice, leading to the exploration of innovative approaches, including the development of predictors to estimate biological age (so-called “ageing clocks”). These predictors offer promising insights into the ageing process and age-related diseases. This study aims to showcase the significance of ageing clocks within a unique, deeply phenotyped longitudinal cohort. By utilising omics-based approaches alongside gold-standard clinical risk predictors, we elucidate the potential of these novel predictors in revolutionising personalised healthcare and better understanding the ageing process.MethodsWe analysed data from the IAM Frontier longitudinal study that collected extensive data from 30 healthy individuals over the timespan of 13 months: DNA methylation data, clinical biochemistry, proteomics and metabolomics measurements as well as data from physical health examinations. For each individual, biological age (BA) and health traits predictions were computed from 29 epigenetic clocks, 4 clinical-biochemistry clocks, 2 proteomics clocks, and 3 metabolomics clocks.FindingsWithin the BA prediction framework, comprehensive analyses can discover deviations in biological ageing. Our study shows that the within-person BA predictions at different time points are more similar to each other than the between-person predictions at the same time point, indicating that the ageing process is different between individuals but relatively stable within individuals. Individual-based analyses show interesting findings for three study participants, including observed hematological problems, that further supported and complemented by the current gold standard clinical laboratory profiles.InterpretationOur analyses indicate that BA predictions can serve as instruments for explaining many biological phenomena and should be considered crucial biomarkers that can complement routine medical tests. With omics becoming routinely measured in regular clinical settings, omics-based BA predictions can be added to the lab results to give a supplementary outlook assisting decision-making in doctors’ assessments.Funding-
APOL1 variants G1, G2 and N264K affect APOL1 plasma protein concentration: a UK Biobank study
Authors: Adamson Walt E. , Noyes Harry , Ogunsola John , Parekh Rulan S. , Cooper Anneli , MacLeod Annette 
Published: February 2024

AbstractBackgroundAPOL1variants G1 and G2 are common in populations with recent sub-Saharan African ancestry. They are known to influence health conditions: most notably being associated with protection from human African trypanosomiasis and increased risk of susceptibility to chronic kidney disease. Association studies have often considered G1 and G2 as equivalent, however we recently presented evidence of substantial phenotypic differences between carriers of the two variants. An additionalAPOL1variant, N264K, has previously been shown to modify the damaging effect of G2 on the kidney. Here, we examine the influence of these variants on APOL1 protein concentration.MethodsUsing a cohort of 1,050 UK Biobank participants with recent African ancestry, we compared APOL1 protein concentration in carriers of variants G1, G2, and N264K and performed a genome-wide association study to identify additional modifiers of APOL1 concentration. We also compared APOL1 concentration across self-reported ethnicities for all 43,330 UK Biobank participants for whom APOL1 concentration data was available.FindingsAPOL1G1 and G2 are both associated with increased APOL1 protein concentration, however the effect of G2 is more marked, and it was the only locus that reached genome-wide significance in terms of association with APOL1 concentration (p = 3×10−155). In a G2 background, the presence of N264K is associated with a reduction in APOL1 concentration (p = 6 × 10−5). People with self-reported Black or Black British ethnicity have higher APOL1 concentrations all other self-reported ethnicities in the UK Biobank.InterpretationThese findings demonstrate the influence ofAPOL1variants and APOL1 protein concentration and identify additional phenotypic differences between the G1 and G2, highlighting the value in considering them as distinct in molecular and association studies. This work also provides further detail on the relationship between the G2 and N264K variants, which has significant implications for diagnosis and therapy in kidney disease.
A structured course of disease dataset with contact tracing information in Taiwan for COVID-19 modelling
Authors: Wu Yu-Heng , Nordling Torbjörn E. M. 
Published: February 2024

ABSTRACTBackgroundThe COVID-19 pandemic has flooded open databases with population-level data. However, individual-level structured data, such as the course of disease and contact tracing information, is almost non-existent in open databases.AimPublish a structured and cleaned COVID-19 dataset with the course of disease and contact tracing information for easy benchmarking of COVID-19 models.MethodsWe gathered data from Taiwanese open databases and daily news reports. The outcome is a structured quantitative dataset encompassing the course of the disease of Taiwanese individuals, alongside their contact tracing information.ResultsOur dataset comprises 579 confirmed cases covering the period from January 21, to November 9, 2020, when the original SARS-CoV-2 virus was most prevalent in Taiwan. The data include features such as travel history, age, gender, symptoms, contact types between cases, date of symptoms onset, confirmed, critically ill, recovered, and dead. We also include the daily summary data at population-level from January 21, 2020, to May 23, 2022.ConclusionsOur data can help enhance epidemiological modelling.
Hippocampal purinergic P2X7 receptor level is increased in Alzheimer’s disease patients, and associated with amyloid and tau pathologies
Authors: Maschio Cinzia A. , Wang Junlong , Maheshwari Upasana , Keller Annika , Rominger Axel , Konietzko Uwe , Nordberg Agneta , Hock Christoph , Nitsch Roger M. , Ni Ruiqing 
Published: February 2024

AbstractINTRODUCTIONThe purinergic receptor P2X7R, which is expressed on microglia and astrocytes, plays an important role in Alzheimer’s disease (AD). We aimed to characterize the alterations in P2X7R expression in AD patients by APOE ε4 allele, age and sex, as well as its association with amyloid and tau pathology.METHODSP2X7R staining and quantitative analysis of amyloid, tau, astrocytes and microglia were performed on postmortem hippocampal tissues from 35 AD patients; 31 nondemented controls; caudate/putamen tissue from corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) patients; and bran tissue from aged 3×Tg mouse model of AD.RESULTSActivated microglia and reactive astrocytes were observed in the hippocampi of AD patients and exhibited altered morphology with denser cells and pronounced ramifications. Hippocampal P2X7R intensity was greater in the hippocampal subfields of AD patients than in those of nondemented controls and was correlated with amyloid level and Braak stage and was not affected by sex, APOEε4 allele, or age. P2X7R expression increased around Aβ plaques, cerebral amyloid angiopathy, tau inclusions in the hippocampus from AD patients and tau inclusions in the caudate/putamen from CBD and PSP patients.DISCUSSIONWe found an increased hippocampal P2X7R level in AD compared to non-demented control, which correlated with amyloid and tau pathologies. P2X7R is a potential marker for neuroinflammation in AD.
A nonlinear code for event probability in the human brain
Authors: Foucault Cedric , Bounmy Tiffany , Demortain Sébastien , Thiririon Bertrand , Eger Evelyn , Meyniel Florent 
Published: February 2024

AbstractAssessing probabilities and predicting future events are fundamental for perception and adaptive behavior, yet the neural representations of probability remain elusive. While previous studies have shown that neural activity in several brain regions correlates with probability-related factors such as surprise and uncertainty, similar correlations have not been found for probability. Here, using 7 Tesla functional magnetic resonance imaging, we uncover a representation of the probability of the next event in a sequence within the human dorsolateral prefrontal and intraparietal cortices. Crucially, univariate and multivariate analyses revealed that this representation employs a highly nonlinear code. Tuning curves for probability exhibit selectivity to various probability ranges, while the code for confidence accompanying these estimates is predominantly linear. The diversity of tuning curves we found recommends that future studies move from assuming linear correlates or simple canonical forms of tuning curves to considering richer representations whose benefits remain to be discovered.
Bringing astrocytes into the spotlight of electrical brain stimulation
Authors: Aroso Miguel , Castro Domingos , Silva Sara Costa , Aguiar Paulo 
Published: February 2024

AbstractAstrocytes, primarily viewed only as supportive units, are now emerging as active players in the information processing of the brain. Accumulated evidence supports that the bidirectional communication between astrocytes and neurons maintains complex animal behaviours such as memory formation and decision-making. The lack of characterisation of astrocytic electrophysiology is, in our opinion, associated with the early idea of a passive electrical nature of astrocytes, in opposition to the electrically active neurons. A better understanding of the effect of electrical stimulation on astrocytes’ physiology and activity will greatly strengthen the current knowledge in neural biology. Here, we assessed if astrocytes may have a role in therapies based on electrical brain stimulation by being able to respond to the same electrical stimulus used to modulate neuronal activity. To do so, we took advantage of microelectrode arrays (MEAs) capability to simultaneously record and deliver extracellular electrical signals. Additionally, we synchronized the recording of electrophysiological data with the recording of calcium activity, a hallmark of astrocytic activity. Here, we show that astrocytes respond to electrical stimulation with the generation of strong membrane voltage oscillations and simultaneous production of calcium waves, demonstrating, unequivocally, that astrocytes respond to electrical stimulation in the same range as neurons do. Importantly, these responses are dependent on the stimuli amplitude. Furthermore, membrane voltage oscillations are significantly reduced in the absence of extracellular calcium, but not abolished, while calcium activity is not detected.
Low microbial abundance and community diversity within the egg capsule of the oviparous cloudy catshark (Scyliorhinus torazame) during oviposition
Authors: Takagi Wataru , Masuda Ayami , Shimoyama Koya , Tokunaga Kotaro , Hyodo Susumu , Sato-Takabe Yuki 
Published: February 2024

AbstractVertebrate embryos are protected from bacterial infection by various maternally derived immune factors before the embryonic organs are fully developed. However, the defense mechanisms employed by elasmobranch embryos during development remain poorly understood. This study attempted to elucidate the embryonic defense mechanism of elasmobranchs by investigating the intracapsular environment of freshly laid eggs of the oviparous cloudy catshark (Scyliorhinus torazame). The egg capsule of oviparous elasmobranchs is tightly sealed until pre-hatching (early opening of the egg capsule), after which seawater flows into the capsule and the embryos are consequently exposed to the surrounding seawater. We first experimentally examined the resistance of embryos to potential bacterial infections and found that the early embryos were highly vulnerable to environmental pathogens, suggesting that the embryos are protected from the threat of infection before pre-hatching. Indeed, the intracapsular environment of freshly laid eggs exhibited a significantly low bacterial density that was maintained until pre-hatching. Furthermore, the microbiome inside eggs just after oviposition differed markedly from the microbiomes of rearing seawater and adult oviducal gland epithelia; these eggs were predominantly populated by an unidentified genus of Sphingomonadaceae. Overall, this study provides compelling evidence that early embryos of oviparous cloudy catshark are incubated in a clean intracapsular environment that potentially plays a significant role in embryonic development in oviparous elasmobranchs. Our results suggest that maintenance of this clean condition might be attributable to bactericidal or bacteriostatic activities associated with the egg jelly and/or oviducal gland.
Prevalence of Class 1 integron in disease-causing carbapenem-resistantEscherichia coliin a tertiary hospital in Kathmandu, Nepal
Authors: Thapa Suchitra , Shrestha Basudha , Shrestha Manisha , Pokhrel Yojana , Tuladhar Reshma , Jauneikaite Elita , Joshi Dev Raj 
Published: February 2024

AbstractBackgroundHigh prevalence of carbapenem resistance genes have been abundantly reported within clinicalE. coliin Nepal but their co-prevalence with class-1 integron is poorly documented. These Class I Integrons play pivotal role in evolution and spread of antimicrobial resistance (AMR). Therefore, it is necessary to highlight their epidemiological significance, so this study determined the prevalence of Class 1 integrons within Carbapenem resistanceEscherichia coli(CREc) population.MethodsFifty-two clinicalE. coliwith confirmed resistance to Meropenem were collected between January 2020–April 2022 in Kathmandu Model Hospital, and undergone antimicrobial susceptibility testing for 11 antimicrobial classes. Carbapenemase production was confirmed by eCIM and mCIM methods. Presence of Class I integron and carbapenemase genes,blaNDM-1,blaKPC,blaIMP,blaVIM,blaOXA-23,blaOXA-48, was confirmed by PCR method.ResultsThe result revealed 92.3% (n=48/52) of the isolates harboredintI1gene. Among integron-positive population, 97.9% (n=47/48) were carbapenemase producers which were further identified as metallo β-lactamase (MBL) producers (82.9%, n=39/47) and serine β-lactamase (SBL) producer (17%, n=8/47). Carbapenemase geneblaNDM-1(79.2%, n=38/48) was highly prevalent within integron-positive isolates, followed byblaOXA-23(62.5%, n=30/48) andblaOXA-48(54.2%, n=26/48). All integron-positive CREc isolates were resistant to minimum 16 antibiotics tested, but were susceptible to Colistin, Polymixin B, and Tigecycline.ConclusionIn conclusion, Class 1 integrons were highly prevalent within clinical CREc in Nepal, and their co-prevalence with other CRE gene is concerning due to possibility of wider spread. Therefore, an in-depth genomic analysis of Class 1 integrons is needed to understand the integron mediated AMR in high risk clones like CREc and inform intervention measures to stop spread of such pathogens.
A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity
Authors: Boggess Steven C. , Gandhi Vaidehi , Tsai Ming-Chi , Marzette Emily , Teyssier Noam , Chou Joanna Yu-Ying , Hu Xiaoyu , Cramer Amber , Yadanar Lin , Shroff Kunal , Jeong Claire G , Eidenschenk Celine , Hanson Jesse E. , Tian Ruilin , Kampmann Martin 
Published: February 2024

AbstractUnderstanding the complex interplay between gene expression and neuronal activity is crucial for unraveling the molecular mechanisms underlying cognitive function and neurological disorders. Here, we developed pooled screens for neuronal activity, using CRISPR interference (CRISPRi) and the fluorescent calcium integrator CaMPARI2. Using this screening method, we evaluated 1343 genes for their effect on excitability in human iPSC-derived neurons, revealing potential links to neurodegenerative and neurodevelopmental disorders. These genes include known regulators of neuronal excitability, such as TARPs and ion channels, as well as genes associated with autism spectrum disorder and Alzheimer’s disease not previously described to affect neuronal excitability. This CRISPRi-based screening platform offers a versatile tool to uncover molecular mechanisms controlling neuronal activity in health and disease.
Unveiling leadership priorities: a comparative study of principal time use across high school types
Authors: Ni Yongmei , Li Bichu , Su Yu , Xia Jiangang 
Published: February 2024

PurposeAs responsibilities of high school principals continue to expand, their workweeks become longer, and their attention is stretched in multiple directions. How principals from various school types use their time is influenced by their organizational structures and external policies. To gain deeper insights into the workload, priorities and constraints faced by high school principals, this study examines principal time use (PTU) patterns across different school types, including traditional public schools (TPSs), charter schools, Catholic schools and non-Catholic private schools.Design/methodology/approachDrawing on the national representative data from the High School Longitudinal Study of 2009 in the USA, this study examines and compares PTU in various leadership tasks across different school types, controlling for school and principal characteristics.FindingsAmong various high school types, principals in TPS had the longest workweeks. However, the extended workweek did not necessarily result in significantly more hours or a larger proportion of their time dedicated to instructional leadership. Instead, TPS principals allocated more time to administrative tasks and student affairs than principals in other school types.Originality/valueBy examining PTU of different school types, this study adds new evidence on the influence of contextual factors on leadership behavior. It also offers policy implications to enhance principals’ capacities, alleviate their workload and to prioritize time use in different leadership domains.
An exploration of mock juror experience during the deliberations of a defendant diagnosed with a personality disorder
Authors: Wootton Sophie , Tkazky Sophia , Bergstrøm Henriette 
Published: February 2024

Purpose
The purpose of this study is to investigate how mock jurors’ experiences of deliberations are impacted by the defendant having a personality disorder.

Design/methodology/approach
This study used a qualitative approach to explore mock jurors’ experiences during the deliberations of a fictional defendant, Sarah Priest. Ten participants formed two mock juries, and each mock jury were given two case studies to deliberate. Case study one described Priest as having “Severe Personality Disorder, Borderline Pattern” whereas case study two described Priest as having “Complex Mental Health Problems”. There were no changes to the content of the case studies aside from the change in language used to describe the defendant.

Findings
An inductive thematic analysis identified two main themes relating to juror experience: “Interaction with Other Mock Jurors” and “Language as a Barrier to a Verdict”. Participants constructed that prosocial interactions with other mock jurors in the deliberations helped them make a verdict decision, but some of these interactions led to disagreements between participants due to a wide variation of opinion. Second, the different description of the defendant in each case study were constructed to have made the deliberations and decision-making difficult, but for different reasons. In case study one, a lack of knowledge surrounding BPD was the reason for this difficulty, and in case study two, participants thought that the applicability of diminished responsibility criteria were unclear, making it hard to reach a verdict.

Practical implications
The findings have key implications for the judicial system; common experiences can be identified and recorded to implement procedures to protect jurors from adverse experiences.

Originality/value
There is a lack of studies that have investigated juror experience in the UK, and the few studies available have used a quantitative methodology. The approach taken in the current study is, therefore, unique in a UK context. The findings have key implications for the judicial system; common experiences can be identified and recorded to implement procedures to protect jurors from adverse experiences.
The role of metaverse and blockchain in enhancing digital Islamic finance: empirical perspective
Authors: Al-Okaily Manaf , Alsmadi Ayman Abdalmajeed 
Published: February 2024

Purpose
This study aims to investigate the connections between the adoption of technology, user experience (UX), financial transparency and accountability, specifically focusing on the moderating influence of cultural sensitivity in the Jordanian context.

Design/methodology/approach
This study gathered data from 272 participants who are working in the operational Islamic banks in Jordan. Partial least squares structural equation modeling (PLS-SEM) is used for the hypotheses testing.

Findings
The results indicate that cultural sensitivity plays a significant role in shaping the UX, consequently influencing perceptions of financial transparency and accountability in e-Islamic finance within the metaverse. This study underscores the intricate interplay between technological advancements, adherence to Sharia principles and diverse cultural expectations, forming the crux of the research.

Originality/value
This research brings a novel perspective by examining the complex connections among technology adoption, UX, financial transparency and accountability, specifically within the distinctive context of Jordan. This research study innovates by checking out how social sensitivity moderates these partnerships, specifically in the context of e-Islamic finance in the metaverse. It adds value to the academic area by shedding light on the intricate interaction between technological development, adherence to Sharia concepts and differing cultural expectations. Ultimately, this adds to a much deeper understanding of the multifaceted nature of this domain.