bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-scale population structure and demographic history of British Pakistanis
Authors: Arciero Elena , Dogra Sufyan A. , Malawsky Daniel S. , Mezzavilla Massimo , Tsismentzoglou Theofanis , Huang Qin Qin , Hunt Karen A. , Mason Dan , Sharif Saghira Malik , van Heel David A. , Sheridan Eamonn , Wright John , Small Neil , Carmi Shai , Iles Mark M. , Martin Hilary C. 
Published: December 2021

AbstractPrevious genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genotype chip data from 2,200 British Pakistanis. We reveal strong recent population structure driven by the biraderi social stratification system. We find that all subgroups have had low recent effective population sizes (Ne), with some showing a decrease 15‒20 generations ago that has resulted in extensive identity-by-descent sharing and homozygosity, increasing the risk of recessive disorders. Our results from two orthogonal methods (one using machine learning and the other coalescent-based) suggest that the detailed reporting of parental relatedness for mothers in the cohort under-represents the true levels of consanguinity. These results demonstrate the impact of cultural practices on population structure and genomic diversity in Pakistanis, and have important implications for medical genetic studies.
Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England
Authors: Amirthalingam Gayatri , Bernal Jamie Lopez , Andrews Nick J. , Whitaker Heather , Gower Charlotte , Stowe Julia , Tessier Elise , Subbarao Sathyavani , Ireland Georgina , Baawuah Frances , Linley Ezra , Warrener Lenesha , O’Brien Michelle , Whillock Corinne , Moss Paul , Ladhani Shamez N. , Brown Kevin E. , Ramsay Mary E. 
Published: December 2021

AbstractThe UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50–89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14–35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65–84 days) compared with those vaccinated with a standard (19–29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14–35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.
The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting
Authors: Zimmer Matthias M. , Kibe Anuja , Rand Ulfert , Pekarek Lukas , Ye Liqing , Buck Stefan , Smyth Redmond P. , Cicin-Sain Luka , Caliskan Neva 
Published: December 2021

AbstractProgrammed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral, structural and replicative enzymes that are encoded in an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshift elements and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the SARS-CoV-2 frameshift element and the host proteome. We reveal that the short isoform of the zinc-finger antiviral protein (ZAP-S) is a direct regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and inhibits viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and interferes with the folding of the frameshift RNA element. Together, these data identify ZAP-S as a host-encoded inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.
Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria
Authors: Reiker Theresa , Golumbeanu Monica , Shattock Andrew , Burgert Lydia , Smith Thomas A. , Filippi Sarah , Cameron Ewan , Penny Melissa A. 
Published: December 2021

AbstractIndividual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We propose using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability.
Correlated states in doubly-aligned hBN/graphene/hBN heterostructures
Authors: Sun Xingdan , Zhang Shihao , Liu Zhiyong , Zhu Honglei , Huang Jinqiang , Yuan Kai , Wang Zhenhua , Watanabe Kenji , Taniguchi Takashi , Li Xiaoxi , Zhu Mengjian , Mao Jinhai , Yang Teng , Kang Jun , Liu Jianpeng , Ye Yu , Han Zheng Vitto , Zhang Zhidong 
Published: December 2021

AbstractInterfacial moiré superlattices in van der Waals vertical assemblies effectively reconstruct the crystal symmetry, leading to opportunities for investigating exotic quantum states. Notably, a two-dimensional nanosheet has top and bottom open surfaces, allowing the specific case of doubly aligned super-moiré lattice to serve as a toy model for studying the tunable lattice symmetry and the complexity of related electronic structures. Here, we show that by doubly aligning a graphene monolayer to both top and bottom encapsulating hexagonal boron nitride (h-BN), multiple conductivity minima are observed away from the main Dirac point, which are sensitively tunable with respect to the small twist angles. Moreover, our experimental evidences together with theoretical calculations suggest correlated insulating states at integer fillings of −5, −6, −7 electrons per moiré unit cell, possibly due to inter-valley coherence. Our results provide a way to construct intriguing correlations in 2D electronic systems in the weak interaction regime.
Electroresistance in multipolar antiferroelectric Cu2Se semiconductor
Authors: Bai Hui , Wu Jinsong , Su Xianli , Peng Haoyang , Li Zhi , Yang Dongwang , Zhang Qingjie , Uher Ctirad , Tang Xinfeng 
Published: December 2021

AbstractElectric field-induced changes in the electrical resistance of a material are considered essential and enabling processes for future efficient large-scale computations. However, the underlying physical mechanisms of electroresistance are currently remain largely unknown. Herein, an electrically reversible resistance change has been observed in the thermoelectric α-Cu2Se. The spontaneous electric dipoles formed by Cu+ ions displaced from their positions at the centers of Se-tetrahedrons in the ordered α-Cu2Se phase are examined, and α-Cu2Se phase is identified to be a multipolar antiferroelectric semiconductor. When exposed to the applied voltage, a reversible switching of crystalline domains aligned parallel to the polar axis results in an observed reversible resistance change. The study expands on opportunities for semiconductors with localized polar symmetry as the hardware basis for future computational architectures.
Divergent functionalization of aldehydes photocatalyzed by neutral eosin Y with sulfone reagents
Authors: Yan Jianming , Tang Haidi , Kuek Eugene Jun Rong , Shi Xiangcheng , Liu Chenguang , Zhang Muliang , Piper Jared L. , Duan Shengquan , Wu Jie 
Published: December 2021

AbstractWhile aldehydes represent a classic class of electrophilic synthons, the corresponding acyl radicals are inherently nucleophilic, which exhibits umpolung reactivity. Generation of acyl radicals typically requires noble metal catalysts or excess oxidants to be added. Herein, we report a convenient and green approach to access acyl radicals, capitalizing on neutral eosin Y-enabled hydrogen atom transfer (HAT) photocatalysis with aldehydes. The generated acyl radicals underwent SOMOphilic substitutions with various functionalized sulfones (X–SO2R’) to deliver value-added acyl products. The merger of eosin Y photocatalysis and sulfone-based SOMOphiles provides a versatile platform for a wide array of aldehydic C–H functionalizations, including fluoromethylthiolation, arylthiolation, alkynylation, alkenylation and azidation. The present protocol features green characteristics, such as being free of metals, harmful oxidants and additives; step-economic; redox-neutral; and amenable to scale-up assisted by continuous-flow technology.
Systematic analysis of PINK1 variants of unknown significance shows intact mitophagy function for most variants
Authors: Ma Kai Yu , Fokkens Michiel R. , van Laar Teus , Verbeek Dineke S. 
Published: December 2021

AbstractPathogenic variants inPINK1cause early-onset Parkinson’s disease. Although manyPINK1variants have been reported, the clinical significance is uncertain for the majority of them. To gain insights into the consequences ofPINK1missense variants in a systematic manner, we selected 50PINK1missense variants from patient- and population-wide databases and systematically classified them using Sherloc, a comprehensive framework for variant interpretation based on ACMG-AMP guidelines. We then performed functional experiments, including mitophagy and Parkin recruitment assays, to assess the downstream consequences ofPINK1variants. Analysis ofPINK1missense variants based on Sherloc showed that the patient databases over-annotate variants aslikely pathogenic. Furthermore, our study shows thatpathogenic PINK1variants are most often linked to a loss-of-function for mitophagy and Parkin recruitment, while this is not observed for variants of unknown significance. In addition to the Sherloc framework, the added layer of evidence of our functional tests suggests a reclassification of 9/50 missense variants. In conclusion, we suggest the assessment of multiple layers of evidence, including functional data on top of available clinical and population-based data, to support the clinical classification of a variant and show that the presence of a missense variant inPINK1in a Parkinson’s disease case does not automatically imply pathogenicity.
A longitudinal analysis of collapsibility with predictions over the southeastern Loess Plateau in China
Authors: Zheng Ziyu , Li Xi-an , Wang Li 
Published: December 2021

AbstractLoess presents very unique collapsible behaviour due to its special under-compactness, weak cementation and porousness. Many environmental issues and geological hazards including subgrade subsidences, slope collapses or failures, building cracking and so on are directly caused by the collapsible deformation of loess. Such collapsible behaviour may also severe accidents due to sinkholes, underground caves or loess gullies. Moreover, with the increasing demand of construction and development in the loess areas, an in-depth research towards effective evaluation of loess collapsibility is urged. Currently no studies have made attempts to explore a rather complete and representative area of Loess Plateau. This paper thus provides a novel approach on spatial modelling over Jin-Shan Loess Plateau as an extension to experimental studies. The in-lab experiment results have shown that shown that the porosity ratio and collapsibility follow a Gaussian distribution and a Gamma distribution respectively for both sampling areas: Yan’an and Lv Liang. This establishes the prior intuition towards spatial modelling which provides insights of potential influential factors on loess collapsibility and further sets a potential direction of the loess studies by considering an extra dimension of spatial correlation. Such modelling allows robust predictions taken into account of longitudinal information as well as structural parameters and basic physical properties. Water contents, dry densities, pressure levels and elevations of samples are determined to be statistically significant factors which affect the loess collapsibility. All regions in Lv Liang area are at risk of high collapsibility with average around 0.03, out of which roughly a third of them are predicted to be at high risk. Clear spatial patterns of higher expected collapsibility in the southwest comparing to the northeast are shown adjusting for influential covariates. On reference guidelines for potential policy makings, county-level regions with the highest expected loess collapsibility are also identified.
The role of calcium oscillations in the phenotype selection in endothelial cells
Authors: Debir Birses , Meaney Cameron , Kohandel Mohammad , Unlu M. Burcin 
Published: December 2021

AbstractAngiogenesis is an important process in the formation and maintenance of tissues which is driven by a complex system of intracellular and intercellular signaling mechanisms. Endothelial cells taking part in early angiogenesis must select their phenotype as either a tip cells (leading, migratory) or a stalk cells (following). Recent experiments have demonstrated that rapid calcium oscillations within active cells characterize this phenotype selection process and that these oscillations play a necessary role in governing phenotype selection and eventual vessel architecture. In this work, we develop a mathematical model capable of describing these oscillations and their role in phenotype selection then use it to improve our understanding of the biological mechanisms at play. We developed a model based on two previously published and experimentally validated mathematical models of calcium and angiogenesis then use our resulting model to simulate various multi-cell scenarios. We are able to capture essential calcium oscillation dynamics and intercellular communication between neighboring cells. The results of our model show that although the late DLL4 (a transmembrane protein that activates Notch pathway) levels of a cell are connected with its initial IP3 (Inositol 1,4,5-trisphosphate) level, cell-to-cell communication determines its eventual phenotype.
Fetal abdominal overgrowth is already present at 20–24 gestational weeks prior to diagnosis of gestational diabetes mellitus
Authors: Kim Wonjin , Park Soo Kyung , Kim Yoo Lee 
Published: December 2021

AbstractFetal abdominal obesity (FAO) was detected at the time of gestational diabetes mellitus (GDM) diagnosis at 24–28 gestational weeks (GW) in older (≥ 35 years) and/or obese (≥ body mass index 25 kg/m2) women and persisted until delivery. We investigated whether FAO is already present at 20–24 GW. Medical records of 7820 singleton pregnancy including 384 GDM were reviewed. Fetal abdominal overgrowth was assessed by the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter or femur length, respectively. FAO was defined as FAOR ≥ 90th percentile. FAORs measured at 20–24 GW in older and/or obese but not in young and non-obese GDM subjects were significantly higher than those in NGT subjects. Relative to NGT subjects without FAO at 20–24 GW, odds ratios for exhibiting FAO at GDM diagnosis and large for gestational age in GDM with FAO at 20–24 GW were 10.15 and 5.57, and their primary cesarean delivery rate was significantly higher than those in GDM without FAO (44% vs. 29%). Earlier diagnosis and active interventions of GDM well before 20–24 GW might be necessary to prevent FAO in the older and/or obese women.
Trends in neonatal intensive care unit admissions by race/ethnicity in the United States, 2008–2018
Authors: Kim Youngran , Ganduglia-Cazaban Cecilia , Chan Wenyaw , Lee MinJae , Goodman David C. 
Published: December 2021

AbstractTo examine temporal trends of NICU admissions in the U.S. by race/ethnicity, we conducted a retrospective cohort analysis using natality files provided by the National Center for Health Statistics at the U.S. Centers for Disease Control and Prevention. A total of 38,011,843 births in 2008–2018 were included. Crude and risk-adjusted NICU admission rates, overall and stratified by birth weight group, were compared between white, black, and Hispanic infants. Crude NICU admission rates increased from 6.62% (95% CI 6.59–6.65) to 9.07% (95% CI 9.04–9.10) between 2008 and 2018. The largest percentage increase was observed among Hispanic infants (51.4%) compared to white (29.1%) and black (32.4%) infants. Overall risk-adjusted rates differed little by race/ethnicity, but birth weight-stratified analysis revealed that racial/ethnic differences diminished in the very low birth weight (< 1500 g) and moderately low birth weight (1500–2499 g) groups. Overall NICU admission rates increased by 37% from 2008 to 2018, and the increasing trends were observed among all racial and ethnic groups. Diminished racial/ethnic differences in NICU admission rates in very low birth weight infants may reflect improved access to timely appropriate NICU care among high-risk infants through increasing health care coverage coupled with growing NICU supply.
Antibacterial efficacy of non-thermal atmospheric plasma against Streptococcus mutans biofilm grown on the surfaces of restorative resin composites
Authors: Nima Gabriel , Harth-Chu Erika , Hiers Rochelle Denise , Pecorari Vanessa Gallego Arias , Dyer David W. , Khajotia Sharukh Soli , Giannini Marcelo , Florez Fernando Luis Esteban 
Published: December 2021

AbstractThe aim of this study was to evaluate the antimicrobial efficacy of non-thermal atmospheric plasma (NTAP) against Streptococcus mutans biofilms. Resin discs were fabricated, wet-polished, UV sterilized, and immersed in water for monomer extraction (37 °C, 24 h). Biofilms of bioluminescent S. mutans strain JM10 was grown on resin discs in anaerobic conditions for (37 °C, 24 h). Discs were divided into seven groups: control (CON), 2% chlorhexidine (CHX), only argon gas 150 s (ARG) and four NTAP treatments (30 s, 90 s, 120 s, 150 s). NTAP was applied using a plasma jet device. After treatment, biofilms were analyzed through the counting of viable colonies (CFU), bioluminescence assay (BL), scanning electron microscopy (SEM), and polymerase chain reaction (PCR). All NTAP-treated biofilm yielded a significant CFU reduction when compared to ARG and CON. BL values showed that NTAP treatment for 90 s, 120 s or 150 s resulted in statistically significantly lower metabolic activity when compared to the other groups. CHX displayed the lowest means of CFU and BL. SEM showed significant morphological changes in NTAP-treated biofilm. PCR indicated damage to the DNA structure after NTAP treatment. NTAP treatment was effective in lowering the viability and metabolism of S. mutans in a time-dependent manner, suggesting its use as an intraoral surface-decontamination strategy.
Formation mechanism of carbide slag composite sustained-alkalinity-release particles for the source control of acid mine drainage
Authors: Bai Jichi , Zhang Haiqin , Xiao Liping 
Published: December 2021

AbstractAcid mine drainage (AMD) has caused serious and long-lasting damage to the environment in many countries. Preventing AMD formation at the source is considered the most direct and effective method of remediation. Carbide slag, an industrial waste, is a potential AMD treatment material due to its strong alkalinity. However, applying carbide slag at the source carries difficulties due to its rapid release of alkalinity. This is the first attempt to mix carbide slag with bentonite to prepare sustained-alkalinity-release particles for source control of AMD. The size of Ca(OH)2 crystallites is decreased from 267 to 211 nm, and the reduced part forms calcium silicate hydrate gel (C–S–H) between the carbide slag and bentonite. C–S–H encapsulated on the surface of the carbide slag, increasing the mechanical strength of the particles, and achieving slow release of alkalinity. The suggested optimum preparation conditions for the particles are as follows: bentonite-to-carbide slag mass ratio of 3:7, Na2CO3 dose of 10 wt%, and calcination temperature of 500 °C for 1 h. The particles can remove 105 mg/g Cu2+ within 12 h, and the loss rate is only 7.4%. The alkalinity release time of the particles is 4 times greater than that of carbide slag.
Sleep as a random walk: a super-statistical analysis of EEG data across sleep stages
Authors: Metzner Claus , Schilling Achim , Traxdorf Maximilian , Schulze Holger , Krauss Patrick 
Published: December 2021

AbstractIn clinical practice, human sleep is classified into stages, each associated with different levels of muscular activity and marked by characteristic patterns in the EEG signals. It is however unclear whether this subdivision into discrete stages with sharply defined boundaries is truly reflecting the dynamics of human sleep. To address this question, we consider one-channel EEG signals as heterogeneous random walks: stochastic processes controlled by hyper-parameters that are themselves time-dependent. We first demonstrate the heterogeneity of the random process by showing that each sleep stage has a characteristic distribution and temporal correlation function of the raw EEG signals. Next, we perform a super-statistical analysis by computing hyper-parameters, such as the standard deviation, kurtosis, and skewness of the raw signal distributions, within subsequent 30-second epochs. It turns out that also the hyper-parameters have characteristic, sleep-stage-dependent distributions, which can be exploited for a simple Bayesian sleep stage detection. Moreover, we find that the hyper-parameters are not piece-wise constant, as the traditional hypnograms would suggest, but show rising or falling trends within and across sleep stages, pointing to an underlying continuous rather than sub-divided process that controls human sleep. Based on the hyper-parameters, we finally perform a pairwise similarity analysis between the different sleep stages, using a quantitative measure for the separability of data clusters in multi-dimensional spaces.