bluuebunny/crossref_metadata_2025_split huggingface dataset:
The variant rs77559646 associated with aggressive prostate cancer disrupts ANO7 mRNA splicing and protein expression
Authors: Wahlström Gudrun , Heron Samuel , Knuuttila Matias , Kaikkonen Elina , Tulonen Nea , Metsälä Olli , Löf Christoffer , Ettala Otto , Boström Peter J , Taimen Pekka , Poutanen Matti , Schleutker Johanna 
Published: January 2022

Abstract
Prostate cancer is among the most common cancers in men, with a large fraction of the individual risk attributable to heritable factors. A majority of the diagnosed cases does not lead to a lethal disease, and hence biological markers that can distinguish between indolent and fatal forms of the disease are of great importance for guiding treatment decisions. Although over 300 genetic variants are known to be associated with prostate cancer risk, few have been associated with the risk of an aggressive disease. One such variant is rs77559646 located in ANO7. This variant has a dual function. It constitutes a missense mutation in the short isoform of ANO7 and a splice region mutation in full-length ANO7. In this study, we have analyzed the impact of the variant allele of rs77559646 on ANO7 mRNA splicing using a minigene splicing assay and by performing splicing analysis with the tools IRFinder (intron retention finder), rMATS (replicate multivariate analysis of transcript splicing) and LeafCutter on RNA sequencing data from prostate tissue of six rs77559646 variant allele carriers and 43 non-carriers. The results revealed a severe disruption of ANO7 mRNA splicing in rs77559646 variant allele carriers. Immunohistochemical analysis of prostate samples from patients homozygous for the rs77559646 variant allele demonstrated a loss of apically localized ANO7 protein. Our study is the first to provide a mechanistic explanation for the impact of a prostate cancer risk SNP on ANO7 protein production. Furthermore, the rs77559646 variant is the first known germline loss-of-function mutation described for ANO7. We suggest that loss of ANO7 contributes to prostate cancer progression.
Effect of a vegetation fire event ban on hospital visits for respiratory diseases in Upper Northern Thailand
Authors: Uttajug Athicha , Ueda Kayo , Seposo Xerxes Tesoro , Honda Akiko , Takano Hirohisa 
Published: January 2022

Abstract

Background
Upper Northern Thailand (UNT) has been episodically affected by air pollution from vegetation burning, which causes adverse respiratory health effects. However, no study has evaluated the effect of regulatory actions to prohibit vegetation burning on respiratory morbidity. We examined the effect of a burning ban enforced in May 2016 on hospital visits for respiratory diseases in UNT.

Methods
This study used data from eight provinces in UNT. Analyses were conducted for January to April of 2014–2016 (before ban enforcement) and January to April of 2017–2018 (after ban enforcement). Particulate matter of 10 microns in diameter or smaller (PM10) concentrations, numbers of satellite fire hotspots and age-standardized rates of hospital visits for respiratory diseases before and after ban enforcement were compared. The effect of the ban on hospital visits for respiratory diseases was evaluated using an interrupted time-series analysis controlled for season-specific temporal trends, day of week, public holiday, temperature, relative humidity, number of hospitals and offset population, with gastrointestinal diseases as a negative control. A meta-analysis was performed to pool province-specific effect estimates.

Results
The daily average PM10 concentration and the number of fire hotspots decreased after ban enforcement in all provinces in UNT, with percent changes ranging from 5.3 to 34.3% and 14.3 to 81.5%, respectively. The adjusted pooled effect estimates of hospital visits for respiratory diseases decreased by 9.1% (95% CI: 5.1, 12.9), whereas a null association was observed for gastrointestinal diseases.

Conclusion
The burning ban had a positive impact on both air pollution levels and rates of hospital visits for respiratory diseases in UNT.
Dual 5-HT3 and 5-HT6 Receptor Antagonist FPPQ Normalizes Phencyclidine-Induced Disruption of Brain Oscillatory Activity in Rats
Authors: Castañé Anna , Cano Montserrat , Ruiz-Avila Luis , Miquel-Rio Lluís , Celada Pau , Artigas Francesc , Riga Maurizio S 
Published: January 2022

Abstract
Schizophrenia is a severe mental disorder featuring psychotic, depressive, and cognitive alterations. Current antipsychotic drugs preferentially target dopamine D2-R and/or serotonergic 5-HT2A/1A-R. They partly alleviate psychotic symptoms but fail to treat negative symptoms and cognitive deficits. Here we report on the putative antipsychotic activity of (1-[(3-fluorophenyl)sulfonyl]-4-(piperazin-1-yl)-1H-pyrrolo[3,2-c]quinoline dihydrochloride) (FPPQ), a dual serotonin 5-HT3-R/5-HT6-R antagonist endowed with pro-cognitive properties. FPPQ fully reversed phencyclidine-induced decrease of low-frequency oscillations in the medial prefrontal cortex of anaesthetized rats, a fingerprint of antipsychotic activity. This effect was mimicked by the combined administration of the 5-HT3-R and 5-HT6-R antagonists ondansetron and SB-399 885, respectively, but not by either drug alone. In freely moving rats, FPPQ countered phencyclidine-induced hyperlocomotion and augmentation of gamma and high-frequency oscillations in medial prefrontal cortex, dorsal hippocampus, and nucleus accumbens. Overall, this supports that simultaneous blockade of 5-HT3R and 5-HT6-R-like that induced by FPPQ-can be a new target in antipsychotic drug development.
Uhlenbeck Compactification as a Bridgeland Moduli Space
Authors: Tajakka Tuomas 
Published: January 2022

Abstract
Let $(X,H)$ be a smooth, projective, polarized surface over ${\mathbb {C}}$, and let $v \in K_{\textrm {num}}(X)$ be a class of positive rank. We prove that for certain Bridgeland stability conditions $\sigma = ({\mathcal {A}}, Z)$ “on the vertical wall” for $v$, the good moduli space $M^\sigma (v)$ parameterizing S-equivalence classes of $\sigma $-semistable objects of class $v$ in ${\mathcal {A}}$ is projective. Moreover, we construct a bijective morphism $M^{\textrm {Uhl}}(v) \to M^\sigma (v)$ from the Uhlenbeck compactification of $\mu $-stable vector bundles.
Patients’, pharmacists’, and prescribers’ attitude toward using blockchain and machine learning in a proposed ePrescription system: online survey
Authors: Aldughayfiq Bader , Sampalli Srinivas 
Published: January 2022

AbstractObjectiveTo evaluate the attitudes of the parties involved in the system toward the new features and measure the potential benefits of introducing the use of blockchain and machine learning (ML) to strengthen the in-place methods for safely prescribing medication. The proposed blockchain will strengthen the security and privacy of the patient’s prescription information shared in the network. Once the ePrescription is submitted, it is only available in read-only mode. This will ensure there is no alteration to the ePrescription information after submission. In addition, the blockchain will provide an improved tracking mechanism to ensure the originality of the ePrescription and that a prescriber can only submit an ePrescription with the patient’s authorization. Lastly, before submitting an ePrescription, an ML algorithm will be used to detect any anomalies (eg, missing fields, misplaced information, or wrong dosage) in the ePrescription to ensure the safety of the prescribed medication for the patient.MethodsThe survey contains questions about the features introduced in the proposed ePrescription system to evaluate the security, privacy, reliability, and availability of the ePrescription information in the system. The study population is comprised of 284 respondents in the patient group, 39 respondents in the pharmacist group, and 27 respondents in the prescriber group, all of whom met the inclusion criteria. The response rate was 80% (226/284) in the patient group, 87% (34/39) in the pharmacist group, and 96% (26/27) in the prescriber group.Key FindingsThe vast majority of the respondents in all groups had a positive attitude toward the proposed ePrescription system’s security and privacy using blockchain technology, with 72% (163/226) in the patient group, 70.5% (24/34) in the pharmacist group, and 73% (19/26) in the prescriber group. Moreover, the majority of the respondents in the pharmacist (70%, 24/34) and prescriber (85%, 22/26) groups had a positive attitude toward using ML algorithms to generate alerts regarding prescribed medication to enhance the safety of medication prescribing and prevent medication errors.ConclusionOur survey showed that a vast majority of respondents in all groups had positive attitudes toward using blockchain and ML algorithms to safely prescribe medications. However, a need for minor improvements regarding the proposed features was identified, and a post-implementation user study is needed to evaluate the proposed ePrescription system in depth.
Evaluation of convection flow and entropy generation in a wavy cubical container with nanofluid and embedded cylinder
Authors: Alsabery Ammar I , Yazdi Mohammad H , Solomin Evgeny , Öztop Hakan F , Hashim Ishak 
Published: January 2022

Abstract
This work examines steady convection heat transfer and entropy generation in a wavy cubical container with Al2O3–water nanofluid and the solid cylinder. An isothermal embedded heater of finite width is located within the left vertical surface center of the container. All surfaces are insulated, except that the right wavy surface is kept cold, and the left wall is partially heated. The Boussinesq approximation is assumed, and three-dimensional simulations of governing equations have been applied to utilize the Galerkin weighted residual finite-element approach. Numerical results for the three-dimensional patterns of nanofluid flow, iso-temperature surfaces, and isentropic lines are given. The local Nusselt number adjacent to the left and interface surfaces within the container and solid cylinder and Bejan number have been examined for different values of the Rayleigh number, nanoparticle volume fraction, number of undulations and heater length, and cylinder radius. The results indicate that the optimal local heat transfer between the solid cylinder and container declines with the increased cylinder radius, which yields an imperfect nanofluid flow circulation.
Shredded
Authors: Ramírez-Gutiérrez Camilo , Quiroga-Villamarín Daniel R 
Published: January 2022

Abstract
From 2012 to 2016, the Colombian Government and the FARC-EP guerilla group sought to end the region’s longest non-international armed conflict. Under the auspices of the international community, this process drew from a complex series of practices and knowledge often known as ‘transitional justice’. Indeed, international expertise — in law and other fields — was also actively mobilized by both parties, as well as civil society and the anti-peace opposition, to contest the meaning of these terms. On paper, the peace agreement adopted a cutting-edge and comprehensive system aimed at delivering truth, justice, reparation, and non-repetition (the SIVJRNR), including both judicial and extrajudicial mechanisms following international standards and best practices. Yet in practice, the situation became increasingly dire after the peace agreement was narrowly voted down in October 2016. Two years later, having entered government, the former populist opposition proudly announced its plan to shred the peace accord and the SIVJRNR (including its crown jewel: the Special Jurisdiction for Peace or JEP). In this context, this article seeks to identify and understand the strategies which might be adopted by transitional justice institutions to prevail against waves of populist misinformation and backlash. The Colombian experiment can offer important insights on how humanitarian actors can generate public narratives of reconciliation in our current dire times of mistrust.
Family Matters: Older Refugee Minors in Vienna and Factors for Resiliency
Authors: Seaman Mackenzie , Stites Elizabeth 
Published: January 2022

Abstract
European migration discourses emphasize that unaccompanied refugee minors (URMs) are one of Europe’s most vulnerable migrant groups. The absence of an adult caregiver often serves as the sole explanation for the heightened vulnerability of URMs vis-à-vis their accompanied counterparts. This article challenges the assumption that the absence of adult caregivers always breeds greater vulnerability among young refugees who have received international protection. Based on 72 surveys and 31 in-depth interviews with refugees who received international protection and who arrived in Vienna, Austria between the ages of 14 and 18, this article contributes to empirical analysis on the complex impact adult relative caregivers specifically have on the integration and resiliency of refugee youth. It explores the influence that family status has on employment, education, social connections and personal outlook and sense of belonging. We hypothesize that refugees who arrived as older URMs experience a financial and social autonomy, as well as benefit from a more advantageous legal and social treatment, speeding up their adaptation process and engendering greater resiliency. While the findings highlight that family matters, they also show that family may not play a ubiquitously positive role in young refugees’ adaptation process as previously assumed.
Influence of Soldiers’ Cardiorespiratory Fitness on Physiological Responses and Dropouts During a Loaded Long-distance March
Authors: Oeschger Regina , Roos Lilian , Wyss Thomas , Buller Mark J , Veenstra Bertil J , Gilgen-Ammann Rahel 
Published: January 2022

ABSTRACT

Introduction
In military service, marching is an important, common, and physically demanding task. Minimizing dropouts, maintaining operational readiness during the march, and achieving a fast recovery are desirable because the soldiers have to be ready for duty, sometimes shortly after an exhausting task. The present field study investigated the influence of the soldiers’ cardiorespiratory fitness on physiological responses during a long-lasting and challenging 34 km march.

Materials and Methods
Heart rate (HR), body core temperature (BCT), total energy expenditure (TEE), energy intake, motivation, and pain sensation were investigated in 44 soldiers (20.3 ± 1.3 years, 178.5 ± 7.0 cm, 74.8 ± 9.8 kg, body mass index: 23.4 ± 2.7 kg × m−2, peak oxygen uptake ($\dot{\rm{V}}$O2peak): 54.2 ± 7.9 mL × kg−1 × min−1) during almost 8 hours of marching. All soldiers were equipped with a portable electrocardiogram to record HR and an accelerometer on the hip, all swallowed a telemetry pill to record BCT, and all filled out a pre- and post-march questionnaire. The influence of aerobic capacity on the physiological responses during the march was examined by dividing the soldiers into three fitness groups according to their $\dot{\rm{V}}$O2peak.

Results
The group with the lowest aerobic capacity ($\dot{\rm{V}}$O2peak: 44.9 ± 4.8 mL × kg−1 × min−1) compared to the group with the highest aerobic capacity ($\dot{\rm{V}}$O2peak: 61.7 ± 2.2 mL × kg−1 × min−1) showed a significantly higher (P &lt; .05) mean HR (133 ± 9 bpm and 125 ± 8 bpm, respectively) as well as peak BCT (38.6 ± 0.3 and 38.4 ± 0.2 °C, respectively) during the march. In terms of recovery ability during the break, no significant differences could be identified between the three groups in either HR or BCT. The energy deficit during the march was remarkably high, as the soldiers could only replace 22%, 26%, and 36% of the total energy expenditure in the lower, middle, and higher fitness group, respectively. The cardiorespiratory fittest soldiers showed a significantly higher motivation to perform when compared to the least cardiorespiratory fit soldiers (P = .002; scale from 1 [not at all] to 10 [extremely]; scale difference of 2.3). A total of nine soldiers (16%) had to end marching early: four soldiers (21%) in the group with the lowest aerobic capacity, five (28%) in the middle group, and none in the highest group.

Conclusion
Soldiers with a high $\dot{\rm{V}}$O2peak showed a lower mean HR and peak BCT throughout the long-distance march, as well as higher performance motivation, no dropouts, and lower energy deficit. All soldiers showed an enormous energy deficit; therefore, corresponding nutritional strategies are recommended.
Purifying Selection Determines the Short-Term Time Dependency of Evolutionary Rates in SARS-CoV-2 and pH1N1 Influenza
Authors: Ghafari Mahan , du Plessis Louis , Raghwani Jayna , Bhatt Samir , Xu Bo , Pybus Oliver G , Katzourakis Aris 
Published: January 2022

Abstract
High-throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Crucially, there are an increasing number of molecular clock analyses using external evolutionary rate priors to infer evolutionary parameters. However, it is not clear which rate prior is appropriate for a given time window of observation due to the time-dependent nature of evolutionary rate estimates. Here, we characterize the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and data set sizes affect the accuracy of parameter estimation. We further use a generalized McDonald–Kreitman test to estimate the number of segregating nonneutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of 1 year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2–4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating nonneutral sites, demonstrating the role of purifying selection in generating the time dependency of evolutionary parameters during pandemics.
Experimental demonstration of operon formation catalyzed by insertion sequence
Authors: Kanai Yuki , Tsuru Saburo , Furusawa Chikara 
Published: January 2022

Abstract
Operons are a hallmark of the genomic and regulatory architecture of prokaryotes. However, the mechanism by which two genes placed far apart gradually come close and form operons remains to be elucidated. Here, we propose a new model of the origin of operons: Mobile genetic elements called insertion sequences can facilitate the formation of operons by consecutive insertion–deletion–excision reactions. This mechanism barely leaves traces of insertion sequences and thus difficult to detect in nature. In this study, as a proof-of-concept, we reproducibly demonstrated operon formation in the laboratory. The insertion sequence IS3 and the insertion sequence excision enhancer are genes found in a broad range of bacterial species. We introduced these genes into insertion sequence-less Escherichia coli and found that, supporting our hypothesis, the activity of the two genes altered the expression of genes surrounding IS3, closed a 2.7 kb gap between a pair of genes, and formed new operons. This study shows how insertion sequences can facilitate the rapid formation of operons through locally increasing the structural mutation rates and highlights how coevolution with mobile elements may shape the organization of prokaryotic genomes and gene regulation.
Gain of C-Ala enables AlaRS to target the L-shaped tRNAAla
Authors: Antika Titi Rindi , Chrestella Dea Jolie , Ivanesthi Indira Rizqita , Rida Gita Riswana Nawung , Chen Kuan-Yu , Liu Fu-Guo , Lee Yi-Chung , Chen Yu-Wei , Tseng Yi-Kuan , Wang Chien-Chia 
Published: January 2022

Abstract
Unlike many other aminoacyl-tRNA synthetases, alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout biology. While Caenorhabditis elegans cytoplasmic AlaRS (CeAlaRSc) retains the prototype structure, its mitochondrial counterpart (CeAlaRSm) contains only a residual C-terminal domain (C-Ala). We demonstrated herein that the C-Ala domain from CeAlaRSc robustly binds both tRNA and DNA. It bound different tRNAs but preferred tRNAAla. Deletion of this domain from CeAlaRSc sharply reduced its aminoacylation activity, while fusion of this domain to CeAlaRSm selectively and distinctly enhanced its aminoacylation activity toward the elbow-containing (or L-shaped) tRNAAla. Phylogenetic analysis showed that CeAlaRSm once possessed the C-Ala domain but later lost most of it during evolution, perhaps in response to the deletion of the T-arm (part of the elbow) from its cognate tRNA. This study underscores the evolutionary gain of C-Ala for docking AlaRS to the L-shaped tRNAAla.
A new twist on graphene: an interview with Pablo Jarillo-Herrero and Allan MacDonald
Authors: Ball Philip 
Published: January 2022

Abstract
Graphene is the building block of graphite, made of carbon atoms bonded into sheets of hexagonal rings just a single atom thick. Although such isolated sheets had been predicted for many decades to exist, and had been grown on other surfaces, interest in this material exploded after the discovery in 2004 that single sheets could be made easily and cheaply by separating them mechanically from graphite flakes (a process called exfoliation). Although graphene is often advertised as a ‘wonder material’—electronically conducting, transparent and extremely strong and flexible—much of the interest in it is more fundamental. As a 2D conductor, graphene shows unusual electronic and magnetic properties that enable the study of quantum-mechanical effects of confinement and of correlations between electron motions—some of which might find applications in electronic devices. The excitement of this discovery was reflected in the award of the 2010 Nobel Prize in Physics to two pioneers in the field: Andre Geim and Konstantin Novoselov of the University of Manchester in the UK.
This rich behavior is broadened still further when two graphene sheets are brought close enough to interact with one another. In particular, the electronic properties may then depend on the relative orientation of the sheets: how aligned the two ‘honeycomb’ lattices are. Two grids superimposed on one another may create ‘superlattices’: regularities at larger scales than the grid spacing, due to registry (commensurability) between the two at certain angles. This so-called moiré effect is sometimes evident for two closely spaced grid-like fences seen from afar. Experimentally exploring the electronic properties of such ‘twisted bilayer graphene’ requires an ability to precisely control the position and orientation of the two sheets. These phenomena are now recognized as generic to other 2D materials, such as hexagonal sheets of boron nitride. They have revealed a fertile playground for condensed-matter physics. In particular, striking electronic properties appear at certain ‘magic-angle’ twists of the layers.
NSR spoke to two of the leading experts in the study of magic-angle twisted bilayer graphene (MATBG): experimentalist Pablo Jarillo-Herrero of the Massachusetts Institute of Technology and theorist Allan MacDonald of the University of Texas at Austin.