bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open access-enabled evaluation of epigenetic age acceleration in colorectal cancer and development of a classifier with diagnostic potential
Authors: Widayati Tyas Arum , Schneider Jadesada , Panteleeva Kseniia , Chernysheva Elizabeth , Hrbkova Natalie , Beck Stephan , Voloshin Vitaly , Chervova Olga 
Published: August 2023

ABSTRACTAberrant DNA methylation (DNAm) is known to be associated with the aetiology of cancer, including colorectal cancer (CRC). In the past, the availability of open access data has been the main driver of innovative method development and research training. However, this is increasingly being eroded by the move to controlled access, particularly of medical data, including cancer DNAm data. To rejuvenate this valuable tradition, we leveraged DNAm data from 1,845 samples (535 CRC tumours, 522 normal colon tissues adjacent to tumours, 72 colorectal adenomas, and 716 normal colon tissues from healthy individuals) from 14 open access studies deposited in NCBI GEO and ArrayExpress. We calculated each sample’s epigenetic age (EA) using eleven epigenetic clock models and derived the corresponding epigenetic age acceleration (EAA). For EA, we observed that most first- and second-generation epigenetic clocks reflect the chronological age in normal tissues adjacent to tumours and healthy individuals (e.g. Horvath (r= 0.77 and 0.79), Zhang EN (r= 0.70 and 0.73)) unlike the epigenetic mitotic clocks (EpiTOC, HypoClock, MiAge) (r <0.3). For EAA, we used PhenoAge, Wu, and the above mitotic clocks and found them to have distinct distributions in different tissue types, particularly between normal colon tissues adjacent to tumours and cancerous tumours, as well as between normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals. Finally, we harnessed these associations to develop a classifier using elastic net regression (with lasso and ridge regularisations) that predicts CRC diagnosis based on a patient’s sex and EAAs calculated from histologically normal controls (i.e. normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals). The classifier demonstrated good diagnostic potential with ROC-AUC=0.886, which suggests that an EAA-based classifier trained on relevant data could become a tool to support diagnostic/prognostic decisions in CRC for clinical professionals. Our study also reemphasises the importance of open access clinical data for method development and training of young scientists. Obtaining the required approvals for controlled access data would not have been possible in the timeframe of this study.
The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia
Authors: Krzisch Marine , Yuan Bingbing , Chen Wenyu , Osaki Tatsuya , Fu Dongdong , Garrett-Engele Carrie , Svoboda Devon , Andrykovich Kristin , Sur Mriganka , Jaenisch Rudolf 
Published: August 2023

AbstractParkinson’s disease (PD) is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for α-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human α-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia. Here, we used 2-dimensional cultures of human iPSC-derived microglia and transplantation of these cells into the mouse brain to assess the effects of the A53T mutation on human microglia. We found that A53T-mutant human microglia had an intrinsically increased propensity towards pro-inflammatory activation upon inflammatory stimulus. Additionally, A53T mutant microglia showed a strong decrease in catalase expression in non-inflammatory conditions, and increased oxidative stress. Our results indicate that A53T mutant human microglia display cell-autonomous phenotypes that may worsen neuronal damage in early-onset PD.
Genome Report: First whole genome sequence and assembly of the Ecuadorian brown-headed spider monkey (Ateles fusciceps fusciceps), a critically endangered species, using Oxford Nanopore Technologies
Authors: Pozo Gabriela , Quintana Martina Albuja , Larreátegui Lizbeth , Gutiérrez Bernardo , Fuentes Nathalia , Alfonso-Cortés Felipe , de Lourdes Torres María 
Published: August 2023

AbstractThe Ecuadorian brown-headed spider monkey (Ateles fusciceps fusciceps) is currently considered one of the most endangered primates in the world and is classified as critically endangered (IUCN). It faces multiple threats, the most significant one being habitat loss due to deforestation in western Ecuador. Genomic tools are key for the management of endangered species, but this requires a reference genome which until now was unavailable forA. f. fusciceps. The present study reports the first whole genome sequence and assembly ofA. f. fuscicepsgenerated using Oxford Nanopore long reads. DNA was extracted from a subadult male and libraries were prepared for sequencing following the Ligation Sequencing Kit SQK-LSK112 workflow. Sequencing was performed using a MinION Mk1C sequencer. The sequencing reads were processed to generate a genome assembly. Two different assemblers were used to obtain draft genomes using raw reads, of which the Flye assembly was found to be superior. The final assembly has a total length of 2.63 Gb and contains 3,861 contigs, with an N50 of 7,560,531 bp. The assembly was analyzed for annotation completeness based on primate ortholog prediction using a high-resolution database, and was found to be 84.3% complete, with a low number of duplicated genes indicating a precise assembly. The annotation of the assembly predicted 31,417 protein-coding genes, comparable to other mammal assemblies. A reference genome for this critically endangered species will allow researchers to gain insight into the genetics of its populations and thus aid conservation and management efforts of this vulnerable species.
Visual looming is a primitive for human emotion
Authors: Thieu Monica K. , Ayzenberg Vladislav , Lourenco Stella F. , Kragel Philip A. 
Published: August 2023

AbstractLooming objects afford threat of collision across the animal kingdom. Defensive responses to looming and neural computations for looming detection are strikingly conserved across species. In mammals, information about rapidly approaching threats is conveyed from the retina to the midbrain superior colliculus, where variables that indicate the position and velocity of approach are computed to enable defensive behavior. Although neuroscientific theories posit that midbrain representations contribute to emotion through connectivity with distributed brain systems, it remains unknown whether a computational system for looming detection can predict both defensive behavior and phenomenal experience in humans. Here, we show that a shallow convolutional neural network based on theDrosophilavisual system predicts defensive blinking to looming objects in infants and superior colliculus responses to optical expansion in adults. Further, the responses of the convolutional network to a broad array of naturalistic video clips predict self-reported emotion largely on the basis of subjective arousal. Our findings illustrate how motor and experiential components of human emotion relate to species-general systems for survival in unpredictable environments.
Repair of CRISPR-guided RNA breaks enables site-specific RNA editing in human cells
Authors: Nemudraia Anna , Nemudryi Artem , Wiedenheft Blake 
Published: August 2023

AbstractGenome editing with CRISPR RNA-guided endonucleases generates DNA breaks that are resolved by cellular DNA repair machinery. However, analogous methods to manipulate RNA remain unavailable. Here, we show that site-specific RNA breaks generated with RNA-targeting CRISPR complexes are repaired in human cells, and this repair can be used for programmable deletions in human transcripts that restore gene function. Collectively, this work establishes a technology for precise RNA manipulation with potential therapeutic applications.One-Sentence SummaryCRISPR-guided RNA breaks are repaired in human cells, and this RNA repair can be used for programmable editing of human transcriptomes.
Logic Gate Activated Lysosome Targeting DNA Nanodevice for Controlled Proteins Degradation
Authors: Shang Yuzhe , Zhu Longyi , Xiao Yang , Du Songyuan , Ji Ruoyang , Li Bin , Chen Jialiang , Deng Shengyuan , Ren Kewei 
Published: August 2023

AbstractTargeted protein degradation (TPD) is a powerful technique for regulation of protein homeostasis. Current TPD mainly focuses on the therapeutical consequences rather than the operation processes of the molecular tools. Herein, we construct a platform for precisely manipulate the protein degradation by activatable lysosome targeting DNA nanodevices. In the design, a lysosome-targeting CD63 aptamer is locked by the single-stranded DNA with a photocleavable group and a disulfide bond. This locked CD63 aptamer is connected with the aptamer targeting the protein of interest via double-stranded DNA linkages to form the logic-gate activated lysosome targeting DNA nanodevice (LALTD). With the UV light and endogenous GSH as inputs, AND logic-gate is built to efficiently manipulate the protein delivery processes by LALTD. The protein of interest could be degraded via efficient lysosome hydrolysis. Further studies shows that the logic-gate operation could be used for modulating the T cell-mediated antitumor immunity. The modularly designed activatable lysosome targeting DNA nanodevices exhibits good stability, controllability, programmability and universality, providing a new prospect for accurate protein degradation and precise therapy.Entry for the Table of ContentsThrough rational integration of dual molecular switches with bispecific aptamer systems, a logic-gate activated lysosome targeting DNA nanodevice (LALTD) was developed for precisely controlled process of protein hydrolysis in living cells. The designed LALTD system provide a general platform for designing accurate protein degradation.
Vaccination status and re-infection among COVID patients admitted in COVID High Dependency Unit (HDU) of a tertiary hospital in Eastern Nepal: A cross-sectional study
Authors: Kafle Sujan , Chhetri Varsha , Bajracharya Joshan Lal , Pokharel Lenish , Dawadi Suyash , Basnet Ujwal , Dhungana Shreya , Neupane Durga 
Published: August 2023

AbstractIntroductionThe relationship between COVID-19 vaccination and Coronavirus disease severity and outcomes remain topics of significant interest. This cross-sectional study done among COVID-19 patients admitted to the High-dependency unit of a tertiary hospital in Eastern Nepal aimed to assess the association between vaccination status, prior infection, and disease outcomes, and the modification of these associations by the presence or absence of comorbidities.MethodologyDemographic and clinical data were collected from 102 COVID-19 patients admitted to the High-Dependency Unit of Mechi Zonal Hospital, including information on vaccination status, comorbidities, disease severity, and outcomes. Statistical analysis, including chi-square tests and Fisher’s exact tests, was performed to examine the associations.ResultsAmong the study participants, 49% had received at least one dose of COVID-19 vaccine. Vaccinated individuals had a significantly lower rate of severe disease compared to non-vaccinated individuals (χ²=10.05, p=0.002). Recovery and mortality rates did not differ significantly between the two groups (χ²=1.008, p=0.315). However, when stratified by comorbidities, vaccinated individuals with comorbidities had higher recovery rates compared to non-vaccinated individuals (85.29% vaccinated vs. 25.00% non-vaccinated, Fisher’s exact test p=0.024). Vaccinated individuals, both with and without comorbidities, had lower rates of severe disease compared to non-vaccinated individuals. However, the association was found to be significant only in individuals with comorbidities (12.50% vaccinated without comorbidities vs. 47.92% non-vaccinated, p=0.017; 23.53% vaccinated with comorbidities vs. 75.00% non-vaccinated, p=0.065).ConclusionOur findings suggest that COVID-19 vaccination is associated with a reduced risk of severe disease among individuals with or without comorbidities and decreased risk of mortality among those with comorbidities. However, larger studies are needed to validate these findings and further explore the impact of vaccination on disease outcomes. These findings support the ongoing efforts to promote COVID-19 vaccination as a crucial public health intervention.
Opto4E-BP, an optogenetic tool for inducible, reversible, and cell type-specific inhibition of translation initiation
Authors: Alapin Jessica M. , Mohamed Muhaned S. , Shrestha Prerana , Khaled Houda G. , Vorabyeva Anna G. , Bowling Heather L. , Oliveira Mauricio M. , Klann Eric 
Published: August 2023

AbstractThe protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is one of the primary triggers for initiating cap-dependent translation. Amongst its functions, mTORC1 phosphorylates eIF4E-binding proteins (4E-BPs), which prevents them from binding to eIF4E and thereby enables translation initiation. mTORC1 signaling is required for multiple forms of protein synthesis-dependent synaptic plasticity and various forms of long-term memory (LTM), including associative threat memory. However, the approaches used thus far to target mTORC1 and its effectors, such as pharmacological inhibitors or genetic knockouts, lack fine spatial and temporal control. The development of a conditional and inducible eIF4E knockdown mouse line partially solved the issue of spatial control, but still lacked optimal temporal control to study memory consolidation. Here, we have designed a novel optogenetic tool (Opto4E-BP) for cell type-specific, light-dependent regulation of eIF4E in the brain. We show that light-activation of Opto4E-BP decreases protein synthesis in HEK cells and primary mouse neurons.In situ, light-activation of Opto4E-BP in excitatory neurons decreased protein synthesis in acute amygdala slices. Finally, light activation of Opto4E-BP in principal excitatory neurons in the lateral amygdala (LA) of mice after training blocked the consolidation of LTM. The development of this novel optogenetic tool to modulate eIF4E-dependent translation with spatiotemporal precision will permit future studies to unravel the complex relationship between protein synthesis and the consolidation of LTM.
Modular control of time and space during vertebrate axis segmentation
Authors: Seleit Ali , Brettell Ian , Fitzgerald Tomas , Vibe Carina , Loosli Felix , Wittbrodt Joachim , Naruse Kiyoshi , Birney Ewan , Aulehla Alexander 
Published: August 2023

AbstractHow temporal and spatial control of developmental processes are linked remains a fundamental question. Do underlying mechanisms form a single functional unit or are these dissociable modules?We address this question by studying the periodic process of embryonic axis segmentation, using genetic crosses of inbred medaka fish strains representing two species,Oryzias sakaizumiiandlatipes. Our analysis revealed correlated interspecies differences with regard to the timing of segmentation, the size of segments and of the presomitic mesoderm (PSM), from which segments are periodically formed. We then did interspecies crosses and real-time imaging quantifications, which revealed extensive phenotypic variation in ∼600 F2 embryos. Importantly, while the F2 analysis showed correlated changes of PSM and segment size, these spatial measures were not correlated to the timing of segmentation. This shows that the control of time and space of axis segmentation can, in principle, be decoupled. In line with this finding, we identified, usingdevelopmentalquantitative trait loci (devQTL) mapping, distinct chromosomal regions linked to either the control of segmentation timing or PSM size. We were able to validate thedevQTL findings using a CRISPR/Cas9 loss-of-function approach on several candidate genesin vivo.Combined, this study reveals that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules. Our findings emphasise the need to reveal the selective constraints linking these modules in the natural environment.
Activity of MukBEF for chromosome management in E. coli and its inhibition by MatP
Authors: Seba Mohammed , Boccard Frédéric , Duigou Stéphane 
Published: August 2023

AbstractStructural maintenance of chromosomes (SMC) complexes share conserved structures and serve a common role in maintaining chromosome architecture. In the bacteriumEscherichia coli, the SMC complex MukBEF is necessary for rapid growth and the accurate segregation and positioning of the chromosome, although the specific molecular mechanisms involved are still unknown. Here we used a number ofin vivoassays to reveal how MukBEF controls chromosome conformation and how the MatP/matSsystem prevents MukBEF activity. Our results indicate that the loading of MukBEF occurs preferentially on newly replicated DNA, at multiple loci on the chromosome where it can promote long-range contacts inciseven though MukBEF can promote long-range contacts in the absence of replication. Using HiC and ChIP-seq analyses in strains with rearranged chromosomes, the prevention of MukBEF activity increases with the number ofmatSsites and this effect likely results from the unloading of MukBEF by MatP. Altogether, our results reveal how MukBEF operates to control chromosome folding and segregation in E. coli.
Breaking the silence: exploring the challenges of oral participation faced by Chinese undergraduate students in a Sino-US university in China
Authors: Noman Mohammad , Xu Ruman 
Published: August 2023

PurposeThis study aimed to explore the underlying reasons for student silence in EMI classrooms and identify the coping strategies employed by students and teachers.Design/methodology/approachEmploying qualitative case study methods, in-depth semi-structured interviews and focus group discussions were conducted with both teachers and students. Thematic analysis was used for the findings.FindingsThematic analysis of the data revealed four primary reasons for student silence, and several effective coping strategies used by students and teachers to mitigate this challenge.Research limitations/implicationsThe findings provide a comprehensive understanding of the phenomenon of silence among Chinese undergraduate students in English as a medium of instruction classrooms and offer valuable insights to students and teachers to adapt and succeed in these challenging environments.Originality/valueThe originality of this study lies in the fact that this is among the few studies conducted on students from a foreign branch campus of an American university in China that explores the explores the phenomenon of silence of Chinese students in such universities.
Stratal movement and microseismic events induced by multi-well hydrofracturing under varying well spacings and initiation sequences
Authors: Wang Yongliang , Li Liangchun , Ju Yang 
Published: August 2023

PurposeMulti-well hydrofracturing is a key technology in engineering, and the evaluation, control and optimization of the fracturing network determine the recovery rate of unconventional oil and gas production. In engineering terms, altering well spacing and perforation initiation sequences changes fracture propagation behavior. Fracture propagation can result in fracture-to-fracture and well-to-well interactions. This may be attributed to the interference between fractures caused by squeezing of the reservoir strata. Meanwhile, the stratal movement caused by the propagation of the fractures may lead to either the secondary fracturing of wells with primary fractures or perforation to begin fracturing. Besides, the stratal compression and squeeze of multi-well hydrofracturing will cause earthquakes; the fracture size is different owing to the different fracturing scenarios, and the occurrence of induced microseismic events is still unknown; microseismic events also affect fracture orientation and deflection. If the mechanism of the above mechanical behavior cannot be clarified, optimizing the fracture network and reduce the induced microseismic disaster becomes difficult.Design/methodology/approachIn this study, combined finite element-discrete element models were used to simulate the multi-well hydrofracturing. Numerical cases compared the fracture network, dynamic stratal movement and microseismic events at 50, 75 and 100 m well spacings, respectively, and varying initiation sequence of multiple horizontal wells.FindingsFrom the results, fracture propagation in multi-well hydrofracturing may simulate the propagation and deflection of adjacent fractures and induce fracture-to-fracture and well-to-well interactions. As the well spacing increases, the effect of fracturing-induced stratal movement and squeezing deformation decrease. In alternate fracturing, starting from a well located in the middle can effectively reduce the influence of stratal movement on fracturing, and the fracturing scenario with cross-perforation can minimize the influence of stratal movement. The stratal movement between multiple wells is positively correlated to microseismic events, which behaviors can be effectively weakened by reducing the strata movement.Originality/valueThe fracture network, thermal-hydro-mechanical coupling, fracturing-induced stratal movement and microseismic events were analyzed. This study analyzed the intersection and propagation behavior of fractures in multi-well hydrofracturing, which can be used to evaluate and study the mechanism of hydrofracturing fracture network propagation in multiple horizontal wells and conduct fracture optimization research to form an optimized hydrofracturing scheme by reasonably arranging the spacing between wells and initiation sequences of perforation clusters.
Towards a complex push-to-pull dynamics in circular construction supply chains: a systematic literature review
Authors: Abadi Mohamed , Huang Jieling , Yeow Jillian , Mohandes Saeed Reza , Zhang Lihong 
Published: August 2023

PurposeThe development of circular construction supply chains (CCSCs) is impeded by various barriers, but the current literature overlooks the interrelationships among these barriers and the varying nature of associated countermeasures with the growth of circular economy (CE). This paper aims to develop new perspectives about the transition to CCSCs through the lens of supply-push (SP)/demand-pull (DP) strategies and related underpinning theories.Design/methodology/approachA systematic literature review including 136 journal articles was undertaken to identify barriers to CCSCs and associated countermeasures that are analysed for their relevance to SP/DP. The interplay between SP/DP approaches was discussed using the “technology acceptance” and “innovation chain” models.Findings(1) Thirty-five barriers were identified and organised into nine main barrier factors; (2) the predominant factors are knowledge and awareness, policy and regulations, technological capabilities, and incentives; (3) CCSCs transition is SP-configured primarily driven by actors above the project network; (4) “push” measures are devised to gradually create a “pull” environment and can be revoked when demand for circularity is created, suggesting a new “push-to-pull” perspective of CCSCs; and (5) a complex adaptative system is witnessed in relationships between barriers and countermeasures, and interactions among actors at all levels.Practical implicationsThe findings offer practitioners countermeasures to barriers encountered in CE initiatives. It also informs policymakers of adjusting policies to accommodate the SP-DP movement in steering the circular transition.Originality/valueThis study uses theoretical models to interpret the dynamics in CCSCs transition and proposes a new definition of CCSCs highlighting their complex and dual transitional/transformational nature.