bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolution of sequence divergence for repeat-mediated deletions shows a polarity that is mediated by MLH1
Authors: Trost Hannah , Merkell Arianna , Lopezcolorado Felicia Wednesday , Stark Jeremy M 
Published: January 2023

Abstract
Repeat-mediated deletions (RMDs) are a type of chromosomal rearrangement between two homologous sequences that causes loss of the sequence between the repeats, along with one of the repeats. Sequence divergence between repeats suppresses RMDs; the mechanisms of such suppression and of resolution of the sequence divergence remains poorly understood. We identified RMD regulators using a set of reporter assays in mouse cells that test two key parameters: repeat sequence divergence and the distances between one repeat and the initiating chromosomal break. We found that the mismatch repair factor MLH1 suppresses RMDs with sequence divergence in the same pathway as MSH2 and MSH6, and which is dependent on residues in MLH1 and its binding partner PMS2 that are important for nuclease activity. Additionally, we found that the resolution of sequence divergence in the RMD product has a specific polarity, where divergent bases that are proximal to the chromosomal break end are preferentially removed. Moreover, we found that the domain of MLH1 that forms part of the MLH1-PMS2 endonuclease is important for polarity of resolution of sequence divergence. We also identified distinctions between MLH1 versus TOP3α in regulation of RMDs. We suggest that MLH1 suppresses RMDs with sequence divergence, while also promoting directional resolution of sequence divergence in the RMD product.
The hnRNP C tetramer binds to CBC on mRNA and impedes PHAX recruitment for the classification of RNA polymerase II transcripts
Authors: Dantsuji Sayaka , Ohno Mutsuhito , Taniguchi Ichiro 
Published: January 2023

AbstractIn eukaryotic cells, various classes of RNAs are exported to the cytoplasm by class-specific factors. Accumulating evidence has shown that export factors affect the fate of RNA, demonstrating the importance of proper RNA classification upon export. We previously reported that RNA polymerase II transcripts were classified after synthesis depending on their length, and identified heterogeneous nuclear ribonucleoprotein (hnRNP) C as the key classification factor. HnRNP C inhibits the recruitment of PHAX, an adapter protein for spliceosomal U snRNA export, to long transcripts, navigating these RNAs to the mRNA export pathway. However, the mechanisms by which hnRNP C inhibits PHAX recruitment to mRNA remain unknown. We showed that the cap-binding complex, a bridging factor between m7G-capped RNA and PHAX, directly interacted with hnRNP C on mRNA. Additionally, we revealed that the tetramer-forming activity of hnRNP C and its strong RNA-binding activity were crucial for the inhibition of PHAX binding to longer RNAs. These results suggest that mRNA is wrapped around the hnRNP C tetramer without a gap from the cap, thereby impeding the recruitment of PHAX. The results obtained on the mode of length-specific RNA classification by the hnRNP C tetramer will provide mechanistic insights into hnRNP C-mediated RNA biogenesis.
Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomized clinical trials
Authors: Golzan S Amirhossein , Movahedian Mina , Haghighat Neda , Asbaghi Omid , Hekmatdoost Azita 
Published: January 2023

AbstractContextThe use of non-nutritive sweeteners (NNSs) is dramatically increasing in food commodities, and their effects on biochemical parameters have been the subject of great controversy. Liver enzymes as markers of liver injury may be helpful measures of non-alcoholic fatty liver disease (NAFLD), but the outcomes of randomized controlled trials (RCTs) suggest their associations with NNSs are contentious.ObjectiveThe current study was designed to provide a GRADE-assessed systematic review and meta-analysis of RCTs studying the consequences of NNS consumption on ALT, AST, and GGT concentrations (ie, the 3 main liver enzymes in adults).Data SourcesScopus, PubMed, and EMBASE were searched for relevant studies up to April 2021, with no time and language limitations.Data ExtractionTwo independent researchers extracted information from qualified studies, and a third researcher rechecked it.Data AnalysisOf 3212 studies, 10 studies that enrolled a total of 854 volunteers were included. A random-effects or fixed-effects model was utilized to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity between studies was evaluated using Cochran’s Q test and quantified using the I2 statistic. The pooled results demonstrated that, compared with control groups, NNS intake led to nonsignificant reductions in ALT (WMD: −.78, 95% CI: –2.14, .57, P = .25) and GGT (WMD: –.21, 95% CI: –1.46, 1.04, P = .74). Also, a small nonsignificant increasing effect on AST level was found (WMD: .02, 95% CI: –1.26, 1.30, P = .97). NNS significantly reduced AST levels in type 2 diabetes patients when subgroup analyses were performed. Also, in trials with ≥24-week intervention or studies that utilized stevioside for intervention, a significant reducing effect on ALT level was observed.ConclusionThe results of this study showed that NNS intake has no significant effect on liver enzyme levels in adults.Systematic Review RegistrationPROSPERO registration no. CRD42021250067.
Shade avoidance in the context of climate change
Authors: Casal Jorge J , Fankhauser Christian 
Published: January 2023

Abstract
When exposed to changes in the light environment caused by neighboring vegetation, shade-avoiding plants modify their growth and/or developmental patterns to access more sunlight. In Arabidopsis (Arabidopsis thaliana), neighbor cues reduce the activity of the photosensory receptors phytochrome B (phyB) and cryptochrome 1, releasing photoreceptor repression imposed on PHYTOCHROME INTERACTING FACTORs (PIFs) and leading to transcriptional reprogramming. The phyB-PIF hub is at the core of all shade-avoidance responses, whilst other photosensory receptors and transcription factors contribute in a context-specific manner. CONSTITUTIVELY PHOTOMORPHOGENIC1 is a master regulator of this hub, indirectly stabilizing PIFs and targeting negative regulators of shade avoidance for degradation. Warm temperatures reduce the activity of phyB, which operates as a temperature sensor and further increases the activities of PIF4 and PIF7 by independent temperature sensing mechanisms. The signaling network controlling shade avoidance is not buffered against climate change; rather, it integrates information about shade, temperature, salinity, drought, and likely flooding. We, therefore, predict that climate change will exacerbate shade-induced growth responses in some regions of the planet while limiting the growth potential in others.
The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods
Authors: Mauck Matthew C , Lotz Jeffrey , Psioda Matthew A , Carey Timothy S , Clauw Daniel J , Majumdar Sharmila , Marras William S , Vo Nam , Aylward Ayleen , Hoffmeyer Anna , Zheng Patricia , Ivanova Anastasia , McCumber Micah , Carson Christiane , Anstrom Kevin J , Bowden Anton E , Dalton Diane , Derr Leslie , Dufour Jonathan , Fields Aaron J , Fritz Julie , Hassett Afton L , Harte Steven E , Hue Trisha F , Krug Roland , Loggia Marco L , Mageswaran Prasath , McLean Samuel A , Mitchell Ulrike H , O’Neill Conor , Pedoia Valentina , Quirk David Adam , Rhon Daniel I , Rieke Viola , Shah Lubdha , Sowa Gwendolyn , Spiegel Brennan , Wasan Ajay D , Wey Hsiao-Ying (Monica) , LaVange Lisa 
Published: January 2023

Abstract
In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program’s goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.
SAFETY IMPROVEMENT OF THE RADIOACTIVE WASTE STORAGE FACILITY IN ALBANIA
Authors: Prifti Dritan , Tushe Kozeta , Bylyku Elida , Daci Brunilda 
Published: January 2023

Abstract
The Albanian National Radioactive Waste Storage Facility (NRWSF) constructed in 1999 consists of an interim waste storage facility for very low level waste, low level waste, intermediate level waste and disused sealed radioactive sources (DSRS) coming from research institutions, agriculture and industrial activities and from applications in nuclear medicine in Albania. The safety assessment of this facility is performed considering its impact to workers, public and environment. In 2018, Albania started a new National project Alb 9010 titled ‘Upgrading the Radioactive Waste Storage Building According to International Standards’. The two fundamental objectives are to ensure the protection of the public, workers and the environment and to ensure retrievability of waste packages for final disposal. The project focuses on ensuring the safety of the treatment, conditioning and storage of radioactive waste and DSRS. Under this project has been done the improvement of the safety of the RWSF and upgrading of the existing building infrastructure. In the end of the project the objective is to improve the safety of the personnel in the RWSF, protection of public and environment, Upgrade the Equipment’s used in the RW Management Activities, Upgrade the existing Infrastructure of the RWSF Building and also ensure retrievability of waste packages for final disposal.
Community Violence and the Stability of Marriages and Cohabitations in Mexico
Authors: Caudillo Mónica L , Lee Jaein 
Published: January 2023

AbstractThis study evaluates the link between local violence and the stability of women’s first co-residential unions in Mexico by exploiting the drastic increase in homicide rates caused by the Mexican War on Drugs in December 2006. We use event history analysis and individual union histories collected by a national survey in 2009 to assess whether increasing homicide rates in the previous 2 years relates to the dissolution of marital and cohabiting unions, and to transitions to marriage among cohabitors. Cox models show that a recent spike in violence is associated with a higher risk of dissolution for first coresidential unions among less educated women. Competing-risks Cox models further show that for first cohabiting unions among the less educated, exposure to increasing violence is not only associated with a higher risk of dissolution, but also with a higher risk of transitioning to marriage. In contrast, recent spikes in violence were not significantly associated with union transitions for more educated women. This suggests that increasing local violence may be pushing disadvantaged women in coresidential unions to accelerate significant transitions in their family trajectories, by either dissolving their relationships, or getting married to their cohabiting partner, which plausibly reflects underlying differences in union quality. By evaluating the link between local criminal violence and union stability, our findings contribute to understanding how disadvantaged families cope with disruptions to their social environments.
The role of visual association cortices during response selection processes in interference-modulated response stopping
Authors: Eggert Elena , Ghin Filippo , Stock Ann-Kathrin , Mückschel Moritz , Beste Christian 
Published: January 2023

AbstractResponse inhibition and the ability to navigate distracting information are both integral parts of cognitive control and are imperative to adaptive behavior in everyday life. Thus far, research has only inconclusively been able to draw inferences regarding the association between response stopping and the effects of interfering information. Using a novel combination of the Simon task and a stop signal task, the current study set out to investigate the behavioral as well as the neurophysiological underpinnings of the relationship between response stopping and interference processing. We tested n = 27 healthy individuals and combined temporal EEG signal decomposition with source localization methods to delineate the precise neurophysiological dynamics and functional neuroanatomical structures associated with conflict effects on response stopping. The results showed that stopping performance was compromised by conflicts. Importantly, these behavioral effects were reflected by specific aspects of information coded in the neurophysiological signal, indicating that conflict effects during response stopping are not mediated via purely perceptual processes. Rather, it is the processing of specific, stop-relevant stimulus features in the sensory regions during response selection, which underlies the emergence of conflict effects in response stopping. The findings connect research regarding response stopping with overarching theoretical frameworks of perception–action integration.
Estimating drug-induced liver injury risk by in vitro molecular initiation response and pharmacokinetic parameters for during early drug development
Authors: Nukaga Takumi , Takemura Akinori , Endo Yuka , Uesawa Yoshihiro , Ito Kousei 
Published: January 2023

AbstractDrug-induced liver injury (DILI) is a major factor influencing new drug withdrawal; therefore, an appropriate toxicity assessment at the preclinical stage is required. Previous in silico models have been established using compound information listed in large data sources, thereby limiting the DILI risk prediction for new drugs. Herein, we first constructed a model to predict DILI risk based on a molecular initiating event (MIE) predicted by quantitative structure–activity relationships, admetSAR parameters (e.g. cytochrome P450 reactivity, plasma protein binding, and water-solubility), and clinical information (maximum daily dose [MDD] and reactive metabolite [RM]) for 186 compounds. The accuracy of the models using MIE, MDD, RM, and admetSAR alone were 43.2%, 47.3%, 77.0%, and 68.9%, while the “predicted MIE + admetSAR + MDD + RM” model’s accuracy was 75.7%. The contribution of MIE to the overall prediction accuracy was little effect or rather worsening it. However, it was considered that MIE was a valuable parameter and that it contributed to detect high DILI risk compounds in the early development stage. We next examined the effect of stepwise changes in MDD on altering the DILI risk and estimating the maximum safety dose (MSD) for clinical use based on structural information, admetSAR, and MIE parameters because it is important to estimate the dose that could prevent the DILI onset in clinical conditions. Low-MSD compounds might increase the DILI risk, as these compounds were classified as “most-DILI concern” at low doses. In conclusion, MIE parameters were especially useful to check the DILI concern compounds and to prevent the underestimation of DILI risk in the early stage of drug development.
Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink
Authors: Porter Ashleigh F , Purcell Damian F J , Howden Benjamin P , Duchene Sebastian 
Published: January 2023

Abstract
To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir. Our findings suggest that the evolutionary rate of SARS-CoV-2 underwent an episodic increase upon introduction into the mink host before returning to the normal range observed in humans. Furthermore, SARS-CoV-2 lineages could have circulated in the mink population for a month before detection, and during this period, evolutionary rate estimates were between 3 × 10–3 and 1.05 × 10–2 (95 per cent HPD, with a mean rate of 6.59 × 10–3) a four- to thirteen-fold increase compared to that in humans. As there is evidence for unique mutational patterns within mink-associated lineages, we explored the emergence of four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, and Q314K. We found that mutation Y453F emerged early in multiple mink outbreaks and that mutations F486L and Q314K may co-occur. We suggest that SARS-CoV-2 undergoes a brief, but considerable, increase in evolutionary rate in response to greater selective pressures during species jumps, which may lead to the occurrence of mink-specific mutations. These findings emphasise the necessity of ongoing surveillance of zoonotic SARS-CoV-2 infections in the future.
Examining the influence of built environment on sleep disruption
Authors: Parks Jaclyn , Baghela Millie , Bhatti Parveen 
Published: January 2023

Background:
Modifying aspects of the built environment may be an effective strategy for population-level improvements to sleep. However, few comprehensive evaluations of built environment and sleep have been completed.

Methods:
We conducted a cross-sectional study among participants of the British Columbia Generations Project (BCGP) who self-reported sleep duration (n = 28,385). Geospatial measures of light-at-night (LAN), greenness, air pollution (PM2.5, NO2, SO2), and road proximity were linked to participant baseline residential postal codes. Logistic regression models, adjusted for age and sex, were used to estimate the association between these factors and self-reported sleep duration (<7 vs. ≥7 hours).

Results:
Interquartile range (IQR) increases in LAN intensity, greenness, and SO2 were associated with 1.04-fold increased (95% CI = 1.02, 1.07), 0.95-fold decreased (95% CI = 0.91, 0.98), and 1.07-fold increased (95% CI = 1.03, 1.11) odds, respectively, of reporting insufficient sleep (i.e., <7 hours per night). Living <100 m from a main roadway was associated with a 1.09-fold greater odds of insufficient sleep (95% CI = 1.02, 1.17). Results were unchanged when examining all factors together within a single regression model. In stratified analyses, associations with SO2 were stronger among those with lower reported annual household incomes and those living in more urban areas.

Conclusions:
BCGP’s rich data enabled a comprehensive evaluation of the built environment, revealing multiple factors as potentially modifiable determinants of sleep disruption. In addition to longitudinal evaluations, future studies should pay careful attention to the role of social disparities in sleep health.
The technological future of percutaneous nephrolithotomy: a Young Academic Urologists Endourology and Urolithiasis Working Group update
Authors: Hameed B.M. Zeeshan , Shah Milap , Pietropaolo Amelia , De Coninck Vincent , Naik Nithesh , Skolarikos Andreas , Somani Bhaskar K. 
Published: January 2023

Purpose of review
With advancements in surgical technology along with procedural techniques, this article throws light on the latest developments and applications of artificial intelligence (AI), extended reality, 3D (three-dimensional) printing and robotics in percutaneous nephrolithotomy (PCNL).

Recent findings
This review highlights the applications of AI in PCNL over the past 2 years. Mostly studies have been reported on development of machine learning (ML) based predicting models and identification of stone composition using deep learning convolutional neural network (DL-CNN). But owing to the complexity of the models and lack of generalizability, it is still not incorporated in the routine clinical practice. Extended reality based simulation and training models have enabled trainees to enhance their skills and shorten the learning curve. Similar advantages have been reported with the use of 3D printed models when used to train young and novice endourologists to improve their skills in percutaneous access (PCA). Applications of robotics in PCNL look promising but are still in nascent stages.

Summary
Future research on PCNL should focus more on generalizability and adaptability of technological advancements in terms of training and improvement of patient outcomes.
Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose
Authors: Kühn Tessa , Speer Claudius , Morath Christian , Bartenschlager Marie , Kim Heeyoung , Beimler Jörg , Buylaert Mirabel , Nusshag Christian , Kälble Florian , Reineke Marvin , Töllner Maximilian , Klein Katrin , Blank Antje , Parthé Sylvia , Schnitzler Paul , Zeier Martin , Süsal Caner , Bartenschlager Ralf , Tran Thuong Hien , Schaier Matthias , Benning Louise 
Published: January 2023

Background.
The impaired immune response to coronavirus disease 2019 (COVID-19) vaccination in kidney transplant recipients (KTRs) leads to an urgent need for adapted immunization strategies.

Methods.
Sixty-nine KTRs without seroconversion after ≥3 COVID-19 vaccinations were enrolled, and humoral response was determined after an additional full-dose mRNA-1273 vaccination by measuring severe acute respiratory syndrome coronavirus 2–specific antibodies and neutralizing antibody activity against the Delta and Omicron variants 1 and 3 mo postvaccination. T-cell response was analyzed 3 mo postvaccination by assessing interferon-γ release. Mycophenolic acid (MPA) was withdrawn in 41 KTRs 1 wk before until 4 wk after vaccination to evaluate effects on immunogenicity. Graft function, changes in donor-specific anti-HLA antibodies, and donor-derived cell-free DNA were monitored in KTRs undergoing MPA withdrawal.

Results.
Humoral response to vaccination was significantly stronger in KTRs undergoing MPA withdrawal 1 mo postvaccination; however, overall waning humoral immunity was noted in all KTRs 3 mo after vaccination. Higher anti-S1 immunoglobulin G levels correlated with better neutralizing antibody activity against the Delta and Omicron variants, whereas no significant association was detected between T-cell response and neutralizing antibody activity. No rejection occurred during study, and graft function remained stable in KTRs undergoing MPA withdrawal. In 22 KTRs with Omicron variant breakthrough infections, neutralizing antibody activity was better against severe acute respiratory syndrome coronavirus 2 wild-type and the Delta variants than against the Omicron variant.

Conclusions.
MPA withdrawal to improve vaccine responsiveness should be critically evaluated because withdrawing MPA may be associated with enhanced alloimmune response, and the initial effect of enhanced seroconversion rates in KTRs with MPA withdrawal disappears 3 mo after vaccination.