bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducible mismatch repair streamlines forward genetic approaches to target identification of cytotoxic small molecules
Authors: Nguyen Thu P , Fang Min , Kim Jiwoong , Wang Baiyun , Lin Elisa , Khivansara Vishal , Barrows Neha , Rivera-Cancel Giomar , Goralski Maria , Cervantes Christopher L , Xie Shanhai , Peterson Johann M , Povedano Juan Manuel , Antczak Monika I , Posner Bruce A , McFadden David G , Ready Joseph M , De Brabander Jef K , Nijhawan Deepak 
Published: February 2023

AbstractOrphan cytotoxins are small molecules for which the mechanism of action (MoA) is either unknown or ambiguous. Unveiling the mechanism of these compounds may lead to useful tools for biological investigation and in some cases, new therapeutic leads. In select cases, the DNA mismatch repair-deficient colorectal cancer cell line, HCT116, has been used as a tool in forward genetic screens to identify compound-resistant mutations, which have ultimately led to target identification. To expand the utility of this approach, we engineered cancer cell lines with inducible mismatch repair deficits, thus providing temporal control over mutagenesis. By screening for compound resistance phenotypes in cells with low or high rates of mutagenesis, we increased both the specificity and sensitivity of identifying resistance mutations. Using this inducible mutagenesis system, we implicate targets for multiple orphan cytotoxins, including a natural product and compounds emerging from a high-throughput screen, thus providing a robust tool for future MoA studies.
Neural responses to repeated noise structure in sounds are invariant to temporal interruptions
Authors: Herrmann Björn 
Published: February 2023

AbstractThe ability to extract meaning from acoustic environments requires sensitivity to repeating sound structure. Yet, how events that repeat are encoded and maintained in the brain and how the brain responds to events that reoccur at later points in time is not well understood. In two electroencephalography experiments, participants listened to a longer, ongoing white-noise sound which comprised shorter, frozen noise snippets that repeated at a regular 2-Hz rate. In several conditions, the snippet repetition discontinued for a brief period after which the noise snippet reoccurred. The experiments aimed to answer whether neural activity becomes entrained by the regular repetition of noise snippets, whether entrained neural activity self-sustains during the discontinuation period, and how the brain responds to a reoccurring noise snippet. Results show that neural activity is entrained by the snippet repetition, but there was no evidence for self-sustained neural activity during the discontinuation period. However, auditory cortex responded with similar magnitude to a noise snippet reoccurring after a brief discontinuation as it responded to a noise snippet for which the snippet repetition had not been discontinued. This response invariance was observed for different onset times of the reoccurring noise snippet relative to the previously established regularity. The results thus demonstrate that the auditory cortex sensitively responds to, and thus maintains a memory trace of, previously learned acoustic noise independent of temporal interruptions.
High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice
Authors: Southwell Nneka , Manzo Onorina , Zhao Dazhi , Sayles Nicole M. , Dash Jalia , Fujita Keigo , D’Aurelio Marilena , Di Lorenzo Annarita , Manfredi Giovanni , Kawamata Hibiki 
Published: February 2023

AbstractMutations inCHCHD10, a mitochondrial protein with undefined functions, are associated with autosomal dominant mitochondrial diseases.Chchd10knock-in mice harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L) develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts, mtISR is accompanied by a metabolic rewiring characterized by increased reliance on glycolysis rather than fatty acid oxidation. To counteract this metabolic rewiring, heterozygous S55L mice were subjected to chronic high fat diet (HFD) to decrease insulin sensitivity and glucose uptake and enhance fatty acid utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant hearts and significantly extended the survival of mutant female mice affected by severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that HFD increased fatty acid utilization and ameliorated cardiomyopathy markers. Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L heart, suggesting activation of quality control mechanisms. Overall, our findings indicate that metabolic therapy can be effective in mitochondrial cardiomyopathies associated with proteotoxic stress.
Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
Authors: Singh Pragyan , Gazy Inbal , Kupiec Martin 
Published: February 2023

ABSTRACTTelomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeastSaccharomyces cerevisiaerevealed that mutations in any of ∼500 genes affects telomere length. One of the genes that, when mutated, causes telomere elongation isELG1, which encodes an unloader of PCNA, the processivity factor for replicative DNA polymerases. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes. We report that SUMOylated PCNA acts as a signal that positively regulates telomerase activity. We also uncovered physical interactions between Elg1 and the CST (Cdc13-Stn1-Ten) complex, and dissected the mechanism by which Elg1 and Stn1 negatively regulates telomere elongation, coordinated by SUMO. We present a model that provides mechanistic insights on how chromosomal replication and telomere elongation are coordinated.
Adaptation of the e-servicescape model to the online exhibition industry
Authors: Leung Wing Ki , Ho Grace , Leung Rosanna 
Published: February 2023

Purpose
The servicescape model has been widely adapted in various service industries, but this model may not be applicable if the exhibition is transformed from physical to online. Moreover, there is only a handful of research on online exhibitions; studies focusing on visitor behaviors from various types of online exhibitions and the differences between genders are still lacking. This study aims to examine the different variables in the e-servicescape model and discuss how e-servicescape affects visitor behavior based on the exhibition types and gender differences.

Design/methodology/approach
The e-servicescape model is adapted in this study. Qualitative interviews were conducted prior to a quantitative online survey to examine by regression analysis the relationships among the dimensions in e-servicescape and how it affects visitor subsequent behavior. Data analyses are based on the differences between exhibition types and gender differences in response to the three environmental dimensions, namely, aesthetic appeal, layout and functionality, and security concern.

Findings
The findings show that visitors pay more attention to artistic enjoyment in art-related exhibitions and focus on informative issues in other types of exhibitions. “Aesthetic appeal” and “layout and functionality” are important to both genders, but little concern is shown to computer security issues. Female visitors are concerned with aesthetic design and male visitors stress layout and functionality elements. In terms of the security concerns, females have no concern about cookies function, while males have no concern on leaving search history on the website.

Originality/value
There is no previous relevant research on the relationships and influence between e-servicescape and online exhibition; this study focuses on the application of e-servicescape to the online exhibition industry and helps fill this research gap.
Measuring research efficiency and its determining factors for Indonesian R&D institutions: does scientific publication make a difference?
Authors: Afriana Finik Mutia , Khoirunurrofik Khoirunurrofik 
Published: February 2023

Purpose
The outcomes of public research institutions (PRIs), also known as research and development (R&D) institutions, in developing countries, including Indonesia, are still dubious. This study aims to measure the efficiency of R&D institutions using the case of the Indonesian Institute of Sciences, with and without an assessment of the role of scientific publication.

Design/methodology/approach
A panel data envelopment analysis (DEA) model is used to estimate the research efficiency of Indonesian R&D institutions during the period 2016–2019 based on the relationship between intellectual property (IP), research budgets and number of active researchers. The Tobit model is subsequently applied to analyze the factors that affect efficiency.

Findings
The DEA analysis shows an average efficiency value of 0.361, implying that 42% of the decision-making units (DMUs) have above-average efficiency scores. When scientific publication is added as an output variable, the efficiency increases to an average of 0.545, resulting in 53% of the DMUs with above-average efficiency.

Research limitations/implications
The main implication is that scientific publications can increase the output of R&D institutions in Indonesia. This study recommends strengthening the research group establishment led by research professors along with setting acceptable high output targets. Researcher competence must be improved together with support for research collaboration among the different fields of science. Scientific publications should be considered part of IP measurement along with the type of mandate of each PRI.

Practical implications
This study offers a method of evaluation of research efficiency that can be applied to institutions outside Indonesia, thus furthering the dialogue on science and technology policy management.

Originality/value
This paper contributes to the literature by using a new and comprehensive method to measure research output – that of IP measurement, including new scientific publication. The implications provide action points for the governments to support R&D institutions and for research practitioners to augment research output.
Decoupling pioneering traits from latitudinal patterns in a north American bird experiencing a southward range shift
Authors: Siefferman Lynn , Bentz Alexandra B. , Rosvall Kimberly A. 
Published: February 2023

Abstract

Ecogeographic rules describe spatial patterns in biological trait variation and shed light on the drivers of such variation. In animals, a consensus is emerging that ‘pioneering’ traits may facilitate range shifts via a set of bold, aggressive and stress‐resilient traits. Many of these same traits are associated with more northern latitudes, and most range shifts in the northern hemisphere indicate northward movement. As a consequence, it is unclear whether pioneering traits are simply corollaries of existing latitudinal variation, or whether they override other well‐trodden latitudinal patterning as a unique ecogeographic rule of phenotypic variation.

The tree swallow Tachycineta bicolor is a songbird undergoing a southward range shift in the eastern United States, in direct opposition of the poleward movement seen in most other native species' range shifts. Because this organic range shift countervails the typical direction of movement, this case study provides for unique ecological insights on organisms and their ability to thrive in our changing world.

We sampled female birds across seven populations, quantifying behavioural, physiological and morphological traits. We also used GIS and field data to quantify a core set of ecological factors with strong ties to these traits as well as female performance.

Females at more southern expansion sites displayed higher maternal aggression, higher baseline corticosterone and more pronounced elevation of corticosterone following a standardized stressor, contrary to otherwise largely conserved latitudinal patterning in these traits. Microhabitat variation explained some quantitative phenotypic variation, but the expansion and historic ranges did not differ in openness, distance to water or breeding density.

This countervailing range shift therefore suggests that pioneering traits are not simply corollaries of existing latitudinal variation, but rather, they may override other well‐trodden latitudinal patterning as a unique ecogeographic rule of phenotypic variation.
New‐onset retroperitoneal fibrosis following COVID‐19 mRNA vaccination: Coincidental or vaccine‐induced phenomenon?
Authors: Ture Hirut Yadeta , Kim Na Ri , Nam Eon Jeong 
Published: February 2023

AbstractThe Pfizer‐BioNTech mRNA vaccine is a US Food and Drug Administration‐approved coronavirus disease 2019 (COVID‐19) vaccine. Although it is reported to be safe and effective, immune dysregulation leading to autoimmunity has become an area of concern. Retroperitoneal fibrosis (RPF) is an immune‐mediated fibroinflammatory disease characterized by the deposition of fibrous tissues, primarily around the abdominal aorta and iliac arteries. Herein, we report a case of RPF following Pfizer BioNTech COVID‐19 mRNA vaccination. To the best of our knowledge, there have been no published reports on RPF after COVID‐19 mRNA vaccination. A 58‐year‐old woman with no history of autoimmune diseases presented with acute onset of epigastric pain 5 weeks after the second dose of the Pfizer‐BioNTech vaccine. She had been diagnosed with stage I breast cancer 9 years ago and was in complete remission on admission. Abdominal computed tomography showed preaortic soft‐tissue infiltration around the origin of the superior mesenteric artery but no evidence of breast cancer recurrence. Considering the temporal relationship between current symptoms and vaccination and the absence of other possible causes, she was diagnosed with RPF secondary to Pfizer‐BioNTech vaccine‐induced autoimmunity. This case may raise awareness of the possibility of RPF development following COVID‐19 mRNA vaccination.
Racial differences in clinical characteristics and readmission burden among patients with a left ventricular‐assist device
Authors: Sherazi Saadia , Alexis Jeffrey D. , McNitt Scott , Polonsky Bronislava , Shah Suhaib , Younis Arwa , Kutyifa Valentina , Vidula Himabindu , Gosev Igor , Goldenberg Ilan 
Published: February 2023

AbstractBackgroundThere are limited data regarding racial disparities in outcomes after left ventricular assist device (LVAD) implantation. The purpose of this study was to compare clinical characteristics and the burden of readmissions by race among patients with LVAD.MethodsThe study population included 461 patients implanted with LVADs at the University of Rochester Medical Center, NY from May 2008 to March 2020. Patients were stratified by race as White patients (N = 396 [86%]) and Black patients (N = 65 [14%]). The Anderson‐Gill recurrent regression analysis was used to assess the independent association between race and the total number of admissions after LVAD implant during an average follow‐up of 2.45 ± 2.30 years.ResultsBlack patients displayed significant differences in baseline clinical characteristics compared to White patients, including a younger age, a lower frequency of ischemic etiology, and a higher baseline serum creatinine. Black patients had a significantly higher burden of readmissions after LVAD implantation as compared with White patients 10 versus 7 (average number of hospitalizations per patient at 5 years of follow‐up, respectively) translated into a significant 39% increased risk of recurrent readmissions after multivariate adjustment (Hazard ratio 1.39, 95% CI; 1.07–1.82, p 0.013).ConclusionBlack LVAD patients experience an increased burden of readmissions compared with White patients, after adjustment for baseline differences in demographics and clinical characteristics. Future studies should assess the underlying mechanisms for this increased risk including the effect of social determinants of health on the risk of readmissions in LVAD recipients.
Editorial: real‐world evidence of tofacitinib and vedolizumab in ulcerative colitis—are we one step closer to better positioning therapies after anti‐TNF failure?
Authors: Ernest‐Suarez Kenneth , Lu Cathy 
Published: February 2023

LINKED CONTENTThis article is linked to Buisson et al papers. To view these articles, visit https://doi.org/10.1111/apt.17305 and https://doi.org/10.1111/apt.17405
Trends in risk factor control and treatment among patients with non‐alcoholic fatty liver disease and type 2 diabetes between 2000 and 2020: A territory‐wide study
Authors: Zhang Xinrong , Yip Terry Cheuk‐Fung , Tse Yee‐Kit , Hui Vicki Wing‐Ki , Li Guanlin , Lin Huapeng , Liang Lilian Yan , Lai Jimmy Che‐To , Lai Mandy Sze‐Man , Cheung Johnny T. K. , Chan Henry Lik‐Yuen , Chan Stephen Lam , Kong Alice Pik‐Shan , Wong Grace Lai‐Hung , Wong Vincent Wai‐Sun 
Published: February 2023

SummaryBackground & AimsWe aimed to determine the trends in risk factor control and treatment among patients with non‐alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000–2020.MethodsWe conducted a territory‐wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti‐diabetic agents, laboratory tests and/or diagnosis codes.ResultsThis study included 16,084 patients with NAFLD and T2D (mean age, 54.8 ± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c) targets increased from 44.5% (95% confidence interval [CI], 42.9–46.1) to 64.8% (95% CI, 64.1–65.5), and percentage of patients achieving individualised low‐density lipoprotein‐cholesterol (LDL‐C) targets increased from 23.3% (95% CI, 21.9–24.7) to 54.3% (95% CI, 53.5–55.1) from 2000–2005 to 2016–2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1–57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL‐C targets, but they were more likely to achieve individualised HbA1c targets than non‐cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18–44 years) were less likely to achieve individualised HbA1c targets than middle‐aged (45–64 years) and older ones (≥65 years).ConclusionsFrom 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D.
Opioid research in the time of the opioid crisis
Authors: Traynor John R. , Moron Jose A. 
Published: February 2023

LINKED ARTICLESThis article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Design, synthesis, in vitro evaluation, and molecular modeling studies of N‐substituted benzomorphans, analogs of LP2, as novel MOR ligands
Authors: Costanzo Giuliana , Patamia Vincenzo , Turnaturi Rita , Parenti Carmela , Zagni Chiara , Lombino Jessica , Amata Emanuele , Marrazzo Agostino , Pasquinucci Lorella , Rescifina Antonio 
Published: February 2023

Abstract6,7‐Benzomorphans have been investigated in medicinal chemistry for developing new drugs. This nucleus could be considered a versatile scaffold. The physicochemical properties of benzomorphan N‐substituent are crucial in achieving a definite pharmacological profile at opioid receptors. Thus, the dual‐target MOR/DOR ligands LP1 and LP2 were obtained through N‐substituent modifications. Specifically, LP2, bearing as N‐substituent the (2R/S)‐2‐methoxy‐2‐ phenylethyl group, is a dual‐target MOR/DOR agonist and is successful in animal models of inflammatory and neuropathic pain. To obtain new opioid ligands, we focused on the design and synthesis of LP2 analogs. First, the 2‐methoxyl group of LP2 was replaced by an ester or acid functional group. Then, spacers of different lengths were introduced at N‐substituent. In‐vitro, their affinity profile versus opioid receptors has been performed through competition binding assays. Molecular modeling studies were conducted to deeply analyze the binding mode and the interactions between the new ligands and all opioid receptors.
Generating inclusive services for children, youth and families: A shift to using complex systems theory
Authors: Lee Jo Ann , Wolf‐Branigin Michael 
Published: February 2023

AbstractService systems for children and families have been shaped by standard approaches to knowledge‐building, which reflect a reductionist approach and assume linearity and/or that individuals and experiences are normally distributed. Yet, these approaches may be inadequate for clients most at‐risk, especially those who would be analytic ‘outliers’. A complexity lens focuses on the whole system and seeks to identify patterns, including the dynamic interactions between components of the system. Social work scholars have begun to apply complexity theory to social work research efforts, demonstrating the conceptual potential of incorporating this theoretical approach into social work theories and models such as the person‐in‐environment framework and the ecosystems perspective. Yet, frameworks informed by complexity theory may require ontological and epistemological shifts in thinking and new methodological approaches in order to fully embody a complexity approach. Complexity theory offers the opportunity to consider social work clients who are most at‐risk, as it is better suited for power law distributions. We can, therefore, reconceptualize the most ‘at‐risk’ clients as being in a state of transition, which is also the space of most creativity and possibility.