bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the SNARE protein Ykt6 function by diprenylation and phosphorylation
Authors: Rikitake Yoshiyuki 
Published: September 2022

Abstract
For proper intracellular vesicle transport, it is essential for transport vesicle membranes to fuse with the appropriate target membranes. Ykt6 is a SNARE protein with functions in diverse vesicle transport pathways, including secretory, endocytotic and autophagic pathways. To exert these functions, the association of Ykt6 with vesicle membranes and the change of its conformation from closed to open play key roles. Recent studies have revealed regulatory mechanisms involved in Ykt6 membrane association and conformation change. When in the cytosol, the vicinal cysteine residues within the C-terminal CCAIM sequence of Ykt6 undergo diprenylation (farnesylation of the distal cysteine residues by farnesyltransferase; this is followed by geranylgeranylation of the proximal cysteine residue by geranylgeranyltransferase-III). Phosphorylation of a serine residue within the SNARE domain triggers the conversion of the Ykt6 conformation from closed to open, allowing Ykt6 membrane association. In this commentary, I briefly summarize and discuss the recently revealed regulatory mechanisms of Ykt6 function by diprenylation and phosphorylation.
Crystal structure of the sliding DNA clamp from the Gram-positive anaerobic bacterium Clostridioides difficile
Authors: Hishiki Asami , Okazaki Sumire , Hara Kodai , Hashimoto Hiroshi 
Published: September 2022

Abstract
The sliding DNA clamp is a ring-shaped protein that encircles DNA within its central channel. It binds to multiple proteins, such as DNA polymerases and DNA repair enzymes, and stimulates their enzymatic activities, thereby playing a crucial role in cell survival and proliferation. Accordingly, the bacterial clamp DnaN is considered to be a promising target for bacterial infection therapy. In this regard, 3D structures of DnaN from pathogenic bacteria are essential for the development of chemical compounds with antimicrobial activity. Here, the crystal structure of DnaN from a Gram-positive bacterium Clostridioides difficile, a human pathogen causing infectious diarrhoea, has been determined at 2.13 Å resolution. A comparison of the structures of DnaN from other bacteria indicates that the structural features of DnaN in terms of overall organization are essentially conserved within Gram-positive and Gram-negative bacteria. However, DnaN from C. difficile has structural differences in the potential binding pocket for partner proteins, implying a non-conventional interaction with its binding partners. Our findings will provide insight into the development of new therapies for C. difficile infection.
The Contribution of Urgenda to the Mitigation of Climate Change
Authors: Mayer Benoit 
Published: September 2022

Abstract
Dutch courts in Urgenda ordered the government of the Netherlands to reduce national greenhouse gas emissions by 25% by 2020, compared with 1990. The case has been presented as a remarkable judicial victory of climate action advocates. With hindsight, this article questions the case’s contribution to the mitigation of climate change. If the Urgenda target has been met, this had little to do with the few measures that the government took too late and too hurriedly to achieve genuine mitigation outcomes. Rather, these measures likely caused a slight increase in global long-term emissions. And while the case has raised awareness, there is no reason to assume that it has translated into momentum for climate action more than it has hindered new policy developments. This case study sheds light on practical limitations of court-imposed climate targets that may justify the greater restraint that other courts have exercised in comparable cases.
Some results on relation algebra reducts: Residuated and semilattice-ordered semigroups
Authors: Rogozin Daniel 
Published: September 2022

Abstract
In this paper, we show that the class of representable residuated semigroups has the finite representation property. That is, every finite representable residuated semigroup is representable over a finite base. This result gives a positive solution to Hirsch and Hodkinson (2002, Relation Algebras by Games). The finite representation property for residuated semigroups also implies that the Lambek calculus has the finite model property with respect to relational models, the so-called $R$-models. We also show that the class of representable join semilattice-ordered semigroups is pseudo-universal and it has a recursively enumerable axiomatization. For this purpose, we introduce representability games for join semilattice-ordered semigroups.
A CLAVATA3-like Gene Acts as a Gynoecium Suppression Function in White Campion
Authors: Kazama Yusuke , Kitoh Moe , Kobayashi Taiki , Ishii Kotaro , Krasovec Marc , Yasui Yasuo , Abe Tomoko , Kawano Shigeyuki , Filatov Dmitry A 
Published: September 2022

Abstract
How do separate sexes originate and evolve? Plants provide many opportunities to address this question as they have diverse mating systems and separate sexes (dioecy) that evolved many times independently. The classic “two-factor” model for evolution of separate sexes proposes that males and females can evolve from hermaphrodites via the spread of male and female sterility mutations that turn hermaphrodites into females and males, respectively. This widely accepted model was inspired by early genetic work in dioecious white campion (Silene latifolia) that revealed the presence of two sex-determining factors on the Y-chromosome, though the actual genes remained unknown. Here, we report identification and functional analysis of the putative sex-determining gene in S. latifolia, corresponding to the gynoecium suppression factor (GSF). We demonstrate that GSF likely corresponds to a Y-linked CLV3-like gene that is specifically expressed in early male flower buds and encodes the protein that suppresses gynoecium development in S. latifolia. Interestingly, GSFY has a dysfunctional X-linked homolog (GSFX) and their synonymous divergence (dS = 17.9%) is consistent with the age of sex chromosomes in this species. We propose that female development in S. latifolia is controlled via the WUSCHEL-CLAVATA feedback loop, with the X-linked WUSCHEL-like and Y-linked CLV3-like genes, respectively. Evolution of dioecy in the S. latifolia ancestor likely involved inclusion of ancestral GSFY into the nonrecombining region on the nascent Y-chromosome and GSFX loss of function, which resulted in disbalance of the WUSCHEL-CLAVATA feedback loop between the sexes and ensured gynoecium suppression in males.
CohesinDB: a comprehensive database for decoding cohesin-related epigenomes, 3D genomes and transcriptomes in human cells
Authors: Wang Jiankang , Nakato Ryuichiro 
Published: September 2022

Abstract
Cohesin is a multifunctional protein responsible for transcriptional regulation and chromatin organization. Cohesin binds to chromatin at tens of thousands of distinct sites in a conserved or tissue-specific manner, whereas the function of cohesin varies greatly depending on the epigenetic properties of specific chromatin loci. Cohesin also extensively mediates cis-regulatory modules (CRMs) and chromatin loops. Even though next-generation sequencing technologies have provided a wealth of information on different aspects of cohesin, the integration and exploration of the resultant massive cohesin datasets are not straightforward. Here, we present CohesinDB (https://cohesindb.iqb.u-tokyo.ac.jp), a comprehensive multiomics cohesin database in human cells. CohesinDB includes 2043 epigenomics, transcriptomics and 3D genomics datasets from 530 studies involving 176 cell types. By integrating these large-scale data, CohesinDB summarizes three types of ‘cohesin objects’: 751 590 cohesin binding sites, 957 868 cohesin-related chromatin loops and 2 229 500 cohesin-related CRMs. Each cohesin object is annotated with locus, cell type, classification, function, 3D genomics and cis-regulatory information. CohesinDB features a user-friendly interface for browsing, searching, analyzing, visualizing and downloading the desired information. CohesinDB contributes a valuable resource for all researchers studying cohesin, epigenomics, transcriptional regulation and chromatin organization.
Serum testosterone concentrations and outcomes in hemodialysis patients enrolled in the EVOLVE trial
Authors: Nilsson Erik , Stenvinkel Peter , Liu Sai , Stedman Margaret R , Chertow Glenn M , Floege Jürgen 
Published: September 2022

ABSTRACT

Background
Hypogonadism is common in end-stage kidney disease and may contribute to morbidity and mortality.

Methods
Using data from the randomized controlled Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial of cinacalcet, we analyzed the associations of total testosterone, free testosterone and sex hormone–binding globulin (SHBG) serum concentrations with mortality and major cardiovascular events in 1692 men and 1059 women receiving hemodialysis. We also describe the effect of cinacalcet treatment on serum concentrations of testosterone.

Results
Among men, lower serum free testosterone [odds ratio (OR) 0.18, 95% confidence interval (CI) 0.04–0.82, P = .026] and higher SHBG (OR 1.05 per 10 nmol/L, 95% CI 1.01–1.10, P = .012), but not total testosterone, were associated with higher risk of death or cardiovascular event. Only SHBG was associated with all-cause mortality (OR 1.07 per 10 nmol/L, 95% CI 1.02–1.12, P = .0073). Among women, neither total nor free testosterone, nor SHBG were associated with outcomes. We found no statistically significant effect of cinacalcet treatment on SHBG, free or total testosterone.

Conclusions
Lower free testosterone and higher SHBG in serum are associated with higher risk of death or cardiovascular event in men undergoing chronic hemodialysis.
TP53 Alterations Are Associated With Poor Survival in Patients With Primary Mediastinal Nonseminoma Germ Cell Tumors
Authors: Bacon Jack V W , Giannatempo Patrizia , Cataldo Giovanna , Fazli Ladan , Saxena Neetu , Ozgun Guliz , Soleimani Maryam , Chi Kim , Nichols Craig , Necchi Andrea , Wyatt Alexander W , Kollmannsberger Christian K , Nappi Lucia 
Published: September 2022

Abstract

Background
Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes.

Methods
DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods.

Results
Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012).

Conclusions
TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients.
Functional metabolite reserves and lipid homeostasis revealed by the MA-10 Leydig cell metabolome
Authors: Koganti Prasanthi P , Tu Lan N , Selvaraj Vimal 
Published: September 2022

Abstract
In Leydig cells, intrinsic factors that determine cellular steroidogenic efficiency is of functional interest to decipher and monitor pathophysiology in many contexts. Nevertheless, beyond basic regulation of cholesterol storage and mobilization, systems biology interpretation of the metabolite networks in steroidogenic function is deficient. To reconstruct and describe the different molecular systems regulating steroidogenesis, we profiled the metabolites in resting MA-10 Leydig cells. Our results identified 283-annotated components (82 neutral lipids, 154 membrane lipids, and 47 other metabolites). Neutral lipids were represented by an abundance of triacyglycerols (97.1%), and low levels of cholesterol esters (2.0%). Membrane lipids were represented by an abundance of glycerophospholipids (77.8%), followed by sphingolipids (22.2%). Acylcarnitines, nucleosides, amino acids and their derivatives were the other metabolite classes identified. Among nonlipid metabolites, we recognized substantial reserves of aspartic acid, choline, creatine, betaine, glutamine, homoserine, isoleucine, and pantothenic acid none of which have been previously considered as a requirement in steroidogenic function. Individually limiting use of betaine, choline, or pantothenic acid, during luteinizing hormone-induced steroidogenesis in MA-10 cells resulted in substantial decreases to acute steroidogenic capacity, explained by intermediary metabolite imbalances affecting homeostasis. As such, our dataset represents the current level of baseline characterization and unravels the functional resting state of steroidogenic MA-10 Leydig cells. In identifying metabolite stockpiles and causal mechanisms, these results serve to further comprehend the cellular setup and regulation of steroid biosynthesis.
Fiction And Content in Hume’s Labyrinth
Authors: Ehli Bridger 
Published: September 2022

Abstract
In the ‘Appendix’ to the Treatise, Hume claims that he has discovered a ‘very considerable’ mistake in his earlier discussion of the self. Hume's expression of the problem is notoriously opaque, leading to a vast scholarly debate as to exactly what problem he identified in his earlier account of the self. I propose a new solution to this interpretive puzzle. I argue that a tension generated by Hume's conceptual scepticism about real ‘principles of union’ and his account of fictions of the imagination is the defect identified in the ‘Appendix’.
Association of sleep with cognitive function during retirement transition: the Whitehall II study
Authors: Teräs Tea , Rovio Suvi , Pentti Jaana , Head Jenny , Kivimäki Mika , Stenholm Sari 
Published: September 2022

AbstractStudy ObjectivesSleep duration and difficulties have been shown to associate with cognitive function. This study examined how changes in sleep and in cognitive function are associated during retirement transition.MethodsThe study population consisted of 2980 Whitehall II study participants, who retired during the follow-up, whose sleep was queried, and cognitive function measured (inductive reasoning and verbal memory) before and after retirement (follow-up 16 years). Using the last information on sleep before and the first after retirement, participants were categorized into constantly without (59%), increasing (13%), decreasing (11%), and constantly with (18%) sleep difficulties; and constantly short (26%), increasing (19%), decreasing (8.5%), and constantly mid-range (47%) sleep duration. Change in cognitive function during retirement transition was examined by sleep change groups using linear regression analyses with generalized estimating equations.ResultsMore pronounced decline in inductive reasoning during retirement transition was observed among participants with increasing sleep difficulties (−1.96, 95% CI −2.52 to −1.41) compared to those constantly without sleep difficulties (−1.25, 95% CI −1.52 to −0.98) and constantly with sleep difficulties (−1.26, 95% CI −1.75 to −0.92). Decreasing sleep difficulties (−0.64, 95% CI −0.86 to −0.43) were associated with a more pronounced decline in verbal memory when compared to constantly without sleep difficulties (−0.42, 95% CI −0.52 to −0.32) in post-retirement period. No statistically significant differences across sleep duration groups in cognitive function were observed.ConclusionsIncreasing and decreasing sleep difficulties may be associated with accelerated decline in cognitive function during retirement transition and post-retirement.
Incrementing and clarifying the diversity and early evolution of termites (Blattodea: Isoptera)
Authors: Jouault Corentin , Engel Michael S , Legendre Frédéric , Huang Diying , Grandcolas Philippe , Nel André 
Published: September 2022

Abstract
The past diversity of Isoptera is relatively poorly documented. Many early-diverging families are only represented today by relicts of their Mesozoic and Cenozoic richness. Therefore, the onset of their evolutionary history and the transitions between families, or even between subsocial and eusocial ways of life, remain difficult to decipher and require additional fossil occurrences. Here, we report the oldest worker/pseudergate trapped in amber and a new Mastotermitidae, both from Hkamti amber. We document a diverse assemblage of species representing early-diverging families from the ‘Mid’-Cretaceous of Myanmar, including two new genera and four new species in as many different genera: Anisotermes bourguignoni sp. nov., Longitermes pulcher gen. et sp. nov., Magnifitermes krishnai gen. et sp. nov. and Mastotermes myanmarensis sp. nov. These descriptions provide significant morphological evidence to discuss the placement of the genus Anisotermes, confidently place the new genera and confirm the monophyly of Mastotermitidae. The diversity of Cretaceous isopterans, in light of the biology of their extant representatives, is used to discuss palaeoecological implications and highlights the radiation of early diverged Isoptera in the complex Cretaceous ecosystem. The validity of the species Meiatermes cretacicus is discussed.
Improving hepatitis C screening and access to treatment
Authors: Alberts Ryan , Zimmermann AnnMarie , Martinez Anthony 
Published: September 2022

ABSTRACT
The rising prevalence of opioid use disorder and injection drug use has resulted in an increasing incidence of chronic hepatitis C virus (HCV) infection. Although older adults historically have represented the bulk of HCV infections in the United States, demographics have shifted and most new infections are presenting in younger patients. As a result, screening guidelines for HCV have evolved, moving toward a near-universal screening paradigm. Rates of screening and linkage to care remain low, attributed to the fact that underserved populations are disproportionately affected and often have limited access to specialty care. Collaborative models to treat HCV using primary care providers have been proposed to facilitate linkage to care and reduce transmission.
Albuterol
Authors: Pitonzo David G. 
Published: September 2022

ABSTRACT
Albuterol has been a cornerstone of asthma treatment for several decades, but evidence suggests that it may be overused at the expense of more efficacious treatment. Albuterol may not even be appropriate for sole first-line rescue medication in some patients. Inflammatory mechanisms have been shown to play a role early in the course of developing bronchospasm, suggesting that inhaled corticosteroids should be included as part of initial rescue treatment. Newer biologics target inflammatory cytokine pathways, which may be needed in patients with moderate to severe disease. Evidence-based recommendations for the management of asthma and bronchospasm are continuing to evolve.
Early diagnosis in polycystic ovary syndrome
Authors: Blanco Christy E. 
Published: September 2022

Abstract:
NPs are in an ideal position to educate patients on the lifelong implications of polycystic ovary syndrome (PCOS). A timely diagnosis and comprehensive plan are needed to appropriately manage patients with PCOS. This article highlights diagnostic criteria, common comorbid conditions, psychological impacts of the clinical manifestations, management approaches, and implications for NPs.
Immunodeficient patient experience of emergency switch from intravenous to rapid push subcutaneous immunoglobulin replacement therapy during coronavirus disease 2019 shielding
Authors: Morgan Clare , Jolles Stephen , Ponsford Mark J. , Evans Kimberly , Carne Emily 
Published: September 2022

Purpose of review
Welsh immunodeficient patients on immunoglobulin replacement therapy (IgRT) who were considered high risk for severe coronavirus disease 2019 (COVID-19) were directed to shield. Consequently, patients receiving hospital-based intravenous immunoglobulin (IVIg) quickly transitioned to home-based self-administered subcutaneous immunoglobulin (SCIg). This evaluation aimed to assess patients’ perceptions and experiences and laboratory outcomes of emergency IgRT transition during COVID-19.

Recent findings
A quick transition from in-hospital IVIg to home-based rapid push SCIg is achievable, however, patient IgRT administration preference remains key outside of emergency shielding measures.

Summary
Subjective self-reported experiences (n = 23) and objective immunoglobulin G (IgG) concentration (n = 28) assessments were prospectively collected from patients pre/post-IgRT switch. In total, 41/55 (75%) patients transitioned from IVIg to rapid push SCIg and all completed training to self-administer subcutaneously within 24 days. Twenty-two percent (n = 5) of patients preferred SCIg and 35% (n = 8) wanted to return to hospital-based IVIg at 6 weeks post-transition. Mean IgG levels were similar pre vs. post-SCIg switch (10.3 g/l vs. 10.6 g/l, respectively). Patients reported greater infection anxiety during COVID-19 and adapted behaviours to mitigate risk. Although a third of patients wished to return to IVIg following cessation of shielding, over time the percentage electing to remain on SCIg rose from 22% to 59%.
Cost minimization analysis of the treatment of olecranon fracture in elderly patients: a retrospective analysis
Authors: Welch Jessica M. , Zhuang Thompson , Shapiro Lauren M. , Gardner Michael J. , Xiao Michelle , Kamal Robin N. 
Published: September 2022

Background:
Operative treatment of olecranon fractures in the elderly can lead to greater complications with similar outcomes to nonoperative treatment. The purpose of this study was to analyze cost differences between operative and nonoperative management of isolated closed olecranon fractures in elderly patients.

Methods:
Using a United States Medicare claims database, the authors identified 570 operative and 1,863 nonoperative olecranon fractures between 2005 and 2014. The authors retrospectively determined cost of treatment from the payor perspective for a 1-year period after initial injury, including any surgical procedure, emergency room care, follow-up care, physical therapy, and management of complications.

Results:
One year after diagnosis, mean costs per patient were higher for operative treatment (United States dollars [US$]10,694 vs. US$2,544). Significant complications were noted in 31.05% of operative cases compared with 4.35% of nonoperative cases. When excluding complications, mean costs per patient were still higher for operative treatment ($7,068 vs. $2,320).

Conclusions:
These findings show that nonoperative management for olecranon fractures in the elderly population leads to fewer complications and is less costly. Nonoperative management may be a higher-value management option for this patient population. These results will help inform management of olecranon fractures as payors shift toward value-based reimbursement models in which quality of care and cost influence surgical decision-making.

Level of Evidence:
Level IV.