bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Torpid Heterothermy in Mammals: Another Category along the Homeothermy–Hibernation Continuum
Authors: Levesque Danielle L , Breit Ana M , Brown Eric , Nowack Julia , Welman Shaun 
Published: July 2023

Synopsis
Variability in body temperature is now recognized to be widespread among whole-body endotherms with homeothermy being the exception rather than the norm. A wide range of body temperature patterns exists in extant endotherms, spanning from strict homeothermy, to occasional use of torpor, to deep seasonal hibernation with many points in between. What is often lost in discussions of heterothermy in endotherms are the benefits of variations in body temperature outside of torpor. Endotherms that do not use torpor can still obtain extensive energy and water savings from varying levels of flexibility in normothermic body temperature regulation. Flexibility at higher temperatures (heat storage or facultative hyperthermia) can provide significant water savings, while decreases at cooler temperatures, even outside of torpor, can lower the energetic costs of thermoregulation during rest. We discuss the varying uses of the terms heterothermy, thermolability, and torpor to describe differences in the amplitude of body temperature cycles and advocate for a broader use of the term “heterothermy” to include non-torpid variations in body temperature.
Topological information retrieval with dilation-invariant bottleneck comparative measures
Authors: Cao Yueqi , Monod Anthea , Vlontzos Athanasios , Schmidtke Luca , Kainz Bernhard 
Published: July 2023

Abstract
Appropriately representing elements in a database so that queries may be accurately matched is a central task in information retrieval; recently, this has been achieved by embedding the graphical structure of the database into a manifold in a hierarchy-preserving manner using a variety of metrics. Persistent homology is a tool commonly used in topological data analysis that is able to rigorously characterize a database in terms of both its hierarchy and connectivity structure. Computing persistent homology on a variety of embedded datasets reveals that some commonly used embeddings fail to preserve the connectivity. We show that those embeddings which successfully retain the database topology coincide in persistent homology by introducing two dilation-invariant comparative measures to capture this effect: in particular, they address the issue of metric distortion on manifolds. We provide an algorithm for their computation that exhibits greatly reduced time complexity over existing methods. We use these measures to perform the first instance of topology-based information retrieval and demonstrate its increased performance over the standard bottleneck distance for persistent homology. We showcase our approach on databases of different data varieties including text, videos and medical images.
Cumulative incidence of anal cancer since HIV or AIDS diagnosis in the United States
Authors: Haas Cameron B , Engels Eric A , Horner Marie-Josèphe , Pfeiffer Ruth M , Luo Qianlai , Kreimer Aimée R , Palefsky Joel M , Shiels Meredith S 
Published: July 2023

Abstract
Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30 years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30 years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.
MEN1 is a regulator of alternative splicing and prevents R-loop-induced genome instability through suppression of RNA polymerase II elongation
Authors: Jin Bangming , Zhu Jiamei , Pan Ting , Yang Yunqiao , Liang Li , Zhou Yuxia , Zhang Tuo , Teng Yin , Wang Ziming , Wang Xuyan , Tian Qianting , Guo Bing , Li Haiyang , Chen Tengxiang 
Published: July 2023

Abstract
The fidelity of alternative splicing (AS) patterns is essential for growth development and cell fate determination. However, the scope of the molecular switches that regulate AS remains largely unexplored. Here we show that MEN1 is a previously unknown splicing regulatory factor. MEN1 deletion resulted in reprogramming of AS patterns in mouse lung tissue and human lung cancer cells, suggesting that MEN1 has a general function in regulating alternative precursor mRNA splicing. MEN1 altered exon skipping and the abundance of mRNA splicing isoforms of certain genes with suboptimal splice sites. Chromatin immunoprecipitation and chromosome walking assays revealed that MEN1 favored the accumulation of RNA polymerase II (Pol II) in regions encoding variant exons. Our data suggest that MEN1 regulates AS by slowing the Pol II elongation rate and that defects in these processes trigger R-loop formation, DNA damage accumulation and genome instability. Furthermore, we identified 28 MEN1-regulated exon-skipping events in lung cancer cells that were closely correlated with survival in patients with lung adenocarcinoma, and MEN1 deficiency sensitized lung cancer cells to splicing inhibitors. Collectively, these findings led to the identification of a novel biological role for menin in maintaining AS homeostasis and link this role to the regulation of cancer cell behavior.
DoubleHelix: nucleic acid sequence identification, assignment and validation tool for cryo-EM and crystal structure models
Authors: Chojnowski Grzegorz 
Published: July 2023

Abstract
Sequence assignment is a key step of the model building process in both cryogenic electron microscopy (cryo-EM) and macromolecular crystallography (MX). If the assignment fails, it can result in difficult to identify errors affecting the interpretation of a model. There are many model validation strategies that help experimentalists in this step of protein model building, but they are virtually non-existent for nucleic acids. Here, I present doubleHelix—a comprehensive method for assignment, identification, and validation of nucleic acid sequences in structures determined using cryo-EM and MX. The method combines a neural network classifier of nucleobase identities and a sequence-independent secondary structure assignment approach. I show that the presented method can successfully assist sequence-assignment step in nucleic-acid model building at lower resolutions, where visual map interpretation is very difficult. Moreover, I present examples of sequence assignment errors detected using doubleHelix in cryo-EM and MX structures of ribosomes deposited in the Protein Data Bank, which escaped the scrutiny of available model-validation approaches. The doubleHelix program source code is available under BSD-3 license at https://gitlab.com/gchojnowski/doublehelix.
Large-scale analysis of mRNA sequences localized near the start and amber codons and their impact on the diversity of mRNA display libraries
Authors: Umemoto Shun , Kondo Taishi , Fujino Tomoshige , Hayashi Gosuke , Murakami Hiroshi 
Published: July 2023

AbstractExtremely diverse libraries are essential for effectively selecting functional peptides or proteins, and mRNA display technology is a powerful tool for generating such libraries with over 1012–1013 diversity. Particularly, the protein-puromycin linker (PuL)/mRNA complex formation yield is determining for preparing the libraries. However, how mRNA sequences affect the complex formation yield remains unclear. To study the effects of N-terminal and C-terminal coding sequences on the complex formation yield, puromycin-attached mRNAs containing three random codons after the start codon (32768 sequences) or seven random bases next to the amber codon (6480 sequences) were translated. Enrichment scores were calculated by dividing the appearance rate of every sequence in protein-PuL/mRNA complexes by that in total mRNAs. The wide range of enrichment scores (0.09–2.10 for N-terminal and 0.30–4.23 for C-terminal coding sequences) indicated that the N-terminal and C-terminal coding sequences strongly affected the complex formation yield. Using C-terminal GGC-CGA-UAG-U sequences, which resulted in the highest enrichment scores, we constructed highly diverse libraries of monobodies and macrocyclic peptides. The present study provides insights into how mRNA sequences affect the protein/mRNA complex formation yield and will accelerate the identification of functional peptides and proteins involved in various biological processes and having therapeutic applications.
Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly using distinct mechanisms
Authors: Lee Wei , Iwasaki Hiroshi , Tsubouchi Hideo , Li Hung-Wen 
Published: July 2023

Abstract
In meiosis, Dmc1 recombinase and the general recombinase Rad51 are responsible for pairing homologous chromosomes and exchanging strands. Fission yeast (Schizosaccharomyces pombe) Swi5-Sfr1 and Hop2-Mnd1 stimulate Dmc1-driven recombination, but the stimulation mechanism is unclear. Using single-molecule fluorescence resonance energy transfer (smFRET) and tethered particle motion (TPM) experiments, we showed that Hop2-Mnd1 and Swi5-Sfr1 individually enhance Dmc1 filament assembly on single-stranded DNA (ssDNA) and adding both proteins together allows further stimulation. FRET analysis showed that Hop2-Mnd1 enhances the binding rate of Dmc1 while Swi5-Sfr1 specifically reduces the dissociation rate during the nucleation, about 2-fold. In the presence of Hop2-Mnd1, the nucleation time of Dmc1 filaments shortens, and doubling the ss/double-stranded DNA (ss/dsDNA) junctions of DNA substrates reduces the nucleation times in half. Order of addition experiments confirmed that Hop2-Mnd1 binds on DNA to recruit and stimulate Dmc1 nucleation at the ss/dsDNA junction. Our studies directly support the molecular basis of how Hop2-Mnd1 and Swi5-Sfr1 act on different steps during the Dmc1 filament assembly. DNA binding of these accessory proteins and nucleation preferences of recombinases thus dictate how their regulation can take place.
Electrochemical flow aziridination of unactivated alkenes
Authors: Wang Shengchun , Wang Pengjie , Li Shu-Jin , Chen Yi-Hung , Sun Zhi-Jun , Lei Aiwen 
Published: July 2023

ABSTRACT
Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.
Arabidopsismetacaspase MC1 localizes in stress granules, clears protein aggregates, and delays senescence
Authors: Ruiz-Solaní Nerea , Salguero-Linares Jose , Armengot Laia , Santos Jaime , Pallarès Irantzu , van Midden Katarina P , Phukkan Ujjal J , Koyuncu Seda , Borràs-Bisa Júlia , Li Liang , Popa Crina , Eisele Frederik , Eisele-Bürger Anna Maria , Hill Sandra Malgrem , Gutiérrez-Beltrán Emilio , Nyström Thomas , Valls Marc , Llamas Ernesto , Vilchez David , Klemenčič Marina , Ventura Salvador , Coll Nuria S 
Published: July 2023

AbstractStress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals. Here, we find that the metacaspase MC1 is dynamically recruited into SGs upon proteotoxic stress in Arabidopsis (Arabidopsis thaliana). Two predicted disordered regions, the prodomain and the 360 loop, mediate MC1 recruitment to and release from SGs. Importantly, we show that MC1 has the capacity to clear toxic protein aggregates in vivo and in vitro, acting as a disaggregase. Finally, we demonstrate that overexpressing MC1 delays senescence and this phenotype is dependent on the presence of the 360 loop and an intact catalytic domain. Together, our data indicate that MC1 regulates senescence through its recruitment into SGs and this function could potentially be linked to its remarkable protein aggregate-clearing activity.
عليم متخصصي شرطة المستقبل وسط كوفيد -19 من منظور الإمارات العربية المتحدة
Authors: امي الشريفين , أماندا ديفيز 
Published: July 2023

الملخص:
ركز العالم في عام 2020 جهودَه على التصدي للتحديات الإنسانية التي واجهت العالم إثر تفشي جائحة كوفيد-19، حيث واجه مجتمع التعليم حول العالم تحديات مماثلة في إظهار مدى المرونة والابتكار لدعم مستوى “الحياة الطبيعية” للطلاب على جميع المستويات والمهن. يعرض البحث المقدم في هذه المقالة نظرة فاحصة عن إعداد ونشر عملية الانتقال التعليمي لطلاب الشرطة سواء التعليم وجهًا لوجه أو عن بُعد في بيئة لم تعتد في الماضي على تلقي التعلم عن بُعد. وتشير النتائج إلى أن الاهتمام الحاسم الذي يولى إلى الانتقال إلى التعليم عن بعد ليس فقط في تقديم المادة العلمية -لكلٍ من الطلاب وأعضاء هيئة التدريس- كان اهتمامًامحوريًا في تحقيق نتائج تعلم إيجابية لدى الطلاب. إن نهج الانتقال إلى بيئة التعلم عن بُعد والحصول على أكثر البيانات الشائعة التي تشير إلى الحد الأدنى من التأثير على مدى تحصيل الطلاب يُساهم في اتخاذ القرار لدى مؤسسات التعليم التي تركز على تطوير متخصصي الجاهزية مثل ضباط الشرطة.
التأثير على العلاقات بين الشرطة والمجتمع في أبو ظبي من خلال نهج القوة الناعمة أثناء جائحة كوفيد 19
Authors: الهنائي محمد , ديفيس ديفيز وأماندا 
Published: July 2023

الملخص
برزت عبارة العمل الشرطي باستخدام القوة الناعمة بِعدّها شعار العمل الشرطي في عام 2021 وقد نشأت نتيجة للعديد من تحديات العلاقات بين الشرطة والمجتمع التي تكتسب تركيزًاعامًا متزايدًا على مستوى العالم. يعرض هذا المقال نهج القوة الناعمة في العمل الشرطي والذي تبنّته شرطة أبو ظبي قبل وأثناء جائحة فيروس كورونا (COVID-19) والاستراتيجيات والمبادرات الداعمة التي تم نشرها للحفاظ على ثقة المجتمع ومستويات الثقة في شرطة أبو ظبي. تروج المؤشرات العالمية لشرطة أبو ظبي كقائدة عالمية في العلاقات بين الشرطة والمجتمع، وهو إنجاز مستدام طوال أزمة فيروس كورونا العالمية COVID-19. يستكشف هذا البحث الطرق التي تتأثر بها الإنجازات من خلال نهج شرطي مستدام وشامل للجميع، يضع القوة الناعمة في مركز العلاقات بين الشرطة والمجتمع.
New finite-type multi-indexed orthogonal polynomials obtained from state-adding Darboux transformations
Authors: Odake Satoru 
Published: July 2023

Abstract
The Hamiltonians of finite-type discrete quantum mechanics with real shifts are real symmetric matrices of order N + 1. We discuss the Darboux transformations with higher-degree (&gt;N) polynomial solutions as seed solutions. They are state-adding and the resulting Hamiltonians after M steps are of order N + M + 1. Based on 12 orthogonal polynomials ((q-)Racah, (dual, q-)Hahn, Krawtchouk, and five types of q-Krawtchouk), new finite-type multi-indexed orthogonal polynomials are obtained, which satisfy second-order difference equations, and all the eigenvectors of the deformed Hamiltonian are described by them. We also present explicit forms of the Krein–Adler-type multi-indexed orthogonal polynomials and their difference equations, which are obtained from the state-deleting Darboux transformations with lower-degree (≤N) polynomial solutions as seed solutions.
Self-reported reasons for having difficulty reaching orgasm in men with diverse etiologies
Authors: Rowland David L , Padilla Sarah , Kӧvi Zsuzsanna , Hevesi Krisztina 
Published: July 2023

Abstract

Background
Difficulty reaching orgasm/ejaculation during partnered sex, a primary characteristic of delayed or absent ejaculation, affects about 5% to 10% of men, but the reasons underlying this problem are poorly understood.

Aim
The study sought to gain insight into possible etiologies of delayed ejaculation by assessing men’s self-perceptions as to why they experience difficulty reaching orgasm.

Methods
We drew 351 men reporting moderately severe to severe difficulty reaching orgasm during partnered sex from a sample of over 3000 respondents obtained through an online survey. As part of the 55-item survey, participants responded to 2 questions asking about their self-perceived reasons for having difficulty reaching orgasm and selected from a list of 14 options derived from the research literature, a series of men’s focus groups, and expert opinion. The first question allowed respondents to select all the reasons that they felt contributed to the problem, the second to select only the most important reason. In addition, both men with and without comorbid erectile dysfunction were investigated and compared.

Outcomes
Hierarchical ordering of men’s self-pereceived reasons for having difficulty reaching orgasm, including typal reasons established through principal component analysis.

Results
The major reasons for difficulty were related to anxiety/distress and lack of adequate stimulation, with relationship and other factors endorsed with lower frequency. Further exploration using principal components analysis identified 5 typal reasons, in descending order of frequency: anxiety/distress (41%), inadequate stimulation (23%), low arousal (18%), medical issues (9%), and partner issues (8%). Few differences emerged between men with and without comorbid ED other than ones related to erectile problems, such as higher level of endorsement of medical issues. Typal reasons showed correlations, albeit mostly weak, with a number of covariates, including sexual relationship satisfaction, frequency of partnered sex, and frequency of masturbation.

Clinical Implications
Until supplemental medical treatments for delayed ejaculation are developed and approved, a number of men’s purported reasons for difficult or absent ejaculation/orgasm—anxiety/distress, inadequate stimulation, low arousal, relationship issues—fall into areas that can be addressed in couples counseling by a trained sex therapist.

Strengths and Limitations
This study is unique in scope and robust in sample size. Drawbacks include those associated with online surveys, including possible bias in sample selection, limitation to Western-based samples, and the lack of differentiation between men with lifelong and acquired difficulty.

Conclusion
Men who have difficulty reaching ejaculation/orgasm identify putative reasons for their problem, ranging from anxiety/stress, inadequate stimulation, and low arousal to partner issues and medical reasons.
Non-melanoma skin cancer event rates in a formalized clinical trial setting: considerations for clinical trial design
Authors: Lozar Taja , Kim Kyungmann , Havighurst Thomas C. , Wood Gary S. , Kolesar Jill M. , Bailey Howard H. 
Published: July 2023

Background
Here we report clinical risk factors and event rates for the development of new non-melanoma skin cancer (NMSC) in a randomized, double-blind, placebo-controlled trial of the irreversible ornithine decarboxylase (ODC) inhibitor, difluromethylornithine (DFMO), over a 3–5-year follow-up.

Methods
147 placebo patients (white; mean age 60.2 years; 60% male) were evaluated for event rates and association of initial skin biomarkers and baseline patient characteristics with the development of squamous cell (SCC) and basal cell (BCC) carcinomas.

Results
Post-study evaluation (median follow-up 4.4 years) indicates the measures of prior NMSCs (P ≤ 0.001), prior BCCs (P ≤ 0.001), prior SCCs (P = 0.011), prior tumor rate (P = 0.002), hemoglobin (P = 0.022), and gender (P = 0.045) as significant predictors for new NMSC development. Similarly, all measures of prior BCCs and NMSCs (P < 0.001), prior tumor rate (P = 0.014), and SCCs in the prior 2 years (P = 0.047) were statistically significant predictors for new BCC development. Total prior NMSCs and those in the prior 5 years (P < 0.001), total prior SCCs and those in the prior 5 years (P < 0.001), total prior BCCs and those in the prior 5 years (P ≤ 0.001), prior tumor rate (P = 0.011) as well as age (P = 0.008), hemoglobin (P = 0.002), and gender (P = 0.003) were statistically significant predictors of new SCC development. TPA-induced ODC activity at baseline showed no statistically significant association with the development of new NMSC (P = 0.35), new BCCs (P = 0.62), or new SCCs (P = 0.25).

Conclusion
In the studied population, the history of and rate at which prior NMSCs occur are predictive and should be controlled for in future NMSC prevention trials.
Head-Tilt Perfluorocarbon-Air Exchange Technique with Heads-Up Surgery for Giant Retinal Tear-Associated Retinal Detachments to Prevent Retinal Slippage without Using Silicone Oil
Authors: Ishida Yuichiro , Saito Seiya , Tsuboi Kotaro , Atsuya Miki , Kamei Motohiro , Wakabayashi Taku 
Published: July 2023

Abstract

Purpose:
To report the efficacy of the perfluorocarbon liquid (PFCL)-air exchange with a head tilt toward the area of the giant retinal tear (GRT) using the heads-up surgery (HUS) system to prevent retinal slippage during vitrectomy for GRT-associated retinal detachments.

Methods:
Eyes with GRT-associated retinal detachments underwent vitrectomy using the HUS system and PFCL-air exchange with a head tilt 45 degrees toward the GRT to put the area of the tear in the most dependent position to drain fluid. We evaluated this technique to prevent the retinal slippage.

Results:
We evaluated 5 consecutive cases. The mean GRT size was 174 degrees (range, 90 to 240 degrees) and the GRT was located temporally in 2 eyes, nasally in 2 eyes, and superiorly in 1 eye. The tamponade types were air (1 eye), sulfur hexafluoride (3 eyes), and perfluoropropane (1 eye). Our technique was feasible and the slippage did not occur in any eyes. Although the microscope needed to be tilted for optimal fundus visualization, HUS allowed surgeons to maintain ergonomic postures. Retinal reattachment was achieved with a single surgery in all eyes.

Conclusion:
The head-tilt PFCL-air exchange with HUS is useful in preventing retinal slippage in eyes with GRT.