bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Bleeding Following Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase
Authors: Tsai Tou-Yuan , Liu Yu-Chang , Huang Wan-Ting , Tu Yu-Kang , Qiu Shang-Quan , Noor Sameer , Huang Yong-Chen , Chou Eric H. , Lai Edward Chia-Cheng , Huang Huei-Kai 
Published: November 2023

ImportanceCurrent guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non–vitamin K antagonist oral anticoagulants (NOACs).ObjectiveTo evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs.Design, Setting, and ParticipantsThis nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan’s National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO.ExposuresNOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment.Main Outcomes and MeasuresThe primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model.ResultsOf the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, −4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, −2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, −4.95% [95% CI, −10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score–matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis.Conclusions and RelevanceIn this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.
Infertility and Risk of Autism Spectrum Disorder in Children
Authors: Velez Maria P. , Dayan Natalie , Shellenberger Jonas , Pudwell Jessica , Kapoor Dia , Vigod Simone N. , Ray Joel G. 
Published: November 2023

ImportancePrevious studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors.ObjectiveTo assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association.Design, Setting, and ParticipantsThis was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks’ gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023.ExposuresThe exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).Main Outcome and MeasuresThe study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity.ResultsA total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%.Conclusions and RelevanceIn this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.
Survival of Patients With Head and Neck Merkel Cell Cancer
Authors: Nayak Ameeta Lubina , Pickett Arthur Travis , Delisle Megan , Dingley Brittany , Mallick Ranjeeta , Hamilton Trevor , Stuart Heather , Talbot Martha , McKinnon Gregory , Jost Evan , Thiboutot Eva , Francescutti Valerie , Samman Sal , Easson Alexandra , Schellenberg Angela , Merchant Shaila , La Julie , Vanderbeck Kaitlin , Wright Frances , Berger-Richardson David , Hebbard Pamela , Hershorn Olivia , Younan Rami , Patocskai Erica , Rodriguez-Qizilbash Samuel , Meguerditichian Ari , Tchuente Vanina , Kazandjian Suzanne , Mathieson Alex , Hossain Farisa , Hetu Jessika , Corsten Martin , Tohmé Angelina , Nessim Carolyn , Johnson-Obaseki Stephanie 
Published: November 2023

ImportanceMerkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Due to its relatively low incidence and limited prospective trials, current recommendations are guided by historical single-institution retrospective studies.ObjectiveTo evaluate the overall survival (OS) of patients in Canada with head and neck MCC (HNMCC) according to American Joint Committee on Cancer 8th edition staging and treatment modalities.Design, Setting, and ParticipantsA retrospective cohort study of 400 patients with a diagnosis of HNMCC between July 1, 2000, and June 31, 2018, was conducted using the Pan-Canadian Merkel Cell Cancer Collaborative, a multicenter national registry of patients with MCC. Statistical analyses were performed from January to December 2022.Main Outcomes and MeasuresThe primary outcome was 5-year OS. Multivariable analysis using a Cox proportional hazards regression model was performed to identify factors associated with survival.ResultsBetween 2000 and 2018, 400 patients (234 men [58.5%]; mean [SD] age at diagnosis, 78.4 [10.5] years) with malignant neoplasms found in the face, scalp, neck, ear, eyelid, or lip received a diagnosis of HNMCC. At diagnosis, 188 patients (47.0%) had stage I disease. The most common treatment overall was surgery followed by radiotherapy (161 [40.3%]), although radiotherapy alone was most common for stage IV disease (15 of 23 [52.2%]). Five-year OS was 49.8% (95% CI, 40.7%-58.2%), 39.8% (95% CI, 26.2%-53.1%), 36.2% (95% CI, 25.2%-47.4%), and 18.5% (95% CI, 3.9%-41.5%) for stage I, II, III, and IV disease, respectively, and was highest among patients treated with surgery and radiotherapy (49.9% [95% CI, 39.9%-59.1%]). On multivariable analysis, patients treated with surgery and radiotherapy had greater OS compared with those treated with surgery alone (hazard ratio [HR], 0.76 [95% CI, 0.46-1.25]); however, this was not statistically significant. In comparison, patients who received no treatment had significantly worse OS (HR, 1.93 [95% CI, 1.26-2.96)].Conclusions and RelevanceIn this cohort study of the largest Canada-wide evaluation of HNMCC survival outcomes, stage and treatment modality were associated with survival. Multimodal treatment was associated with greater OS across all disease stages.
Assessing the effectiveness of mitigating pesticide‐related disease risk among pesticide‐spraying drone operators in Taiwan
Authors: Wu Wei‐Te , Chen Jyun‐Ming , Chang Yu‐Yin , Lin Shian‐Da , Chen Shih‐Tzong , Hung Yu‐Tang 
Published: November 2023

AbstractObjectivesThe purpose of this study was to evaluate the risk of pesticide poisoning, liver and renal failure, dermatitis, respiratory problems, hypersensitivity pneumonitis, keratitis, and epilepsy among pesticide‐spraying personnel and to assess the effectiveness of a new method of aerial pesticide application in reducing this risk.MethodsA total of 2268 pesticide spraying operators (1651 ground‐based field crop operators and 617 aerial pesticide spraying drone operators) who passed the national certification examination between 2010 and 2020 in Taiwan were included. Ground‐based operators served as the positive control group, while 2463 farmer controls were matched from the Farmers' Health Insurance database as the negative control group. Data from the National Health Insurance Research Database were used to track possible pesticide‐related disease cases. Logistic regression was employed to calculate odds ratios and 95% confidence intervals (95% CI).ResultsDrone operators had significantly reduced risks of dermatitis, asthma and chronic bronchitis compared to ground‐based operators. This was observed in allergic contact dermatitis (OR = 0.40, 95% CI: 0.24–0.68), unspecified contact dermatitis (OR = 0.58, 95% CI: 0.35–0.97), asthma (OR = 0.27, 95% CI: 0.12–0.60), and chronic bronchitis (OR = 0.24, 95% CI: 0.06–0.93), after adjusting for age, sex, working areas, and licensing years. However, no significant differences were found when comparing drone operators to matching farmers.ConclusionsAerial pesticide spraying using drones may contribute to a decreased risk of dermatitis, asthma and chronic bronchitis, suggesting potential health benefits for operators. Further field pesticide exposure surveys are recommended to validate these findings and assess health risk indicators.
Evaluating the effect of targeting body shape concerns on long‐term weight change
Authors: Olson KayLoni L. , Thaxton Tyler T. , Landers Jacob D. , Emery Charles F. 
Published: November 2023

AbstractObjectiveThe goal of this follow‐up to a randomized proof‐of‐concept study was to determine if targeting body shape concern (BSC) has a clinically significant impact on long‐term weight change among adult women of higher body weight with BSC. A secondary aim was to observe the maintenance of body image improvements during follow‐up.MethodIn the original 4‐week trial, women were randomized to behavioral weight loss recommendations alone (control; n = 15) or combined with the evidence‐based body project intervention (n = 17). All participants were directed to continue monitoring diet and exercise through Week 8. The current analysis focused on follow‐up data collected on weight, BSC, internalized weight bias, internalized thin ideal, and body appreciation at 8 weeks, 6 months, and 12 months. Percent weight change was calculated from baseline and compared against clinical milestones of −2.5% and −5%. An intent‐to‐treat approach was used for individuals lost to follow‐up (n = 11).ResultsBody project participants achieved the clinically significant target of −2.5% weight loss by 12 months. Control participants did not reach the milestone and regained lost weight at 12 months. Neither condition reached the 5% clinical target. Both groups experienced improved body image, but body project participants maintained a greater magnitude of improvement in all measures except internalized thin ideal at 12 months.ConclusionThe current study provides preliminary evidence that targeting BSC among women with BSC who want to lose weight may improve long‐term weight loss. Further intervention development and testing are warranted.Public SignificanceThe results of this study suggest that targeting negative body image among adult women with high BSC might be a pathway to improve long‐term weight loss in behavioral weight management. This is aligned with precision medicine priorities to optimize weight‐related health care.
Conformational energies of biomolecules in solution: Extending the MPCONF196 benchmark with explicit water molecules
Authors: Plett Christoph , Grimme Stefan , Hansen Andreas 
Published: November 2023

AbstractA prerequisite for the computational prediction of molecular properties like conformational energies of biomolecules is a reliable, robust, and computationally affordable method usually selected according to its performance for relevant benchmark sets. However, most of these sets comprise molecules in the gas phase and do not cover interactions with a solvent, even though biomolecules typically occur in aqueous solution. To address this issue, we introduce a with explicit water molecules solvated version of a gas‐phase benchmark set containing 196 conformers of 13 peptides and other relevant macrocycles, namely MPCONF196 [J. Řezáč et al., JCTC 2018, 14, 1254–1266], and provide very accurate PNO‐LCCSD(T)‐F12b/AVQZ' reference values. The novel solvMPCONF196 benchmark set features two additional challenges beyond the description of conformers in the gas phase: conformer–water and water–water interactions. The overall best performing method for this set is the double hybrid revDSDPBEP86‐D4/def2‐QZVPP yielding conformational energies of almost coupled cluster quality. Furthermore, some (meta‐)GGAs and hybrid functionals like B97M‐V and B97M‐D with a large basis set reproduce the coupled cluster reference with an MAD below 1 kcal mol . If more efficient methods are required, the composite DFT‐method rSCAN‐3c (MAD of 1.2 kcal mol) is a good alternative, and when conformational energies of polypeptides or macrocycles with more than 500–1000 atoms are in the focus, the semi‐empirical GFN2‐xTB or the MMFF94 force field (for very large systems) are recommended.
Understanding healthcare engagement for people who inject drugs
Authors: Heidari Omeid , Winiker Abigail , Dangerfield Derek T. , Wenzel Jennifer , Rodney Tamar , Mehta Shruti , Genberg Becky 
Published: November 2023

AbstractPeople who inject drugs (PWID) are at an increased risk of multimorbid mental health and chronic diseases, which are frequently underdiagnosed and under‐treated due to systemic barriers and ongoing substance use. Healthcare engagement is essential to address these conditions and prevent excess morbidity and mortality. The goal of this study was to understand how PWID engage in care for their chronic health conditions and substance use treatment given the known historic and pervasive barriers. We conducted 24 semistructured qualitative interviews informed by the Behavioral Model for Vulnerable Populations between July–September 2019. Participants were sampled across a range of comorbidities, including co‐occurring mental health disorders. Thematic analysis was conducted to explore experiences of healthcare engagement for multimorbid chronic diseases, mental health, and treatment for substance use disorder. Mean age for participants was 58 years; 63% reported male sex and 83% reported Black race. Interviews yielded themes regarding healthcare access and wraparound services, positive patient–provider relationships, service integration for substance use treatment and mental health, healthcare needs alignment, medication of opioid use disorder stigma, and acceptance of healthcare. Taken together, participants described how these themes enabled healthcare engagement. Engagement in care is crucial to support health and recovery. Clinical implications include the importance of strengthening patient–provider relationships, encouraging integration of medical and mental health services, and counseling on substance use treatment options in a non‐ stigmatizing manner. Additionally, policy to reimburse wrap‐around support for substance use recovery can improve care engagement and outcomes related to chronic diseases, mental health, and substance use among PWID.No Patient or Public Contribution: While we acknowledge and thank ALIVE participants for their time for data collection and sharing their perspectives, no ALIVE participants, other people who use drugs, and service users were involved in data collection, analysis or interpretation of data, or in preparation of the manuscript.
Role of QCD in moduli stabilization during inflation and axion dark matter
Authors: Kitano Ryuichiro , Suzuki Motoo , Yin Wen 
Published: November 2023

Abstract
Ignorance of the initial condition for the axion dynamics in the early Universe has led us to consider an O(1) valued initial amplitude, and that prefers the decay constant, Fa, of the QCD axion to be an intermediate scale such as 1012 GeV in order to explain the dark matter abundance. We explore a cosmological scenario of Fa being much larger than 1012 GeV by considering the axion and modulus dynamics during inflation to set the initial amplitude. We show that if the volume modulus (radion) of the extra-dimension is stabilized mainly by the QCD contribution to the modulus potential during inflation, the QCD axion with the string-scale decay constant obtains a mass around the inflationary Hubble parameter. This means that the axion rolls down to the θ = 0 minimum during the inflation realizing almost vanishing initial amplitude, and the inflationary quantum fluctuation can be the dominant source of the current number density of axions. We find natural parameter regions where the axion explains the cold dark matter of the Universe, while the constraint on the isocurvature perturbation is avoided. The presence of the axion miniclusters or axion stars are predicted in a wide range of parameters, including the one explains the Subaru-HCS microlensing event.
Unconventional roles of chromatin remodelers and long non-coding RNAs in cell division
Authors: Prozzillo Yuri , Santopietro Maria Virginia , Messina Giovanni , Dimitri Patrizio 
Published: November 2023

AbstractThe aim of this review article is to focus on the unconventional roles of epigenetic players (chromatin remodelers and long non-coding RNAs) in cell division, beyond their well-characterized functions in chromatin regulation during cell differentiation and development. In the last two decades, diverse experimental evidence has shown that subunits of SRCAP and p400/TIP60 chromatin remodeling complexes in humans relocate from interphase nuclei to centrosomes, spindle or midbody, with their depletion yielding an array of aberrant outcomes of mitosis and cytokinesis. Remarkably, this behavior is shared by orthologous subunits of the Drosophila melanogaster DOM/TIP60 complex, despite fruit flies and humans diverged over 700 million years ago. In short, the available data support the view that subunits of these complexes are a new class of moonlighting proteins, in that they lead a "double life": during the interphase, they function in chromatin regulation within the nucleus, but as the cell progresses through mitosis, they interact with established mitotic factors, thus becoming integral components of the cell division apparatus. By doing so, they contribute to ensuring the correct distribution of chromosomes in the two daughter cells and, when dysfunctional, can cause genomic instability, a condition that can trigger tumorigenesis and developmental diseases. Research over the past few years has unveiled a major contribution of long non-coding RNAs (lncRNAs) in the epigenetics regulation of gene expression which also impacts on cell division control. Here, we focus on possible structural roles of lncRNAs in the execution of cytokinesis: in particular, we suggest that specific classes of lncRNAs relocate to the midbody to form an architectural scaffold ensuring its proper assembly and function during abscission. Drawing attention to experimental evidence for non-canonical extranuclear roles of chromatin factors and lncRNAs has direct implications on important and novel aspects concerning both the epigenetic regulation and the evolutionary dynamics of cell division with a significant impact on differentiation, development, and diseases.
Mentale Flexibilität durch implizites soziales Lernen
Authors: Taubner Svenja , Sharp Carla 
Published: November 2023

ZusammenfassungIn diesem Beitrag wird die Idee eines transtheoretischen Metamodells entwickelt, das besonders auf Veränderungsprozesse bei schweren psychischen Erkrankungen wie Persönlichkeitsstörungen ausgerichtet ist. Als ein Kernprozess der Veränderung wird mentale Flexibilität definiert; diese kann durch implizites soziales Lernen gefördert werden. Empfohlen werden bestimmte Haltungen und Techniken, die abgeleitet werden, aus der Mentalisierungsbasierten Therapie (MBT) und den Lernkomponenten, die in dem Bezugspersonen-Kind-Programm „Mediational Intervention for Sensitizing Caregivers (MISC)“ entwickelt wurden. Ziel der Therapie ist, den epistemischen Lern-Highway zu öffnen und das Mentalisieren während der Sitzungen zu trainieren, um letztlich die kognitive Flexibilität außerhalb des Therapieraums zu verbessern. Der Veränderungsprozess in Richtung mentaler Flexibilität ersetzt die Idee einer korrigierenden emotionalen Erfahrung, weil sich diese – zumindest für die Behandlung von Persönlichkeitsstörungen – als weniger wirksam oder sogar schädlich erwiesen hat. Durch die Integration von MBT und MISC entsteht zudem die Möglichkeit, auf einer granularen Ebene verhaltensverankerte und daher beobachtbare Handlungen von Therapeut:innen zu trainieren und zu beobachten. Dies eröffnet die Möglichkeit, Mikroprozesse zu beobachten und zu steuern. Daher wird vorgeschlagen, die Aufmerksamkeit und das Verständnis auf implizites Lernen innerhalb therapeutischer Beziehungen zu lenken, d. h. auf die Verinnerlichung einer neuen Denkweise in Bezug auf spezifische Lebensereignisse, die eine Anpassung erfordern. Durch mentale Flexibilität entstehen flexible Anpassungsfähigkeiten, die Patient:innen autonom machen und in Zukunft in der Prozessforschung weiteruntersucht werden sollten.