bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex‐related differences in pattern of ethanol drinking under the intermittent‐access model and its impact on exploratory and anxiety‐like behavior in Long‐Evans rats
Authors: Pirino Breanne E. , Martin Cydney R. , Carpenter Brody A. , Curtis Genevieve R. , Curran‐Alfaro Christina M. , Samels Shanna B. , Barker Jacqueline M. , Karkhanis Anushree N. , Barson Jessica R. 
Published: May 2022

AbstractBackgroundWhile men in the United States consume more alcohol than women, rates of drinking are converging. Nevertheless, females remain underrepresented in preclinical alcohol research. Here, we examined rats' sex‐related differences in patterns of ethanol (EtOH) drinking and the effects of this drinking on exploratory and anxiety‐like behavior.MethodsAdult male and female Long‐Evans rats were given 20% ethanol under the intermittent‐access two‐bottle‐choice paradigm. Their intake was measured daily for the first 7 weeks. During the eighth week, intake was measured over the 24 h of daily access. During the ninth week, they, along with EtOH‐naive controls, were tested prior to daily access in a novel chamber, light–dark box, and hole board apparatus. During the tenth week, blood ethanol concentration (BEC) was assessed after 30 to 40 min of access.ResultsFemales overall demonstrated higher ethanol intake and preference across all access weeks than males, although only half of females drank significantly more than males. Across 24 h of daily access, both sexes had their highest intake in the first 30 min and their lowest in the middle of the light phase of the light/dark cycle. Despite their greater ethanol intake, females did not show significantly different BECs than males. In behavioral tests, females showed less vertical time in a novel activity chamber, more movement between chambers in a light–dark box, and more nose pokes in a hole‐board apparatus than males. While a history of ethanol drinking led to a trend for lower vertical time in the activity chamber and greater chamber entries in the light–dark box, the effects were not sex‐dependent.ConclusionsThese results suggest that female and male rats could both be tested for acute effects of ethanol after 30 min of daily access, but that nuanced considerations are needed in the design of these experiments and the interpretation of their findings.
Identifying prospective subpopulations of combustible and electronic cigarette dual users in the United States via finite mixture modeling
Authors: Sutton Steven K. , Brandon Karen O. , Harrell Paul T. , Martínez Úrsula , Simmons Vani N. , Gore L. Robert , Bullen Christopher R. , Brandon Thomas H. 
Published: May 2022

AbstractAimsTo identify subpopulations of dual users of combustible and electronic cigarettes using current smoking and vaping behaviors.DesignSecondary analysis of baseline data from a randomized controlled trial testing a smoking cessation intervention for dual users. Finite mixture modeling of frequency, quantity, and dependence on combustible and electronic cigarettes was used to identify classes. Demographics and additional smoking and vaping variables were used to further characterize the classes.SettingUnited States.ParticipantsA total of 2896 adults who smoked weekly for the past year and vaped weekly for the past month.MeasurementsSelf‐report baseline measures assessed demographics and smoking and vaping behaviors and characteristics including days of use per week, frequency of use within a day, time to first use after waking, urges to smoke, smoking cessation motivation, self‐efficacy to abstain from smoking, months since vaping initiation, reasons for initiating and maintaining vaping, and future plans to stop vaping.FindingsEight probabilistic classes were identified and well‐defined (relative entropy = 0.95, Lo–Mendell–Rubin adjusted likelihood ratio test P < 0.0001; class probabilities 0.89–0.97). In general, classes crossed two levels of smoking with four levels of vaping. The largest class (31%) had relatively high levels of smoking (72% daily, 56% 11+ cigarettes per day [CPD], 96% within 30 minutes of waking) and vaping (74% daily, 100% 20+ electronic‐CPD, 74%  <30 minutes). The next largest class (27%) had relatively high levels of vaping (93% daily, 100% 20+ electronic‐CPD, 82%  <30 minutes) and very low levels of smoking (28% daily, 12% 11+ CPD, 0%  <30 minutes). The six smaller classes (3%–13%) also had distinct smoking and vaping behaviors. All eight classes exhibited distinguishing characteristics beyond current smoking and vaping behaviors.ConclusionsDual users of combustible and electronic cigarettes are not a homogeneous population, having eight well‐defined prospective subpopulations.
Identifying predictors of systemic immunosuppressive treatment of vulvovaginal lichen planus: A retrospective cohort study of 122 women
Authors: Kherlopian Ashod , Fischer Gayle 
Published: May 2022

AbstractBackgroundBetween 20% and 40% of women with vulvovaginal lichen planus (VLP) fail to respond to first‐line ultra‐potent topical corticosteroid treatment and require systemic immunosuppression to control disease. No data exist regarding risk factors for patients with severe VLP requiring systemic immunosuppression. We aimed to identify clinical features that predict women with VLP who are at risk of severe, recalcitrant disease requiring eventual escalation to systemic treatment.MethodsA chart review was performed on a cohort of 122 adult women with VLP followed prospectively for 15 years by the same clinician in a private dermatology practice in Australia between 1 January 2004 and 1 October 2021. Uni‐ and multivariable binary logistical regression analyses were performed to identify clinical features distinguishing women eventually requiring systemic treatment of VLP against those whose VLP was controlled with topical corticosteroids alone.ResultsThe mean age at diagnosis of VLP was 61 years, with 35 women (28.7%) requiring systemic treatment of VLP. A multivariable regression model utilising ‘Age at Diagnosis’ (adjusted OR = 0.97, 95% CI 0.94–0.99), ‘Non‐Caucasian Ethnicity’ (adjusted OR = 10.3, 95% CI 2.27–73.9) and ‘Vulvar Pruritus’ (adjusted OR = 2.69, 95% CI 1.11–6.86) demonstrated moderate predictive capacity, with specificity and sensitivity for predicting whether a patient will require systemic treatment for VLP of 95.3% and 40.5%, respectively.ConclusionsOur findings may indicate women with VLP who are younger, of non‐Caucasian ethnicity, and presenting with vulval pruritus are the highest risk of severe disease requiring systemic immunosuppressive treatment and may benefit most from earlier initiation of systemic treatment.
Comparing the levels of CTLA‐4‐dependent biological defects in patients with LRBA deficiency and CTLA‐4 insufficiency
Authors: Catak Mehmet C. , Akcam Bengu , Bilgic Eltan Sevgi , Babayeva Royala , Karakus Ibrahim S. , Akgun Gamze , Baser Dilek , Bulutoglu Alper , Bayram Feyza , Kasap Nurhan , Kiykim Ayca , Hancioglu Gonca , Kokcu Karadag Sefika I. , kendir Demirkol Yasemin , Ozen Selime , Cekic Sukru , Ozcan Dilek , Edeer Karaca Neslihan , Sasihuseyinoglu Ayse S. , Cansever Murat , Ozek Yucel Esra , Tamay Zeynep , Altintas Derya U. , Aydogmus Cigdem , Celmeli Fatih , Cokugras Haluk , Gulez Nesrin , Genel Ferah , Metin Ayse , Guner Sukru N. , Kutukculer Necil , Keles Sevgi , Reisli Ismail , Kilic Sara S. , Yildiran Alisan , Karakoc‐Aydiner Elif , Lo Bernice , Ozen Ahmet , Baris Safa 
Published: May 2022

AbstractBackgroundLipopolysaccharide‐responsive beige‐like anchor protein (LRBA) deficiency and cytotoxic T‐lymphocyte protein‐4 (CTLA‐4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long‐term follow‐up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA‐4 insufficiency.MethodsPatients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post‐stimulation.ResultsLRBA‐deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA‐4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non‐transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA‐4‐insufficient patients (p = 0.04). The T‐cell subsets showed more deviation to memory cells in CTLA‐4‐insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA‐4 expression was significantly diminished in LRBA deficiency and CTLA‐4 insufficiency, but significant induction in CTLA‐4 was observed after short‐term T‐cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA‐4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%).ConclusionThis cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA‐4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA‐4 pathway.
A Logic of Care and Black Grassroots Claims to Home in Detroit
Authors: Quizar Jessi 
Published: May 2022

AbstractThis article examines the ways in which Detroit Eviction Defense (DED) and other activist organisations employ a logic of care to argue for Black Detroiters’ right to define who may claim home and place in the city. The article uses the foreclosure case of longtime Detroiter Lela Whitfield to examine the ways in which DED successfully resists eviction by arguing publicly that legitimate claims to land and home should be based on how one cares for it—in terms of stewardship, in terms of relationships on and with places, and based on how one uses it. This essay argues that this logic of care has roots in a Black radical tradition and in the particular conditions of racial capitalism in Detroit. Ultimately, DED and other Detroiters offer care as an alternate logic to resist “racial banishment” and establish alternate place‐claiming logics in the context of urban housing crisis, austerity, and financialisation.
A Compound Decision Approach to Covariance Matrix Estimation
Authors: Xin Huiqin , Zhao Sihai Dave 
Published: May 2022

AbstractCovariance matrix estimation is a fundamental statistical task in many applications, but the sample covariance matrix is suboptimal when the sample size is comparable to or less than the number of features. Such high-dimensional settings are common in modern genomics, where covariance matrix estimation is frequently employed as a method for inferring gene networks. To achieve estimation accuracy in these settings, existing methods typically either assume that the population covariance matrix has some particular structure, for example, sparsity, or apply shrinkage to better estimate the population eigenvalues. In this paper, we study a new approach to estimating high-dimensional covariance matrices. We first frame covariance matrix estimation as a compound decision problem. This motivates defining a class of decision rules and using a nonparametric empirical Bayes g-modeling approach to estimate the optimal rule in the class. Simulation results and gene network inference in an RNA-seq experiment in mouse show that our approach is comparable to or can outperform a number of state-of-the-art proposals.
Substitution of SERCA2 Cys674 accelerates aortic aneurysm by inducing endoplasmic reticulum stress and promoting cell apoptosis
Authors: Wang Langtao , Yang Zhen , Wang Sai , Que Yumei , Shu Xi , Wu Fuhua , Liu Gang , Li Siqi , Hu Pingping , Chen Hao , Shi Jian , Tong Xiaoyong 
Published: May 2022

Background and PurposeThe Cys674 residue (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is key to maintaining its enzyme activity. The irreversible oxidation of C674 occurs broadly in aortic aneurysms. Substitution of C674 promotes a phenotypic transition of aortic smooth muscle cells (SMCs) and exacerbates angiotensin II‐induced aortic aneurysm. However, its underlying mechanism remains enigmatic.Experimental ApproachHeterozygous SERCA2 C674S knock‐in (SKI) mice, in which half of C674 was replaced by serine, were used to mimic partially irreversible oxidation of C674 thiol. The aortas of SKI mice and their littermate wild‐type mice under an LDL receptor‐deficient background were collected for histological and immunohistochemical analysis. Cultured aortic SMCs were used for protein expression, apoptosis analysis, and cell function studies.Key ResultsThe substitution of SERCA2 C674 caused endoplasmic reticulum (ER) stress and induced SMC apoptosis. The inhibition of ER stress by 4‐phenylbutyric acid (4‐PBA) in SKI aortic SMCs decreased the expression of marker proteins for cell apoptosis as well as phenotypic transition, and prevented cell apoptosis, proliferation, migration, and macrophage adhesion to SMCs. 4‐PBA also ameliorated angiotensin II‐induced aortic aneurysm in SKI mice.Conclusions and ImplicationsThe irreversible oxidation of SERCA2 C674 promotes the development of aortic aneurysm by inducing ER stress and subsequent SMC apoptosis. Our study illustrates that ER stress caused by oxidative inactivation of C674 is related to the pathogenesis of aortic aneurysm. Therefore, ER stress and SERCA2 are potential therapeutic targets for treating aortic aneurysm.
Association between vitiligo and relevant components of metabolic syndrome: a systematic review and meta‐analysis
Authors: Kang Pan , Zhang Wei‐Gang , Ji Zhao‐Hua , Shao Zhong‐Jun , Li Chun‐Ying 
Published: May 2022

SummaryBackground and objectivesThis study aimed to investigate the association of vitiligo with metabolic syndrome (MetS) and its relevant components.Material and methodsWe searched PubMed, Web of Science, Cochrane Library and Embase databases from inception to March 30, 2021, for relevant studies. Cross‐sectional and case‐control studies that reported either the prevalence or odds ratio [OR] of MetS or its components in vitiligo patients were included. Data were pooled using either random‐effects model or fixed‐effects model according to the heterogeneity.ResultsThirty studies with a total of 28,325 vitiligo patients were included. Significant associations were found between vitiligo and diabetes mellitus (pooled OR, 3.30; 95 % confidence interval [CI], 2.10–5.17) and between vitiligo and obesity (pooled OR, 2.08; 95 % CI, 1.40–3.11). The overall prevalence of hypertension in the patients with vitiligo was 19.0 % (95 % CI, 2.0 %–36.0 %).ConclusionsOur findings suggest the association of vitiligo with diabetes mellitus, obesity, and hypertension. It is recommended for dermatologists to take these associations into account so as to identify potential comorbidities promptly in vitiligo patients. Additionally, vitiligo patients are advised to monitor the indexes including BMI, blood glucose, and blood pressure levels and the consultation with specialists is necessary upon abnormal changes of these indexes.
Non‐inferiority and clinical superiority of glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors: Systematic analysis of cardiorenal outcome trials in type 2 diabetes
Authors: Zaccardi Francesco , Kloecker David E. , Khunti Kamlesh , Davies Melanie J. 
Published: May 2022

AbstractAimsMost trials leading to the approval of glucagon‐like peptide receptor agonists (GLP‐1RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) were primarily designed to confirm their non‐inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non‐inferiority.Materials and MethodsWe searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan‐Meier plots individual‐level data for the primary outcome or all‐cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio) <0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment.ResultsWe extracted data from 27 Kaplan‐Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP‐1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes.ConclusionsThe probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP‐1RAs or SGLT2is compared with placebo. These results showed within‐ and between‐class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non‐inferiority trials, and have implications for decision makers and future clinical recommendations.
Case–control exercise challenge study on the pathogenesis of high serum gamma‐glutamyl transferase activity in racehorses
Authors: Mann Sabine , Abuelo Angel , Stokol Tracy , Wakshlag Joseph J. , Bayly Warwick , Reed Steven , Gandy Jeff , Ramsay Joshua David , Divers Thomas J. 
Published: May 2022

AbstractBackgroundHigh serum γ‐glutamyl‐transferase (GGT) activity syndrome in racehorses has been associated with maladaption to exercise. Investigation of affected horses before and immediately after standard exercise may provide critical insight into the syndrome's pathophysiology.ObjectivesTo investigate blood biomarker changes in actively competing racehorses with high GGT activity associated with an exercise challenge.Study designCase–control study.MethodsHigh GGT case (age: 2–3 years) and normal GGT control (age: 2–7 years) pairs (3 Thoroughbred, 4 Standardbred pairs) at least 3 months into their training/racing season were included. Horses with a recent history of high GGT activity (≥50 IU/L) without additional biochemical evidence of liver disease were identified by veterinarians. Horses were tested again in the week prior to a planned exercise challenge to confirm persistent increases in GGT activity. Controls from the same stable with similar training/racing intensity and serum GGT activity ≤36 IU/L were matched with each case. Blood samples were obtained immediately before, 15 and 120 min after exercise. Pre‐exercise serum samples were analysed for baseline select serum chemistries, selenium and vitamin E concentrations. Cortisol concentration and markers of oxidative status were measured in serum or plasma for all time points. Individual serum bile acid and coenzyme Q10 concentrations, plasma lipid mediator (fatty acids, oxylipids, isoprostanes) concentrations and targeted metabolomics analyses were performed using liquid chromatography‐mass spectrometry. Serum viral PCR for equine hepaci‐ and parvovirus was performed in each animal.ResultsCases had higher baseline concentrations of total glutathione, taurocholic acid, cortisol and cholesterol concentrations and higher or lower concentrations of specific oxylipid and isoprostane mediators, but there were no case‐dependent changes after exercise.Main limitationsSmall sample size.ConclusionsResults indicated that glutathione metabolism was altered in high GGT horses. Enhanced glutathione recycling and mild cholestasis are possible explanations for the observed differences.
5‐α reductase inhibition by Epilobioum fleischeri extract modulates facial microbiota structure
Authors: Sfriso Riccardo , Claypool Joshua , Roche Magalie , Imfeld Dominik 
Published: May 2022

AbstractBackgroundFacial skin is a particularly complex environment made of different skin types such as sebaceous (forehead) and dry (cheeks). The skin microbiota composition on different facial sites has not yet been addressed.MethodsWe conducted a 4‐week‐long, single‐centre, randomized and placebo‐controlled clinical study involving 23 Caucasian females. We assessed both bacterial composition on five different facial areas and the microbiome modulatory effects resulting from the topical application of a plant extract (Epilobium fleischeri). Skin microbiome samples were collected before and after 4 weeks of product application. Microbiota profiling was performed via 16S rRNA gene sequencing, and relative abundance data were used to calculate differentials via a multinomial regression model.ResultsVia ‘reference frames’, we observed shifts in microbial composition after 4 weeks of twice‐daily product application and identify certain microbiota species, which were positively associated with the application of the product containing the Epilobium fleischeri extract. Staphylococcus hominis, Staphylococcus epidermidis, and Micrococcus yunnanensis appeared to be significantly enriched in the final microbiota composition of the active treatment group.ConclusionFacial skin was found to be colonized by an heterogenous microbiota, and the Epilobium fleischeri extract had a modulatory effect on commensal bacteria on the different facial sites.