bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain‐specific loss of Abcg1 disturbs cholesterol metabolism and aggravates pyroptosis and neurological deficits after traumatic brain injury
Authors: Xu Heng , Zheng Le‐xin , Chen Xue‐Shi , Pang Qiu‐yu , Yan Ya‐nan , Liu Rong , Guo Han‐mu , Ren Zhi‐yang , Yang Yan , Gu Zhi‐ya , Gao Cheng , Gao Yuan , Luo Cheng‐liang , Zhao Ying , Wang Ying , Wang Tao , Tao Lu‐yang 
Published: October 2022

AbstractBased on accumulating evidence, cholesterol metabolism dysfunction has been suggested to contribute to the pathophysiological process of traumatic brain injury (TBI) and lead to neurological deficits. As a key transporter of cholesterol that efflux from cells, the ATP‐binding cassette (ABC) transporter family exerts many beneficial effects on central nervous system (CNS) diseases. However, there is no study regarding the effects and mechanisms of ABCG1 on TBI. As expected, TBI resulted in the different time‐course changes of cholesterol metabolism‐related molecules in the injured cortex. Considering ABCG1 is expressed in neuron and glia post‐TBI, we generated nestin‐specific Abcg1 knockout (Abcg1‐KO) mice using the Cre/loxP recombination system. These Abcg1‐KO mice showed reduced plasma high‐density lipoprotein cholesterol levels and increased plasma lower‐density lipoprotein cholesterol levels under the base condition. After TBI, these Abcg1‐KO mice were susceptible to cholesterol metabolism turbulence. Moreover, Abcg1‐KO exacerbated TBI‐induced pyroptosis, apoptosis, neuronal cell insult, brain edema, neurological deficits, and brain lesion volume. Importantly, we found that treating with retinoid X receptor (RXR, the upstream molecule of ABCG1) agonist, bexarotene, in Abcg1‐KO mice partly rescued TBI‐induced neuronal damages mentioned above and improved functional deficits versus vehicle‐treated group. These data show that, in addition to regulating brain cholesterol metabolism, Abcg1 improves neurological deficits through inhibiting pyroptosis, apoptosis, neuronal cell insult, and brain edema. Moreover, our findings demonstrate that the cerebroprotection of Abcg1 on TBI partly relies on the activation of the RXRalpha/PPARgamma pathway, which provides a potential therapeutic target for treating TBI.
Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer
Authors: Ishii Takeshi , Akiyama Yoshimitsu , Shimada Shu , Kabashima Ayano , Asano Daisuke , Watanabe Shuichi , Ishikawa Yoshiya , Ueda Hiroki , Akahoshi Keiichi , Ogawa Kosuke , Ono Hiroaki , Kudo Atsushi , Tanabe Minoru , Tanaka Shinji 
Published: October 2022

AbstractAlthough histone H3K4 methyltransferase SETD1A is overexpressed in various cancer types, the molecular mechanism underlying its overexpression and its target genes in pancreatic ductal adenocarcinoma (PDAC) remain unclarified. We conducted immunohistochemical staining for SETD1A in 105 human PDAC specimens to assess the relationship between SETD1A overexpression and clinicopathological features. The function and target genes of SETD1A were investigated using human pancreatic cancer cell lines. SETD1A expression was upregulated in 51.4% of patients with PDAC and was an independent prognostic factor associated with shorter disease‐free survival after resection (p < 0.05). Knockdown and overexpression of SETD1A showed that SETD1A plays a crucial role in increasing the proliferation and motility of PDAC cells. SETD1A overexpression increased tumorigenicity. RNA sequencing of SETD1A‐knockdown cells revealed downregulation of RUVBL1, an oncogenic protein ATP‐dependent DNA helicase gene. ChIP analysis revealed that SETD1A binds to the RUVBL1 promoter region, resulting in increased H3K4me3 levels. Knockdown of RUVBL1 showed inhibition of cell proliferation, migration, and invasion of PDAC cells, which are similar biological effects to SETD1A knockdown. High expression of both SETD1A and RUVBL1 was an independent prognostic factor not only for disease‐free survival but also for overall survival (p < 0.05). In conclusion, we identified RUVBL1 as a novel downstream target gene of the SETD1A‐H3K4me3 pathway. Co‐expression of SETD1A and RUVBL1 is an important factor for predicting the prognosis of patients with PDAC.
Effects of aromatase inhibitor therapy on visceral adipose tissue area and cardiometabolic health in postmenopausal women with early and locally advanced breast cancer
Authors: Cheung Yee‐Ming M. , Hoermann Rudolf , Van Karen , Wu Damian , Healy Jenny , Chao Michael , White Shane , Yeo Belinda , Zajac Jeffrey , Grossmann Mathis 
Published: October 2022

AbstractObjectiveAromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor‐positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT.MethodsWe conducted a prospective 12‐month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X‐ray absorptiometry. Other risk markers of cardiometabolic health were also assessed.ResultsIn women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of −5.00 cm2 (−16.9, 6.91), p = .55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12 months. Findings were similar after adjustments for activity levels and coronavirus disease 2019 lockdown duration.ConclusionsThese data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.
Pairwise comparison of hydrochlorothiazide and chlorthalidone responses among hypertensive patients
Authors: Chekka Lakshmi Manasa S. , Cooper‐DeHoff Rhonda M. , Gums John G. , Chapman Arlene B. , Johnson Julie A. 
Published: October 2022

AbstractThis study conducted a pairwise comparison of antihypertensive and metabolic effects of hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) at 25 mg/day in the same individuals to address the clinical dilemma on preferred thiazide for hypertension (HTN) management. We included 15 African American (AA) and 35 European American (EA) patients with HTN treated with HCTZ and CTD as part of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR‐2 trials, respectively. Mean reduction in systolic/diastolic blood pressure (SBP/DBP) with HCTZ versus CTD was 8/5 versus 16/8 mmHg among EA patients (p < 1.0e−5 SBP, p = 0.002 DBP) and 11/8 versus 20/11 mmHg among AA patients (p = 0.03 SBP, p = 0.22 DBP). While CTD showed clinically meaningful benefit over HCTZ in two‐thirds of participants with respect to SBP reduction and half of EA patients with respect to DBP reduction, a majority of AA patients (53%) showed similar DBP reduction with both thiazides. Sixty percent of AA patients and 29% of EA patients attained blood pressure (BP) <140/90 mmHg with both thiazides. Mean potassium (K+) reduction was greater with CTD compared to HCTZ both in EA patients (mean difference = 0.35, p = 0.0002) and AA patients (0.49, p = 0.043). While 31% of AA patients developed severe hypokalemia on CTD, <5% of others developed severe hypokalemia. Although 46% of AA patients on CTD required K+ supplementation, only 6%–11% of others required supplementation. Overall, in the majority of EA patients, CTD was superior to HCTZ, whereas among AA patients, it was superior in a minority, and was associated with significant potassium‐related risk, suggesting that guideline preferences for CTD over HCTZ are reasonable in EA patients but may be less reasonable in AA patients, particularly if the target is <140/90 mmHg.
Screening and characterization of myositis‐related autoantibodies in COVID‐19 patients
Authors: Teo Kai‐Fa , Chen Der‐Yuan , Hsu Jeh‐Ting , Lai Yi‐Hua , Chang Ching‐Kun , Hsueh Po‐Ren , Lan Joung‐Liang , Hsu Jye‐Lin 
Published: October 2022

AbstractAn efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2, COVID‐19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID‐19 patients. Moreover, clinical observations have revealed that COVID‐19‐associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)‐ILD. This study explored this phenomenon by seeking to identify and characterize myositis‐specific and related autoantibodies in 25 COVID‐19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID‐19 with one or more autoantibodies against several myositis‐related antigens (Jo‐1, Ku, Mi‐2β, PL‐7, PL‐12, PM‐Scl 75, PM‐Scl 100, Ro‐52, and SRP); no anti‐MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [35S]methionine‐labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti‐Ku70 and anti‐Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID‐19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases.
Extramammary myofibroblastoma of the oral cavity
Authors: Weigelt Maximillian A. , Franklin Matthew J. , Patel Manojkumar T. , Bergfeld Wilma F. 
Published: October 2022

AbstractMyofibroblastoma is a rare, benign mesenchymal tumor first described as a neoplasm of the breast. Extramammary myofibroblastoma is a histopathologically and genetically identical lesion occurring outside the breast. Herein is presented a case of extramammary myofibroblastoma arising in the oral cavity. A 59‐year‐old woman presented with a 1.5 cm nodule on the buccal surface of the lower lip. Wide local excision was performed. Histopathologic examination revealed haphazard fascicles of monomorphic spindle cells with hyalinized collagen bundles without fat. The spindled cells were diffusely positive for CD34, and focally for progesterone receptor. Desmin, smooth muscle actin, estrogen receptor, androgen receptor, S100, and STAT6 were negative. Rb1 expression was lost in tumor cells. Thus, the diagnosis of extramammary myofibroblastoma was made. Differential diagnoses include spindle‐cell lipoma and angiofibroma. All three tumors are members of the 13q14 deletion/RB1 loss family. Indolent but locally aggressive (solitary fibrous tumor, desmoid fibromatosis) and frankly malignant (low‐grade peripheral nerve sheath tumor, dermatofibrosarcoma protuberans) entities can be excluded by immunohistochemistry and careful microscopic examination. Extensive sampling extramammary myofibroblastoma is important to exclude the possibility of malignancy. Clinicians and pathologists alike should be aware of this entity and its potential to arise rarely in unusual locations.
Diabetes mellitus and the risk of post‐acute COVID‐19 hospitalizations—a nationwide cohort study
Authors: Nørgård Bente Mertz , Zegers Floor Dijkstra , Juhl Claus Bogh , Kjeldsen Jens , Nielsen Jan 
Published: October 2022

AbstractAimsThis cohort study, based on Danish health registers, examined the post‐acute consequences of hospitalization for COVID‐19 in patients with diabetes.MethodsThe study population comprised all Danish citizens (≥18 years old) who had diabetes when the pandemic started. A patient was exposed if he/she had a hospitalization with COVID‐19 after 1 March 2020. A patient was unexposed when he/she was not hospitalized with COVID‐19 between 1 March 2020 and the end of follow‐up (4 January 2022), or the first registered event of interest. The outcomes included post‐COVID‐19 hospitalizations and death. We used a Cox proportional hazards model with time varying exposure estimating the hazards ratio (HR) to analyze if the hazard for an outcome of interest was impacted by being hospitalized with COVID‐19.ResultsIn patients with type 1 diabetes, 101 were hospitalized with COVID‐19, and 25,459 were not. We did not have sufficient statistical power to identify differences in risk for those with type 1 diabetes. In type 2 diabetes, 1515 were hospitalized with COVID‐19, and 95,887 were not. The adjusted HRs of post‐acute hospitalization for respiratory diseases and infections were 1.71 (95% CI 1.45–2.03) and 1.87 (95% CI 1.61–2.18), respectively. The HR of death was 2.05 (95% CI 1.73–2.43). Patients with uncertain type had results similar to those with type 2 diabetes.Conclusions/InterpretationIn type 2 diabetes and diabetes of uncertain type, hospitalization with COVID‐19 was associated with an increased risk of post‐acute hospitalization for respiratory diseases, infections and death.
Evaluation of a broken instrument removal training course for general dentistry residents
Authors: Xie Kexian , Li Yuangao , Wang Xiao 
Published: October 2022

AbstractIntroductionTo help general dentistry residents better manage the intracanal broken instrument situation, we introduced a hands‐on training course into the endodontic curriculum of a general dentistry residency programme.Materials and MethodsThirty general dentistry residents and 30 residents with endodontic specialty training background in a general hospital served as the experimental group and reference group, respectively. The experimental group underwent a training course including a 30‐min lecture and two hands‐on sessions (2 h each). After the course, residents from both groups were asked to perform the instrument removal procedure on simulated root canals. Success rate, procedure time and canal volume change were compared between groups. Questionnaire results were also analysed.ResultsAll residents successfully managed to remove the broken instruments in the test. Procedure time was significantly longer for general dentistry residents (15.8 ± 5.7 min vs 13.7 ± 4.5 min, Mann–Whitney U test, p = .038). Canal volume change was significantly greater for general dentistry residents (8.53 ± 3.82 μl vs 5.94 ± 2.73 μl, independent‐samples t‐test, p = .004). In the questionnaires, trainees gave overall positive ratings for the course. The marginal homogeneity test on before and after scores of the questionnaire items showed the training helped the trainees to reduce the stress level associated with instrument breakage (p < .001). It also motivated the trainees to remove the broken instrument in some straightforward cases (p < .001).ConclusionThe broken instrument removal training course could help the general dentistry residents better manage the intracanal broken instrument situation.
Improving dental student confidence through the use of simulated patient cases
Authors: Marsden Jonathan E. , Deboo Stephen P. , Cripps Matt , Longridge Nicholas N. , Aspden Michael , Fox Kathryn 
Published: October 2022

AbstractIntroductionThis study investigates whether student confidence could be improved through the use of simulated patient case‐based scenarios.Materials and MethodsStudents in their 4th and 5th year of undergraduate study completed an online e‐portfolio workbook consisting of activities related to five simulated patient cases. Following completion of the relevant learning activities within the e‐portfolio, students then viewed a tutor case presentation video and attended simulated clinic sessions to complete corresponding exercises involving 3D‐printed teeth related to the case. Subsequently, students undertook online self‐reflection and goal‐setting activities to aid their development. An anonymous questionnaire was distributed to all participants to gain insight into the themes of student confidence and learning support. The Cronbach's Alpha coefficient was calculated for both sections of the student questionnaire. The values for “student confidence” and “learning support” were α = 0.91 and α = 0.87, respectively.ResultsThere was a total of 89 valid student responses to the questionnaire (65%). A Spearman's correlation of rs = 0.50 (p < .001) suggests a tentative causative correlation between the learning support offered through the simulated patient cases and student confidence. There was a positive directional relationship between engagement with the learning support of the simulated patient cases and student confidence scores.ConclusionStudent confidence increased following the completion of simulated patient cases and students found the learning support offered beneficial to their development. This learning intervention has the potential to improve student self‐efficacy, develop contextual competency and facilitate reflective practice. Simulated patient cases may be a useful precursor or adjunct to traditional patient clinics.
Prognostic scores in status epilepticus: A systematic review and meta‐analysis
Authors: Yuan Fang , Damien Charlotte , Gaspard Nicolas 
Published: October 2022

AbstractThe performance of prognostic scores of status epilepticus (SE) has been reported in very heterogeneous cohorts. We aimed to provide a summary of the available evidence on their respective performance. PubMed and EMBASE were searched for relevant articles. Studies were reviewed for eligibility for meta‐analysis of the area under the receiver‐operating characteristic curve (AUC) and for meta‐analysis of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting in‐hospital mortality with scores in which at least two external evaluations had been published. This study was registered with PROSPERO (international prospective register of systematic reviews) (CRD42022325766). Study quality was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). In the meta‐analysis of AUC, 21 studies were pooled for STESS (Status Epilepticus Severity Score), five for EMSE‐EAC (Epidemiology‐based Mortality Score in Status Epilepticus ‐ Etiology, Age, level of Consciousness), five for EMSE‐EACE (EMSE ‐ Etiology, Age, level of Consciousness, EEG), and two for ENDIT (Encephalitis, nonconvulsive status epilepticus, Diazepam resistance, Imaging abnormalities, Tracheal intubation). The pooled AUC of STESS, EMSE‐EAC, EMSE‐EACE, and ENDIT was 0.74 (95% CI: 0.71–0.78), 0.68 (95% CI 0.63–0.72), 0.77 (95% CI: 0.72–0.81), and 0.78 (95% CI: 0.70–0.87), respectively. The pooled sensitivity of STESS‐3, STESS‐4, EMSE‐EACE‐64, and ENDIT‐4 was 0.83 (95% CI: 0.80–0.86), 0.60 (95% CI: 0.55–0.65), 0.76 (95% CI: 0.67–0.83), and 0.70 (95% CI: 0.55–0.82), respectively. Their pooled specificity was 0.50 (95% CI: 0.48–0.52), 0.74 (95% CI: 0.72–0.76), 0.63 (95% CI: 0.59–0.67), and 0.65 (95% CI: 0.61–0.70), respectively. Their pooled PPV was 0.27 (95% CI: 0.24–0.30), 0.35 (95% CI: 0.29–0.41), 0.33 (95% CI: 0.24–0.43), and 0.20 (95% CI: 0.13–0.27). Their pooled NPV was 0.94 (95% CI: 0.93–0.96), 0.90 (95% CI: 0.89–0.92), 0.89 (95% CI: 0.80–0.98), and 0.95 (95% CI: 0.92–0.98). Variations in performance were observed in patients' subgroups, such as critically ill patients and refractory cases. Investigated scores only have acceptable AUC, sensitivity, and specificity for predicting in‐hospital mortality, with the EMSE‐EAC having a lower discriminative power. STESS‐3 has the highest sensitivity, and STESS‐4 the highest specificity, but neither combines acceptable sensitivity and specificity. All these scores had high NPV but very low PPV. Caution should be exercised in their clinical use. Further studies are required to develop more accurate scores.
Getting the clock back on its feet: targeting the circadian clock to treat osteoarthritis
Authors: Mortimer Thomas 
Published: October 2022

Growing evidence suggests that circadian clock dysfunction may contribute to the pathology of osteoarthritis. In this issue, He et al. use in vivo and human‐derived osteoarthritis models to demonstrate the therapeutic potential of pharmacologically manipulating components of the cartilage circadian clock. In doing so, the authors provide an important proof‐of‐principle supporting circadian clock‐targeted therapy as a treatment option for osteoarthritis.Comment on: https://doi.org/10.1111/febs.16601
Capacity of deep‐sea corals to obtain nutrition from cold seeps aligned with microbiome reorganization
Authors: Osman Eslam O. , Vohsen Samuel A. , Girard Fanny , Cruz Rafaelina , Glickman Orli , Bullock Lena M. , Anderson Kaitlin E. , Weinnig Alexis M. , Cordes Erik E. , Fisher Charles R. , Baums Iliana B. 
Published: October 2022

AbstractCold seeps in the deep sea harbor various animals that have adapted to utilize seepage chemicals with the aid of chemosynthetic microbes that serve as primary producers. Corals are among the animals that live near seep habitats and yet, there is a lack of evidence that corals gain benefits and/or incur costs from cold seeps. Here, we focused on Callogorgia delta and Paramuricea sp. type B3 that live near and far from visual signs of currently active seepage at five sites in the deep Gulf of Mexico. We tested whether these corals rely on chemosynthetically‐derived food in seep habitats and how the proximity to cold seeps may influence; (i) coral colony traits (i.e., health status, growth rate, regrowth after sampling, and branch loss) and associated epifauna, (ii) associated microbiome, and (iii) host transcriptomes. Stable isotope data showed that many coral colonies utilized chemosynthetically derived food, but the feeding strategy differed by coral species. The microbiome composition of C. delta, unlike Paramuricea sp., varied significantly between seep and non‐seep colonies and both coral species were associated with various sulfur‐oxidizing bacteria (SUP05). Interestingly, the relative abundances of SUP05 varied among seep and non‐seep colonies and were strongly correlated with carbon and nitrogen stable isotope values. In contrast, the proximity to cold seeps did not have a measurable effect on gene expression, colony traits, or associated epifauna in coral species. Our work provides the first evidence that some corals may gain benefits from living near cold seeps with apparently limited costs to the colonies. Cold seeps provide not only hard substrate but also food to cold‐water corals. Furthermore, restructuring of the microbiome communities (particularly SUP05) is likely the key adaptive process to aid corals in utilizing seepage‐derived carbon. This highlights that those deep‐sea corals may upregulate particular microbial symbiont communities to cope with environmental gradients.
Foreword: Rising temperatures
Authors: Kennedy‐Pipe Caroline , Depledge Duncan 
Published: October 2022

AbstractAs an introduction to a special section on remote politics in the Arctic. We introduce how the various authors have analysed the consequences of a warming Arctic for the peoples who inhabit it and for those states seeking to retain or expand influence in this resource‐rich region. We hope to start a conversation between scholars in International Relations and those in Geography to understand this rapdily warming region.