bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the landscape of cervical squamous cell carcinoma immune microenvironment by integrating the single‐cell transcriptomics and RNA‐Seq
Authors: Yin Ruiling , Zhai Xiuming , Han Hongyan , Tong Xuedong , Li Yan , Deng Kun 
Published: May 2022

AbstractBackgroundCervical squamous cell carcinoma (CSCC), caused by the infection of high‐risk human papillomavirus, is one of the most common malignancies in women worldwide.MethodsRNA expression data, including those from the Cancer Genome Atlas, Gene Expression Omnibus, and Genotype‐Tissue Expression databases, were used to identify the expression of RNAs in normal and tumor tissue. Correlation analysis was performed to identify the immune‐related long noncoding RNAs (IRLs) and hypoxia‐related genes (IRHs) that can influence the activity of the immune system. Prognosis models of immune‐related RNAs (IRRs) were used to construct a coexpression network of the immune system. We identified the role of IRRs in immunotherapy by correlation analysis with immune checkpoint genes (ICGs). We then validated the expression data by integrating two single‐cell sequencing data sets of CSCC to identify the key immune features.ResultsIn total, six immune‐related gene (IRG), four IRL, and five IRH signatures that can significantly influence the characteristics of the tumor immune microenvironment (TIME) were selected using machine learning methods. The expression level of ICGs was significantly upregulated in GZMB+CD8+ T‐cells and tumor‐associated macrophages (TAMs) in tumor tissues. TGFBI+ TAMs are a kind of blood‐derived monocyte‐derived M0‐like TAM linked to hypoxia and a poor prognosis. IFI30+ M1‐like TAMs participate in the process of immune‐regulation and showed a role in the promotion of CD8+ T‐cells and Type 1 T helper (Th1)/Th2 cells in the coexpression network, together with several IRLs, IRGs, and ICGs.ConclusionsCD16+ monocyte‐derived IFI30+ TAMs participated in our coexpression network to regulate the TIME, showing the potential to be a novel immunotherapy target. The enrichment of M0‐like TAMs was associated with a worse prognosis in the high‐risk score group with IRH signatures. Remarkably, M0‐like TAMs in tumor tissues overexpressed TGFBI and were associated with several well‐known tumor‐proliferation pathways.
Groundwater modelling of a shallow aquifer for the assessment of water logging: A case study of the Cebala‐Borj Touil irrigation perimeter, northern Tunisia
Authors: Rzigui Houda , Bogacki Wolfgang , Hörmann Georg , Hachicha Mohamed 
Published: May 2022

AbstractThe Cebala‐Borj Touil (Cebala) Plain in Tunisia is a large perimeter with an area of 3,200 ha. In 1990, a drainage and irrigation system was installed. The groundwater system is complex due to the proximity to the sea, the low slope, and the low performance of natural drainage. It is characterized by shallow groundwater and soil water logging. The flooded area is controlled by natural and artificial factors. The natural parameters are the flat slope and the soil texture. The man‐made problems are caused by inappropriate irrigation and drainage deficiency. The numerical groundwater flow simulation model FEFLOW (Finite Element Subsurface Flow System) was used to simulate the groundwater depth variability. The calculated water table depth ranged from less than 0.5 m from the ground surface to more than 8 m. Based on the calibrated model, several management scenarios were investigated to study the possibilities to mitigate the problem of water logging in the perimeter. The model results showed that improving the drainage efficiency and reducing the irrigation amounts could solve the water logging problem, but not entirely. For the low flooded parts, a pumping option could be considered. The final management scheme might include the combination of all the tested management scenarios.
In vitro fungicide sensitivity of Clarireedia, Fusarium, and Microdochium isolates from grasses
Authors: Gagkaeva Tatiana , Orina Aleksandra , Gavrilova Olga , Usoltseva Marina , Crouch Jo Anne , Normann Karin , Entwistle Kate , Torp Torfinn , Espevig Tatsiana 
Published: May 2022

AbstractClarireedia spp., Fusarium culmorum, and Microdochium nivale are destructive and widespread fungal pathogens causing turfgrass disease. Chemical control is a key tool for managing these diseases on golf greens but are most effective when used in a manner that reduces overall inputs, maximizes fungicide efficacy, and minimizes the risk of fungicide resistance. In this study, sensitivity to eight commonly used fungicides was tested in 13 isolates of Clarireedia spp., F. culmorum, and M. nivale via in vitro toxicity assays. Fungicide sensitivity varied significantly among the three species, with isolates of F. culmorum showing the least sensitivity. The sensitivity of M. nivale to all tested fungicides was high (with the exception of tebuconazole), but only four fungicides (Banner Maxx®, Instrata® Elite, Medallion TL, and Switch® 62,5 WG) suppressed the growth of M. nivale completely at a concentration of 1% of the recommended dose. All three fludioxonil‐containing fungicides either alone (Medallion TL) or in combination with difeconazole (Instrata® Elite) or cyprodinil (Switch® 62,5 WG) had the same high efficacy against isolates of both M. nivale and Clarireedia spp. On average, the Clarireedia isolates tested in this study showed high sensitivity to the tested fungicides, except for Heritage (azoxystrobin). The observed variation in sensitivity among isolates within the same fungal species to different fungicides needs further investigation, as an analysis of the differences in fungal growth within each fungal group revealed a significant isolate × fungicide interaction (p < .001).
Nowcasting tail risk to economic activity at a weekly frequency
Authors: Carriero Andrea , Clark Todd E. , Marcellino Massimiliano 
Published: May 2022

SummaryThis paper focuses on nowcasts of tail risk to GDP growth, with a potentially wide array of monthly and weekly information used to produce nowcasts on a weekly basis. We consider Bayesian mixed frequency regressions with stochastic volatility and Bayesian quantile regressions. Our results show that, within some limits, more information helps the accuracy of nowcasts of tail risk to GDP growth. Accuracy typically improves as time moves forward within a quarter, making additional data available, with monthly data more important to accuracy than weekly data. Accuracy also typically improves with the use of financial indicators in addition to a base set of macroeconomic indicators.
Robust inference under time‐varying volatility: A real‐time evaluation of professional forecasters
Authors: Demetrescu Matei , Hanck Christoph , Kruse‐Becher Robinson 
Published: May 2022

SummaryIn many forecast evaluation applications, standard tests as well as tests allowing for time‐variation in relative forecast ability build on heteroskedasticity‐and‐autocorrelation consistent (HAC) covariance estimators. Yet, the finite‐sample performance of these asymptotics is often poor. “Fixed‐
” asymptotics, used to account for long‐run variance estimation, improve finite‐sample performance under homoskedasticity, but lose asymptotic pivotality under time‐varying volatility. Moreover, loss of pivotality due to time‐varying volatility is found in the standard HAC framework in certain cases as well. We prove a wild bootstrap implementation to restore asymptotically pivotal inference for the above and new CUSUM‐ and Cramér‐von Mises‐based tests in a fairly general setup, allowing for estimation uncertainty from either a rolling window or a recursive approach when fixed‐
asymptotics are adopted to achieve good finite‐sample performance. We then investigate the (time‐varying) performance of professional forecasters relative to naive no‐change and model‐based predictions in real‐time. We exploit the Survey of Professional Forecasters (SPF) database and analyze nowcasts and forecasts at different horizons for output and inflation. We find that not accounting for time‐varying volatility seriously affects outcomes of tests for equal forecast ability: wild bootstrap inference typically yields convincing evidence for advantages of the SPF, while tests using non‐robust critical values provide remarkably less. Moreover, we find significant evidence for time‐variation of relative forecast ability, the advantages of the SPF weakening considerably after the “Great Moderation.”
Linear ubiquitination modification of NR6A1 by LUBAC inhibits RIPK3 kinase activity and attenuates apoptosis of vascular smooth muscle cells
Authors: Cai Zhou , He Xin , Liu Shuai , Bai Yang , Pan Baihong , Wu Kemin 
Published: May 2022

AbstractNuclear receptor subfamily 6 group A member 1 (NR6A1) is involved in promoting the apoptotic process of vascular smooth muscle cells (VSMCs) which is a critical process involved in atherosclerosis, but the action mechanism remains to be determined. Therefore, we studied the underlying mechanisms by which NR6A1 accelerated VSMC apoptosis in atherosclerosis. An atherosclerosis model has been established in apolipoprotein E‐deficient rats with a high‐fat diet for 12 weeks, which was characterized by pathological aortic plaques, increased lipid deposition and collagen content in aortic tissues, and high cholesterol and triglycerides levels in the serum. NR6A1 was experimentally shown to increase at protein level rather than messenger RNA level in atherosclerotic rats. Immunofluorescence exhibited the main location of NR6A1 in the cell nucleus of rat aortic tissues. By performing ectopic expression experiments, NR6A1 was demonstrated to suppress the viability and expedite the apoptosis of VSMCs, corresponding to augmented caspase‐3, caspase‐8, and caspase‐9 activities. It was further unraveled that NR6A1 could activate receptor‐interacting serine/threonine‐protein kinase 3 (RIPK3) by inducing its phosphorylation. Conversely, RIPK3 inhibitor GSK872 undermined the proapoptotic effect of NR6A1 on VSMCs. The co‐immunoprecipitation assay identified that linear ubiquitin chain assembly complex (LUBAC) can be pulled down by NR6A1. Furthermore. LUBAC inhibited the expression of NR6A1 by promoting its linear ubiquitination, thereby dephosphorylating RIPK3 and consequently inhibiting the VSMC apoptosis. Overall, LUBAC‐induced linear ubiquitination of NR6A1 can potentially arrest the apoptosis of VSMCs in atherosclerosis by downregulating RIPK3 and attenuating caspase activity. This finding suggests promising athero‐protective targets by limiting VSMC apoptosis.
Simulation studies of polypeptoids using replica exchange with dynamical scaling and dihedral biasing
Authors: Raubenolt Bryan A. , Rick Steven W. 
Published: May 2022

AbstractPolypeptoids differ from polypeptides in that the amide bond can more frequently adopt both cis and trans conformations. The transition between the two conformations requires overcoming a large energy barrier, making it difficult for conventional molecular simulations to adequately visit the cis and trans structures. A replica‐exchange method is presented that allows for easy rotations of the amide bond and also an efficient linking to a high temperature replica. The method allows for just three replicas (one at the temperature and Hamiltonian of interest, a second high temperature replica with a biased dihedral potential, and a third connecting them) to overcome the amide bond sampling problem and also enhance sampling for other coordinates. The results indicate that for short peptoid oligomers, the conformations can range from all cis to all trans with an average cis/trans ratio that depends on side chain and potential model.
Comparison of Race‐Based and Non–Race‐Based Equations for Kidney Function Estimation in Critically Ill Thai Patients for Vancomycin Dosing
Authors: Sitaruno Sirima , Santimaleeworagun Wichai , Pattharachayakul Sutthiporn , DeBacker Kenneth C. , Vattanavanit Veerapong , Binyala Wanrada , Pai Manjunath P. 
Published: May 2022

AbstractEmpiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New non–race‐based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10‐year period. A nonlinear mixed‐effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty‐three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1‐compartment linear elimination with zero‐order input and proportional error model. A Thai‐specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population‐specific eGFR equation.
Impact of prenatally diagnosed congenital heart defects on outcomes and management
Authors: Wong Jennifer , Kohari Katherine , Bahtiyar Mert Ozan , Copel Joshua 
Published: May 2022

AbstractFetal echocardiogram aids in prenatal identification of neonates at high risk for congenital heart defects (CHD). Prenatal detection rates for CHD have increased with improved ultrasound technology, the use of the early fetal echocardiography, and standardization of the performance of the fetal echocardiogram. Accurate prenatal detection of CHD, particularly complex CHD, is an important contributor to improved survival rates for patients with CHD. Early detection allows for families to choose whether or not to continue with pregnancy, referral to pediatric cardiology specialists for patient education, and delivery planning. Better psychosocial supports are needed for families with CHD.
Chronic fibrosing esophagitis with diffuse esophageal intramural pseudo‐diverticulosis
Authors: Hentschel Florian 
Published: May 2022

AbstractDiffuse esophageal intramural pseudo‐diverticulosis (DEIPD) is a chronic fibrosing inflammation of the esophagus of unknown origin. Its name derives from the characteristic pseudo‐diverticula formed by dilated ducts of submucosal glands. With an assumed prevalence of approximately 5–50/100 000, DEIPD is more frequent than previously estimated. It preferentially affects men between 50 and 70 years of age with a history of alcohol and tobacco abuse. Key symptoms are chronic dysphagia and food impactions. Typical endoscopic findings are multiple small, longitudinally aligned pseudo‐diverticle openings and trachealization of the esophagus. Additionally, the usually gray mucosa may show a fine‐grained pattern of very small red dots that merge into a pink tint, called “faux uni pattern.” Once established, clinical symptoms and endoscopic changes persist throughout life. Although there is no known causal therapy, complications like bolus impactions, candida infections, or reflux can and should be treated.
Oral pre‐exposure prophylaxis preference, uptake, adherence and continuation among adolescent girls and young women in Kampala, Uganda: a prospective cohort study
Authors: Mayanja Yunia , Kamacooko Onesmus , Lunkuse Jane Frances , Muturi‐Kioi Vincent , Buzibye Allan , Omali Denis , Chinyenze Kundai , Kuteesa Monica , Kaleebu Pontiano , Price Matt A. 
Published: May 2022

AbstractIntroductionOral pre‐exposure prophylaxis (PrEP) has been scaled up; however, data from real‐world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub‐Saharan Africa.MethodsWe conducted a prospective cohort study among 14‐ to 24‐year‐old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long‐acting injectable PrEP and anti‐retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was “preferred” if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self‐reports.ResultsBetween January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2–9 partners (aRR = 2.36, 95% CI: 1.20–4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41–9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08–2.19) and being separated (aRR 1.55, 95% CI 1.04–2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 μg/L) of which only three were protective (>40 μg/L).ConclusionsHalf of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end‐user preferences and, community delivery promoted during restricted movement.
Research priorities for mitochondrial disorders: Current landscape and patient and professional views
Authors: Thomas Rhys H. , Hunter Amy , Butterworth Lyndsey , Feeney Catherine , Graves Tracey D. , Holmes Sarah , Hossain Pushpa , Lowndes Jo , Sharpe Jenny , Upadhyaya Sheela , Varhaug Kristin N. , Votruba Marcela , Wheeler Russell , Staley Kristina , Rahman Shamima 
Published: May 2022

AbstractPrimary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease‐modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively funded research designed by academics meets the core needs of people with mitochondrial disorders and their clinicians. Priority setting partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web‐based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment and psychological impact. Following the removal of “answered questions”, the process resulted in a list of 42 discrete, answerable questions. This was further refined by web‐based ranking by the community to 24 questions. These were debated at a face‐to‐face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive “Top 10 of unanswered research questions for primary mitochondrial disorders”. These Top 10 questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support and optimal management of stroke‐like episodes and fatigue.
Regional Analysis of Liver Surface Nodularity in a Single Axial MR Image for Staging Liver Fibrosis
Authors: Kim Tae‐Hoon , Kim Youe Ree , Jeong Chang‐Won , Kim Hyung Joong , Kim Jin Woong , Lee Young Hwan , Yoon Kwon‐Ha 
Published: May 2022

BackgroundThe assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time‐consuming procedures. A simplified method to estimate LSN score may be useful in the clinic.PurposeTo evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis.Study TypeRetrospective.PopulationA total of 210 subjects, a multicenter study.Field Strength/SequenceA 3 T/noncontrast gradient echo T1WI.AssessmentSubjects were divided into five fibrosis groups (F0 = 29; F1 = 20; F2 = 32; F3 = 50; F4 = 79) based on the METAVIR fibrosis scoring system. The mean LSN (on three slices) and regional LSN (on one slice) measurements, and the processing times, are compared. The regional LSN scores in five regions‐of‐interests (ROI1‐5) were analyzed in a single axial MRI at the level of the hilum by two independent observers.Statistical TestsRegional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland–Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value < 0.05 was considered statistically significant.ResultsTotal processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROI5 showed the highest AUROC (0.871 at cut‐off 1.12) for discriminating F0‐2 vs. F3‐4 and the best correlation with mean LSN score (r = 0.800, −0.07 limit of agreement).ConclusionQuantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI5 LSN score might be useful for clinical decision‐making and for distinguishing the difference between early fibrosis (F0‐2) and advanced fibrosis (F3−4) in the liver.Evidence Level3Technical EfficacyStage 2