bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung’s disease
Authors: Chen Ko-Chin , Song Zan-Min , Croaker Geoffrey D. 
Published: June 2021

AbstractBackgroundETBhas been reported to regulate neurogenesis and vasoregulation in foetal development. Its dysfunction was known to cause HSCR, an aganglionic colonic disorder with syndromic forms reported to associate with both small heads and developmental delay. We therefore asked, "is CNS maldevelopment a more general feature of ETBmutation?" To investigate, we reviewed the micro-CT scans of an ETB−/−model animal,sl/slrat, and quantitatively evaluated the structural changes of its brain constituents.MethodsEleven neonatal rats generated from ETB+/−cross breeding were sacrificed. Micro-CT scans were completed following 1.5% iodine-staining protocols. All scans were reviewed for morphological changes. Selected organs were segmented semi-automatically post-NLM filtering: TBr, T-CC, T-CP, OB, Med, Cer, Pit, and S&I Col. Volumetric measurements were made using Drishti rendering software. Rat genotyping was completed following analysis. Statistical comparisons on organ volume, organ growth rate, and organ volume/bodyweight ratios were made betweensl/sland the control groups based on autosomal recessive inheritance. One-way ANOVA was also performed to evaluate potential dose-dependent effect.Resultssl/slrat has 16.32% lower body weight with 3.53% lower growth rate than the control group. Gross intracranial morphology was preserved insl/slrats. However, significant volumetric reduction of 20.33% was detected in TBr; similar reductions were extended to the measurements of T-CC, T-CP, OB, Med, and Pit. Consistently, lower brain and selected constituent growth rates were detected insl/slrat, ranging from 6.21% to 11.51% reduction. Lower organ volume/bodyweight ratio was detected insl/slrats, reflecting disproportional neural changes with respect to body size. No consistent linear relationships exist between ETBcopies and intracranial organ size or growth rates.ConclusionAlthough ETB−/−mutant has a normal CNS morphology, significant size reductions in brain and constituents were detected. These structural changes likely arise from a combination of factors secondary to dysfunctional ET-1/ET-3/ETBsignalling, including global growth impairment from HSCR-induced malnutrition and dysregulations in the neurogenesis, angiogenesis, and cerebral vascular control. These changes have important clinical implications, such as autonomic dysfunction or intellectual delay. Although further human study is warranted, our study suggested comprehensive managements are required for HSCR patients, at least in ETB−/−subtype.
Combining QTL-seq and linkage mapping to fine map a candidate gene in qCTS6 for cold tolerance at the seedling stage in rice
Authors: Yang Luomiao , Wang Jingguo , Han Zhenghong , Lei Lei , Liu Hua Long , Zheng Hongliang , Xin Wei , Zou Detang 
Published: June 2021

AbstractBackgroundCold stress caused by low temperatures is an important factor restricting rice production. Identification of cold-tolerance genes that can stably express in cold environments is crucial for molecular rice breeding.ResultsIn this study, we employed high-throughput quantitative trait locus sequencing (QTL-seq) analyses in a 460-individual F2:3mapping population to identify major QTL genomic regions governing cold tolerance at the seedling stage in rice. A novel major QTL (qCTS6) controlling the survival rate (SR) under low-temperature conditions of 9°C/10 days was mapped on the 2.60-Mb interval on chromosome 6. Twenty-seven single-nucleotide polymorphism (SNP) markers were designed for theqCST6region based on re-sequencing data, and local QTL mapping was conducted using traditional linkage analysis. Eventually, we mappedqCTS6to a 96.6-kb region containing 13 annotated genes, of which seven predicted genes contained 13 non-synonymous SNP loci. Quantitative reverse transcription PCR analysis revealed that only Os06g0719500, anOsbZIP54transcription factor, was strongly induced by cold stress. Haplotype analysis confirmed that +376 bp (T>A) in theOsbZIP54coding region played a key role in regulating cold tolerance in rice.ConclusionWe identifiedOsbZIP54as a novel regulatory gene associated with rice cold-responsive traits, with its Dongfu-104 allele showing specific cold-induction expression serving as an important molecular variation for rice improvement. This result is expected to further exploration of the genetic mechanism of rice cold tolerance at the seedling stage and improve cold tolerance in rice varieties by marker-assisted selection.
Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study
Authors: Chen Zhao-Ming , Li Zheng-Tu , Li Shao-Qiang , Guan Wei-Jie , Qiu Ye , Lei Zi-Ying , Zhan Yang-Qing , Zhou Hua , Lin Sheng , Wang Xinni , Li Zhun , Yang Feng , Zeng Wen , Lin Ye , Liu Jing , Zhang Jian-Quan , Ye Feng 
Published: June 2021

Abstract
Background
Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.

Methods
Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.

Results
Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.

Conclusion
T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.
Automated left atrial time-resolved segmentation in MRI long-axis cine images using active contours
Authors: Gonzales Ricardo A. , Seemann Felicia , Lamy Jérôme , Arvidsson Per M. , Heiberg Einar , Murray Victor , Peters Dana C. 
Published: June 2021

AbstractBackgroundSegmentation of the left atrium (LA) is required to evaluate atrial size and function, which are important imaging biomarkers for a wide range of cardiovascular conditions, such as atrial fibrillation, stroke, and diastolic dysfunction. LA segmentations are currently being performed manually, which is time-consuming and observer-dependent.MethodsThis study presents an automated image processing algorithm for time-resolved LA segmentation in cardiac magnetic resonance imaging (MRI) long-axis cine images of the 2-chamber (2ch) and 4-chamber (4ch) views using active contours. The proposed algorithm combines mitral valve tracking, automated threshold calculation, edge detection on a radially resampled image, edge tracking based on Dijkstra’s algorithm, and post-processing involving smoothing and interpolation. The algorithm was evaluated in 37 patients diagnosed mainly with paroxysmal atrial fibrillation. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC) and Hausdorff distance (HD), with manual segmentations in all time frames as the reference standard. For inter-observer variability analysis, a second observer performed manual segmentations at end-diastole and end-systole on all subjects.ResultsThe proposed automated method achieved high performance in segmenting the LA in long-axis cine sequences, with a DSC of 0.96 for 2ch and 0.95 for 4ch, and an HD of 5.5 mm for 2ch and 6.4 mm for 4ch. The manual inter-observer variability analysis had an average DSC of 0.95 and an average HD of 4.9 mm.ConclusionThe proposed automated method achieved performance on par with human experts analyzing MRI images for evaluation of atrial size and function.
Risks associated with continuation of potentially inappropriate antihypertensive medications in older adults receiving hemodialysis
Authors: Hall Rasheeda K. , Morton Sarah , Wilson Jonathan , Ephraim Patti L. , Boulware L. Ebony , St. Peter Wendy L. , Colón-Emeric Cathleen , Pendergast Jane , Scialla Julia J. 
Published: June 2021

Abstract
Background and objectives
After dialysis initiation, older adults may experience orthostatic or post-dialysis hypotension. Some orthostasis-causing antihypertensives (i.e., central alpha agonists and alpha blockers), are considered potentially inappropriate medications (PIMs) for older adults because they carry more risk than benefit. We sought to (1) describe antihypertensive PIM prescribing patterns before and after dialysis initiation and (2) ascertain the potential risk of adverse outcomes when these medications are continued after dialysis initiation.

Design, setting, participants, and measurements
Using United States Renal Data System data, we evaluated monthly prevalence of antihypertensive PIM claims in the period before and after dialysis initiation among older adults aged ≥66 years initiating in-center hemodialysis in the US between 2013 and 2014. Patients with an antihypertensive PIM prescription at hemodialysis initiation and who survived for 120 days were classified as ‘continuers’ or ‘discontinuers’ based on presence or absence of a refill within the 120 days after initiation. We compared rates of hospitalization and risk of death across these groups from day 121 through 24 months after dialysis initiation.

Results
Our study included 30,760 total patients, of whom 5981 (19%) patients had an antihypertensive PIM claim at dialysis initiation and survived ≥120 days. Most [65% (n = 3920)] were continuers. Those who continued (versus discontinued) were more likely to be black race (26% versus 21%), have dual Medicare-Medicaid coverage (31% versus 27%), have more medications on average (12 versus 9) and have no functional limitations (84% versus 80%). Continuers experienced fewer all-cause hospitalizations and deaths, but neither were statistically significant after adjustment (Hospitalization: RR 0.93, 95% CI 0.86, 1.00; Death: HR 0.89, 95% CI: 0.78–1.02).

Conclusions
Nearly one in five older adults had an antihypertensive PIM at dialysis initiation. Among those who survived ≥120 days, continuation of an antihypertensive PIM was not associated with increased risk of all-cause hospitalization or mortality.
A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma
Authors: Hong Liang , Zhou Yu , Xie Xiangbang , Wu Wanrui , Shi Changsheng , Lin Heping , Shi Zhenjing 
Published: June 2021

Abstract
Background
Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear.

Methods
Molecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature.

Results
We identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature.

Conclusions
Findings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.
Viral hepatitis associated hepatocellular carcinoma on the African continent, the past, present, and future: a systematic review
Authors: Dakurah Ottovon Bismark , Tamandjou Cynthia Raissa Tchuem , Zunza Moleen , Preiser Wolfgang , Maponga Tongai Gibson 
Published: June 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa.

Aim
The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980–2019).

Methods
A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed.

Results
A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63–1.71, p < 0.001), 0.82% (95% CI: 0.45–1.18, p < 0.001), and 3.34% (95% CI: 2.44–4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by − 0.50% (95% CI: − 0.74 – − 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased.

Conclusion
Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa.
This systematic review is registered with PROSPERO®, number CRD42020169723.
Local treatment for triple-negative breast cancer patients undergoing chemotherapy: breast-conserving surgery or total mastectomy?
Authors: Guo Leqian , Xie Guilan , Wang Ruiqi , Yang Liren , Sun Landi , Xu Mengmeng , Yang Wenfang , Chung Mei Chun 
Published: June 2021

AbstractBackgroundBecause there is no exact therapeutic target, the systemic treatment of triple-negative breast cancer (TNBC) still relies on chemotherapy. In terms of local treatment, based on the highly malignant characteristics of TNBC, it is still uncertain whether patients should be given more aggressive local treatment.MethodsThis study was based on the SEER database. 13,262 TNBC patients undergoing chemotherapy were included. According to local treatment methods, patients were divided into breast-conserving surgery with radiotherapy (BCS + RT), total mastectomy alone and total mastectomy with radiotherapy (Mastectomy+RT). Kaplan-Meier survival analysis drew the survival curves of Overall Survival (OS) and Breast Cancer Specific Survival (BCSS), and Cox proportional risk regression models were used to analyze the impact of different local treatments on OS and BCSS.ResultsAfter adjusting confounding factors, Mastectomy alone group (HR = 1.57; 95%CI: 1.40–1.77) and Mastectomy+RT group (HR = 1.28; 95%CI: 1.12–1.46) were worse in OS than BCS + RT group, and Mastectomy+RT group (HR = 0.81; 95%CI: 0.73–0.91) was better in OS than Mastectomy alone group. The effect of local treatment for BCSS was similar to that of OS. After stratification according to age, tumor size and lymph node status, when the age was less than 55 years old, at T4, N2 or N3 category, there was no statistical significance between the BCS + RT group and the Mastectomy+RT group in OS or BCSS (allP > 0.05). When the age was less than 65 years old, at T1, T2 or N0 category, there was no statistical significance between the Mastectomy alone group and the Mastectomy+RT group in OS or BCSS (allP > 0.05). The results of other stratified analyses were basically consistent with the results of total population analysis.ConclusionThe survival benefit of breast-conserving surgery with radiotherapy was higher than or similar to that of total mastectomy TNBC patients.
A qualitative study of stakeholder views on the use of a digital app for supported self-management in early intervention services for psychosis
Authors: Steare Thomas , Giorgalli Maria , Free Katherine , Harju-Seppänen Jasmine , Akther Syeda , Eskinazi Michelle , O’Hanlon Puffin , Rostill Helen , Amani Sarah , Lloyd-Evans Brynmor , Osborn David , Johnson Sonia 
Published: June 2021

Abstract
Background
Digital tools such as Smartphones have the potential to increase access to mental health support including self-management interventions for individuals with psychosis, and ultimately to improve outcomes. Self-management strategies, including relapse prevention and crisis planning and setting personal recovery goals, are intended to assist people with long-term conditions to take an active role in their recovery, with evidence for a range of benefits. However, their implementation is inconsistent, and access and uptake need to be improved. The current study explores the acceptability of a Smartphone app (My Journey 3) that has been developed to facilitate supported self-management in Early Intervention in Psychosis (EIP) services.

Methods
Semi-structured one-to-one interviews were conducted with twenty-one EIP service users who had access to My Journey 3 as part of a feasibility trial, and with thirteen EIP service clinicians who were supporting service users with the app. Interviews focused on the acceptability and usability of My Journey 3. Data was coded to themes based on the Acceptability of Healthcare Interventions framework.

Results
Many service user participants found My Journey 3 to be acceptable. The symptom and medication trackers in particular were described as helpful. A smaller number of service users disliked the intervention. Individual-level factors that appeared to influence acceptability and engagement included recovery stage and symptom severity. Clinicians tended to report that My Journey 3 was a potentially positive addition to service users’ care, but they often felt unable to provide support due to competing demands in their work, which in turn may have impacted acceptability and usage of the app.

Conclusions
Our findings suggest that the app is perceived as having potential to improve users’ capacity to self-manage and work towards recovery goals, but barriers prevented many clinicians providing consistent and effective support as intended. Further evaluation of supported self-management apps in psychosis is warranted but needs to address implementation challenges from the start.
Do psychological factors affect outcomes in musculoskeletal shoulder disorders? A systematic review
Authors: Sheikhzadeh Ali , Wertli Maria M. , Weiner Shira Schecter , Rasmussen-Barr Eva , Weiser Sherri 
Published: June 2021

Abstract
Background
Psychological factors may impact recovery in patients undergoing treatment for shoulder complaints. The aim of this review is to systematically analyse the evidence for the effect of modifiable psychological factors (MPF) on outcome, for patients with musculoskeletal shoulder disorders undergoing conservative or surgical treatment. MPF refers to factors that may change with intervention.

Methods
This is a systematic literature review. Five databases searched (MEDLINE, CINAHL, Cochrane Library, Embase and PsycInfo), for longitudinal studies investigating the influence of MPF on prognosis of patients with shoulder disorders, all diagnoses, undergoing clinical interventions (conservative or surgical). Level of evidence was determined using Scottish Intercollegiate Guidelines Network (SIGN) methodology. Moderate and high quality evidence was included. We extracted all MPF, categorized constructs into the following domains: beliefs (self-efficacy, expectation of recovery), coping (catastrophizing, avoidant coping), and affect (depression, anxiety). We evaluated constructs for its predictive value of at least one outcome. Outcomes were informed by this review. Evidence was classified into three categories: evidence for, inconclusive evidence, and evidence against.

Results
Of 1170 references, 40 distinct publications based on 35 datasets were included (intervention type: 20 surgical; 20 conservative). Overall, 22 studies (20 cohort studies and 2 RCTs) were classified as high quality and 18 studies (16 cohort studies, 2 RCTs) were classified as moderate quality. Outcomes reported included pain, disability/function, perceived recovery, physical and mental health, and work status. Based on the review, of the psychological constructs explored, these data would suggest that expectation of recovery, catastrophizing, avoidant coping, depression, and anxiety may predict outcome for patients managed surgically. In patients undergoing conservative intervention the evidence was either against (catastrophizing, depression, anxiety) or inconclusive (self-efficacy, expectation of recovery, avoidant coping) for the predictive value of psychological factors on outcome.

Conclusions
Five constructs were predictive of outcome for surgically managed patients. This suggests that implementing the biopsychosocial approach (i.e., preoperative screening, intervention by a trained clinician) may be advantageous for patients recommended for shoulder surgery,,. The same is not indicated for conservatively managed patients as no conclusive association of MPF with outcomes was noted. The importance of other MPF on outcome requires further investigation.