bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Associations Between BDNF and Memory Across Older Black and White Adults With HIV Disease
Authors: Fazeli Pariya L. , Woods Steven P. , Lambert Crystal C. , Li Wei , Hopkins Cierra N. , Vance David E. 
Published: October 2021

Background:
Brain-derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and memory functioning in people living with HIV (PWH).

Methods:
A sample of 173 adults aged 50+ (n = 100 HIV+ and n = 73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, and recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions.

Results:
For learning and delayed recall, significant (P < 0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, whereas for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small–medium associations between BDNF and learning and delayed recall (rho = 0.29, P < 0.01; rho = 0.22, P = 0.045), but no recognition (rho = 0.12, P = 0.29) were found among Black/African American PWH. BDNF was not significantly associated with memory domains in White PWH or either HIV- sample. Follow-up analyses showed BDNF-memory specificity, such that race X BDNF interactions did not emerge for other cognitive domains.

Conclusions:
While limited by cross-sectional design among a small sample, particularly of White individuals, results indicate that BDNF may serve as a promising biomarker reflecting memory functioning in PWH, particularly Black/African Americans. Further work is needed to replicate findings and determine mechanisms for racial differences in BDNF associations with memory.
Pitfalls and Practical Challenges in Imaging of the Pediatric Scrotum
Authors: Chaudhry Humaira , Siddiqi Madheea , Simpson William L. , Rosenberg Henrietta Kotlus 
Published: October 2021

Abstract
Ultrasound is the modality of choice for evaluation of the pediatric scrotum, as it provides excellent image quality without the use of radiation, need for sedation/anesthesia, or use of contrast material and can be used for serial examination. Ultrasound of the scrotum has proven to be useful for assessment of a wide gamut of congenital, infectious, inflammatory, endocrine, neoplastic, and traumatic abnormalities in pediatric patients of all ages from the tiniest premature infant to a fully grown young adult. This review article presents a varied spectrum of conditions that may affect the pediatric scrotum, what the radiologist needs to know to meet the challenge of limiting the differential diagnosis, and how to avoid pitfalls when imaging the scrotum.
Cost-effectiveness of Early Surgery Versus Endoscopy-first Approach for Painful Chronic Pancreatitis in the ESCAPE Trial
Authors: Kempeneers Marinus A. , Issa Yama , Bruno Marco J. , van Santvoort Hjalmar C. , Besselink Marc G. , Boermeester Marja A. , Dijkgraaf Marcel G. ,   for the Dutch Pancreatitis Study Group
Published: October 2021

Objective:
Economic evaluation of early surgery compared to the endoscopy-first approach in CP.

Background:
In patients with painful CP and a dilated main pancreatic duct, early surgery, as compared with an endoscopy-first approach, leads to more pain reduction with fewer interventions. However, it is unknown if early surgery is more cost-effective than the endoscopy-first approach.

Methods:
The multicenter Dutch ESCAPE trial randomized patients with CP and a dilated main pancreatic duct between early surgery (surgery within 6 weeks) or the endoscopy-first approach in 30 centers (April 2011–September 2016). Healthcare utilization was prospectively recorded up to 18 months after randomization. Unit costs of resources were determined, and cost-effectiveness and cost–utility analyses were performed from societal and healthcare perspectives. Primary outcomes were the costs per unit decrease on the Izbicki pain score and per gained quality-adjusted life-year.

Results:
In total, 88 patients were included in the analysis, with 44 patients randomized to each group. Total costs were lower in the early surgery group but did not reach statistical significance (mean difference €−4,815 (95% bias-corrected and accelerated confidence interval €−13,113 to €3411; P = 0.25). Early surgery had a probability percentage of 88.4% of being more cost-effective than the endoscopy-first approach at a willingness-to-pay threshold of €0 per day per unit decrease on the Izbicki pain score. The probability percentage per additional gained quality-adjusted life-year was 75.7% at a willingness-to-pay threshold of €50,000.

Conclusion:
In patients with painful CP and a dilated main pancreatic duct, early surgery was more cost-effective than the endoscopy-first approach.
Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma
Authors: Otsuka Shimpei , Mizuno Takashi , Yamaguchi Junpei , Onoe Shunsuke , Watanabe Nobuyuki , Shimoyama Yoshie , Igami Tsuyoshi , Uehara Kay , Yokoyama Yukihiro , Nagino Masato , Ebata Tomoki 
Published: October 2021

Objective:
The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure.

Background:
In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH).

Methods:
Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures.

Results:
Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% (P = 0.432) and 24% versus 0% in advanced tumors (P = 0.011). Tumor size ≥ 18 mm (P = 0.041), portal vein invasion (P = 0.009), and conventional LH (P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years (P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group (P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor (P = 0.009) along with ductal margin status (P = 0.030).

Conclusions:
The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.
Extraocular Muscle Volumetry for Assessment of Thyroid Eye Disease
Authors: Bontzos Georgios , Papadaki Efrosini , Mazonakis Michael , Maris Thomas G. , Tsakalis Nikolaos G. , Drakonaki Eleni E. , Detorakis Efstathios T. 
Published: October 2021

Background:
In this study we evaluate the diagnostic accuracy of extraocular muscle volumetry in detecting thyroid eye disease and to compare the results with simple measurements of maximal medial rectus (MR) diameter.

Methods:
Cross-sectional study that included 47 eyes of 47 patients with thyroid eye disease and 47 healthy controls. Patients underwent slitlamp examination and imaging consisting of computed tomography scans. Image segmentation and volume measurements were performed by 2 independent researchers. Intraobserver and interobserver reliability testing was also conducted.

Results:
Total extraocular muscle volume was 7.31 ± 1.88 cm3 and medial volume was 2.38 ± 0.73 cm3 in the study group. In this group, the maximum measured diameter of the MR was 6.67 ± 0.35 mm. MR volume was statistically associated with maximum MR diameter (r = 9.78; P < 0.001). Both MR volume and maximum MR diameter measurements showed good predictive efficacy as shown using receiver operator characteristic curve analysis.

Conclusions:
Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.
Remote monitoring of progression in early Parkinson’s disease: reliability and validity of the Roche PD Mobile Application v2
Authors: Lipsmeier Florian , Taylor Kirsten I. , Postuma Ronald B. , Volkova-Volkmar Ekaterina , Kilchenmann Timothy , Mollenhauer Brit , Bamdadian Atieh , Popp Werner L. , Cheng Wei-Yi , Zhang Yan Ping , Wolf Detlef , Schjodt-Eriksen Jens , Boulay Anne , Svoboda Hanno , Zago Wagner , Pagano Gennaro , Lindemann Michael 
Published: October 2021

AbstractDigital health technologies (DHTs) enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v1 was revised to v2 to include more measures of bradykinesia, and bradyphrenia and speech tests, to optimize suitability for early-stage PD. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (studyNCT03100149). Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society - Unified Parkinson’s Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.
Sampling Statistical Errors in Big Data Research: 3 Cases of Breast Cancer Research
Authors: Cho Han-Jun , Jeong Eui Seok 
Published: October 2021

AbstractBreast cancer is a major cause of female death, and various big data analysis methods have been applied to breast cancer. This study lists cases in which big data analysis was applied to breast cancer research. In addition, statistics and percentages from each specific sample were proposed. However, research on the use of big data has a blind spot that relies on sample characteristics. Therefore, before sampling big data, statistical inference should be discussed more precisely through pre-examination and sample statistical errors should be reduced by professional statistical evaluation of the analysis method. In particular, the control and experimental groups should be statistically equivalent.
Dual modulation of phase-transitioning licenses the Bicc1 network of ciliopathy proteins to bind specific target mRNAs
Authors: Rothé Benjamin , Fortier Simon , Constam Daniel B. 
Published: October 2021

SUMMARYPerturbations in biomolecular condensates that form by phase-transitioning are linked to a growing number of degenerative diseases. For example, mutations in a multivalent interaction network of the Ankyrin (ANK) and sterile alpha motif (SAM) domain-containing ANKS3 and ANKS6 proteins with the RNA-binding protein Bicaudal-C1 (Bicc1) associate with laterality defects and chronic kidney diseases known as ciliopathies. However, insights into the mechanisms that control RNA condensation in ribonucleoprotein particles (RNPs) are scarce. Here, we asked whether heterooligomerization modulates Bicc1 binding to RNA. Reconstitution assays in vitro and live imaging in vivo show that a K homology (KH) repeat of Bicc1 self-interacts and synergizes with SAM domain self-polymerization independently of RNA to concentrate bound mRNAs in gel-like granules that can split or fuse with each other. Importantly, emulsification of Bicc1 by ANKS3 inhibited binding to target mRNAs, whereas condensation by ANKS6 co-recruitment increased it by liberating the KH domains from ANKS3. Our findings suggest that the perturbation of Bicc1-Anks3-Anks6 RNP dynamics is a likely cause of associated ciliopathies.
2-Deoxy-D-Glucose as an Adjunct to Standard of Care in the Medical Management of COVID-19: A Proof-of-Concept & Dose-Ranging Randomised Clinical Trial
Authors: Bhatt Anant Narayan , Shenoy Srinivas , Munjal Sagar , Chinnadurai Vijayakumar , Agarwal Apurva , Kumar A. Vinoth , Shanavas A , Kanwar Ratnesh , Chandna Sudhir 
Published: October 2021

ABSTRACTObjectiveTo evaluate the efficacy and safety of 2-deoxy-D-glucose (2-DG) in the treatment of COVID-19.Participants110 adults aged 18 to 65 years with moderate to severe COVID-19.Interventions63, 90, and 126 mg/kg/day 2-DG plus standard of care (SOC) versus SOC only.Main Outcome MeasuresTimes to maintaining SpO2 ≥94% on room air discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO 10-point ordinal scale, negative conversion on RT-PCR, intensive care, and mortality.ResultsPatients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs 5 days, Hazard ratio [95% confidence interval]=2.3 [1.14, 4.64], p=0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalisation were significantly shorter for the 2-DG 90 mg group.All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild.Conclusion2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefits over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase-II study encourage confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase-III trial.
Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study
Authors: Debik Julia , Schaefer Hartmut , Andreassen Trygve , Wang Feng , Fang Fang , Cannet Claire , Spraul Manfred , Bathen Tone F. , Giskeødegård Guro F. 
Published: October 2021

AbstractBackgroundThe aim of this study was to investigate if serum lipoprotein and metabolic profiles of healthy women can predict the risk of developing breast cancer in the future, and to gain a better understanding of the etiology of the disease.MethodsFrom a cohort of 70 000 participants within the Trøndelag Health Study (HUNT study), we identified 1199 women who developed breast cancer within a 22 year follow-up period. Through a nested case-control study design, future breast cancer patients and matching controls (n = 2398) were analysed. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 112 lipoprotein subfractions were quantified from prediagnostic serum samples. Logistic regression was used to test metabolites and lipoprotein subfractions for associations with breast cancer risk and partial least-squares discriminant analysis (PLS-DA) models were built to predict future disease.ResultsAmong premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. For total VLDL: apolipoprotein B, cholesterol, free cholesterol and phospholipids were inversely associated with premenopausal breast cancer risk, and in addition total and HDL-4 triglycerides. No significant association was found in postmenopausal women.ConclusionsWe identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.
Pattern of fibrin stabilizing factor (FXIII) expression in placentas of women suffering with gestational diabetes mellitus in Saint John, New Brunswick
Authors: Mercer Victoria J. , Obenson Kenneth 
Published: October 2021

AbstractGestational diabetes mellitus (GDM) affects 2-5% of all pregnancies and is known to place the fetus at risk for adverse fetal outcomes. Previous studies have reported the increased presence of villous immaturity in the placentas of women with gestational diabetes. Villous immaturity poses a great risk of restricted diffusion capacity across the placenta and may be a marker for some of the placental insufficiency associated with diabetes mellitus. The present study looks at the possibility of using fibrin stabilizing factor, or Factor XIII (FXIII), as a biomarker of villous immaturity. The aim of the present study is to establish a baseline pattern of FXIII expression in placentas of women in Saint John, NB with GDM, without villous immaturity using a scoring formula adapted from surgical pathology. While the small sample size precludes definitive conclusions regarding the expression of FXIII in normal placentas in women with GDM, there appears to a baseline of strong FXIII expression in normal placental tissues from the second and third trimester of pregnancy. Further study using a larger sample size is required to determine if a correlation exists between level of FXIII expression and degree of villous maturity in patients with GDM, which could improve the histologic assessment of placental development.
Comparing lateral flow testing with a rapid RT-PCR method for SARS-CoV-2 detection in the UK
Authors: Taylor Andrew , Calvez Ronan , Atkins Mark , Fink Colin G 
Published: October 2021

AbstractIn late 2019, SARS-CoV-2 emerged in the Wuhan province of China. Rapid global spread led to the Covid-19 pandemic. Rapid and accurate detection of SARS-CoV-2 has become a vitally important tool in controlling the spread of the virus. Lateral flow devices (LFDs) offer the potential advantage of speed and on-site testing. The sensitivity of these devices compared to the gold standard RT-PCR has been questioned. We compared the performance of the Innova lateral flow kit, recommended by the UK government, with our rapid in-house RT-PCR protocol using stored positive patient samples. The LFD device was found to be 6,000-10,000 times less sensitive than RT-PCR for the detection of SARS-CoV-2. Overall, the LFD detected 46.2% of the positives detected by RT-PCR. 50% of the LFD results were observed to be weak positives, only visible after careful examination by experienced laboratory staff. At lower viral loads, such as 10,000-100,000 RNA copies/ml, the LFD detected 22.2% of positives. In addition, two strong positives (3 and 1.5 million RNA copies/ml) were not detected by the LFD. The argument for use of LFD kits, despite their lack of sensitivity, is that they detect infectious virus and hence contagious individuals. At present, there is a lack of scientific evidence supporting this claim. The LFD used in the UK fails to identify individuals with considerable viral loads and has been subject to a class I recall by the US FDA but is still approved and recommended for use by the UK government. We believe that using LFD testing for assessing SARS-CoV-2 infection risk is a strategy which has risks that outweigh any benefits.
Psychiatric polygenic risk scores: Child and adolescent psychiatrists’ knowledge, attitudes, and experiences
Authors: Pereira Stacey , Muñoz Katrina A. , Small Brent J. , Soda Takahiro , Torgerson Laura N. , Sanchez Clarissa E. , Austin Jehannine , Storch Eric A. , Lázaro-Muñoz Gabriel 
Published: October 2021

AbstractObjectivePsychiatric polygenic risk scores (PRS) have the potential to transform aspects of psychiatric care and prevention, but there are concerns about their implementation. We sought to assess child and adolescent psychiatrists’ (CAP) experiences, perspectives, and potential uses of psychiatric PRS.MethodsA survey of 960 US-based practicing CAP.ResultsMost respondents (54%) believed psychiatric PRS are currently at least slightly useful and 87% believed they will be so in five years. Yet, 77% rated their knowledge of PRS as poor or very poor. Ten percent have had a patient/family bring PRS to them, and 25% would request PRS if a patient/caregiver asked. Respondents endorsed different actions in response to a hypothetical child with a top 5th percentile psychiatric PRS but no diagnosis: 48% would increase prospective monitoring of symptoms, 42% would evaluate for current symptoms, and 4% would prescribe medications. Most respondents were concerned that high PRS results could lead to overtreatment and negatively impact patients’ emotional well-being.ConclusionFindings indicate emerging use of psychiatric PRS within child and adolescent psychiatry in the US. Thus, it is critical to examine the ethical and clinical challenges that PRS may generate and begin efforts to promote their informed and responsible use.
Poly-glutamine-dependent self-association as a potential mechanism for regulation of androgen receptor activity
Authors: Roggero Carlos M. , Esser Victoria , Duan Lingling , Rice Allyson M. , Ma Shihong , Raj Ganesh V. , Rosen Michael K. , Liu Zhi-Ping , Rizo Josep 
Published: October 2021

AbstractThe androgen receptor (AR) plays a central role in prostate cancer. Development of castration resistant prostate cancer (CRPC) requires androgen-independent activation of AR, which involves its large N-terminal domain (NTD) and entails dramatic epigenetic changes depending in part on histone lysine demethylases (KDMs) that interact with AR. The AR-NTD is rich in low-complexity sequences, including a polyQ repeat. Longer polyQ sequences were reported to decrease transcriptional activity and to protect against prostate cancer. However, the molecular mechanisms underlying these observations are unclear. Using NMR spectroscopy, here we identify weak interactions between the AR-NTD and the KDM4A catalytic domain, and between the AR ligand-binding domain and a central KDM4A region that also contains low-complexity sequences. We also show that the AR-NTD can undergo liquid-liquid phase separation in vitro, with longer polyQ sequences phase separating more readily. Moreover, longer polyQ sequences hinder nuclear localization in the absence of hormone and increase the propensity for formation of AR-containing puncta in the nucleus of cells treated with dihydrotestosterone. These results lead us to hypothesize that polyQ-dependent liquid-liquid phase separation may provide a mechanism to decrease the transcriptional activity of AR, potentially opening new opportunities to design effective therapies against CRPC.