bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilising red cell antigen genotyping and serological phenotyping in sickle cell disease patients to risk‐stratify patients for alloimmunisation risk
Authors: Shih Andrew W. , Yan Matthew T.S. , Elahie Allahna L. , Barty Rebecca L. , Liu Yang , Berardi Philip , Azzam Mona , Siddiqui Reda , Parvizian Michael K. , Mcdougall Tara , Heddle Nancy M. , Al‐Habsi Khalid S. , Goldman Mindy , Cote Jacqueline , Athale Uma , Verhovsek Madeleine M. 
Published: May 2020

AbstractBackgroundAlloimmunisation and haemolytic transfusion reactions (HTRs) can occur in patients with sickle cell disease (SCD) despite providing phenotype‐matched red blood cell (RBC) transfusions. Variant RBC antigen gene alleles/polymorphisms can lead to discrepancies in serological phenotyping. We evaluated differences between RBC antigen genotyping and phenotyping methods and retrospectively assessed if partial antigen expression may lead to increased risk of alloimmunisation and HTRs in SCD patients at a tertiary centre in Canada.MethodsRBC antigen phenotyping and genotyping were performed by a reference laboratory on consenting SCD patients. Patient demographic, clinical and transfusion‐related data were obtained from a local transfusion registry and chart review after research ethics board approval.ResultsA total of 106 SCD patients were enrolled, and 91% (n = 96) showed additional clinically relevant genotyping information when compared to serological phenotyping alone. FY*02N.01 (FY*B GATA‐1) (n = 95; 90%) and RH variant alleles (n = 52, 49%; majority accompanied by FY*02N.01) were common, the latter with putative partial antigen expression in 25 patients. Variability in genotype‐phenotype antigen prediction occurred mostly in the Rh system, notably with the e antigen (kappa: 0.17). Fifteen (14.2%) patients had a history of alloimmunisation, with five having HTR documented; no differences in clinical outcomes were found in patients with partial antigen expression. Genotype/extended‐phenotype matching strategies may have prevented alloimmunisation events.ConclusionWe show a high frequency of variant alleles/polymorphisms in the SCD population, where genotyping may complement serological phenotyping. Genotyping SCD patients before transfusion may prevent alloimmunisation and HTRs, and knowledge of the FY*02N.01 variant allele increases feasibility of finding compatible blood.
Vitamin D status is seasonally stable in northern European dogs
Authors: Hurst Emma A. , Homer Natalie Z. , Gow Adam G. , Clements Dylan N. , Evans Helen , Gaylor Donna , Campbell Susan , Handel Ian , Mellanby Richard J. 
Published: May 2020

AbstractBackgroundNumerous studies in veterinary species have recently linked vitamin D status with nonskeletal health disorders. Previous studies have indicated that dogs cannot produce endogenous vitamin D via cutaneous production and rely solely on dietary intake of vitamin D. The seasonal variation of vitamin D seen in humans due to changes in ultraviolet (UV) exposure, therefore, is unlikely to be replicated in these animals.ObjectivesThe objective of this study was to investigate the natural variation in 25‐hydroxyvitamin‐D concentrations in dogs subject to seasonal UV exposure.MethodsThis longitudinal study followed 18 healthy dogs fed a standardized diet over 1 year, with blood samples obtained monthly. Two key vitamin D metabolites, 25‐hydroxyvitamin‐D2 and 25‐hydroxyvitamin‐D3, were assessed by liquid chromatography‐tandem mass spectrometry in serum samples. Various other biochemical parameters were also measured. Seasonality was assessed using cosinor statistical analysis.ResultsAlthough the dogs were subject to seasonally varying UV radiation, 25‐hydroxyvitamin‐D and related biomarkers (including calcium and parathyroid hormone) remained stable over time and did not follow a seasonal pattern. 25‐hydroxyvitamin‐D was not positively correlated with exposure to UV radiation. Nonetheless, variation in 25‐hydroxyvitamin‐D concentrations between individual dogs was detected.ConclusionsGiven the standardization of diet, we concluded that the seasonal stability of 25‐hydroxyvitamin‐D concentration (vitamin D status) was likely a direct result of lack of cutaneous vitamin D production in this species and highlights the importance of dietary intake. The variation in 25‐hydroxyvitamin‐D concentration between animals warrants further investigation.
A Qualitative Exploration of Immigrant Muslim Older Adults’ Experiences and Perceptions of Physical Activity
Authors: Salma Jordana , Jones Allyson , Ali Savera Aziz , Salami Bukola , Yamamoto Shelby 
Published: May 2020

Physical activity is essential for healthy aging; however, there has been little exploration of physical activity in Muslim older immigrants in Canada. Over one million Canadians identify as Muslim, the majority is first-generation immigrants, with increasing cohorts entering older age. A community-based participatory research project on healthy aging was conducted with 68 older adults and community members from South Asian, Arab, and African Muslim ethnocultural communities in a Canadian urban center. A combination of individual interviews and focus groups discussions were completed, followed by thematic analysis of data. Participating community groups emphasized the importance of physical activity in older age and prioritized the need for physical activity programs. The four themes highlight Muslim older immigrants’ perspectives on physical activity in Canada: (a) values and approaches to staying active; (b) health factors: pain and health limitations; (c) social factors: culture, religion, and belonging; and (d) environmental factors: safety and accessibility.
KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
Authors: Yang Xuanxin , Yang Rongshuai , Chen Min , Zhou Qingde , Zheng Yingying , Lu Chao , Bi Jianing , Sun Wenzhe , Huang Tongzhou , Li Lijia , Gong Jianxiang , Li Xiaokun , Hui Qi , Wang Xiaojie 
Published: May 2020

ObjectiveThe present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats.Research design and methodsIn this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0.ResultsA 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31.ConclusionsA KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.
Vaginal probiotic adherence and acceptability in Rwandan women with high sexual risk participating in a pilot randomised controlled trial: a mixed-methods approach
Authors: Verwijs Marijn C , Agaba Stephen , Umulisa Marie Michele , Uwineza Mireille , Nivoliez Adrien , Lievens Elke , van de Wijgert Janneke H H M 
Published: May 2020

ObjectivesTo evaluate adherence and acceptability of intermittent vaginal probiotic or antibiotic use to prevent bacterial vaginosis (BV) recurrence.DesignRepeated adherence and acceptability assessments using mixed methods within a pilot randomised controlled trial.SettingResearch clinic in Kigali, Rwanda.ParticipantsRwandan women with high sexual risk.InterventionsWomen diagnosed with BV and/or trichomoniasis were randomised to four groups (n=17 each) after completing metronidazole treatment: behavioural counselling only, or behavioural counselling plus 2-month intermittent use of oral metronidazole, Ecologic Femi+ (EF+) vaginal capsule or Gynophilus LP (GynLP) vaginal tablet.Outcome measuresAdherence and acceptability were assessed by structured face-to-face interviews, semi-structured focus group discussions and in-depth interviews, daily diaries and counting of used/unused study products in randomised women (n=68). Vaginal infection knowledge was assessed by structured face-to-face interviews in randomised women and women attending recruitment sessions (n=131).ResultsMost women (93%) were sex workers, 99.2% were unfamiliar with BV and none had ever used probiotics. All probiotic users (n=32) reported that insertion became easier over time. Triangulated adherence data showed that 17/17 EF+ users and 13/16 GynLP users used ≥80% of required doses (Fisher’s exact p=0.103). Younger age (p=0.076), asking many questions at enrolment (p=0.116), having menses (p=0.104) and reporting urogenital symptoms (p=0.103) were non-significantly associated with lower perfect adherence. Women believed that the probiotics reduced BV recurrence, but reported that partners were sometimes unsupportive of study participation. Self-reported vaginal washing practices decreased during follow-up, but sexual risk behaviours did not. Most women (12/15) with an uncircumcised steady partner discussed penile hygiene with him, but many women found this difficult, especially with male clients.ConclusionsHigh-risk women require education about vaginal infections. Vaginal probiotic acceptability and adherence were high in this cohort. Our results can be used to inform future product development and to fine-tune counselling messages in prevention programmes.Trial registration numberNCT02459665.
Quality of informed consent documents among US. hospitals: a cross-sectional study
Authors: Spatz Erica S , Bao Haikun , Herrin Jeph , Desai Vrunda , Ramanan Sriram , Lines Lynette , Dendy Rebecca , Bernheim Susannah M , Krumholz Harlan M , Lin Zhenqiu , Suter Lisa G 
Published: May 2020

ObjectiveTo determine whether informed consent for surgical procedures performed in US hospitals meet a minimum standard of quality, we developed and tested a quality measure of informed consent documents.DesignRetrospective observational study of informed consent documents.Setting25 US hospitals, diverse in size and geographical region.CohortAmong Medicare fee-for-service patients undergoing elective procedures in participating hospitals, we assessed the informed consent documents associated with these procedures. We aimed to review 100 qualifying procedures per hospital; the selected sample was representative of the procedure types performed at each hospital.Primary outcomeThe outcome was hospital quality of informed consent documents, assessed by two independent raters using an eight-item instrument previously developed for this measure and scored on a scale of 0–20, with 20 representing the highest quality. The outcome was reported as the mean hospital document score and the proportion of documents meeting a quality threshold of 10. Reliability of the hospital score was determined based on subsets of randomly selected documents; face validity was assessed using stakeholder feedback.ResultsAmong 2480 informed consent documents from 25 hospitals, mean hospital scores ranged from 0.6 (95% CI 0.3 to 0.9) to 10.8 (95% CI 10.0 to 11.6). Most hospitals had at least one document score at least 10 out of 20 points, but only two hospitals had >50% of their documents score above a 10-point threshold. The Spearman correlation of the measures score was 0.92. Stakeholders reported that the measure was important, though some felt it did not go far enough to assess informed consent quality.ConclusionAll hospitals performed poorly on a measure of informed consent document quality, though there was some variation across hospitals. Measuring the quality of hospital’s informed consent documents can serve as a first step in driving attention to gaps in quality.
Initial experience with the Scepter Mini dual-lumen balloon for transophthalmic artery embolization of anterior cranial fossa dural arteriovenous fistulae
Authors: Pulli Benjamin , Sussman Eric S , Mayercik Vera , Steinberg Gary K , Do Huy M , Heit Jeremy J 
Published: May 2020

BackgroundPrecise delivery of liquid embolic agents (LEAs) remains a challenge in the endovascular treatment of dural arteriovenous fistulae (dAVFs) and cerebral arteriovenous malformations (cAVMs). Despite significant advances in the past decade, LEA reflux and catheter navigability remain shortcomings of current endovascular technology, particularly in small and tortuous arteries. The Scepter Mini dual-lumen balloon microcatheter aims to address these issues by decreasing the distal catheter profile (1.6 French) while allowing for a small (2.2 mm diameter) balloon at its tip.MethodsWe report our initial experience with the Scepter Mini in two patients with anterior cranial fossa dAVFs that were treated with transophthalmic artery embolization.ResultsIn both patients, the Scepter Mini catheter was able to be safely advanced into the distal ophthalmic artery close to the fistula site, and several centimeters past the origins of the central retinal and posterior ciliary arteries. A single Onyx injection without any reflux resulted in angiographic cure of the dAVF in both cases, and neither patient suffered any vision loss.ConclusionsThese initial experiences suggest that the Scepter Mini represents a significant advance in the endovascular treatment of dAVFs and cAVMs and will allow for safer and more efficacious delivery of LEAs into smaller and more distal arteries while diminishing the risk of LEA reflux.
Minimizing SARS-CoV-2 exposure when performing surgical interventions during the COVID-19 pandemic
Authors: Pandey Aditya S , Ringer Andrew J , Rai Ansaar T , Kan Peter , Jabbour Pascal , Siddiqui Adnan H , Levy Elad I , Snyder Kenneth V , Riina Howard , Tanweer Omar , Levitt Michael R , Kim Louis J , Veznedaroglu Erol , Binning Mandy J , Arthur Adam S , Mocco J , Schirmer Clemens , Thompson Byron Gregory , Langer David 
Published: May 2020

BackgroundInfection from the SARS-CoV-2 virus has led to the COVID-19 pandemic. Given the large number of patients affected, healthcare personnel and facility resources are stretched to the limit; however, the need for urgent and emergent neurosurgical care continues. This article describes best practices when performing neurosurgical procedures on patients with COVID-19 based on multi-institutional experiences.MethodsWe assembled neurosurgical practitioners from 13 different health systems from across the USA, including those in hot spots, to describe their practices in managing neurosurgical emergencies within the COVID-19 environment.ResultsPatients presenting with neurosurgical emergencies should be considered as persons under investigation (PUI) and thus maximal personal protective equipment (PPE) should be donned during interaction and transfer. Intubations and extubations should be done with only anesthesia staff donning maximal PPE in a negative pressure environment. Operating room (OR) staff should enter the room once the air has been cleared of particulate matter. Certain OR suites should be designated as covid ORs, thus allowing for all neurosurgical cases on covid/PUI patients to be performed in these rooms, which will require a terminal clean post procedure. Each COVID OR suite should be attached to an anteroom which is a negative pressure room with a HEPA filter, thus allowing for donning and doffing of PPE without risking contamination of clean areas.ConclusionBased on a multi-institutional collaborative effort, we describe best practices when providing neurosurgical treatment for patients with COVID-19 in order to optimize clinical care and minimize the exposure of patients and staff.
Variance Counterbalancing for Stochastic Large-scale Learning
Authors: Lagari Pola Lydia , Tsoukalas Lefteri H. , Lagaris Isaac E. 
Published: May 2020

Stochastic Gradient Descent (SGD) is perhaps the most frequently used method for large scale training. A common example is training a neural network over a large data set, which amounts to minimizing the corresponding mean squared error (MSE). Since the convergence of SGD is rather slow, acceleration techniques based on the notion of “Mini-Batches” have been developed. All of them however, mimicking SGD, impose diminishing step-sizes as a means to inhibit large variations in the MSE objective. In this article, we introduce random sets of mini-batches instead of individual mini-batches. We employ an objective function that minimizes the average MSE and its variance over these sets, eliminating so the need for the systematic step size reduction. This approach permits the use of state-of-the-art optimization methods, far more efficient than the gradient descent, and yields a significant performance enhancement.
The Role of Lysosome-associated Membrane Protein 2 in Prostate Cancer Chemopreventive Mechanisms of Sulforaphane
Authors: Hahm Eun-Ryeong , Singh Krishna B. , Kim Su-Hyeong , Powolny Anna A. , Singh Shivendra V. 
Published: May 2020

Abstract
Prostate cancer chemoprevention by sulforaphane, which is a metabolic by-product of glucoraphanin found in broccoli, in preclinical models is associated with induction of both apoptosis and autophagy. However, the molecular mechanism underlying sulforaphane-mediated autophagy, which is protective against apoptotic cell death by this phytochemical, is still poorly understood. This study demonstrates a role for lysosome-associated membrane protein 2 (LAMP2) in sulforaphane-mediated autophagy and apoptosis. Western blotting revealed dose-dependent induction of LAMP2 protein after treatment with sulforaphane as well as its naturally occurring analogs in PC-3 and 22Rv1 human prostate cancer cell lines that was confirmed by microscopy (sulforaphane). The mRNA level of LAMP2 was also increased upon treatment with sulforaphane in both cell lines. Sulforaphane-mediated increase in the level of autophagy marker microtubule-associated protein light-chain 3B was augmented by RNAi of LAMP2 in PC-3 and 22Rv1 cells. Apoptosis induction by sulforaphane treatment was also increased significantly by knockdown of the LAMP2 protein in PC-3 and 22Rv1 cells. Augmentation of sulforaphane-mediated apoptosis by RNAi of LAMP2 was accompanied by induction and activation of proapoptotic protein Bak. Oral administration of sulforaphane to TRAMP mice also resulted in induction of LAMP2 protein expression. Targeted microarray in sulforaphane-treated PC-3 cells revealed induction of many autophagy-related genes (e.g., HSP90AA1, NRF2, etc.) and their expression positively correlated with that of LAMP2 in prostate cancer The Cancer Genome Atlas. In conclusion, this study reveals that induction of LAMP2 by sulforaphane inhibits its ability to induce apoptotic cell death at least in human prostate cancer cells.
Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer
Authors: Kieffer Yann , Hocine Hocine R. , Gentric Géraldine , Pelon Floriane , Bernard Charles , Bourachot Brigitte , Lameiras Sonia , Albergante Luca , Bonneau Claire , Guyard Alice , Tarte Karin , Zinovyev Andrei , Baulande Sylvain , Zalcman Gerard , Vincent-Salomon Anne , Mechta-Grigoriou Fatima 
Published: May 2020

Abstract

A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular matrix proteins and TGFβ signaling, respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF upregulates PD-1 and CTLA4 protein levels in regulatory T lymphocytes (Tregs), which, in turn, increases CAF-S1 cluster 3/TGFβ-myCAF cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.

Significance:
Our work provides a significant advance in characterizing and understanding FAP+ CAF in cancer. We reached a high resolution at single-cell level, which enabled us to identify specific clusters associated with immunosuppression and immunotherapy resistance. Identification of cluster-specific signatures paves the way for therapeutic options in combination with immunotherapies.
This article is highlighted in the In This Issue feature, p. 1241
Physical Activity and the Risk for Sudden Cardiac Death in Patients With Coronary Artery Disease
Authors: Tulppo Mikko P. , Kiviniemi Antti M. , Lahtinen Minna , Ukkola Olavi , Toukola Tomi , Perkiömäki Juha , Junttila M. Juhani , Huikuri Heikki V. 
Published: May 2020

Background:
The association between leisure-time physical activity (LTPA) and the risk of sudden cardiac death (SCD) in coronary artery disease patients is not well known. We aim to assess whether there is an association between LTPA and the risk of SCD and non-SCD in patients with coronary artery disease.

Methods:
Patients with angiographically verified coronary artery disease (n=1946) underwent a clinical evaluation, including filling in an LTPA questionnaire and extensive risk profiling at the baseline. The patients were classified into 4 groups according to LTPA: (1) inactive; (2) irregularly active; (3) active, exercise regularly 2× to 3× weekly; (4) highly active, exercise regularly ≥4× weekly. Age, sex, body mass index, left ventricular ejection fraction, type 2 diabetes mellitus, history of myocardial infarction, Canadian Cardiovascular Society grading of angina pectoris class, and exercise capacity were used as covariates in the multivariate Cox regression analysis.

Results:

During follow-up (median 6.3 years), 52 SCDs and 49 non-SCDs occurred. Inactive patients had increased risk for SCD compared with active patients (hazard ratio, 2.45 [95% CI, 1.01–5.98];
P
<0.05). A significant LTPA×Canadian Cardiovascular Society grading of angina pectoris class interaction was observed in SCD risk (
P
=0.019 in highly active patients). LTPA was not associated with SCD in patients with Canadian Cardiovascular Society grading of angina pectoris class 1 (n=1107, 18 events). Among patients with Canadian Cardiovascular Society grading of angina pectoris class 2 or higher (n=839, 34 events), increased risk for SCD was encountered in highly active patients (hazard ratio, 7.46 [95% CI, 2.32–23.9];
P
<0.001) and inactive patients (hazard ratio, 3.64 [95% CI, 1.16–11.5];
P
<0.05) as compared to active patients. A linear association was observed between LTPA and non-SCD; those with high LTPA had the lowest risk for non-SCD.

Conclusions:
Inactive coronary artery disease patients had increased risk for SCD. In subgroup analysis among symptomatic patients, the risk of SCD was increased in highly active and inactive patients compared with active patients.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01426685.