bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel hydrogen‐producing Si‐based agent reduces oxidative stress, and improves sperm motility and in vitro fertilization rate in varicocoele
Authors: Inagaki Yusuke , Fukuhara Shinichiro , Imamura Ryoichi , Kobayashi Yuki , Kuribayashi Sohei , Okada Koichi , Sekii Yosuke , Takezawa Kentaro , Kiuchi Hiroshi , Uemura Motohide , Kobayashi Hikaru , Nonomura Norio 
Published: August 2020

AbstractBackgroundVaricocoele‐induced male infertility potentially involves oxidative stress. Although varicocoelectomy is recommended for varicocoele patients presenting abnormal semen findings, no pharmacotherapeutic methods currently exist. We have recently developed a silicon‐based agent that produces hydrogen by the reaction with water.ObjectivesThis study aimed to investigate the therapeutic effects of oral administration of a Si‐based agent on varicocoele rat.Materials and methodsTwenty‐one rats were divided into four groups: varicocoele + normal diet (n = 5), varicocoele + Si‐based agent‐supplemented diet (n = 6), sham + normal diet (n = 5), and sham + Si‐based agent‐supplemented diet (n = 5). All rats were euthanized four weeks after surgery.ResultsThe mean left epididymal sperm motility was 74.4% in the sham group, 72.3% in the sham + Si group, 57.6% in the varicocoele group, and 66.9% in the varicocoele + Si group. Epididymal sperm motility was significantly lower in the varicocoele group, but was significantly higher upon Si‐based agent ingestion (P < .01). The mean left testicular weight, Johnsen's score, and left epididymal sperm concentration did not differ significantly between groups. The 8‐OHdG concentration and DNA fragmentation rate were significantly increased in the varicocoele group, but were significantly decreased in the Si‐based agent intake group (P < .01). Additionally, the IVF rate was significantly lower in the varicocoele group (26.3%) compared with the sham group (73.4%; P < .01), and was significantly higher in the varicocoele + Si group (51.8%) compared with the varicocoele group (P < .05), indicating that the Si‐based agent improves IVF rates.Discussion and conclusionOral intake of the silicon‐based agent improves epididymal sperm motility and in vitro fertilization rates through hydrogen production and subsequent reduction of oxidative stress. Considering the lack of effective noninvasive methods, this Si‐based agent is potentially applicable for treating varicocoele‐induced abnormal semen parameters.
The ethical consequences of “going dark”
Authors: Spinello Richard A. 
Published: August 2020

AbstractThe adoption of hyper‐strong encryption for mobile devices, such as the iPhone, has reignited debate about the need for exceptional access and the relative priority of privacy rights. Many software programs and algorithms are not neutral but “value‐laden,” and unbreakable encryption software virtually absolutizes the right to privacy, though it has justified limits in ethics and law. High tech companies have resisted any exceptional access solutions and generally opposed cooperation with law enforcement agencies for the sake of protecting the data of their customers. We argue that this strategy is ethically flawed based on the priority of the right to physical security over the right to privacy along with the need to ensure peace and order in the name of the common good. To support this line of reasoning we amplify the undifferentiated conception of the common good presented in the literature and sketch out the grounds for limiting rights based on the need to conform to the just requirements of the public order in a democratic society. The discussion culminates in a proposal for an exceptional access scheme that has the potential to minimize risk to innocent users.
Covariate‐driven factorization by thresholding for multiblock data
Authors: Gao Xing , Lee Sungwon , Li Gen , Jung Sungkyu 
Published: August 2020

AbstractMultiblock data, where multiple groups of variables from different sources are observed for a common set of subjects, are routinely collected in many areas of science. Methods for joint factorization of such multiblock data are being developed to explore the potentially joint variation structure of the data. While most of the existing work focuses on delineating joint components, shared across all data blocks, from individual components, which is only relevant to a single data block, we propose to model and estimate partially joint components across some, but not all, data blocks. If covariates, with potential multiblock structures, are available, then the components are further modeled to be driven by the covariate information. To estimate such a covariate‐driven, block‐structured factor model, we propose an iterative algorithm based on thresholding, by transforming the problem of signal segmentation into a grouped variable selection problem. The proposed factorization provides accurate estimation of individual and (partially) joint structures in multiblock data, as confirmed by simulation studies. In the analysis of a real multiblock genomic dataset from the Cancer Genome Atlas project, we demonstrate that the estimated block structures provide straightforward interpretation and facilitate subsequent analyses.
High blood pressure in pregnancy, DNA methylation, and later blood pressure in African American women enrolled in the InterGEN Study
Authors: Barcelona Veronica , Wang Zeyuan , Crusto Cindy , Hui Qin , Sun Yan V. , Taylor Jacquelyn Y. 
Published: August 2020

AbstractBackgroundFew studies have examined the effects of high blood pressure (BP) in pregnancy, preeclampsia, or eclampsia on later BP, and the epigenetics of this phenomenon is similarly poorly understood, especially among African Americans. The purpose of this study was to examine the association between high BP in pregnancy, epigenomics, and later BP in African American women in the InterGEN Study (n = 250).MethodsIn cross‐sectional analyses, regression and linear mixed‐effects models were employed to examine the effects of high BP in pregnancy on: (a) epigenetic associations (DNA methylation) and (b) BP 3‐5 years after birth. The 850K Illumina EPIC BeadChip was used for evaluating epigenome‐wide DNA methylation. High BP in pregnancy, preeclampsia, or eclampsia was self‐reported by women, and BP was measured 3‐5 years after birth, per JNC‐7 guidelines. DNA methylation and clinical BP were the main outcomes.ResultsMean age of enrolled women was 31.2 years, 21.8% were smokers, 58% had some college or higher education, 46.6% reported an annual income <$15 000, and 13.6% reported high BP in pregnancy. After adjustment for obesity, smoking, and age, women with a history of high BP in pregnancy had significantly higher BP than those who did not report this complication (5.39 ± 2.4 mm Hg, P = .030). Epigenome‐wide analysis revealed no significant sites after multiple testing correction.ConclusionsWe observed a small, but clinically significant, increase in BP in women who reported high BP in pregnancy 3‐5 years after that pregnancy. Future studies with larger sample sizes should examine epigenetic contributions to this finding.
Neutropenia in patients with hyperthyroidism: Systematic review and meta‐analysis
Authors: Scappaticcio Lorenzo , Maiorino Maria Ida , Maio Antonietta , Esposito Katherine , Bellastella Giuseppe 
Published: August 2020

AbstractBackground and ObjectiveNeutropenia, a low absolute neutrophil count (ANC), may be a sign of new‐onset hyperthyroidism. The aim of this systematic review and meta‐analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting.MethodsA comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non‐English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta‐analysis was performed with DerSimonian and Laird method (random‐effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two‐sided P‐value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included.ResultsThe literature search yielded 1880 studies of which 13 studies were included for systematic review and meta‐analysis. Results of the meta‐analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves’ hyperthyroidism was 10% (CI 5%‐19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 109/L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable.ConclusionsGraves’ disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.
‘It's so much better than contact’: A qualitative study exploring children and young people's experiences of a sibling camp in the United Kingdom
Authors: Rogers Justin Mark , Ali Mariya 
Published: August 2020

AbstractThis article explores children and young people's experiences of a sibling camp based in the United Kingdom. Sibling camps are an intervention based on children's activity holidays that aim to promote meaningful contact for siblings separated in public care. This study adopted a qualitative approach using semi‐structured interviews with 11 children and young people; this included one sibling group of three and four sibling groups of two. The children's ages ranged from 8 to 17 years old, and they had all attended at least one camp with their sibling. Findings highlighted how the children valued the extended time they could spend with their siblings at camp, and how they felt this enabled them to better understand their siblings and improve their relationships. Findings also showed how the children developed close supportive relationships with the staff at the camps, who ensured they were cared for, and they also supported them with managing their relationships, which some participants acknowledged at times could be challenging. The participants also valued spending time with other sibling groups who also experienced separation. The study found camps provided a space for these children to maintain links with their siblings and to strengthen their sibling bonds.
Novel pathogenic EIF2S3 missense variants causing clinically variable MEHMO syndrome with impaired eIF2γ translational function, and literature review
Authors: Kotzaeridou Urania , Young‐Baird Sara K. , Suckow Vanessa , Thornburg Alexis G. , Wagner Matias , Harting Inga , Christ Stine , Strom Tim , Dever Thomas E. , Kalscheuer Vera M. 
Published: August 2020

AbstractRare pathogenic EIF2S3 missense and terminal deletion variants cause the X‐linked intellectual disability (ID) syndrome MEHMO, or a milder phenotype including pancreatic dysfunction and hypopituitarism. We present two unrelated male patients who carry novel EIF2S3 pathogenic missense variants (p.(Thr144Ile) and p.(Ile159Leu)) thereby broadening the limited genetic spectrum and underscoring clinically variable expressivity of MEHMO. While the affected male with p.(Thr144Ile) presented with severe motor delay, severe microcephaly, moderate ID, epileptic seizures responsive to treatments, hypogenitalism, central obesity, facial features, and diabetes, the affected male with p.(Ile159Leu) presented with moderate ID, mild motor delay, microcephaly, epileptic seizures resistant to treatment, central obesity, and mild facial features. Both variants are located in the highly conserved guanine nucleotide binding domain of the EIF2S3 encoded eIF2γ subunit of the heterotrimeric translation initiation factor 2 (eIF2) complex. Further, we investigated both variants in a structural model and in yeast. The reduced growth rates and lowered fidelity of translation with increased initiation at non‐AUG codons observed for both mutants in these studies strongly support pathogenicity of the variants.
Development of a new expanded next‐generation sequencing panel for genetic diseases involved in dyslipidemia
Authors: Marmontel Oriane , Rollat‐Farnier Pierre Antoine , Wozny Anne‐Sophie , Charrière Sybil , Vanhoye Xavier , Simonet Thomas , Chatron Nicolas , Collin‐Chavagnac Delphine , Nony Séverine , Dumont Sabrina , Mahl Muriel , Jacobs Chantal , Janin Alexandre , Caussy Cyrielle , Poinsot Pierre , Tauveron Igor , Bardel Claire , Millat Gilles , Peretti Noël , Moulin Philippe , Marçais Christophe , Di Filippo Mathilde 
Published: August 2020

AbstractThe aim of this study was to provide an efficient tool: reliable, able to increase the molecular diagnosis performance, to facilitate the detection of copy number variants (CNV), to assess genetic risk scores (wGRS) and to offer the opportunity to explore candidate genes. Custom SeqCap EZ libraries, NextSeq500 sequencing and a homemade pipeline enable the analysis of 311 dyslipidemia‐related genes. In the training group (48 DNA from patients with a well‐established molecular diagnosis), this next‐generation sequencing (NGS) workflow showed an analytical sensitivity >99% (n = 532 variants) without any false negative including a partial deletion of one exon. In the prospective group, from 25 DNA from patients without prior molecular analyses, 18 rare variants were identified in the first intention panel genes, allowing the diagnosis of monogenic dyslipidemia in 11 patients. In six other patients, the analysis of minor genes and wGRS determination provided a hypothesis to explain the dyslipidemia. Remaining data from the whole NGS workflow identified four patients with potentially deleterious variants. This NGS process gives a major opportunity to accede to an enhanced understanding of the genetic of dyslipidemia by simultaneous assessment of multiple genetic determinants.
Arteriovenous malformation phenotype resembling congenital hemangioma contains KRAS mutations
Authors: Sudduth Christopher L. , McGuire Anna M. , Smits Patrick J. , Konczyk Dennis J. , Al‐Ibraheemi Alyaa , Fishman Steven J. , Greene Arin K. 
Published: August 2020

AbstractExtracranial arteriovenous malformation (AVM) is most commonly caused by a somatic mutation in MAP2K1. We report two patients with vascular anomalies that had an unclear clinical diagnosis most consistent with either an AVM or congenital hemangioma. Lesions were cutaneous, reddish‐purple with telangiectasias, present at birth, and had defined borders. Histopathology indicated AVM and both lesions contained somatic KRAS mutations. A rare AVM phenotype exists that shares clinical features with congenital hemangioma.
Randomized clinical trial evaluating the effect of splinting crowns on short implants in the mandible 3 years after loading
Authors: Al‐Sawaf Omar , Tuna Taskin , Rittich Anne , Kern Thomas , Wolfart Stefan 
Published: August 2020

AbstractObjectiveTo compare the radiographic marginal bone loss and clinical parameters of splinted and non‐splinted fixed dental prostheses on short implants in the posterior region of the lower jaw 3 years after loading.Material and MethodsTwenty patients, 15 female and five males, with uni‐ or bilateral free‐end situations in the mandible participated in the study. Two short implants (7 mm) in the posterior mandible were placed and patients were randomized to receive splinted (n = 11) or non‐splinted (n = 13) cemented crowns. Marginal bone loss (MBL) was assessed on radiographs taken with customized positioning jigs at baseline, 1 and 3 years after loading. Plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing (BOP) were measured. (ClinicalTrials.gov; identifier: NCT03558347).ResultsAfter 3‐year survival rate of altogether 48 implants was 100% for both groups. Success rate (according to Papaspyridakos, Chen, Singh, Weber, & Gallucci, 2012) was 84.6% for non‐splinted and 86.4% for splinted implants. At restoration level survival rate was 100% for both groups. Marginal bone level changes showed mean gain of 0.3 ± 0.8 mm for non‐splinted and 0.1 ± 0.5 mm for splinted implants 3 years after loading. Statistical analysis showed no significant difference in PI, GI, PD, BOP, and marginal bone loss between both groups (p > .05).ConclusionWithin the limitations of this study it can be concluded that splinting crowns on short implants neither seems to affect the amount of marginal bone loss nor peri‐implant health 3 years after loading.
Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease
Authors: Panigrahi Trailokyanath , D’Souza Sharon , Shetty Rohit , Padmanabhan Nair Archana , Ghosh Anuprita , Jacob Remington Nelson Everette , Ghosh Arkasubhra , Sethu Swaminathan 
Published: August 2020

Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors, such as cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in hyperosmotic stress‐associated inflammation in patients with DED and in vitro. Conjunctival impression cytology samples from control subjects (n = 11) and patients with DED (n = 15) were used to determine the status of hyperosmotic stress (TonEBP/NFAT5), inflammation (IL‐6, IL‐8, IL‐17A/F, TNFα, MMP9, and MCP1), VDR, and intracellular chloride ion (GLRX5) by quantitative polymerase chain reaction and/or immunofluorescence. Human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (genistein) and vitamin D (calcitriol) in hyperosmotic stress (HOs)‐induced response in vitro. Western blotting was used to determine the expression of these proteins, along with p‐p38. Significantly, higher expression of inflammatory factors, TonEBP, GLRX5, and reduced VDR were observed in patients with DED and in HOs‐induced HCECs in vitro. Expression of TonEBP positively correlated with expression of inflammatory genes in DED. Increased TonEBP and GLRX5 provides confirmation of osmotic stress and chloride ion imbalance in OS epithelium in DED. These along with reduced VDR suggests dysregulated OS homeostasis in DED. Combination of genistein and calcitriol reduced HOs‐induced TonEBP, inflammatory gene expression, and p‐p38, and abated VDR degradation in HCECs. Henceforth, this combination should be further explored for its relevance in the management of DED.
Factors influencing hospital conveyance following ambulance attendance for people with diabetes: A retrospective observational study
Authors: van Woerden H. , Bucholc M. , Clubbs Coldron B. , Coates V. , Heaton J. , McCann M. , Perrin N. , Waterson R. , Watson A. , MacRury S. 
Published: August 2020

AbstractAimTo assess variables contributing to hospital conveyance for people with diabetes and the interactions between them. A secondary aim was to generate hypotheses for further research into interventions that might reduce avoidable hospital admissions.MethodsA national retrospective data set including 30 999 diabetes‐related callouts from the Scottish Ambulance Service was utilized covering a 5‐year period between 2013 and 2017. The relationship between diabetes‐related hospital conveyance and seven potential risk factors was analysed. Independent variables included: age, gender, deprivation, paramedic attendance, treatment at the scene, first blood glucose measurement and day of the week.ResultsIn Scotland, hyperglycaemia was associated with a higher number of people being conveyed to hospital than hypoglycaemia (49.8% with high blood glucose vs. 39.3% with low glucose, P ≤ 0.0001). Treatment provided in pre‐hospital care was associated with reduced conveyance rates (47.3% vs. 58.2% where treatment was not administered, P ≤ 0.0001). Paramedic attendance was also associated with reduced conveyance to hospital (51.4% vs. 59.5% where paramedic was not present, P ≤ 0.0001). Paramedic attendance in hyperglycaemic cases was associated with significantly reduced odds of conveyance (odds ratio 0.52, P ≤ 0.001).ConclusionsA higher rate of conveyance associated with hyperglycaemic cases indicates a need for more resources, education and training in this area. Higher conveyance rates were also associated with no paramedic being present and no treatment being administered. This suggests that paramedic attendance may be crucial in reducing avoidable admissions. Developing and validating protocols for pre‐hospital services and treatment may help to reduce hospital conveyance rates.
Can an interactive case‐based activity help bridge the theory‐practice gap in operative dentistry?
Authors: Chutinan Supattriya , Kim Jiyeon , Chien Tiffany , Meyer Helen Yang , Ohyama Hiroe 
Published: August 2020

AbstractIntroductionA theory‐practice gap in pre‐doctoral dental education is a common source of stress for dental students. An interactive, small‐group, case‐based activity was designed to bridge the gap between pre‐clinical and clinical experiences. The aim of our study was to assess the effectiveness of the case‐based activity by evaluating students' comfort level in operative procedures.Materials and MethodsOver 5 years, a total of 172 second‐year students from the classes of 2017 through 2021 participated in the case‐based activity delivered after the completion of the core operative dentistry course. The exercise included a pre‐activity online quiz, an in‐class case‐based session and a laboratory exercise. Students' self‐reported comfort levels in performing operative procedures were collected by surveys at three different times. They included thepost‐coursesurvey distributed after the completion of the core operative dentistry course, thepost‐activitysurvey distributed after the completion of the case‐based activity, and thefollow‐upsurvey distributed after students completed their first operative procedures in clinic.ResultsThere was a 93% response rate. The average rating of all eight statements revealed statistically significant increase in students' comfort level after completing the case‐based activity and after performing their first operative procedures in the teaching practice.ConclusionThis observation suggests that the case‐based activity was effective in raising students' comfort levels. The activity may serve as an important tool in bridging the theory‐practice gap between pre‐clinical and clinical operative experiences.