bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term outcome with focus on pulmonary hypertension in Obesity Hypoventilation Syndrome
Authors: Budweiser Stephan , Tratz Florian , Gfüllner Florian , Pfeifer Michael
Published: June 2020

Introduction

Pulmonary Hypertension (PH) is a frequent comorbidity in Obesity Hypoventilation Syndrome (OHS).

Objective

We investigated long‐term outcome of OHS with a particular emphasis on PH.

Methods

In a prospective design, 64 patients with OHS and established noninvasive positive pressure ventilation (NPPV), were assessed by serum biomarkers, right heart catheterization, blood gases analysis, lung function, Epworth‐Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), World Health Organization‐functional class (WHO‐FC) and health‐related quality of life (HRQL) via the Severe Respiratory Insufficiency (SRI) questionnaire. After a planned follow‐up of 5 years patients were reassessed regarding vital status, WHO‐FC, ESS, SRI, PSQI, body mass index (BMI) and NPPV use. Prognostic markers were explored using univariate and multivariate Cox regression analyses.

Results

At the 5‐year follow‐up, BMI tended to decrease (P = 0.05), while WHO‐FC, ESS and PSQI remained unchanged. HRQL deteriorated in terms of SRI summary score and most subdomains (P < .05 each). NPPV adherence still was high (89%), while daily NPPV use increased from 6.7 (5.1; 8.0) h/d to 8.2 (7.4; 9.0) h/d (P < .05). After a 5‐year follow‐up, mortality was 25.8%. In univariate regression analyses only age > 69.5 years (HR = 4.145, 95%‐CI = 1.180‐14.565, P = 0.016), NT‐proBNP > 1256 pg/mL (HR = 5.162, 95%‐CI = 1.136‐23.467, P = 0.018), diffusion capacity for carbon monoxide (DLCO, %pred) (HR = 0.341, 95%‐CI = 0.114‐1.019, P = 0.043) and higher oxygen use during daytime (HR = 5.236, 95%‐CI = 1.489‐18.406, P = 0.004) predicted mortality. No independent factor predicting mortality was detected in multivariate analysis.

Conclusion

Despite a high long‐term NPPV use HRQL worsened. Age, oxygen use at baseline, DLCO (%pred) and NT‐proBNP, as a surrogate parameter for PH, were related to long‐term survival.
Predicting harmful alcohol relapse after liver transplant: The HALT score
Authors: Satapathy Sanjaya K. , Thornburgh Cody , Heda Rajiv , Jiang Yu , Kedia Satish K. , Nair Satheesh P. , Eason James D. , Maluf Daniel
Published: June 2020

Background

Alcohol‐associated liver disease (AALD) is a rapidly growing indication for liver transplantation (LT). We aimed to examine various clinical, demographic, and behavioral factors to predict post‐LT alcohol relapse and graft survival.

Methods

Retrospective analysis was performed on 241 LT recipients with AALD as either a primary or secondary indication for LT (2006‐2015).

Results

Patients with <6 months of alcohol abstinence had significantly increased cumulative incidence for alcohol relapse compared to those with >6 months of abstinence (P = .0041, Log‐Rank). We identified four variables to predict harmful alcohol relapse post‐LT: age at LT, non‐alcohol‐related criminal history, pre‐LT abstinence period (Ref >6 months of alcohol abstinence), and drinks per day (Ref <10 drinks/day). Area under the curve (AUC) for the final model was 0.79 (95% CI: 0.68‐0.91). Our multivariable model was evaluated with internal cross‐validation; random sampling of the study subjects 100 times yielded a median C statistic of 75 (±SD 0.097) and accuracy of 91 (±SD 0.026). The four‐variable model served to form the harmful alcohol use post‐LT (HALT) score. Graft survival remained significantly lower in patients with <6 months of pre‐LT alcohol abstinence and those with blue‐collar jobs.

Conclusion

The HALT score identifies LT candidates with AALD at significant risk for alcohol relapse, potentially guiding transplant centers for pre‐ and post‐LT interventions for improved patient outcomes.
Evaluation of the Effect of Maribavir on Cardiac Repolarization in Healthy Participants: Thorough QT/QTc Study
Authors: Ilic Katarina , Song Ivy , Wu Jingyang , Martin Patrick
Published: June 2020

Maribavir is an orally bioavailable benzimidazole riboside in clinical development for treatment of cytomegalovirus infection in patients who undergo transplantation. Maribavir was evaluated in a thorough QT (TQT) study to determine any effects on cardiac repolarization. The effect of maribavir 100 and 1,200 mg oral doses on the baseline‐adjusted and placebo‐adjusted corrected QT (QTc) interval (delta delta QTc (ddQTc)) and other electrocardiogram (ECG) parameters was assessed in a randomized, phase I, placebo‐controlled, four‐period crossover study in healthy participants (men and women ages 18–50 years). Additionally, maribavir pharmacokinetics, safety, and tolerability were investigated. Moxifloxacin (400 mg) was used as a positive control to demonstrate the study’s ability to detect QT prolongation. Digital 12‐lead Holter ECG monitoring was performed over 22 hours following study drug administration. Individual, Fridericia’s, and Bazett’s QTc intervals were calculated. Of 52 randomized participants (29 ± 8.1 years old; 31 men (60%)), 50 (96%) completed the study. For both 100‐mg and 1200‐mg doses of maribavir, analysis of ddQTc demonstrated that the upper bound of the two‐sided 90% confidence interval was below the 10‐ms threshold at all time points. The concentration–effect analysis demonstrated no relationship between ddQTc and plasma concentrations of maribavir (and its metabolite). There were no clinically meaningful changes in heart rate and systolic blood pressure. The most common adverse event was dysgeusia; no serious adverse events were reported. This TQT study demonstrated that maribavir did not have impact on cardiac repolarization.
Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant
Authors: Chen Jun , Perez Richard , de Mattos Angelo Mario , Wang Cecilia , Li Zhongmin , Applegate Richard L. , Liu Hong
Published: June 2020

Graft function is crucial for successful kidney transplantation. Many factors may affect graft function or cause delayed graft function (DGF), which decreases the prognosis for graft survival. This study was designed to evaluate whether the perioperative use of dexmedetomidine (Dex) could improve the incidence of function of graft kidney and complications after kidney transplantation. A total of 780 patients underwent kidney transplantations, 315 received intravenous Dex infusion during surgery, and 465 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes are major adverse complications, including DGF and acute rejection in the early post‐transplantation phase. The secondary outcomes included length of hospital stay (LOS), infection, overall complication, graft functional status, post‐transplantation serum creatinine values, and estimated glomerular filtration rate (eGFR). Dex use significantly decreased DGF (19.37% vs. 23.66%; adjusted odds ratio, 0.744; 95% confidence interval, 0.564–0.981; P = 0.036), risk of infection, risk of acute rejection in the early post‐transplantation phase, the risk of overall complications, and LOS. However, there were no statistical differences in 90‐day graft functional status or 7‐day, 30‐day, and 90‐day eGFR. Perioperative Dex use reduced incidence of DGF, risk of infection, risk of acute rejection, overall complications, and LOS in patients who underwent kidney transplantation.
CYP2C19 Allele Frequencies in Over 2.2 Million Direct‐to‐Consumer Genetics Research Participants and the Potential Implication for Prescriptions in a Large Health System
Authors: Ionova Yelena , Ashenhurst James , Zhan Jianan , Nhan Hoang , Kosinski Cindy , Tamraz Bani , Chubb Alison
Published: June 2020

Understanding the prevalence of clinically relevant pharmacogenetic variants using large unselected populations is critical for gauging the potential clinical impact of widespread preemptive pharmacogenetic testing. To this end, we assessed the frequencies and ethnic distribution of the three most common CYP2C19 alleles (*2, *3, and *17) in 2.29 million direct‐to‐consumer genetics research participants (23andMe, Sunnyvale, CA). The overall frequencies of *2, *3, and *17 were 15.2%, 0.3%, and 20.4%, respectively, but varied by ethnicity. The most common variant diplotypes were *1/*17 at 26% and *1/*2 at 19.4%. The less common *2/*17, *17/*17, and *2/*2 genotypes occurred at 6.0%, 4.4%, and 2.5%, respectively. Overall, 58.3% of participants had at least one increased‐function or no‐function CYP2C19 allele. To better understand how this high frequency might impact a real patient population, we examined the prescription rates (Rx) of high‐pharmacogenetic‐risk medications metabolized by CYP2C19 using the University of California at San Francisco (UCSF) health system’s anonymized database of over 1.25 million patients. Between 2012 and 2019, a total of 151,068 UCSF patients (15.8%) representing 5 self‐reported ethnicities were prescribed one or more high‐pharmacogenetic‐risk CYP2C19 medications: proton pump inhibitors (145,243 Rx), three selective serotonin reuptake inhibitor antidepressants (54,463 Rx), clopidogrel (14,376 Rx), and voriconazole (2,303 Rx).
Safety, Pharmacokinetics, and Pharmacodynamics of TD‐0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects
Authors: Kanodia Jitendra , Lo Arthur , Baldwin R. Michael , Colley Ken , Zhou Kefei , Bourdet David L.
Published: June 2020

TD‐0714 is an orally active, potent, and selective inhibitor of human neprilysin (NEP) in development for the treatment of chronic heart failure. Oral administration of TD‐0714 in rats resulted in dose‐dependent and sustained increases in plasma cyclic guanosine monophosphate (cGMP) over 24 hours consistent with NEP target engagement. Randomized, double‐blind, placebo controlled, single ascending dose (50–600 mg TD‐0714) and multiple ascending dose (10–200 mg TD‐0714 q.d. for 14 days) studies were conducted in healthy volunteers. TD‐0714 was generally well‐tolerated and no serious adverse events or clinically significant effects on vital signs or electrocardiogram parameters were observed. TD‐0714 exhibited dose‐proportional pharmacokinetics (PKs) with high oral bioavailability, minimal accumulation after once daily dosing, and negligible renal elimination. Pharmacodynamic (PD) responses were observed at all dose levels studied, as reflected by statistically significant increases in plasma cGMP concentrations. The increases in cGMP were significantly above the baseline (~ 50–100%) on day 14 for the entire 24‐hour interval indicating that sustained cGMP elevations are achieved at steady‐state. Maximal steady‐state cGMP response was observed in plasma and urine at doses ≥ 50 mg. The TD‐0714 PK‐PD relationship and safety profile were similar in elderly vs. younger adult subjects. The TD‐0714 PK and PD profiles support further clinical development of TD‐0714 and suggest the potential for once‐daily administration and predictable exposure in patients with cardiorenal diseases regardless of their renal function.
Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles
Authors: LeBlanc Robert E. , Carter Joi B. , Kaur Prabhjot , Lansigan Frederick
Published: June 2020

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B‐cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61‐year‐old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B‐cells colonizing germinal center follicles; however, faint CD5 and CD23 co‐expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL‐type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B‐cell lymphomas presenting in the skin.
Review of different platforms to perform rapid onsite evaluation via telecytology
Authors: Yao Keluo , Li Zaibo
Published: June 2020

There is increased utilisation of cytopathology to provide a rapid onsite evaluation (ROSE) of fine needle aspiration and touch preparations of small biopsies. A well‐executed ROSE procedure can significantly impact the diagnostic quality and appropriate specimen triage of procured biopsy materials. To accommodate the demand for ROSE, telecytology has been increasingly implemented to facilitate ROSE occurring remotely. Telecytology can be categorised based on camera systems including eyepiece system, camera port system and robotic microscope/whole slide image scanner system. Image sharing methods include static images, broadcast only live video streaming, teleconferencing and whole slide image management system. In this review, we will discuss the advantages and disadvantages of each of these systems and deployment considerations.
Bridging ears and eyes when learning spoken words: On the effects of bilingual experience at 30 months
Authors: Havy Mélanie , Zesiger Pascal E.
Published: June 2020

From the very first moments of their lives, infants selectively attend to the visible orofacial movements of their social partners and apply their exquisite speech perception skills to the service of lexical learning. Here we explore how early bilingual experience modulates children's ability to use visible speech as they form new lexical representations. Using a cross‐modal word‐learning task, bilingual children aged 30 months were tested on their ability to learn new lexical mappings in either the auditory or the visual modality. Lexical recognition was assessed either in the same modality as the one used at learning (‘same modality’ condition: auditory test after auditory learning, visual test after visual learning) or in the other modality (‘cross‐modality’ condition: visual test after auditory learning, auditory test after visual learning). The results revealed that like their monolingual peers, bilingual children successfully learn new words in either the auditory or the visual modality and show cross‐modal recognition of words following auditory learning. Interestingly, as opposed to monolinguals, they also demonstrate cross‐modal recognition of words upon visual learning. Collectively, these findings indicate a bilingual edge in visual word learning, expressed in the capacity to form a recoverable cross‐modal representation of visually learned words.
Retinal optical coherence tomography for children with cerebral palsy
Authors: Williams Cathy
Published: June 2020

This commentary is on the case series by Jacobsen et al. on pages 1100–1106 of this issue.
Chinese Development Finance and its determinants: Does global governance matter?
Authors: Yoo Eunhye
Published: June 2020

Motivation

What motivates China to offer development finance in recipient countries? Research on Chinese development finance focuses on China’s political and economic interests in allocating development finance. Few studies, however, have assessed the impact of international norms and regulation—a neo‐institutional perspective—on China’s development finance.

Purpose

The article tests the three sets of hypotheses on Chinese development finance, positing that countries will receive more Chinese aid if: (1) they have a UN General Assembly voting alliance with China and do not recognize Taiwan; (2) the more oil and gas reserves they have; and (3) the more memberships of intergovernmental organizations (IGOs), such as the UN agencies, and international non‐governmental organizations (INGOs), which include non‐profit organizations and charities, such as Oxfam, as well as foundations and professional associations.

Approach and Methods

This study models the amount of Chinese aid received by developing countries as a function of its integration to IGOs/INGO networks. It draws on data from AidData’s Global Chinese Official Finance Dataset, 2000–2014. The model used is ordinary least square regression using fixed effects.

Conclusions

Chinese aid allocation does not only reflect its political and economic interests. Taiwan recognition continues to be the dominant factor for Chinese development finance. IGO and INGO memberships of recipient countries increase the chance of receiving more Chinese development funding, especially for least developed countries.

Policy Implications

Chinese development finance provides many developmental opportunities for less developed countries. A key aspect of getting Chinese development finance has been alliance with China. Linkages to IGOs and INGOs also matter. Countries aiming to get Chinese development finance should consider increasing their memberships to transnational networks of IGOs and INGOs.
Exacerbation of mitral regurgitation after tricuspid valve replacement for isolated tricuspid regurgitation
Authors: Nishiwaki Shushi , Hayashi Hideyuki , Yamamoto Yuki , Nakane Eisaku , Hanyu Michiya , Inoko Moriaki
Published: June 2020

A 74‐year‐old woman, with a history of aortic valve replacement and open mitral commissurotomy due to rheumatic aortic and mitral stenosis, presented with dyspnea. She developed severe tricuspid regurgitation (TR), requiring tricuspid valve replacement (TVR). Despite an uneventful postoperative course, she was readmitted for dyspnea 2 months later. Trans‐thoracic echocardiogram revealed severe mitral regurgitation (MR), despite mild MR at the time of TVR, which has not been previously reported. The main MR mechanism was increased left ventricular preload due to improved TR. Increased diuresis has controlled her congestive heart failure, but her MR remained moderate.
The changing face of family medicine in the COVID and post‐COVID era
Authors: Grattagliano Ignazio , Rossi Alessandro , Cricelli Iacopo , Cricelli Claudio
Published: June 2020

This article describes the prospective changes and the fundamental values of the relationships between family doctors, patients and community according to an ethical‐social concept of medicine. New aspects of the organization of the activity and of the roles of family doctors are reported in order to build hypotheses pointing to a modern and efficient management of patients in the coming the post‐COVID era.
Biological senescence risk score. A practical tool to predict biological senescence status
Authors: Ortiz-Morales Ana M. , Alcala-Diaz Juan F. , Rangel-Zuñiga Oriol A. , Corina Andreea , Quintana-Navarro Gracia , Cardelo Magdalena P. , Yubero-Serrano Elena , Malagon Maria M. , Delgado-Lista Javier , Ordovas Jose M. , Lopez-Miranda Jose , Perez-Martinez Pablo
Published: June 2020

Background

Ageing and biological senescence, both related to cardiovascular disease, are mediated by oxidative stress and inflammation. We aim to develop a predictive tool to evaluate the degree of biological senescence in coronary patients.

Methods

Relative telomere length (RTL) of 1002 coronary patients from the CORDIOPREV study (NCT00924937) was determined at baseline in addition to markers of inflammatory response (hs‐C‐Reactive Protein, monocyte chemoattractant protein‐1, IL‐6, IL‐1β, TNF‐α, adiponectin, resistin and leptin) and oxidative stress (nitric oxide, lipid peroxidation products, carbonylated proteins, catalase, total glutathione, reduced glutathione, oxidized glutathione, superoxide dismutase and peroxidated glutathione). Biological senescence was defined using the cut‐off value defined by the lower quintile of relative telomere length in our population (RTL = 0.7629). We generated and tested different predictive models based on logistic regression analysis to identify biological senescence. Three models were designed to be used with different sets of information.

Results

We selected those patients with all the variables proposed to develop the predictive models (n = 353). Statistically significant differences between both groups (Biological senescence vs. Nonbiological senescence) were found for total cholesterol, catalase, superoxide dismutase, IL‐1β, resistin and leptin. The area under the curve of receiver‐operating characteristic to predict biological senescence for our models was 0.65, 0.75 and 0.72.

Conclusions

These predictive models allow us to calculate the degree of biological senescence in coronary patients, identifying a subgroup of patients at higher risk and who may require more intensive treatment.
Lack of association between LGMN and Alzheimer’s disease in the Southern Han Chinese population
Authors: Zhang Xinyue , Jiao Bin , Weng Ling , Zhou Yafang , Guo Lina , Wang Xin , Zhou Lu , Liu Xixi , Xiao Xuewen , Liu Hui , Zhu Xiangyu , Li Chenping , Zhu Yuan , Yang Qijie , Lin Zhuojie , Jiang Yaling , Wen Yafei , Zhou Hui , Shen Lu , Liao Xinxin
Published: June 2020

Recently, functional studies have demonstrated that legumain (LGMN) cleaves both amyloid β‐protein precursor and tau, promoting senile plaques and formation of neurofibrillary tangles, which may play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the genetic role of LGMN in AD has not been clearly elucidated. Here, we used Sanger sequencing to investigate the single independent (single‐variant association test) and cumulative (gene‐based association test) effects of variants in the LGMN gene as potential susceptibility factors for AD, in a cohort comprising 676 AD cases and 365 elderly controls from the Han population of South China. In single‐variant association analysis, none of the common variants in LGMN were statistically significant. In gene‐based analysis, the LGMN gene also showed no association with AD. The results of our replication study in the Alzheimer's Disease Neuroimaging Initiative cohort also showed no association between LGMN and AD. These findings suggest that the LGMN gene may not be a critical factor for AD development.
Detection of atrial fibrillation with implantable loop recorders in horses
Authors: Buhl Rikke , Hesselkilde Eva M. , Carstensen Helena , Fenner Merle F. , Jespersen Thomas , Tfelt‐Hansen Jacob , Michael Sattler Stefan
Published: June 2020

Background

Cardiac arrhythmias in horses are diagnosed by auscultation or electrocardiogram (ECG), which results in a low sensitivity for detecting arrhythmias that occur sporadically. Implantable loop recorders (ILRs) are small ECG devices placed subcutaneously, to automatically detect arrhythmias in human patients.

Objectives

To test ILRs ability to detect atrial fibrillation (AF) in horses. Furthermore, we hypothesised that anatomical location of the implant site might influence signal quality. Signal quality was evaluated both during exercise and over time.

Study design

Experimental study.

Methods

In five Standardbred mares, eleven ILRs were implanted subcutaneously in up to three different positions (Front: pectoral region, Left‐6: sixth left intercostal space and Ventral: xiphoid region) and AF induced. The R‐ and T‐wave amplitudes were measured in all positions over time during AF. AF burden automatically registered by the ILRs over a 2‐month period was compared with selected Holter ECG recordings.

Results

All three positions had stable R‐ and T‐wave amplitudes during the study period and were of sufficient quality to allow AF detection at rest. The position Left‐6 showed significantly higher R‐ and T‐wave amplitudes compared with the other positions. During submaximal exercise only the Left‐6 position was able to record ECG signals of diagnostic quality. No position yielded diagnostic signals at maximum exercise due to artefacts.

Main limitations

Few horses and ILRs included and no spontaneous AF episodes were studied.

Conclusions

This preliminary study indicates that ILRs can be used for AF detection in horses, but the anatomical location is important for optimal ECG quality. Despite insufficient quality during exercise, ILRs were suitable for AF detection at rest. Therefore, the ILR may be a valuable diagnostic tool for detecting paroxysmal AF in horses.
Cross‐sectional study reveals that HLA‐C*07:02 is a potential biomarker of early onset/lesion severity of psoriasis
Authors: Li Junqin , Li Xiaofang , He Fusheng , Zhao Xincheng , Hou Ruixia , Lin Haoxiang , Shen Juan , Wu Xueli , Liao Qijun , Xing Jianxiao , Yin Guohua , Li Xinhua , Zhang Kaiming
Published: June 2020

Psoriasis is a common chronic autoimmune skin disease, with T cells playing a predominant role in its pathogenesis. Here, we aimed to investigate the relation of T‐cell repertoires (TCR) and major histocompatibility complex (MHC) in psoriatic patients to further understand mechanisms in disease pathogenesis. We conducted a cross‐sectional study involving nine pairs of monozygotic twins with inconsistent psoriasis and examined the TCR diversity and MHC haplotype of the individuals using multiple‐PCR and high‐throughput sequencing. Additionally, 665 psoriatic patients were applied to validate the relation of human leucocyte antigen (HLA) class I allele HLA‐C*07:02 and early onset or lesion severity of psoriasis. The immune diversity was lower in psoriatic patients compared with unaffected individuals within the twin pairs, although the difference was not significant. The clonotypes of TCR significantly decreased in psoriatic patients with high PASI score and early onset. HLA‐C*07:02, a haplotype associated with psoriasis, was positively correlated with the diversity of the TCRV gene. Moreover, HLA‐C*07:02 clustered in patients with high PASI and early onset. In the replication stage, we found that the PASI and onset age in psoriasis with HLA‐C*07:02 were significantly different from those without HLA‐C*07:02 and without HLA‐C*06:02. Our observations indicate that HLA‐C*07:02 is positively correlated with the diversity of TCRV gene in psoriasis and maybe a potential biomarker of early onset/severe lesions of psoriasis.
Secure third‐party data clustering using SecureCL, Φ‐data and multi‐user order preserving encryption
Authors: Almutairi Nawal , Coenen Frans , Dures Keith
Published: June 2020

Secure collaborative data clustering using SecureCL is presented. SecureCL is founded on the concept of Φ‐data implemented using Super Secure Chain Distance Matrices and encrypted using Multi‐User Order Preserving Encryption. The advantage offered, unlike comparable systems, is that SecureCL does not require any user participation once the Φ‐data proxy has been encrypted; it does not require recourse to Secure Multi‐Party Computation protocols or ‘secret sharing’ mechanisms. The utility of SecureCL is illustrated using Nearest Neighbour Clustering and Density‐Based Spatial Clustering of Applications with Noise, although it can be applied to any data clustering algorithm that involves distance comparison. The reported experiments demonstrate that SecureCL can produce securely cluster configurations comparable to those produced using standard, non‐encrypted, approaches without entailing any significant computational overhead, thus indicating its suitability in the context of Data Mining as a Service.
Innovation and Integration of Sexuality in Family Life Education
Authors: Russell Stephen T. , Mallory Allen B. , Bishop Meg D. , Dorri Armin A.
Published: June 2020

As a fundamental aspect of the human experience, sexuality is experienced at every stage in the life span. Sexual values, behaviors, and health are important components of individual and family well‐being. Educating about such a fundamental aspect of life is both obvious and crucial. In this article, we consider the potential of sexuality education in the field and profession of family life education (FLE). We critique sexuality education in the United States and the marginal place of human sexuality in the FLE field. We then offer recommendations for incorporating life span, socioecological, family systems, and intersectionality perspectives into sexuality education, and recommendations for FLE and sexuality education research and practice. We argue that educating about sexuality in the context of FLE—and activating the profession of FLE for sexuality education—will strategically advance sexuality education, sexual health, and the field of FLE.
Close‐up: HIV/SIV intasome structures shed new light on integrase inhibitor binding and viral escape mechanisms
Authors: Engelman Alan N. , Cherepanov Peter
Published: June 2020

Integrase strand transfer inhibitors (INSTIs) are important components of drug formulations that are used to treat people living with HIV, and second‐generation INSTIs dolutegravir and bictegravir impart high barriers to the development of drug resistance. Reported 10 years ago, X‐ray crystal structures of prototype foamy virus (PFV) intasome complexes explained how INSTIs bind integrase to inhibit strand transfer activity and provided initial glimpses into mechanisms of drug resistance. However, comparatively low sequence identity between PFV and HIV‐1 integrases limited the depth of information that could be gleaned from the surrogate model system. Recent high‐resolution structures of HIV‐1 intasomes as well as intasomes from a closely related strain of simian immunodeficiency virus (SIV), which were determined using single‐particle cryogenic electron microscopy, have overcome this limitation. The new structures reveal the binding modes of several advanced INSTI compounds to the HIV/SIV integrase active site and critically inform the structural basis of drug resistance. These findings will help guide the continued development of this important class of antiretroviral therapeutics.
Neighborhood Dynamics and Long‐Term Change
Authors: Hallowell George , Baran Perver
Published: June 2020

Patterns of change in neighborhoods can be discordantly different, even within the same city district. A little understood factor in how urban neighborhoods form and grow is structural inertia, which is the tendency of an urban area to resist change due to its existing physical and socio‐economic fabric. This study explores how patterns of buildings, plots, blocks, and streets affect change or inertia in neighborhoods over time. We integrate Conzenian morphology and space syntax approaches within a geographic information system (GIS) framework to study two historic neighborhoods in Charlotte and Raleigh, N.C. at four points in time over a 96‐year span. Aerial images, historic maps, and GIS sources help to create spatial configuration and building data for each time period. We then analyze these data to identify statistical and map‐pattern morphological and syntactic relationships both in the aggregate and in detail. Our research finds that most of the independent variables of block size, plot size, building footprint, global integration, local integration, and connectivity predicted long‐term change measured in building inventory in almost every occurrence. Our study also suggests design implications and possible future tools and research for measuring change and its relation to the physical characteristics of our cities.
Dextran deposition in reticuloendothelial organs in hemodialysis patients: A forgotten adverse effect of low‐molecular weight dextran
Authors: Yokokawa Toru , Ikura Yoshihiro , Okabe Hidetoshi , Iwai Yasuhiro
Published: June 2020

We present two autopsy cases of refractory ascites/hydrothorax associated with systemic deposition of low‐molecular weight dextran that had been used in hemodialysis over an extended period. The most striking autopsy findings in both cases were dense accumulation of dextran‐laden macrophages in sinusoids of reticuloendothelial organs. These accumulated macrophages seemed to have disturbed blood and lymph flow. Based on these findings, we concluded that the persistent ascites and hydrothorax were attributable to systemic deposition of dextran, especially the accumulation of dextran‐laden macrophages in the reticuloendothelial organs. We suggest that dextran solution should immediately be designated as contraindicated for hemodialysis patients.
Reflections, impact and recommendations of a co‐produced qualitative study with young people who have experience of mental health difficulties
Authors: Dewa Lindsay H. , Lawrence‐Jones Anna , Crandell Caroline , Jaques Jack , Pickles Katy , Lavelle Mary , Pappa Sofia , Aylin Paul
Published: June 2020

Background

There is limited evidence of genuine equal partnership where power is shared with young people with mental health difficulties throughout all research stages, particularly in data collection and analysis.

Objective

To describe how our qualitative study, exploring young peoples’ perceptions on the feasibility of using technology to detect mental health deterioration, was co‐produced using principles of co‐production, whilst reflecting on impact, challenges and recommendations.

Methods

Young people with experience of mental health difficulties were appointed and then worked with researchers throughout all research stages. The study was evaluated against the five principles of co‐production. Reflections from researchers and young people were collected throughout.

Results

Seven young people formed an initial Young People's Advisory Group (YPAG); three became co‐researchers. Reflection was key throughout the process. Sharing power became easier and more evident as trust, confidence and mutual respect grew over time, particularly after a safe space was established. The safe space was crucial for open discussions, and our WhatsApp group enabled continual communication, support and shared decision‐making. The resulting co‐produced topic guide, coding framework, thematic map, papers and presentations demonstrated significant impact.

Conclusions

To our knowledge, this is the first qualitative mental health study to be co‐produced using the principles of co‐production. Our rigorous assessment can be utilized as an informative document to help others to produce meaningful co‐produced future research. Although co‐production takes time, it makes significant impact to the research, researchers and co‐researchers. Flexible funding for spontaneous suggestions from co‐researchers and more time for interview training is recommended.
Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel
Authors: Wolf Janina L , van Nederveen Francien , Blaauwgeers Hans , Marx Alexander , Nicholson Andrew G , Roden Anja C , Ströbel Philipp , Timens Wim , Weissferdt Annika , von der Thüsen Jan , den Bakker Michael A
Published: June 2020

Aims

Thymic tumours are rare in routine pathology practice. Although the World Health Organization (WHO) classification describes a number of well‐defined categories, the classification remains challenging. The aim of this study was to investigate the reproducibility of the WHO classification among a large group of international pathologists with expertise in thymic pathology and by using whole slide imaging to facilitate rapid diagnostic turnover.

Methods and results

Three hundred and five tumours, consisting of 90 biopsies and 215 resection specimens, were reviewed with a panel‐based virtual microscopy approach by a group of 13 pathologists with expertise in thymic tumours over a period of 6 years. The specimens were classified according to the WHO 2015 classification. The data were subjected to statistical analysis, and interobserver concordance (Fleiss kappa) was calculated. All cases were diagnosed within a time frame of 2 weeks. The overall level of agreement was substantial (κ = 0.6762), and differed slightly between resection specimens (κ = 0.7281) and biopsies (κ = 0.5955). When analysis was limited to thymomas only, and they were grouped according to the European Society for Medical Oncology Clinical Practice Guidelines into B2, B3 versus A, AB, B1 and B3 versus A, AB, B1, B2, the level of agreement decreased slightly (κ = 0.5506 and κ = 0.4929, respectively). Difficulties arose in distinguishing thymoma from thymic carcinoma. Within the thymoma subgroup, difficulties in distinction were seen within the B group.

Conclusions

Agreement in diagnosing thymic lesions is substantial when they are assessed by pathologists with experience of these rare tumours. Digital pathology decreases the turnaround time and facilitates access to what is essentially a multinational resource. This platform provides a template for dealing with rare tumours for which expertise is sparse.
MYC expression has limited utility in the distinction of undifferentiated radiation‐associated sarcomas from sporadic sarcomas and sarcomatoid carcinoma
Authors: Mito Jeffrey K , Qian Xiaohua , Jo Vickie Y , Doyle Leona A
Published: June 2020

Aims

MYC is a proto‐oncogene that is frequently dysregulated in various malignancies, through translocation or amplification. Radiation‐associated angiosarcoma frequently shows MYC amplification, and immunohistochemical expression has been shown to be a reliable surrogate marker for amplification, but less is known about MYC expression in other sarcoma types, despite reports of MYC amplification in some undifferentiated/unclassified radiation‐associated sarcomas (RASs). Distinguishing putative RAS from non‐radiation‐associated sarcoma or sarcomatoid carcinoma can be difficult. The aim of this study was to determine the prevalence and potential diagnostic utility of MYC in this context, by evaluating MYC expression in a cohort of RASs, non‐radiation‐associated sarcomas, and sarcomatoid carcinomas.

Methods and results

Three hundred and eighty‐five neoplasms were evaluated, including 81 RASs (18 angiosarcomas; 57 undifferentiated sarcomas; three leiomyosarcomas; and three malignant peripheral nerve sheath tumours), 267 non‐radiation‐associated sarcomas, and 37 sarcomatoid carcinomas. Immunohistochemistry was performed with a monoclonal anti‐MYC antibody. Staining in tumour cells was scored on the basis of extent (focal, 1–4%; multifocal, 5–49%; and diffuse, ≥50%) and intensity (strong, moderate, and weak). One hundred percent of radiation‐associated angiosarcomas expressed MYC diffusely. Expression was infrequent among other types of RAS (9.5%), and the frequency was similar to that in non‐radiation‐associated sarcomas (9.7%). MYC expression was more common in sarcomatoid carcinomas, occurring in 43%. The extent and intensity of staining were variable in all groups.

Conclusion

MYC expression is infrequent among RASs other than angiosarcoma, and has a similar prevalence in sporadic sarcomas. Given the frequency of expression in sarcomatoid carcinomas, MYC expression outside the context of radiation‐associated angiosarcoma is of limited diagnostic utility, and should be interpreted with caution after exclusion of sarcomatoid carcinoma where relevant.
A comparative case‐control study of diagnostic criteria for atopic dermatitis and proposal of new diagnostic criteria from Tunisia
Authors: Lahouel Maha , Lahouel Ines , Belhadjali Hichem , Ben Hammouda Mouna , Youssef Monia , Zili Jameleddine
Published: June 2020

Background

Atopic dermatitis (AD) is a heterogeneous disease. Thus, it is difficult to set up standard diagnostic criteria that cover the entire spectrum of AD patients. Our objectives were to study the epidemiologic characteristics of AD in Tunisia and to evaluate five diagnostic criteria (Hanifin and Rajka, Williams, Taieb and Boralevi, REACH and ISAAC questionnaire).

Methods

This prospective case‐control study was carried out in our Dermatology Department in Tunisia. The cases and controls were collected over a period of one year (January 3, 2017, to January 2, 2018).

Results

We collected 101 patients with AD and 101 controls. Patients and controls were comparable by age and gender. The mean age of patients was 9 years and 9 months with sex ratio 1.02. Children accounted for more than half of the patients (61.39%). The sensitivity and specificity of the criteria were, respectively: 90.1% and 90.1% for the Hanifin and Rajka criteria, 53.47% and 96.04% for the Williams criteria, 62.50% and 92.3% for the Taieb and Boralevi criteria, 41.58% and 92.08% for ISAAC questionnaire, 49.5% and 91.09% for REACH questionnaire. A new version of AD diagnostic criteria has been proposed. By applying these new criteria retrospectively to our patients, the sensitivity rises to 90.1%.

Conclusion

The new version of AD criteria is a practical diagnostic tool compared to the Hanifin and Rajka criteria and seems to correct the problem of low sensitivity of the Williams criteria. Large validation studies are needed.
Executive function phenotypes in pediatric obesity
Authors: Gowey Marissa , Redden David , Lim Crystal , Janicke David , Dutton Gareth
Published: June 2020

Objective

To comprehensively examine the behavioral phenotypes of children with and without executive function (EF) impairments in a clinical sample of youth with obesity.

Methods

Youth aged 8 to 17 years (Mean age = 12.97) attending a medical clinic for obesity and their caregivers (N = 195 dyads) completed a battery of behavioral questionnaires. Caregiver‐proxy report of EF was assessed using the Behavior Rating Inventory of Executive Function. Latent Class Analysis was conducted to identify EF groupings. Analysis of variance and chi‐square tests were conducted to examine associations between EF groups and behavioral phenotypes.

Results

Four latent classes of EF impairment were identified (No/Low Impairment; Behavioral Regulation Impairment; Metacognition Impairment; Global Impairment). There was an overall positive pattern of associations between these EF groups and behavioral/emotional symptoms, such that behavioral/emotional symptoms tended to increase with EF impairment.

Conclusions

Children with obesity and EF impairment demonstrate a dysregulated behavioral phenotype ranging from internalizing to externalizing behavioral and weight‐related symptoms. This phenotype framework may be clinically beneficial for utilizing screening/assessment results to develop, tailor, and/or match treatment approaches in pediatric obesity.
CXCL8high inflammatory B cells in the peripheral blood of patients with biliary atresia are involved in disease progression
Authors: Zhang Yu , Zhou Lin , Gu Guangxiang , Feng Mingxuan , Ding Xuping , Xia Qiang , Lu Liming
Published: June 2020

Biliary atresia (BA), the most common cause of pediatric end‐stage liver disease, results from fibroinflammatory obstruction of the intrahepatic and extrahepatic bile ducts. The etiology of BA has been extensively studied, and inflammation and imbalanced immune system have been identified as the main pathogenesis of BA. B cells play roles in innate and adaptive immunity, but few studies have investigated the role of B cells in BA. This study aimed to elucidate the role of B cells in the development of BA. The percentage and numbers of total B cells (23.81 ± 11.14%，P < 0.0001, 1.22 ± 0.67 × 109 L–1, P = 0.0014) and immature B cells (25.33 ± 14.32%, P = 0.0013, 0.19 ± 0.20 × 109 L–1, P < 0.0001) were significantly increased in the peripheral blood of patients with BA and the number of total B cells was positively correlated with gamma‐glutamyl‐transpeptidase in the serum of BA. High C–X–C motif chemokine ligand 8 (CXCL8) levels were detected in the serum of patients with BA. As an important source of CXCL8, B cells from patients with BA secreted more CXCL8 into peripheral blood than those from control patients. Moreover, immature B cells can secrete more CXCL8 than mature B cells, and B cells secreted CXCL8 upon activation of the nuclear factor‐κB pathway. Taken together, the results revealed that B cells have a strong ability to secrete CXCL8, which is associated with the pathogenesis of BA, and exert a proinflammatory effect on the development of BA.
Temperature stability of a pure metakaolin based K‐geopolymer: Part 2. Variations in the mesoporous network and its rehydration stability
Authors: Gomes Sandrine , Petit Elodie , Frezet Lawrence , Nedelec Jean‐Marie , Gharzouni Ameni , Rossignol Sylvie , Renaudin Guillaume
Published: June 2020

The thermal behavior of a model MK‐based K‐geopolymer was investigated between room temperature and 1400°C in order to evaluate its potentiality for high‐temperature applications. The purpose of our study was to monitor the behavior of a geopolymer during a temperature rise in order to better understand its variations with respect to temperature. The works from the present paper focus only changes in the porous network; it follows a first part devoted to variations in the mineral matrix. The results obtained here show that the geopolymer material preserves its porous integrity up to 800°C, while maintaining the reversibility of water exchanges corresponding to about 25 weight percent. Together with the results of part 1, the findings of this study allow us to affirm that geopolymer materials are only very little affected by temperatures up to 800°C, or even 900°C (keeping its mesoporous amorphous structure).
Hot Isostatically Pressed (HIPed) fluorite glass‐ceramic wasteforms for fluoride molten salt wastes
Authors: Gregg Daniel J. , Vance Eric R. , Dayal Pranesh , Farzana Rifat , Aly Zaynab , Holmes Rohan , Triani Gerry
Published: June 2020

Molten pyroprocessing salts can be used to dissolve used nuclear fuel from a reactor allowing recovery of the actinides. Previously, ANSTO have demonstrated hot isostatically pressed (HIPed) sodalite glass‐ceramic wasteforms for eutectic (Li,K)Cl salts containing fission products, but this system cannot be used for the analogous molten alkali fluoride salts (eg, FLiNaK), which have utility in the application of the next generation of nuclear reactors. In this work, a novel glass‐ceramic composite wasteform has been prepared by HIPing, as a candidate for the immobilization of fission product‐bearing FLiNaK salts. The wasteform has been tailored to immobilize the high fluoride content of the waste within fluorite, whereas the waste alkali elements are incorporated in a durable sodium aluminoborosilicate glass, with total waste loadings of ~17‐21 wt% achieved. It was also demonstrated that the speciation of Mo‐ and Sb‐simulated fission products was altered by adding Ti metal due to a controlled redox environment. The resulting candidate wasteform has been studied by X‐ray diffraction and scanning electron microscopy, including the HIP canister‐wasteform interaction zone, and its performance assessed via leaching studies using the PCT and ASTM C1220 leaching protocols. Dr Vance very much enjoyed the challenge of wasteform design for problematic nuclear wastes, for which fission product‐bearing FLiNaK salts are a clear example. His ability to hone in on a wasteform solution with viable waste loadings that meet performance requirements was testament to his nearly 40 years experience in nuclear waste immobilization. The samples discussed in this work represent the last wasteform materials that he prepared.