bluuebunny/crossref_metadata_2025 huggingface dataset:
Oestradiol and the risk of myocardial infarction in women: a cohort study of UK Biobank participants
Authors: Peters Sanne A E , Woodward Mark
Published: December 2020

Background

It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.

Methods

We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.

Results

After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).

Conclusions

Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors.
Factors Affecting Image Quality and Lesion Evaluability in Breast Diffusion-weighted MRI: Observations from the ECOG-ACRIN Cancer Research Group Multisite Trial (A6702)
Authors: Whisenant Jennifer G , Romanoff Justin , Rahbar Habib , Kitsch Averi E , Harvey Sara M , Moy Linda , DeMartini Wendy B , Dogan Basak E , Yang Wei T , Wang Lilian C , Joe Bonnie N , Wilmes Lisa J , Hylton Nola M , Oh Karen Y , Tudorica Luminita A , Neal Colleen H , Malyarenko Dariya I , McDonald Elizabeth S , Comstock Christopher E , Yankeelov Thomas E , Chenevert Thomas L , Partridge Savannah C
Published: December 2020

Objective

The A6702 multisite trial confirmed that apparent diffusion coefficient (ADC) measures can improve breast MRI accuracy and reduce unnecessary biopsies, but also found that technical issues rendered many lesions non-evaluable on diffusion-weighted imaging (DWI). This secondary analysis investigated factors affecting lesion evaluability and impact on diagnostic performance.

Methods

The A6702 protocol was IRB-approved at 10 institutions; participants provided informed consent. In total, 103 women with 142 MRI-detected breast lesions (BI-RADS assessment category 3, 4, or 5) completed the study. DWI was acquired at 1.5T and 3T using a four b-value, echo-planar imaging sequence. Scans were reviewed for multiple quality factors (artifacts, signal-to-noise, misregistration, and fat suppression); lesions were considered non-evaluable if there was low confidence in ADC measurement. Associations of lesion evaluability with imaging and lesion characteristics were determined. Areas under the receiver operating characteristic curves (AUCs) were compared using bootstrapping.

Results

Thirty percent (42/142) of lesions were non-evaluable on DWI; 23% (32/142) with image quality issues, 7% (10/142) with conspicuity and/or localization issues. Misregistration was the only factor associated with non-evaluability (P = 0.001). Smaller (≤10 mm) lesions were more commonly non-evaluable than larger lesions (p <0.03), though not significant after multiplicity correction. The AUC for differentiating benign and malignant lesions increased after excluding non-evaluable lesions, from 0.61 (95% CI: 0.50–0.71) to 0.75 (95% CI: 0.65–0.84).

Conclusion

Image quality remains a technical challenge in breast DWI, particularly for smaller lesions. Protocol optimization and advanced acquisition and post-processing techniques would help to improve clinical utility.
How Do Consumers React to Company Moral Transgressions? The Role of Power Distance Belief and Empathy for Victims
Authors: Xu Haiyue (Felix) , Bolton Lisa E , Winterich Karen Page
Published: December 2020

This research proposes that consumers vary in their response to company moral transgressions as a function of power distance belief (PDB), which is the extent that consumers accept inequality (a prominent moral principle). Specifically, consumers with lower PDB tend to feel more empathy for victims, which in turn heightens harm perceptions and negative moral emotions, leading to less favorable reactions toward the transgressing company. A series of nine studies and four supplementary experiments provides converging evidence for the PDB effect and underlying empathy-based process, while identifying victim salience and company crisis response strategy as theoretically and pragmatically relevant moderators. Specifically, the PDB effect emerges when victim salience is high (evoking greater empathy among lower-PDB consumers) but is attenuated when victim salience is low (and empathy is not evoked). Likewise, the PDB effect on company evaluations can be mitigated when the transgressing company offers both an apology and remedy, which together signal the company’s empathy for victims and remedy for harm that are salient to low-PDB consumers. Together, these findings shed light on how consumer reactions to company moral transgressions vary by culture, transgression characteristics, and company response strategies, providing guidance to companies in crisis.
Perceptual Facilitators for and Barriers to Career Progression: A Qualitative Study With Female Early Stage Investigators in Health Sciences
Authors: Fernandez Sofia B. , Clarke Rachel D. , Sheehan Diana M. , Trepka Mary Jo , Rose Suzanna M.
Published: December 2020

Purpose

Despite efforts to increase the representation of women in the national scientific workforce, results still lag. While women’s representation in health-related sciences has increased substantially, women remain underrepresented in senior leadership roles. This study was conducted to elucidate influences at the individual, interpersonal, organizational, and societal levels that present as barriers to and facilitators for advancement in research careers for women, with the goal of promoting and retaining a more diverse leadership.

Method

The authors conducted individual, 1-hour, in-depth, semistructured interviews with 15 female early stage investigators pursuing careers in health sciences research at a large minority-serving institution in Florida in 2018. Interview guides were designed by using a social ecological framework to understand the influence of multilevel systems. Employing a qualitative approach, drawing from a phenomenological orientation, 2 researchers independently coded transcripts and synthesized codes into broad themes.

Results

Barriers and facilitators were reported at all ecological levels explored. Illustrative quotations reflect the unequal distribution of familial responsibilities that compete with career advancement, family members’ lack of understanding of the demands of a research career, the importance of female mentors, perceived differences in the roles and expectations of female and male faculty at institutions, and normative upheld values that influence early career progression.

Conclusions

Achieving pervasive and sustained changes that move toward gender equity in research requires solutions that address multilevel, explicit and implicit influences on women’s advancement in science. Suggestions include shifting familial and institutional norms, creating support systems for women with female mentors, and enforcing consistent policies regarding the roles and expectations of faculty. Findings shed light on the influence of gender on career progression by providing context for the experiences of women and underscore the importance of addressing pervasive societal and structural systems that maintain inequities hindering women’s progress in the scientific workforce.
Sildenafil Misuse for its Psychoactive Properties? A Case Report
Authors: Mathur Rahul , Parmar Arpit , Rajpurohit Surendra Singh , Tundup Tashi , Bhad Roshan , Rao Ravindra
Published: December 2020

Sildenafil is a widely used drug for the treatment of erectile dysfunction in a dosage ranging from 50 to 100 mg per day. Recreational use is reported among youth for its sexual function enhancing effects. To date, however, no study has reported the use of sildenafil for its nonsexual, psychoactive effects. We report a case of a 38-year-old male with opioid and sedative use disorder who self-administered sildenafil orally in a dose of up to 2000 mg per day for its psychoactive effects (primarily) for 10 years before seeking treatment and discuss the literature relevant to the case.
Gastroenterologists’ attitudes on the detection and management of gastric premalignant conditions: results of a nationwide survey in Spain
Authors: Delgado-Guillena Pedro Genaro , Morales-Alvarado Victor Jair , Elosua-González Alfonso , Murcia Pomares Oscar , Pérez-Aisa Angeles , Córdova Henry , Alcedo Javier , Calvet Xavier , Fernández-Esparrach Gloria
Published: December 2020

Introduction

Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists’ attitudes on the detection and management of GPC

Methods

A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología.

Results

The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery.

Conclusion

There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized.
Calcium intake, levels and supplementation and effect modification by genetic variation of calcium homeostasis on the risk of colorectal cancer: the Rotterdam study
Authors: Araghi Sadaf Oliai , Jayakkumaran Abi , Mulder Marlies , Stricker Bruno H. , Ruiter Rikje , Kiefte-de Jong Jessica C.
Published: December 2020

Objectives

Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether calcium intake from diet and supplements, as well as the calcium levels itself, were associated with the CRC risk in middle-aged and older individuals. Also, we evaluated whether these associations were modified by genetic variation of calcium homeostasis.

Design

This study was embedded in the Rotterdam study, a prospective cohort study among adults aged 55 years and older without CRC at baseline, from the Ommoord district of Rotterdam, The Netherlands (N = 10 941). Effect modification by a predefined polygenetic risk score (PRS) from seven loci known to be associated with calcium concentrations, was evaluated.

Results

The incidence rate of CRC in the study population was 2.9 per 1000 person-years. Relative to the recommended dietary calcium intake, only higher than the recommended dietary calcium intake (≥1485 mg/day) was associated with a reduced risk of CRC [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.44–1.00]. No significant associations were found for calcium supplementation and only in the subgroup analysis, albumin-adjusted calcium levels were associated with an increased risk of CRC (HR = 1.11; 95% CI, 1.00–1.23). PRS showed effect modification in the association between calcium intake and CRC (P for interaction = 0.08). After stratification of PRS into low, intermediate and high, we found a lower CRC risk for low-weighted PRS per increase in calcium intake.

Conclusion

There is no consistent association between calcium indices on CRC. However, the association between calcium intake and CRC may be modified by genetic variation associated with serum calcium concentrations that deserves further replication in other studies with different population.
The quantification and clinical analysis of depression and anxiety in patients undergoing Da Vinci robot-assisted radical gastrectomy and open radical gastrectomy
Authors: Ma Jiachi , Li Lei , Du Jun , Pan Chengwu , Zhang Chensong , Chen Yuzhong
Published: December 2020

The purpose of paper is to investigate the depression and anxiety as well as independent influential factors between patients who underwent Da Vinci robot-assisted radical gastrectomy and radical gastrectomy. This study is a partially randomized patient preference trial. A total of 98 patients with gastric cancer were divided into the Da Vinci robot-assisted radical gastrectomy group (46 patients, observation group) and open radical gastrectomy group (52 patients, control group). They were also postoperatively and preoperatively measured with Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). The postoperative and preoperative data of each group were compared. The postoperative and preoperative standard scores of SDS and SAS in patients with the observation group were NS differences (P > 0.05). In the conventional control group, the postoperative mean scores of SDS and SAS were significantly higher than those in the preoperative mean scores and the postoperative mean scores of the observation group, respectively (P < 0.01). The multivariate logistic regression analysis indicated that the independent influential factors of depression and anxiety in patients with radical gastrectomy included tumor, node, metastases stage, pain grading, other postoperative complications and postoperative insomnia (P < 0.05). Robot-assisted radical gastrectomy for gastric carcinoma is conductive to relieving patients’ anxiety and depression and improving their quality of life due to the advantages of relatively low incidence of pain, reduced complications and relatively good sleep.
Microbial Contamination Risk and Disinfection of Radiation Protective Garments
Authors: Balter Stephen , Rodriguez Michelle A. , Pike Janett A. , Kleiman Norman J.
Published: December 2020

Healthcare-associated infections are a major public health concern for both patients and medical personnel. This has taken on greater urgency during the current COVID-19 pandemic. Radiation Personal Protective Equipment (RPPE) may contribute to risks of microbial contamination. This possibility was tested in 61 personal or shared-use lead aprons and thyroid collars at Columbia Presbyterian Irving Medical Center. Fifty percent tested positive for either bacterial or fungal contamination, mostly around the neckline of lead vests and thyroid collars. Repeated testing of garments some weeks to months later confirmed continued presence of microbial contamination. The possibility that hospital-approved disinfection agents could degrade the radio-protective features of these garments was also examined. Samples of identical construction to garments in regular use were subjected to either daily or weekly wipes with hypochlorite or alcohol-based hospital-approved cleaning agents for 6 mo. A third group of samples was maintained in contact with the cleaning agents for 6 mo. All samples were fluoroscoped four times during the study. None demonstrated any degradation in radioprotection. All samples were photographed monthly. Physical degradation of the outer plastic covering by concentrated hypochlorite and limited mechanical damage around stitched seams of the samples cleaned daily with alcohol was noted. Based on the high prevalence of microbial contamination, regular cleaning and disinfection protocols should be implemented. Regular cleaning with medical-facility-approved cleaning and disinfecting agents is likely to be effective at reducing the microbial load and unlikely to result in significant reduction in radioprotective properties of these garments.
Ink Retention and Endothelial Cell Viability After the Application of an Orientation Stamp Over an Air Bubble During Descemet Membrane Endothelial Keratoplasty Graft Preparation
Authors: Straiko Megan M. W. , Odell Kelly , Dye Philip K. , Hikes Matthew T. , Andersen Allison , Trolli Giulia , Tsering Dolkar T. , Galloway Joshua D. , Tran Khoa D.
Published: December 2020

Purpose:

To investigate stamp visibility and endothelial cell loss (ECL) after the application of an orientation mark to Descemet membrane endothelial keratoplasty (DMEK) grafts supported by an air bubble.

Methods:

Eighteen DMEK grafts were prepared at an eye bank using a technique where an orientation mark was applied to the stromal surface of a DMEK graft that was supported by a small air bubble placed at the edge of the 2 endothelial surfaces of the graft. Grafts were evaluated at 2 and 5 days for stamp visibility and at 5 days with calcein-AM staining for ECL. Nine grafts underwent cross-country shipping, and the ECL of shipped and nonshipped grafts was compared using unpaired t test.

Results:

All 18 DMEK grafts exhibited a single, solid, readily visible orientation mark 2 and 5 days after preparation with a mean ECL of 13.5% ± 4.9%. Shipping conditions had no effect on stain retention or ECL.

Conclusions:

The application of an orientation stamp to a DMEK graft over an air bubble in an eye bank setting results in a single, solid orientation mark that is readily visible within the period in which most eye bank-prepared tissue is used. This technique produces no further ECL compared with the methods where the orientation stamp is applied through a stromal window. Eye bank technicians and surgeons can be confident that this modified preparation technique results in transplant-quality DMEK grafts with the additional benefit of conserving the stromal cap for use in other anterior lamellar procedures, thereby making efficient use of donor tissue.
Berlin Excor Cannulation of Left Atrial Appendage in Left Ventricular Restrictive Physiology: A Novel Bailout Strategy
Authors: Marey Gamal M. , Said Sameh M. , Ameduri Rebecca , Steiner Marie E. , Bowler Michael , Loomis Ashley , Jang Subin , Griselli Massimo
Published: December 2020

Ventricular assist device (VAD) management continues to be a challenge in the presence of restrictive physiology. Left atrial (LA) decompression is not satisfactory even with good function and position of the left ventricular cannula. We describe an alternate approach with LA cannulation via the left atrial appendage (LAA) as a rescue strategy in a patient who had restrictive physiology, in our case was secondary to viral myocarditis acute systolic heart failure with subsequent insidious diffuse endomyocardial fibrosis and superimposed massive calcification, causing inadequate emptying of the left ventricle despite optimal VAD apical cannula position.
Is There Evidence That Stimulus Parameters and Electrode Placement Affect the Cognitive Side Effects of Electroconvulsive Therapy in Patients With Schizophrenia and Schizoaffective Disorder?
Authors: Cicek Mustafa , McCall William V. , Yao Zhixing , Sackeim Harold A. , Rosenquist Peter , Youssef Nagy A.
Published: December 2020

Seventy percent of patients with treatment-resistant schizophrenia do not respond to clozapine. Electroconvulsive therapy (ECT) can potentially offer significant benefit in clozapine-resistant patients. However, cognitive side effects can occur with ECT and are a function of stimulus parameters and electrode placements. Thus, the objective of this article is to systematically review published clinical trials related to the effect of ECT stimulus parameters and electrode placements on cognitive side effects. We performed a systematic review of the literature up to July of 2020 for clinical studies published in English or German examining the effect of ECT stimulus parameters and/or electrode placement on cognitive side effects in patients with schizophrenia or schizoaffective disorder. The literature search generated 3 randomized, double-blind, clinical trials, 1 randomized, nonblinded trial, and 1 retrospective study. There are mixed findings regarding whether pulse width and stimulus dose impact on cognitive side effects. One study showed less cognitive side effect for right unilateral (RUL) than bitemporal (BT) electrode placement, and 2 studies showed a cognitive advantage for bifrontal (BF) compared with BT ECT. Only 1 retrospective study measured global cognition and showed post-ECT cognitive improvement with all treatment modalities using Montreal Cognitive Assessment in comparison to pre-ECT Montreal Cognitive Assessment scores. Current data are limited, but evolving. The evidence suggests that RUL or BF ECT have more favorable cognitive outcomes than BT ECT. Definitive larger clinical trials are needed to optimize parameter and electrode placement selection to minimize adverse cognitive effects.
Bias reduction and inference for electronic health record data under selection and phenotype misclassification: three case studies
Authors: Beesley Lauren J. , Mukherjee Bhramar
Published: December 2020

Electronic Health Records (EHR) are not designed for population-based research, but they provide access to longitudinal health information for many individuals. Many statistical methods have been proposed to account for selection bias, missing data, phenotyping errors, or other problems that arise in EHR data analysis. However, addressing multiple sources of bias simultaneously is challenging. Recently, we developed a methodological framework (R package, SAMBA) for jointly handling both selection bias and phenotype misclassification in the EHR setting that leverages external data sources. These methods assume factors related to selection and misclassification are fully observed, but these factors may be poorly understood and partially observed in practice. As a follow-up to the methodological work, we explore how these methods perform for three real-world case studies. In all three examples, we use individual patient-level data collected through the University of Michigan Health System and various external population-based data sources. In case study (a), we explore the impact of these methods on estimated associations between gender and cancer diagnosis. In case study (b), we compare corrected associations between previously identified genetic loci and age-related macular degeneration with gold standard external estimates. In case study (c), we evaluate these methods for modeling the association of COVID-19 outcomes and potential risk factors. These case studies illustrate how to utilize diverse auxiliary information to achieve less biased inference in EHR-based research.
Macrolevel Association of COVID-19 with Non-Communicable Disease Risk Factors in India
Authors: Gaur Kiran , Khedar RS , Mangal Kishore , Sharma Arvind K , Dhamija Rajinder K , Gupta Rajeev
Published: December 2020

Objective

Greater COVID-19 related mortality has been reported among persons with various non-communicable diseases (NCDs). We performed an ecological study to determine the association of state-level cases and deaths with NCD risk factors and healthcare and social indices.

Methods

We obtained cumulative national and state-level data on COVID-19 cases and deaths from publicly available database www.covid19india.org from February to end November 2020. To identify association with major NCD risk factors, NCDs, healthcare related and social variables we obtained data from public sources. Association was determined using univariate and multivariate statistics.

Results

More than 9.5 million COVID-19 cases and 135,000 deaths have been reported in India at end November 2020. There is significant positive correlation (Pearson’s r) of state-level COVID-19 cases and deaths per million, respectively, with NCD risk factors- obesity (0.64, 0.52), hypertension (0.28, 0.16), diabetes (0.66, 0.46), literacy, NCD epidemiological transition index (0.58, 0.54) and ischemic heart disease mortality (0.22, 0.33). Correlation is also observed with indices of healthcare access and quality (0.71, 0.61), urbanization (0.75, 0.73) and human (0.61, 0.56) and sociodemographic (0.70, 0.69) development. Multivariate adjusted analyses shows strong correlation of COVID-19 burden and deaths with NCD risk factors (r2=0.51, 0.43), NCDs (r2=0.32, 0.16) and healthcare related factors (r2=0.52, 0.38).

Conclusions

COVID-19 disease burden and mortality in India is ecologically associated with greater state-level burden of NCDs and risk factors, especially obesity and diabetes.

KEY MESSAGES

There is significant state-level variability in COVID-19 cases and deaths in India.

In a macrolevel statistical analysis we find that Indian states with better human and sociodemographic indices, more literacy, longer age, greater burden of non-communicable diseases and risk factors have greater COVID-19 case burden and mortality.

Non-communicable disease risk factors- obesity and diabetes are the most important determinants on multivariate analyses.
Knowledge, Attitudes, and Practices of People living with SCI towards COVID-19 and their Psychological State during In-patient Rehabilitation in Bangladesh
Authors: Hossain Mohammad Anwar , Hossain K M Amran , Sakel Mohamed , Kabir Md. Feroz , Saunders Karen , Faruqui Rafey , Hossain Mohammad Sohrab , Uddin Zakir , Kader Manzur , Walton Lori Maria , Haque Md. Obaidul , Shafin Rubayet , Jahid Iqbal Kabir
Published: December 2020

Study Design

A prospective cross-sectional survey.

Objective

The study aimed to examine the Knowledge, Attitudes, and Practices (KAP) of people living with Spinal cord injury (SCI) towards COVID-19 and their psychological status during in-patient rehabilitation in Bangladesh.

Setting

The Centre for the Rehabilitation of the Paralyzed (CRP) and the National Institute of Traumatology and Orthopedic Rehabilitation (NITOR), two tertiary level hospitals in Dhaka, Bangladesh.

Methods

From July to September 2020, a prospective, cross-sectional survey of SCI subjects, 13-78 years of age, carried out in two SCI rehab centers in Bangladesh. Data has been collected by face to face interview through a pretested, and language validated questionnaire on KAP and Depression, Anxiety, Stress (DASS). Ethical approval and trial registration obtained prospectively. As all the patients were previously living with Spinal cord injury (SCI), therefore, all the patients admitted/ attend SCI rehab centers were considered as SCI positive samples.

Results

A total of 207 people with SCI responded, 87%were male, and 13% were female with mean age34.18±12.9 years. 33.8% was tetraplegic and 66.2% was paraplegic and 63.8% of them were diagnosed ASIA-A, with motor score 45.38±19.5, sensory score 97.2±52, SpO2 95.07±3.3, and Vo2max 35.7±3.7mL/kg/min. 178 people had at least one health issue. Overall knowledge score was 8.59±2.3 out of 12, depression 11.18±8, anxiety 7.72±5.1, and stress was 9.32±6.7 from a total of 21 scores each. There was a correlation between Knowledge and DASS with age (P<.05); and Knowledge with gender (P<.05), and education (P<.01). Binary logistic regression found a higher association of Knowledge and DASS with gender (OR 6.6, 6.6, .95, 6.6; P<.01); and young age (OR.418, P<.01), illiterate (OR3.81, P<.01), and rural people (OR.48, P<.05) with knowledge. A linear relation was noted between depression and anxiety scores (r.45, P<.01) and stress scores (r.58, P<.01). A positive attitude was reported for the majority of subjects. SCI Persons reported they and the caregiver followed health advisory in consulting health professionals (65.7%), isolation (63.8%), droplet precaution (87.4%), and hygiene (90.3%).

Conclusions

During in-patient rehabilitation in Bangladesh, the majority of SCI reported that they had communicated with health professionals and practiced behaviors that would reduce transmission and risk of COVID-19.
Chlorzoxazone, A BKCa Channel Agonist, Rescues The Pathological Phenotypes Of Williams-Beuren Syndrome In A Preclinical Model
Authors: Piquemal Marion , Abdulkarim-Abdalla Noura , Ortiz-Romero Paula , Lemaire-Mayo Valerie , Crusio Wim E. , Louette Eric , Campuzano Victoria , Pietropaolo Susanna
Published: December 2020

Williams-Beuren syndrome (WBS) is a rare developmental disorder caused by the deletion of a 1.5 Mb region in chromosome 7 (7q11.23). WBS has been recently modelled by a mutant mouse line having a complete deletion (CD) of the equivalent locus on mouse chromosome 5, thus resembling the genetic defect found in WBS patients. CD mice have been shown to have physical and neurobehavioral abnormalities that recapitulate most of the symptoms associated with human WBS, including cardiovascular, motor, social, emotional and sensory alterations. This model has been largely used to investigate the etiopathological mechanisms of WBS; nonetheless, pharmacological therapies for this syndrome have not been identified yet. Here we propose a novel treatment for WBS, chlorzoxazone (CHLOR), i.e., a molecule targeting calcium-activated large conductance potassium (BKCa) channels, since a reduction in the expression of these channels has been recently described in neurons from WBS patients, as well as in other rare developmental pathologies. Our results demonstrate both the acute and chronic effects of CHLOR on some major pathological phenotypes of CD mice, including several behavioural alterations and cardiac hypertrophy. We conclude that BKCa channels are a therapeutic target of high potential for clinical applications and are likely to play a key role in the etiopathology of WBS.
Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2
Authors: Yu Dalang , Yang Xiao , Tang Bixia , Pan Yi-Hsuan , Yang Jianing , Duan Guangya , Zhu Junwei , Hao Zi-Qian , Mu Hailong , Dai Long , Hu Wangjie , Zhang Mochen , Cui Ying , Jin Tong , Li Cui-Ping , Ma Lina ,   Language translation team, Su Xiao , Zhang Guoqing , Zhao Wenming , Li Haipeng
Published: December 2020

Genomic epidemiology is important to study the COVID-19 pandemic and more than two million SARS-CoV-2 genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a movie maker strategy. In total, 1,002,739 high quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and on-going positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.
Emotional Adaptation During A Crisis: Decline in Anxiety and Depression After the Initial Weeks of COVID-19 in the United States
Authors: Shuster Anastasia , O’Brien Madeline , Luo Yi , Heflin Matthew , Chung Dongil , Na Soojung , Perl Ofer , Kulkarni Kaustubh , Fiore Vincenzo G. , Gu Xiaosi
Published: December 2020

Objective

Crises such as the COVID-19 pandemic are known to exacerbate depression and anxiety, though their temporal trajectories remain unclear. The present study aims to investigate fluctuations in depression and anxiety using COVID-19 as a model crisis.

Methods

1,512 adults living in the U.S. enrolled in this online study on April 2nd, 2020 and were assessed weekly for 10 weeks (until June 4th, 2020; final n=537). Depression and anxiety were measured using the Zung Self-Rating Depression scale and State-Trait Anxiety Inventory (state subscale), respectively, along with demographic and COVID-related questions. Mixed-effects linear regression models were used to examine factors contributing to longitudinal changes in depression and anxiety.

Results

Depression and anxiety levels were high in early April, but declined over time (F(9,4824)=17.53,p<.001 andF(9,4824)=23.35,p<.001, respectively). In addition to demographic factors such as sex, age, income, and psychiatric diagnoses, we identified some overlapping and some distinct dynamic factors contributing to changes in depression and anxiety: worsening of weekly individual economic impact of COVID-19 increased both depression and anxiety, while increased seven-day change in COVID-19 cases, social media use, and projected pandemic duration were positively associated with anxiety, but not depression.

Conclusions

Alongside evidence for overall emotional adaptation, these findings highlight overlapping (economic), yet distinct (change in COVID-19 cases, social media use, and projected COVID-19 duration) factors contributing to fluctuations in depression and anxiety throughout the first wave of COVID-19. These results provide insight into socioeconomic policies and behavioral changes that can increase emotional adaptation in times of crisis.
Left Hippocampus to Anterior Cingulate Cortex Connectivity Correlates with Worse Recent Verbal Memory in Pornography Addicted Juveniles
Authors: Prawiroharjo Pukovisa , Edison Rizki Edmi , Ellydar Hainah , Pratama Peter , Suaidy Sitti Evangeline Imelda , Amani Nya’ Zata , Carissima Diavitri , Hatta Ghina Faradisa
Published: December 2020

Background and aims

Imperil by the convenience of information and knowledge access, children exposed to pornography have worsened. As such, this study aims to gain insight into brain connectivity and cognitive function effect of pornography addiction in juveniles, as the best of our knowledge, this study is the first to specifically learn about memory function in juvenile’s pornography addiction.

Methods

We screened 30 juveniles with 4 dropouts (13 non-addiction vs 13 addiction group). Subjects underwent neuropsychiatric tests (memory, attention, and intelligence) and fMRI image acquisition. We carried correlation analysis of brain connectivity and neuropsychiatric test results.

Results

Significant disconnection between left hippocampus to ACC (Z-transformed r-value, non-addiction vs addiction = 0.07 ± 0.19 vs −0.08 ± 0.17, p=0.04, cohen d=0.83) followed by worse verbal recent memory in pornography addicted juveniles (RAVLT A6 sub-score, p < 0.01, d=0.67; A7 sub-score, p=0.01). Attention and intelligence test resulted to insignificant correlation.

Discussion

This data-driven analysis result strongly promotes the involvement of cortico-subcortical systems in pornography addiction, emphasizing the role of reward system pathology, indifferent to addiction pathophysiology in general. Decline in working memory, which are maintained by corticolimbic network, including hippocampus and ACC, affects goal-oriented behaviour greatly. This, correspond to our significant result of addiction group’s decline in memory, regardless of its association with attention and intelligence.

Conclusion

Disconnection between left hippocampus to ACC suggested similar neurobiological abnormalities as seen on other addictive disorders. Its disconnection was also correlated with worse verbal recent memory in pornography addicted juveniles, without affecting attention and intelligence, results showed.
The mechanism underlying transient weakness in myotonia congenita
Authors: Myers Jessica H , Denman Kirsten , DuPont Chris , Hawash Ahmed A , Novak Kevin R , Koesters Andrew , Grabner Manfred , Dayal Anamika , Voss Andrew A , Rich Mark M
Published: December 2020

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We made intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to −25 to −35 mV in the genetic and pharmacologic models of Becker disease. Both Na+and Ca2+currents contribute to plateau potentials. Na+persistent inward current (NaPIC) through Naγ1.4 channels is the key trigger of plateau potentials and current through Cav1.1 Ca2+channels contributes to the duration of the plateau. Inhibiting NaPIC with ranolazine prevents the development of plateau potentials and eliminates transient weaknessin vivo.These data suggest that targeting NaPIC may be an effective treatment to prevent transient weakness in myotonia congenita.

Impact Statement

Transient weakness in myotonia congenita is caused by depolarization secondary to activation of persistent Na+current in skeletal muscle.
Embodiment of sleep-related words: evidence from event-related potentials
Authors: Hülsemann Mareike J. , Rasch Björn
Published: December 2020

Our thoughts, plans and intentions can influence physiological sleep, but the underlying mechanisms are unknown. According to the theoretical framework of “embodied cognition”, the semantic content of cognitive processes is represented by multimodal networks in the brain which also include body-related functions. Such multimodal representation could offer a mechanism which explains mutual influences between cognition and sleep. In the current study we tested whether sleep-related words are represented in multimodal networks by examining the effect of congruent vs. incongruent body positions on word processing during wakefulness.

We experimentally manipulated the body position of 66 subjects (50 females, 16 males, 19-40 years old) between standing upright and lying down. Sleep- and activity-related words were presented around the individual speech recognition threshold to increase task difficulty. Our results show that word processing is facilitated in congruent body positions (sleep words: lying down and activity words: standing upright) compared with incongruent body positions, as indicated by a reduced N400 of the event-related potential (ERP) in the congruent condition with the lowest volume. In addition, early sensory components of the ERP (N180 and P280) were enhanced, suggesting that words were also acoustically better understood when the body position was congruent with the semantic meaning of the word. However, the difference in ERPs did not translate to differences on a behavioural level.

Our results support the prediction of embodied processing of sleep- and activity-related words. Body position potentially induces a pre-activation of multimodal networks, thereby enhancing the access to the semantic concepts of words related to current the body position. The mutual link between semantic meaning and body-related function could be a key element in explaining influences of cognitive processing on sleep.
Development of A Decellularized Meniscus Matrix-Based Nanofibrous Scaffold for Meniscus Tissue Engineering
Authors: Xia Boao , Kim Dong-Hwa , Bansal Sonia , Bae Yongho , Mauck Robert L. , Heo Su-Jin
Published: December 2020

The meniscus plays a critical role in knee mechanical function but is commonly injured given its central load bearing role. In the adult, meniscus repair is limited, given the low number of endogenous cells, the density of the matrix, and the limited vascularity. Menisci are fibrocartilaginous tissues composed of a micro-/nano-fibrous extracellular matrix (ECM) and a mixture of chondrocyte-like and fibroblast-like cells. Here, we developed a fibrous scaffold system that consists of bioactive components (decellularized meniscus ECM (dME) within a poly(e-caprolactone) material) fashioned into a biomimetic morphology (via electrospinning) to support and enhance meniscus cell function and matrix production. This work supports that the incorporation of dME into synthetic nanofibers increased hydrophilicity of the scaffold, leading to enhanced meniscus cell spreading, proliferation, and fibrochondrogenic gene expression. This work identifies a new biomimetic scaffold for therapeutic strategies to substitute or replace injured meniscus tissue.

STATEMENT OF SIGNIFICANCE

In this study, we show that a scaffold electrospun from a combination of synthetic materials and bovine decellularized meniscus ECM provides appropriate signals and a suitable template for meniscus fibrochondrocyte spreading, proliferation, and secretion of collagen and proteoglycans. Material characterization andin vitrocell studies support that this new bioactive material is susceptible to enzymatic digestion and supports meniscus-like tissue formation.
LigEGFR: Spatial graph embedding and molecular descriptors assisted bioactivity prediction of ligand molecules for epidermal growth factor receptor on a cell line-based dataset
Authors: Virakarin Puri , Saengnil Natthakan , Boonyarit Bundit , Kinchagawat Jiramet , Laotaew Rattasat , Saeteng Treephop , Nilsu Thanasan , Suvannang Naravut , Rungrotmongkol Thanyada , Nutanong Sarana
Published: December 2020

Abstract

Motivation

Lung cancer is a chronic non-communicable disease and is the cancer with the world’s highest incidence in the 21stcentury. One of the leading mechanisms underlying the development of lung cancer in nonsmokers is an amplification of the epidermal growth factor receptor (EGFR) gene. However, laboratories employing conventional processes of drug discovery and development for such targets encounter several pain-points that are cost- and time-consuming. Moreover, high failure rates are caused by efficacy and safety problems during research and development. Therefore, it is imperative to develop improved methods for drug discovery. Herein, we developed a deep learning model with spatial graph embedding and molecular descriptors based on predicting pIC50potency estimates of small molecules and classifying hit compounds against the human epidermal growth factor receptor (LigEGFR). The model was generated with a large-scale cell line-based dataset containing broad lists of chemical features.

Results

LigEGFR outperformed baseline machine learning models for predicting pIC50. Our model was notable for higher performance in hit compound classification, compared to molecular docking and machine learning approaches. The proposed predictive model provides a powerful strategy that potentially helps researchers overcome major challenges in drug discovery and development processes, leading to a reduction of failure to discover novel hit compounds.

Availability

We provide an online prediction platform and the source code that are freely available athttps://ligegfr.vistec.ist, andhttps://github.com/scads-biochem/LigEGFR, respectively.

Key points

LigEGFR is a regression model for predicting pIC50that was developed for the human EGFR target. It can also be applied to hit compound classification (pIC50≥ 6) and has a higher performance than baseline machine learning algorithms and molecular docking approaches.

Our spatial graph embedding and molecular descriptors based approach notably exhibited a high performance in predicting pIC50of small molecules against human EGFR.

Non-hashed and hashed molecular descriptors were revealed to have the highest predictive performance by using in a convolutional layers and a fully connected layers, respectively.

Our model used a large-scale and non-redundant dataset to enhance the diversity of the small molecules. The model showed robustness and reliability, which was evaluated by y-randomization and applicability domain analysis (ADAN), respectively.

We developed a user-friendly online platform to predict pIC50of small molecules and classify the hit compounds for the drug discovery process of the EGFR target.
HgH2meets relativistic quantum crystallography. How to teach relativity to a non-relativistic wavefunction
Authors: Podhorský Michal , Bučinský Lukáš , Jayatilaka Dylan , Grabowsky Simon
Published: December 2020

The capability of X-ray constrained wavefunction (XCW) fitting to introduce relativistic effects into a non-relativistic wavefunction is tested. It is quantified how much of the reference relativistic effects can be absorbed in the non-relativistic XCW calculation when fitted against relativistic structure factors of a model HgH2molecule. Scaling of the structure-factor sets to improve the agreement statistics is found to introduce a significant systematic error into the XCW fitting of relativistic effects.