bluuebunny/crossref_metadata_2025 huggingface dataset:
JC-10 probe as a novel method for analyzing the mitochondrial membrane potential and cell stress in whole zebrafish embryos
Authors: Younes Nadin , Alsahan Bana S , Al-Mesaifri Asmaa J , Da’as Sahar I , Pintus Gianfranco , Majdalawieh Amin F , Nasrallah Gheyath K
Published: November 2021

Background

A sensitive method to investigate cellular stress and cytotoxicity is based on measuring mitochondrial membrane potential. Recently, JC-10, was developed to measure mitochondrial membrane potential in vitro and used as an indicator for cytotoxicity. Yet, JC-10 has never been used in vivo (whole organism). In normal cells, JC-10 concentrates in the mitochondrial matrix, where it forms red fluorescent aggregates. However, in apoptotic/necrotic cells, JC-10 diffuses out of the mitochondria, changes to monomeric form, and stains cells in green. Here, we aimed to develop and optimize a JC-10 assay to measure cytotoxicity in zebrafish embryo. We also investigated the effectiveness of JC-10 assay by comparing it to common cytotoxicity assays.

Methods

Zebrafish embryos were exposed to a toxic surfactant AEO-7 at no observed effect concentration (6.4 μg/L), and then cytotoxicity was measured using (i) JC-10 mitochondrial assay, (ii) acridine orange (AO), (iii) TUNEL assay, and (iv) measuring the level of Hsp70 by western blotting.

Results

As compared to the negative control, embryos treated with NOEC of AEO-7 did not show significant cytotoxicity when assessed by AO, TUNEL or western blotting. However, when JC-10 was used under the same experimental conditions, a significant increase of green:red fluorescent ratio signal was detected in the AEO-7 treated embryos, indicating mitochondrial damage and cellular cytotoxicity. Noteworthy, the observed green: red ratio increase was dose dependent, suggesting specificity of the JC-10 assay.

Conclusion

JC-10 is a sensitive in vivo method, thus, can be used as surrogate assay to measure cytotoxicity in whole zebrafish embryos.
Transmission of the Invasive Pathogen Phytophthora ramorum from Symptomatic to Healthy Host Plants During a Five-Year Period in California
Authors: Schweigkofler Wolfgang , Pastalka Tomas , Abeysekara Nilwala , Huffman Vernon , Suslow Karen
Published: December 2021

Reliable data on the transmission of airborne plant pathogens are crucial for the development of epidemiological models and implementation of management strategies. The short-distance vertical transmission of the forest pathogen Phytophthora ramorum from a symptomatic California bay laurel (Umbellularia californica) to healthy containerized rhododendrons (Rhododendron caucasicum × R. ponticum var. album) was monitored for five winters (2016/17 to 2020/21) in a field experiment in Northern California. Transmission events were observed during four winters at a frequency of 1 to 17 per season, but not during the extremely dry winter of 2020/21, and were positively correlated to total rainfall rates. The first leaf symptoms were detected around mid-December and reached the highest numbers in January of most years. Only limited symptom development was observed in the spring, with the last detections in May. The exposure time (the time between the first rainfall after placing a bait plant under the bay laurel and development of symptoms) varied between 3 and over 150 days, with an average between 14 and 21 days. P. ramorum was detected from water samples collected from the canopy of the symptomatic California bay laurel. No horizontal pathogen spread was detected from symptomatic to healthy rhododendrons placed at a distance of 2 to 6 m.
Obstetric Complications in Women With Congenital Uterine Anomalies According to the 2013 European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy Classification
Authors: Panagiotopoulos Michail , Tseke Paraskevi , Michala Lina
Published: December 2021

OBJECTIVE:

To assess the risk for obstetric complications in women with congenital uterine anomalies and the risk in each main class of uterine anomaly (U2 [septate], U3 [bicorporeal], U4 [hemi-uterus]), based on the 2013 classification by the ESHRE (European Society of Human Reproduction and Embryology) and the ESGE (European Society for Gynaecological Endoscopy).

DATA SOURCES:

MEDLINE, Scopus, and ClinicalTrials.gov were searched from inception until January 2021. The reference list of all included articles and previous systematic reviews were also screened to identify potential additional articles.

METHODS OF STUDY SELECTION:

Comparative and noncomparative studies that investigated the obstetric outcomes of women with any type of known congenital uterine anomaly were considered eligible for inclusion. Screening and eligibility assessment was performed independently by two reviewers.

TABULATION, INTEGRATION, AND RESULTS:

Forty-seven studies were included. The quality of included comparative studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Odds ratios (ORs), pooled proportions of each obstetric outcome, and 95% CIs were calculated in RevMan and Stata accordingly, using random effects models. Congenital uterine anomalies were associated with increased risk of preterm birth (OR 3.89, 95% CI 3.11–4.88); cervical insufficiency (OR 15.13, 95% CI 11.74–19.50); prelabor rupture of membranes (OR 2.48, 95% CI 1.38–4.48); fetal malpresentation (OR 11.11, 95% CI 5.74–21.49); fetal growth restriction (OR 3.75, 95% CI 1.88–7.46); placental abruption (OR 5.21, 95% CI 3.34–8.13); placenta previa (OR 4.00, 95% CI 1.87–8.56); placental retention (OR 1.71, 95% CI 1.16–2.52); and cesarean birth (OR 4.52, 95% CI 2.19–9.31); when compared with those without anomalies. Pooled estimated risks were 25% for preterm birth, 40% for fetal malpresentation, 64% for cesarean birth, 12% for prelabor rupture of membranes, 15% for fetal growth restriction, 4% for placental abruption, 5% for preeclampsia, 13% for cervical insufficiency, and 2% for placenta previa. Classes U2 (septate), U3 (bicorporeal), and U4 (hemi-uterus) were also associated independently with preterm birth, fetal malpresentation, cesarean birth, and placental abruption.

CONCLUSION:

Congenital uterine anomalies are associated with obstetric complications across all examined ESHRE and ESGE classifications.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42021244487.
Novel Minimally-Invasive Triple Pelvic Osteotomy: JiShuiTan Minimally-Invasive Approach
Authors: Lyu XueMin , Yang Zheng , Wang Yukun , Zhang Tao , Lu Ming , Bian Zhen
Published: November 2021

Purpose:

Triple pelvic osteotomy (TPO) is often performed to improve femoral head coverage, correct deformity, and stabilize the hip joint in a variety of pediatric orthopaedic conditions. After the TPO was first reported, many modifications were developed to simplify or improve the procedure, however, because of the specific anatomy with several critical nerves and vessels passing through the approaches, extensive exposure and prolonged intraoperative fluoroscopy are often required for TPO. This report introduces a novel, minimally-invasive surgical approach that minimizes the time of intraoperative fluoroscopy and size of the surgical incision, and reviews our experience.

Methods:

A total of 48 hips in 43 patients with a mean age of 8.3±1.7 years (range: 6.0 to 12.2 y) were included in this study. Of these, 21 patients (22 hips) had Legg-Calvé-Perthes disease (LCPD) and 22 patients (26 hips) had developmental dysplasia of the hip (DDH). The TPOs were performed using the novel, minimally-invasive TPO approach, with a mean postoperative follow-up of 38 months (range: 24 to 54 mo) in the DDH group and 44 months (range: 23 to 58 mo) in the LCPD group. The acetabular index (AI), femoral head migration rate (MP), center edge angle (CEA) and the Severin and Stulberg classification systems were used to evaluate the preoperative and postoperative results. SPSS software was used to analyze the data.

Results:

The AI decreased from 33.8 degrees±9.2 to 2.9 degrees±10.1, the lateral CEA increased from −10.8 degrees±23.8 to 34.1 degrees±9.9, and the femoral head MP decreased from 64.0%±19.8% to 1.1%±2.6% in the DDH group at last follow-up, indicating significant improvement. The AI decreased from 20.8 degrees±4.7 to −1.3 degrees±7.3, the lateral CEA increased from 6.8 degrees±11.5 to 42.3 degrees±6.4, and the femoral head MP decreased from 42.2%±13.0% to 1.3%±3.3% in the LCPD group at last follow-up, also indicating significant improvement.

Conclusion:

This approach can simplify the TPO, making the complex operation safer, more effective, and capable of achieving satisfactory correction.
Propensity-Matched Comparison of 90-Day Complications in Robotic-Assisted Versus Non-Robotic Assisted Lumbar Fusion
Authors: Yu Charles C. , Carreon Leah Y. , Glassman Steven D. , Brown Morgan E. , Daniels Christy L. , Polly David W. , Gum Jeffrey L.
Published: November 2021

Study Design.

Retrospective single center propensity-matched observational cohort study that included patients who underwent 1- to 3-level lumbar fusion surgery for degenerative conditions.

Objective.

To compare 90-day complication rates between robotic-assisted and non-robotic-assisted lumbar spinal fusions in propensity-matched cohorts.

Summary of Background Data.

A recent administrative database (PearlDiver) study reported increased 30-day complications with the utilization of robotic-assisted enabling technology.

Methods.

Of 146 robotic-assisted cases that met inclusion criteria, 114 were successfully propensity matched to 114 patients from 214 cases who had 1 to 3 level lumbar fusion without robotic assistance based on age, sex, body mass index, smoking status, American Society of Anesthesiologist grade, number of surgical levels, primary versus revision, and surgical approach (posterior-only or anterior-posterior). We excluded tumor, trauma, infection, or deformity cases. Outcomes included surgical and medical (major/minor) complications at intraoperative, immediately postoperative, 30- and 90-day postoperative intervals, including reoperations, and readmissions within 90 days.

Results.

All cause intraoperative complication rates were similar between non-robotic-assisted (5.3%) and robotic-assisted groups (10.5%, P = 0.366). Immediate postoperative medical complication rate was also similar between non-robotic-assisted (6.1%) and robotic-assisted groups (1.8%, P = 0.089). Thirty-day complication rates, 90-day complication rates, reoperation rates, and readmission rates showed no difference between non-robotic-assisted and robotic-assisted groups. There was no difference between return to OR for infection between the cohorts (non-robotic-assisted: 6 [5%] vs. robotic-assisted: 1 [0.8%], P = 0.119). There was however improved length of stay (LOS) in the robotic-assisted group compared with non-robotic-assisted group (2.5 vs. 3.17 days, P = 0.018).

Conclusion.

In propensity-matched cohorts, patients undergoing 1- to 3-level robotic-assisted posterior lumbar fusion for degenerative conditions did not have increased 90-day complication rate, and had a shorter length of stay compared with non-robotic-assisted patients. There findings differ from a prior administrative database study as the robotic-assisted group in the current study had 0% return to OR for malpositioned screws and 0.8% return to OR for infection.

Level of Evidence: 2
Digital Ocular Compressions Reduce Intraocular Pressure in Eyes With Tube Shunts
Authors: Welburn Kyle , Slagle Grant , Mancha Saoul , Sponsel William E.
Published: November 2021

Précis:

Digital ocular compressions (DOCs) decrease intraocular pressure in eyes with tube shunts by significantly greater magnitude and duration when compared with fellow eyes without filtering surgery.

Purpose:

DOCs are commonly used by glaucoma surgeons to reduce intraocular pressure (IOP) in the early postoperative period. Little is known, however, about the effects of DOC in eyes with tube shunts. We therefore examined these effects in eyes with long-established, functional glaucoma tube shunts.

Methods:

In this masked prospective study, adult subjects with primary open angle glaucoma and an Ahmed tube shunt in only 1 eye were recruited. After obtaining baseline IOP with Goldmann applanation tonometry a single transpalpebral DOC was applied to each eye (in random order). Postcompression IOP was measured after 10, 20, 30, 60, 90, 120, 150, 180, 210, and 240 minutes or until the measured IOP returned to baseline. The fellow (nonsurgical) eye was a control. Magnitude and duration of IOP reduction were evaluated using Kaplan-Meier analysis. The pressure applied to eyes in each cohort was standardized through the use of a force sensitive resistor and impulse was analyzed for differences.

Results:

Twenty-two eyes of 11 patients underwent DOC. There was no significant difference in the impulse applied to eyes in each cohort (P=0.6). A mean initial IOP reduction of 5.36 mm Hg occurred in tube shunt eyes and 2.55 in control eyes (P=0.014). Log-rank analysis demonstrated longer survival in the tube shunt group (P=0.049).

Conclusions:

DOC is an effective method for transiently reducing IOP in eyes with long-established, patent tube shunts for about an hour. To maintain this decrease in pressure, compressions will have to be performed on a scheduled basis.
Impact of Depression and Nicotine Dependence on Executive Functioning in Rural Older Adult Smokers
Authors: Noonan Devon , Silva Nikolas J. , McClintock Shawn M. , Silva Susan G.
Published: December 2021

Introduction

Rural older adults are an underserved population with high rates of smoking and related morbidity and mortality. Age-related executive function deficits are common in older smokers; however, the association of depression and nicotine dependence on executive function has not been explored. This study addressed whether depression and nicotine dependence are related to executive dysfunction in rural older adult smokers.

Methods

The sample included 40 rural older adults recruited from two primary care clinics in North Carolina. Executive function was evaluated with the Behavioral Regulation Index (BRI), Metacognition Index, and Global Executive Composite (GEC) T scores from the Behavior Rating Inventory of Executive Function-Adult. Nicotine dependence and depression symptoms were assessed using the Fagerstrom Test and Center for Epidemiologic Depression Scale-10, respectively. Analysis of variance was used to explore whether depression and/or nicotine dependence influences executive function. Nondirectional tests were performed with significance set at .10.

Results

Smokers who screened positive for depression had significantly greater executive dysfunction than those who did not (BRI: p = .0003, Metacognition Index: p < .0001, GEC: p < .0001), and moderate/high dependence was associated with greater executive function deficits compared with those with mild dependence (BRI: p = .0942). Together, depression and nicotine dependence explained 50% of the variability of the GEC overall scores.

Conclusions

Executive dysfunction is common in rural older adult smokers and associated with depression and nicotine dependence severity. Futures studies should test the relationship of executive function and smoking cessation in the older adult population as it may have implications for cessation in this population.
Dental Implant Supported Thumb Prosthesis with Friction Fit Retention System
Authors: Gupta Mahimaa , Singh Saumyendra V. , Arya Deeksha , Mishra Brijesh , Keshri Rishabh , Chand Pooran
Published: November 2021

Introduction

An amputated thumb causes aesthetic deficit and functional loss. Reconstruction can be surgical or prosthetic. A small residuum leaves little scope for rehabilitation with suction-retained prosthesis. Prosthetic management requires implant placement or distraction osteogenesis to be successful.

This report presents the use of bone-anchored dental implants to support a prosthesis for rehabilitation of an amputated thumb.

Case Description

Satisfactory osseointegration of a dental implant placed in the amputated right pollex of a 24-year-old woman was achieved, after a two-stage surgical procedure. A healing abutment, which is normally placed transitionally after second-stage surgery, was modified to create a permanent friction fit coping. This was used to retain the silicone thumb.

Discussion and Conclusions

The study to some extent established off-the-label use of dental implants in rehabilitating amputated digits. Also, the friction fit retention system proved to be a cost- and armamentarium-effective method of retaining thumb prosthesis for cases with small residuum.

Clinical Relevance

This report describes a procedure for two-stage surgical placement of an osseointegrated dental implant in an amputated thumb with fabrication of prosthesis, which was effectively retained by a modified healing abutment.
The current understanding and future directions for sputum microbiome profiling in chronic obstructive pulmonary disease
Authors: Tiew Pei Yee , Mac Aogáin Micheál , Chotirmall Sanjay H.
Published: November 2021

Purpose of review

Next-generation sequencing (NGS) has deepened our understanding of the respiratory microbiome in health and disease. The number of microbiome studies employing sputum as an airway surrogate has continued to increase over the past decade to include multiple large multicentre and longitudinal studies of the microbiome in chronic obstructive pulmonary disease (COPD). In this review, we summarize the recent advances to our understanding of the bacteriome, virome and mycobiome in COPD.

Recent findings

Diverse microbiome profiles are reported in COPD. The neutrophilic Haemophilus-predominant bacteriome remains a prominent COPD phenotype, relatively stable over time and during exacerbations. Studies of the virome remain limited but reveal a potential involvement of viruses and bacteriophages particularly during COPD exacerbations and advancing disease severity. Mycobiome signatures, even in stable COPD are associated with poorer clinical outcomes including mortality.

The sputum microbiome in COPD is being increasingly recognized for its clinical relevance, even in the stable state. Future studies integrating microbial kingdoms holistically (i.e. bacterial, viral and fungal) will provide deeper insight into its functionality including the relevance of microbial interactions and effect of treatment on microbiome-associated clinical outcomes.
Body composition in sexual precocity
Authors: Gonc Elmas Nazli , Kandemir Nurgun
Published: November 2021

Purpose of review

In this review, we have summarized the current data on the effect of sexual precocity and treatment with gonadotropin-releasing hormone analogues (GnRHa) on body composition.

Recent findings

Higher body weight and weight gain in infancy and childhood may increase the risk of early puberty in girls. The relation between BMI and pubertal onset in boys is controversial. Current studies draw attention to the fact that a similar relationship may exist in boys too. Obesity prevalence is high among girls with central precocious puberty (CPP) and treatment with GnRHa has a different effect on BMI according to baseline body composition. Although BMI values of normal weight girls tend to increase under treatment, they return to normal following treatment. The few studies that have followed up body composition longitudinally in girls show a gradual increase in adiposity, decrease in muscle mass and bone mineral density during GnRHa treatment, whereas bone mass was preserved after treatment. Adequate data are not available in boys to determine the effect of GnRHa therapy on body composition.

Body composition and fat distribution should be monitored longitudinally in patients with CPP treated with GnRHa to ascertain the long-term effects of therapy.
Applying implementation science to improve care for familial hypercholesterolemia
Authors: Jones Laney K. , Brownson Ross C. , Williams Marc S.
Published: November 2021

Purpose of review

Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation.

Recent findings

A search using the term ‘familial hypercholesterolemia’ returned 1350 articles from November 2018 to July 2021. Among these, there were 153 articles related to improving FH care; 1156 were excluded and the remaining 37 were mapped to the ERIC compilation of strategies: assess for readiness and identify barriers and facilitators [9], develop and organize quality monitoring systems [14], create new clinical teams [2], facilitate relay of clinical data to providers [4], and involve patients and family members [8]. There were only 8 of 37 studies that utilized an implementation science theory, model, or framework and two that explicitly addressed health disparities or equity.

The mapping of the studies to implementation strategies from the ERIC compilation provides a framework for organizing current strategies to improve FH care. This study identifies potential areas for the development of implementation strategies to target unaddressed aspects of FH care.
Advances in the care of lipodystrophies
Authors: Shamsudeen Isabel , Hegele Robert A.
Published: November 2021

Purpose of review

Lipodystrophies are a group of rare, heterogeneous disorders characterized by a lack or maldistribution of adipose tissue. Treatment focusses on the management of complications, including hypertriglyceridemia, which can be severe. Patients are predisposed to early atherosclerotic cardiovascular disease and acute pancreatitis. This review summarizes the recent advances in the treatment of lipodystrophies, with a particular focus on the treatment of hypertriglyceridemia in familial partial lipodystrophy (FPLD).

Recent findings

Treatment of dyslipidemia in FPLD requires management of secondary exacerbating factors, particularly insulin resistance and diabetes, together with modification of atherosclerotic cardiovascular disease risk factors. In addition, specific lipid-lowering therapies are usually needed, starting with statins and fibrates. Leptin therapy improves triglycerides. Several emerging treatments for hypertriglyceridemia include apo C-III antagonists (volanesorsen, AKCEA-APOCIII-LRx and ARO-APOC3) and angiopoietin-like 3 antagonists (evinacumab, vupanorsen and ARO-ANG3); efficacy observed in clinical trials of these agents in nonlipodystrophic patients with severe hypertriglyceridemia suggests that they may also be helpful in lipodystrophy.

Emerging therapies for dyslipidemia show promise in advancing the care of patients with lipodystrophy. However, these treatments are not yet approved for use in lipodystrophy. Further study of their efficacy and safety in this patient population is needed.
Why the Utilization of Ready-to-Administer Syringes During High-Stress Situations Is More Important Than Ever
Authors: Malik Pashmina , Rangel Melissa , VonBriesen Tracy
Published: November 2021

The COVID-19 pandemic has led to a high-stress environment causing a significant impact on frontline workers, including pharmacists and nurses. In addition to the increased workload, scarcity of resources, and emotional challenges, the frontline health care workers are required to wear additional personal protective equipment that can further limit their range of movement and decrease efficiency. The potential for errors can increase in these types of high-stress situations. One way to reduce the risk of errors is to use manufacturer-prepared, ready-to-administer (RTA) prefilled syringes, when appropriate. The use of RTA prefilled syringes is supported by literature evidence, recommendations, and guidelines from various professional organizations and societies.
Deep Learning-Based Image Conversion Improves the Reproducibility of Computed Tomography Radiomics Features
Authors: Lee Seul Bi , Cho Yeon Jin , Hong Youngtaek , Jeong Dawun , Lee Jina , Kim Soo-Hyun , Lee Seunghyun , Choi Young Hun
Published: November 2021

Objectives

This study aimed to evaluate the usefulness of deep learning–based image conversion to improve the reproducibility of computed tomography (CT) radiomics features.

Materials and Methods

This study was conducted using an abdominal phantom with liver nodules. We developed an image conversion algorithm using a residual feature aggregation network to reproduce radiomics features with CT images under various CT protocols and reconstruction kernels. External validation was performed using images from different scanners, consisting of 8 different protocols. To evaluate the variability of radiomics features, regions of interest (ROIs) were drawn by targeting the liver parenchyma, vessels, paraspinal area, and liver nodules. We extracted 18 first-order, 68 second-order, and 688 wavelet radiomics features. Measurement variability was assessed using the concordance correlation coefficient (CCC), compared with the ground-truth image.

Results

In the ROI-based analysis, there was an 83.3% improvement of CCC (80/96; 4 ROIs with 3 categories of radiomics features and 8 protocols) in synthetic images compared with the original images. Among them, the 56 CCC pairs showed a significant increase after image synthesis. In the radiomics feature–based analysis, 62.0% (3838 of 6192; 774 radiomics features with 8 protocols) features showed increased CCC after image synthesis, and a significant increase was noted in 26.9% (1663 of 6192) features. In particular, the first-order feature (79.9%, 115/144) showed better improvement in terms of the reproducibility of radiomics feature than the second-order (59.9%, 326/544) or wavelet feature (61.7%, 3397/5504).

Conclusions

Our study demonstrated that a deep learning model for image conversion can improve the reproducibility of radiomics features across various CT protocols, reconstruction kernels, and CT scanners.
White Matter Hyperintensity Distribution Differences in Aging and Neurodegenerative Disease Cohorts
Authors: Dadar Mahsa , Mahmoud Sawsan , Zhernovaia Maryna , Camicioli Richard , Maranzano Josefina , Duchesne Simon ,   For the CCNA Group
Published: November 2021

Introduction

White matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders.

Methods

Data included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimer’s dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinson’s disease (PD-CIE), cognitively impaired Parkinson’s disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women.

Results

All cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH loads than the left.

Conclusions

There were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.
Emergence and Spread of the SARS-CoV-2 Variant of Concern Delta Across Different Brazilian Regions
Authors: Arantes Ighor , Naveca Felipe Gomes , Gräf Tiago ,   COVID-19 Fiocruz Genomic Surveillance Network, Miyajima Fábio , Faoro Helisson , Wallau Gabriel Luz , Delatorre Edson , Appolinario Luciana Reis , Pereira Elisa Cavalcante , Martins Venas Taina Moreira , Rocha Alice Sampaio , Lopes Renata Serrano , Siqueira Marilda Mendonça , Bello Gonzalo , Resende Paola Cristina
Published: November 2021

The SARS-CoV-2 Variant of Concern (VOC) Delta was first detected in India in October 2020. The first imported cases of the Delta variant in Brazil were identified in April 2021 in the Southern region, followed by more cases in different country regions during the following months. By early September 2021, Delta was already the dominant variant in the Southeastern (87%), Southern (73%), and Northeastern (52%) Brazilian regions. This work aimed to understand the spatiotemporal dissemination dynamics of Delta in Brazil. To this end, we employed a combination of Maximum Likelihood (ML) and Bayesian methods to reconstruct the evolutionary relationship of 2,264 of VOC Delta complete genomes (482 from this study) recovered across 21 out of 27 Brazilian federal units. Our phylogeographic analyses identified three major transmission clusters of Delta in Brazil. The clade BR-I (n= 1,560) arose in Rio de Janeiro in late April 2021 and was the major cluster behind the dissemination of the VOC Delta in the Southeastern, Northeastern, Northern, and Central-Western regions. The clade BR-II (n= 207) arose in the Paraná state in late April 2021 and aggregated the largest fraction of sampled genomes from the Southern region. Lastly, the clade BR-III emerged in the São Paulo state in early June 2021 and remained mostly restricted to this state. In the rapid turnover of viral variants characteristic of the SARS-CoV-2 pandemic, Brazilian regions seem to occupy different stages of an increasing prevalence of the VOC Delta in their epidemic profiles. This process demands continuous genomic and epidemiological surveillance toward identifying and mitigating new introductions, limiting their dissemination, and preventing the establishment of more significant outbreaks in a population already heavily affected by the COVID-19 pandemic.
Development and Implementation of Dried Blood Spot-based COVID-19 Serological Assays for Epidemiologic Studies
Authors: Wong Marcus P , Meas Michelle A , Adams Cameron , Hernandez Samantha , Green Valerie , Montoya Magelda , Hirsch Brett M , Horton Mary , Quach Hong L , Quach Diana L , Shao Xiaorong , Fedrigo Indro , Zermeno Alexandria , Huffaker Julia , Montes Raymond , Madden Alicia , Cyrus Sherri , McDowell David , Williamson Phillip , Contestable Paul , Stone Mars , Coloma Josefina , Busch Michael P , Barcellos Lisa F , Harris Eva
Published: November 2021

Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at- home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months post-infection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an eight-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible.
A cross-sectional survey of burnout in a sample of resident physicians in Sudan
Authors: Mohamed Elhadi Yasir Ahmed , Ahmed Abdelmuniem , Salih Elhadi B. , Abdelhamid Osman S. , Hamid Ahmed Mohamed Hayder , El Dabbah Noha Ahmed
Published: November 2021

Background

Resident physicians in Sudan suffer multiple physical and psychological stressors. Nevertheless, the prevalence of burnout among this critical population remains unknown. The purpose of this study was to estimate the prevalence of burnout and its related factors in a sample of Sudanese resident physicians.

Methods

A cross-sectional design was used to assess burnout among resident physicians at the teaching hospitals of Wad-Medani, Gezira state in Sudan. All resident physicians across nine hospitals were asked to join the study. The Arabic version of Maslach Burnout Inventory was distributed to respondents from July to October 2021.

Results

Out of 300 resident physicians 69.3% responded. The study population had a mean age of 29.99 ± 3.01 years, more than half were females (56.7%) and single (59.6%). In total, 86.1% met the criteria for burnout in at least one dimension, and 13.9 % in all three dimensions.70.7% suffer from a high level of burnout on the dimension of emotional exhaustion (EE), while 44.2% reported a high level on depersonalization (DP) and 73.1% experienced a sense of decreased professional accomplishment (PA). There were significant differences in the levels of burnout, EE and DP among different specialties. Burnout syndrome was associated with working hours per single duty; with participants working for more than 24 hours had experienced higher levels of burnout, EE and DP.

Conclusions

High prevalence of burnout syndrome was found in this sample of resident physicians in Sudan. Stakeholders should urgently implement effective remedies to protect the mental health of resident physicians.
Relationships among High School Student-Athletes’ Mental Health, Stressors, and Social Support during the COVID-19 Pandemic in Japan
Authors: Yamaguchi Kaori , Katagami Eriko , Shinohara Ryoji , Tsuji Taishi , Yamagata Zentaro , Tsuchiya Hironobu
Published: November 2021

Objectives

The impact of the spread of COVID-19 on the mental health and its mitigating factors of high school athletes is not fully understood. The aims of this study were 1) to describe the psychological distress and stressors experienced by high school athletes during the COVID-19 pandemic and to elucidate the relationships between them and 2) to determine the relationship between psychological distress and social support.

Methods

Participants of this cross-sectional study were recruited from public high schools in East Japan. We conducted either an online or paper-based questionnaire survey from July 12 to 31, 2020, and used data collected from 3017 high school student athletes (valid response rate: 88.7%) for the analyses. We evaluated psychological distress (K6 ≥10), stressors to athletes during the COVID-19 pandemic (SAC-19), and perceived social support from others. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for developing psychological distress.

Results

Among the participants, 764 (25.3%) experienced psychological distress. Among the five factors extracted from the SAC-19, self-restraint requests (OR = 1.03, 95% CI: 1.01– 1.04), pressure from the surrounding environment (OR = 1.15, 95% CI: 1.12–1.18), and difficulties in maintaining athletic activities (OR = 1.16, 95% CI: 1.12–1.21) increased the risk of psychological distress. On the other hand, participants who were satisfied with the support from family members (OR = 0.77, 95% CI: 0.67–0.90), teammates (the same grade) (OR = 0.81, 95% CI: 0.67–0.98), and coaches and instructors (OR = 0.77, 95% CI: 0.65–0.91) showed lower psychological distress.

Conclusions

During the COVID-19 pandemic, high school athletes experienced more psychological distress than usual. Stressors such as self-restraint requests, pressure from the surrounding environment, and difficulties in maintaining athletic activities increased the risk. On the other hand, social support from family members, teammates (the same grade), and coaches and instructors can help alleviate these stressors.
Single-cell generalized trend model (scGTM): a flexible and interpretable model of gene expression trend along cell pseudotime
Authors: Cui Elvis Han , Song Dongyuan , Wong Weng Kee , Li Jingyi Jessica
Published: November 2021

Motivation

Modeling single-cell gene expression trends along cell pseudotime is a crucial analysis for exploring biological processes. Most existing methods rely on nonparametric regression models for their flexibility; however, nonparametric models often provide trends too complex to interpret. Other existing methods use interpretable but restrictive models. Since model interpretability and flexibility are both indispensable for understanding biological processes, the single-cell field needs a model that improves the interpretability and largely maintains the flexibility of nonparametric regression models.

Results

Here we propose the single-cell generalized trend model (scGTM) for capturing a gene’s expression trend, which may be monotone, hill-shaped, or valley-shaped, along cell pseudotime. The scGTM has three advantages: (1) it can capture non-monotonic trends that are still easy to interpret, (2) its parameters are biologically interpretable and trend informative, and (3) it can flexibly accommodate common distributions for modeling gene expression counts. To tackle the complex optimization problems, we use the particle swarm optimization algorithm to find the constrained maximum likelihood estimates for the scGTM parameters. As an application, we analyze several single-cell gene expression data sets using the scGTM and show that it can capture interpretable gene expression trends along cell pseudotime and reveal molecular insights underlying the biological processes.

Availability and implementation

The Python package scGTM is open-access and available athttps://github.com/ElvisCuiHan/scGTM.

Contact

jli@stat.ucla.edu
Analytical sensitivity and effectiveness of different SARS-CoV-2 testing options
Authors: Lelie Nico , Koppelman Marco , van Drimmelen Harry , Bruisten Sylvia
Published: November 2021

We prepared severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) working standards and reference panels from a pool of swab fluid samples before and after inactivation by beta-propiolactone and quantified viral load in nucleic acid amplification technology (NAT) detectable RNA copies/mL using limiting dilution analysis. The following 50% lower limits of detection (LOD) were estimated by probit analysis as compared to detection limits of rapid antigen tests on 1.5 fold dilutions of the native material: Roche cobas PCR 1.8 (1.0-3.3), Hologic Aptima TMA 6.6 (4.4-9.9), DRW SAMBA 15 (7-30), Molgen LAMP 23 (13-42), Fluorecare antigen 50,000, Abbott Panbio antigen 75,000 and Roche antigen 100,000 copies/mL. One 50% Tissue Culture Infectious Dose (TCID50)/mL of culture fluid was estimated to be equivalent to approximately 1000 RNA copies/mL (2700-4300 International Units) in our working standard. When assuming this level as start of contagiousness in a log-linear ramp up viremia model with 10-fold rise of viral load per day for the B.1 (Wuhan) type we estimated relative time points of first detectability of early infection by the different SARS-CoV-2 assays from the LODs mentioned above. The four NAT assays would be able to detect early viremia 40-66 hours earlier than the 1000 copies/mL infectivity threshold, whereas the three antigen tests would become positive 41-48 hours later. Our modeling of analytical sensitivity data was found to be compatible with clinical sensitivity data of rapid antigen tests and confirms that NAT assays are more reliable than antigen assays for identifying early infected asymptomatic individuals who are potentially infectious.
Mendelian randomization analysis identifies blood tyrosine levels as a biomarker of non-alcoholic fatty liver disease
Authors: Gobeil Émilie , Maltais-Payette Ina , Taba Nele , Brière Francis , Ghodsian Nooshin , Abner Erik , Bourgault Jérôme , Gagnon Éloi , Manikpurage Hasanga D. , Couture Christian , Mitchell Patricia L. , Mathieu Patrick , Julien François , Corbeil Jacques , Vohl Marie-Claude , Thériault Sébastien , Esko Tõnu , Tchernof André , Arsenault Benoit J.
Published: November 2021

Non-alcoholic fatty liver disease (NAFLD) is a complex cardiometabolic disease associated with premature mortality. The diagnosis of NAFLD is challenging and the identification of biomarkers causally influenced by NAFLD may be clinically useful. We aimed at identifying blood metabolites causally impacted by NAFLD using two-sample Mendelian randomization (MR) with validation in a population-based biobank and a cohort of patients undergoing bariatric surgery. Our instrument for genetically-predicted NAFLD (the study exposure) included all independent genetic variants (n=7 SNPs) from a recent genome-wide association study on NAFLD. The study outcomes included 123 blood lipids, lipoproteins and metabolites measured in 24,925 individuals from 10 European cohorts. After correction for multiple testing, we identified a positive effect of NAFLD on plasma tyrosine levels but not on other metabolites. The association between NAFLD and tyrosine levels was consistent across MR methods and robust to outliers and pleiotropy. In observational analyses performed in the Estonian Biobank (10,809 individuals including 359 patients with NAFLD), after multivariable adjustment, tyrosine levels were positively associated with the presence of NAFLD (odds ratio per 1-SD increment = 1.23 (95% confidence interval = 1.12-1.36, p = 2.19e-05). In a sample of 138 patients undergoing bariatric surgery, compared to patients without NAFLD, blood tyrosine levels were higher in those with NAFLD, but were comparable among patients with or without non-alcoholic steatohepatitis. This analysis revealed a potentially causal effect of NAFLD on blood tyrosine levels, suggesting that blood tyrosine levels may represent a new biomarker of NAFLD.

Graphical abstract
The relationship of COVID-19 related stress and media consumption with schizotypy, depression and anxiety
Authors: Daimer Sarah , Mihatsch Lorenz , Neufeld Sharon A.S. , Murray Graham K. , Knolle Franziska
Published: November 2021

Studies report a strong impact of the COVID-19 pandemic and related stressors on the mental wellbeing of general population. In this paper, we investigated whether COVID-19 related concerns and social adversity affected schizotypal traits, anxiety and depression using structural equational modelling. In mediation analyses, we furthermore explored whether these associations were mediated by healthy (sleep and physical exercise) or unhealthy behaviours (drug and alcohol consumption, excessive media use).

We assessed schizotypy, depression and anxiety as well as, healthy and unhealthy behaviours and a wide range of sociodemographic scores using online surveys from residents of Germany and the United Kingdom over one year during the COVID-19 pandemic. Four independent samples were collected (April/ May 2020: N=781, September/ October 2020: N=498, January/ February 2021: N=544, May 2021: N= 486). The results revealed that COVID-19 related life concerns were significantly associated with schizotypy in the autumn 2020 and spring 2021 surveys, and with anxiety and depressive symptoms in all surveys; and social adversity significantly affected the expression of schizotypal traits in all but the spring 2020 survey, and depressive and anxiety symptoms in all samples. Importantly, we found that excessive media consumption (>4h per day) fully mediated the relationship of COVID-19 related life concerns and schizotypal traits in the winter 2021 survey. Furthermore, several of the surveys showed that excessive media consumption was associated with increased depressive and anxiety- related symptoms in people burdened by COVID-19 related life.

The ongoing uncertainties of the pandemic and the restrictions on social life have a strong impact on mental well-being and especially the expression of schizotypal traits. The negative impact is further boosted by excessive media consumption, which is especially critical for people with high schizotypal traits.
Differences in medication reconciliation interventions between six hospitals: a mixed method study
Authors: Stuijt C C M , vd Bemt B J F , Boerlage V E , Janssen M J A , Taxis K , Karapinar F
Published: November 2021

Background

Although medication reconciliation (MedRec) is mandated and effective in decreasing preventable medication errors during transition of care, hospitals implement MedRec differently.

Objective

Quantitatively compare the number and type of MedRec interventions between hospitals upon admission and discharge, followed by a qualitative analysis on potential reasons for these differences.

Methods

This explanatory retrospective mixed method study included patients from six hospitals and various wards in case MedRec was performed both on hospital admission and discharge. Information on pharmacy interventions to resolve unintended discrepancies and medication optimizations were collected. Based on these quantitative results, interviews and a focus group was performed to give insight in MedRec processes. Descriptive analysis was used for the quantitative-, content analysis for the qualitative part.

Results

On admission, patients with at least one discrepancy varied from 36-95% (mean per patient 2.2 (SD± 2.4) Upon discharge, these numbers ranged from 5-28% while optimizations reached 2% (admission) to 95% (discharge).The main themes explaining differences in numbers of interventions were patient-mix, healthcare professionals involved, location and moment of the interview plus embedding and extent of medication optimization.

Conclusions

Hospitals differed greatly in the number of interventions performed during MedRec. A combination of patient-mix, healthcare professionals involved, location and timing of the interview plus embedding and extent of medication optimization resulted in the highest yield of MedRec interventions on unintended medication discrepancies and optimizations. This study supports to give direction to optimize MedRec processes in hospitals.