bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation and Cultural Adaptation of the Ages and Stages Questionnaires (ASQ) Worldwide: A Scoping Review
Authors: Rousseau Michel , Dionne Carmen , Savard Roselyne T. , Schonhaut Luisa , Londono Maria
Published: May 2021

Objective:

This scoping review aims to provide a data mapping and narrative synthesis of the available peer-reviewed scientific literature on the translation and cultural adaptation processes relative to the Ages and Stages Questionnaires (ASQ) as reported by the authors. It also seeks to paint an overall portrait of the implementation of the translated and culturally adapted ASQ worldwide.

Methods:

Articles published between 1995 and May 11, 2018, were identified via systematic searches of peer-reviewed literature carried out using CINAHL, Scopus, MEDLINE, Education Source, PsycINFO, and ERIC. The articles included in the qualitative synthesis were coded based on an extraction form developed for the study.

Results:

In the 46 articles surveyed, 37 different cultural adaptations were identified in 29 languages and 27 countries. Translations were included in 33 cultural adaptations, and language modifications were reported in 18 adaptations. The forward-backward translation method was reported in 25 cases. The authors declared having made cultural content, language, visual, and/or conceptual modifications in 26 adaptations. Cultural content modifications were reported in 24 adaptations. At least one method (pilot study, individual interview, survey or focus group with respondents) was reported in 24 adaptations.

Conclusion:

Cultural modifications were relatively minor and were, in general, made to establish equivalence with the source version. As well, the processes used to translate and culturally adapt the ASQ varied widely based on the types of methods. Additional work should be conducted to document the process of this crucial phase.
Colorectal Cancer Screening and Postpolypectomy Surveillance
Authors: Affi Koprowski Marina , Lu Kim C.
Published: May 2021

CASE SUMMARY:

A healthy 52-year-old woman without any family history presents for a health maintenance appointment and opts for a fecal immunochemical test for colorectal cancer screening after reviewing her options. After a positive result, she is referred for colonoscopy. She is found to have 3 small (<10 mm) polyps that are completely resected via snare polypectomy and return as tubular adenomas on histologic examination. It is recommended that she return for repeat colonoscopy in 3 years, at which point she has a normal examination with excellent preparation by an experienced endoscopist and is given the option to return to her average-risk screening interval.
Inclisiran: A Novel Agent for Lowering Apolipoprotein B–containing Lipoproteins
Authors: Warden Bruce A. , Duell Paul Barton
Published: May 2021

Hypercholesterolemia is a leading cause of cardiovascular morbidity and mortality. Accordingly, efforts to lower apolipoprotein B–containing lipoproteins in plasma are the centerpiece of strategies for cardiovascular prevention and treatment in primary and secondary management. Despite the importance of this endeavor, many patients do not achieve appropriate low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non-HDL-C) goals, even among those who have experienced atherosclerotic cardiovascular disease. The development of new LDL-C-lowering medications with alternative mechanisms of action will facilitate improved goal achievement in high-risk patients. Inclisiran is a novel small interfering RNA–based drug that is experimental in the United States and approved for clinical use in the European Union. It lowers LDL-C and other apolipoprotein B–containing lipoproteins by reducing production of proprotein convertase subtilisin/kexin Type 9 (PCSK9), a protein that normally contributes to LDL-receptor degradation, thereby increasing LDL-receptor density and recycling in hepatocytes. Although the lipid-lowering efficacy of inclisiran is comparable with results achieved with PCSK9-blocking monoclonal antibodies (alirocumab and evolocumab), there are several important differences between the 2 drug classes. First, inclisiran reduces levels of PCSK9 both intracellularly and extracellularly by blocking translation of and degrading PCSK9 messenger RNA. Second, the long biological half-life of inclisiran produces sustained LDL-C lowering with twice yearly dosing. Third, although PCSK9-blocking monoclonal antibodies drugs are proven to reduce atherosclerotic cardiovascular disease events, clinical outcomes trials with inclisiran are still in progress. In this article, we review the clinical development of inclisiran, its mechanism of action, lipid-lowering efficacy, safety and tolerability, and potential clinical role of this promising new agent.
Circ_CHFR Promotes Platelet-Derived Growth Factor-BB–Induced Proliferation, Invasion, and Migration in Vascular Smooth Muscle Cells via the miR-149-5p/NRP2 Axis
Authors: Wang Meixue , Li Chengliang , Cai Tianzhi , Zhang Anji , Cao Jinlong , Xin Hong
Published: May 2021

Circular RNA checkpoint with forkhead and ring finger domains (circ_CHFR) were reported to regulate vascular smooth muscle cell (VSMC) dysfunction during atherosclerosis (AS). However, the molecule mechanism of circ_CHFR in AS remains largely unclear. Human VSMCs (HVSMCs) were exposed to platelet-derived growth factor-BB (PDGF-BB) in vitro. Levels of circ_CHFR, microRNA (miR)-149-5p, and neuropilin 2 (NRP2) were determined using quantitative real-time polymerase chain reaction and western blot. Cell proliferation, migration, and invasion were analyzed using cell counting kit-8, colony formation, flow cytometry, wound healing, and transwell assays. The binding interaction between miR-149-5p and circ_CHFR or NRP2 was investigated using the dual-luciferase reporter and RNA immunoprecipitation assays. Circ_CHFR was elevated in PDGF-BB–induced HVSMCs in a dose-independent manner. Silencing of circ_CHFR reversed PDGF-BB–evoked promotion of cell proliferation, migration and invasion, as well as suppression of cell apoptosis in HVSMCs. Mechanistically, circ_CHFR directly bound to miR-149-5p, and miR-149-5p inhibition attenuated the effects of circ_CHFR knockdown on PDGF-BB–induced HVSMCs. Besides, NRP2 was confirmed to be a target of miR-149-5p, and circ_CHFR could regulate NRP2 expression through sponging miR-149-5p. Moreover, miR-149-5p overexpression abolished PDGF-BB–triggered enhancement of cell proliferation, migration, and invasion by targeting NRP2. Circ_CHFR promoted the proliferation, invasion, and migration of PDGF-BB–induced HVSMCs through miR-149-5p/NRP2 axis, providing a new insight into the pathogenesis of AS and a potential therapeutic target for AS treatment.
Comparison of Lean Mass in Women With and Without Heart Disease
Authors: Graham Helen L. , Benton Melissa J.
Published: May 2021

Purpose:

This proof-of-concept study compared lean mass (LM) between women with heart disease (HD) and without HD.

Methods:

Fifty-six community-dwelling women were pair-matched by age. Heart disease was defined using criteria from the US Behavioral Risk Factor Surveillance System. Body composition was measured using multifrequency bioelectrical impedance analysis. Relative LM was calculated against height (kg/m2) as the lean mass index (LMI). Sarcopenia was defined as an LMI <15.0 kg/m2. Strength was measured with a handgrip dynamometer, arm curl test, and chair stand test.

Results:

Those with HD had significantly less absolute (38.2 ± 0.8 vs 43.5 ± 1.0 kg; P < .001) and relative (15.3 ± 0.3 vs 16.2 ± 0.3 kg/m2, P = .015) LM compared with those without HD. Body mass was significantly greater for those without HD (76.1 ± 2.1 vs 68.4 ± 2.1 kg; P = .013) and there were no differences in fat mass. Upper body strength was significantly less and lower body strength was diminished but not significantly different in those with HD compared to those without HD (handgrip: P = .016; arm curl: P < .001; chair stand: P = .066).

Conclusions:

In this group of community-dwelling women, those who reported a diagnosis of HD had significantly less LM than those without HD. Although neither group was classified as sarcopenic, women with HD were at greater risk due to lower relative LM. Based on our findings, during cardiac rehabilitation clinicians should counsel women regarding resistance exercise for maintenance of LM in addition to strength.
An Open Trial of the Effectiveness, Program Usage, and User Experience of Internet-based Cognitive Behavioural Therapy for Mixed Anxiety and Depression for Healthcare Workers on Disability Leave
Authors: Miki Andrew , Lau Mark A. , Moradian Hoora
Published: May 2021

Objective:

An open trial of an internet-based Cognitive Behavioural Therapy (iCBT) program for healthcare workers was conducted.

Methods:

Healthcare workers on disability leave who used the iCBT program were assessed on: self-reported depression and anxiety symptoms using the Depression Anxiety Stress Scales-21; and, program usage. Healthcare workers’ experience of using iCBT was evaluated in a separate survey.

Results:

Of the 497 healthcare workers referred to the iCBT program, 51% logged in, 25% logged in more than once, and 12% logged in more than once and completed at least two assessments. For the latter group, self-reported depression and anxiety symptoms significantly decreased from the first assessment.

Conclusions:

This iCBT program was perceived to be of benefit to healthcare workers, with program usage and effectiveness that was similar to what has been previously reported for unguided iCBT.
Anxiety and COVID-19 Related Stressors Among Healthcare Workers Who Performed Shift Work at Four COVID-19 Dedicated Hospitals in Korea
Authors: Park Sungjin , Lee Youngrong , Kim Taehun , Jung Sun Jae
Published: May 2021

Objective:

To assess the relationship between anxiety and shift work of healthcare workers (HCWs) during COVID-19 pandemic.

Methods:

From four COVID-19-dedicated hospitals in Korea, 381 HCWs were analyzed to estimate anxiety in relation to four COVID-19 job stressors and the impact of shift work on this relationship. Anxiety was measured with a generalized anxiety disorder 7-item scale. Multiple logistic regression models were utilized after stratification by sex, occupation, and shift work, after adjusting for a number of variables.

Results:

Anxiety prevalence was 32%. Among female nurses or nursing assistants who performed shift work, anxiety risk was significantly associated with three COVID-19 related job stressors: contact with confirmed cases or patients, dealing with unpleasant patients, and discomfort from wearing protective equipment.

Conclusions:

Special attention is required for mental health of HCWs working shifts during the COVID-19 pandemic.
Trimester-Specific Association of Maternal Exposure to Fine Particulate Matter and its Components With Birth and Placental Weight in Japan
Authors: Takeda Yuki , Michikawa Takehiro , Morokuma Seiichi , Yamazaki Shin , Nakahara Kazushige , Yoshino Ayako , Sugata Seiji , Takami Akinori , Saito Shinji , Hoshi Junya , Kato Kiyoko , Nitta Hiroshi , Nishiwaki Yuji
Published: May 2021

Objective:

We investigated which trimester of exposure to PM2.5 and its components was associated with birth and placental weight, and the fetoplacental weight ratio.

Methods:

The study included 63,990 women who delivered singleton term births within 23 Tokyo wards between 2013 and 2015. Each day, we collected fine particles on a filter, and analyzed their chemical constituents, including carbons and ions. Trimester-specific exposure to each pollutant was estimated based on the average daily concentrations.

Results:

Over the third trimester, sulfate exposure tended to be inversely associated with birth weight, and decreased placental weight (difference for highest vs lowest quintile groups = −6.7 g, 95% confidence interval = −12.5 to −0.9). For fetoplacental weight ratio, there was no relationship.

Conclusions:

Sulfate exposure over the third trimester may reduce birth weight, particularly placental weight.
Exploration of Three Incidence Trend Prediction Models Based on the Number of Diagnosed Pneumoconiosis Cases in China From 2000 to 2019
Authors: Zhou Dongnan , Zhu Di , Li Nana , Han Bing
Published: May 2021

Objective:

To predict the future incidence trend of pneumoconiosis in China, and to evaluate three predictive models.

Methods:

We selected pneumoconiosis cases (2000–2019) to fit Generalized Additive Model (GAM), Curve Fitting Method, and GM (1,1) Model, chosen average fitting relative error, relative error of prediction, and coefficient of determination to evaluate models.

Results:

Chinese incidence trend of pneumoconiosis would decrease in the future. Predicted value of GAM (14,566) and Curve Fitting Method (15,781) in 2019 was close to the actual value (15,898). Relative error of prediction of GAM and Curve Fitting Method was −8.38% and −0.73%, respectively.

Conclusions:

The government needs to strengthen prevention and control since pneumoconiosis cases might remain huge in the future. Besides, we advise that GAM and Curve Fitting Method can be used to predict Chinese incidence trend of pneumoconiosis.
Participation in the Healthy Rewards Program Predicts Staying Employed, Medical Costs, and Utilization
Authors: Merrill Ray M. , Aldana Steven G.
Published: May 2021

Objective:

To identify who is participating in the healthy rewards program (HRP), how participation corresponds with employment, and to compare health care costs and utilization between partial and full participants with non-participants.

Methods:

A retrospective analysis of employees in a large US company during 2016 to 2019, with statistically significant results reported, adjusted for sex, age, and year.

Results:

Women, ages 30 to 59, and those employed in more recent years correspond with higher HRP participation. Participants were 15.7% more likely to remain employed from year to year. Compared with non-participants, partial and full participants experienced $740.43 and $884.07 lower annual costs. If all employees experienced the same health care costs as non-participants, partial participants, and full participants, there would be an 8% increase, 13% decrease, and 17% decrease in costs, respectively.

Conclusions:

HRP participation is a marker of interest in healthier living.
Depression, Healthcare Utilization, Missed Work, and Health Behaviors Among US Young Workers
Authors: Leung Cherry Y. , Lee Soo-Jeong
Published: May 2021

Objective:

We examined the prevalence of depression and its impact on healthcare utilization, work absenteeism, and health behaviors among United States (US) young workers.

Methods:

Data of 1053 young workers (ages 18 to 25) from the 2015 US National Health Interview Survey were analyzed to examine these associations.

Results:

Seven percent of US young workers reported feeling often depressed (daily or weekly). Often depressed young workers had increased odds for healthcare provider visits, mental healthcare use, 1 to 2 emergency department visits, and 3 to 5 and more than or equal to 6 missed work days, smoking, and sleeping less than 7 hours.

Conclusions:

Our findings suggest that depressed young workers have increased needs for healthcare utilization and are at increased risk for missing work, smoking, and reduced sleep. Resources should be prioritized for depression screening and prevention programs at the workplace and healthcare settings.
Burnout Among Primary Care Healthcare Workers During the COVID-19 Pandemic
Authors: Apaydin Eric A. , Rose Danielle E. , Yano Elizabeth M. , Shekelle Paul G. , McGowan Michael G. , Antonini Tami L. , Valdez Cassandra A. , Peacock Michelle , Probst Laura , Stockdale Susan E.
Published: May 2021

Objective:

To measure the prevalence of burnout among healthcare workers (HCWs) in primary care during the COVID-19 pandemic and to understand the association between burnout, job-person fit, and perceptions of the pandemic.

Methods:

We surveyed 147 HCWs (73% response rate) in two clinics in the summer of 2020 on their burnout, job-person fit, perceptions of the pandemic, and demographic/job characteristics. Logistic regression analyses were conducted to explore relationships between these variables.

Results:

Forty-three percent of HCWs reported burnout. Lower HCW burnout was associated with better job-person fit in the areas of recognition or appreciation at work (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.10 to 0.67) and congruent worker-organization goals and values (OR 0.30, 95% CI 0.11 to 0.76).

Conclusions:

Working environments with better job-person fit may be key to reducing HCW burnout even after the current crisis.
Chronic Effects of Breaching Blast Exposure on Sensory Organization and Postural Limits of Stability
Authors: Haran F.J. , Zampieri Cris , Wassermann Eric M. , Polejaeva Elena , Dell Kristine C. , LoPresti Matthew L. , Stone James R. , Ahlers Stephen T. , Carr Walter
Published: May 2021

Objective:

The goal of this effort to investigate if experienced breachers, professionals with a career history of exposure to repeated low-level blasts, exhibited postural instability.

Methods:

Postural data were examined using traditional tests of means and compared to normative data.

Results:

Breachers had significantly lower NeuroCom Sensory Organization Test (SOT) visual scores (within normative limits), prolonged Limits of Stability (LOS) test reaction time (30% of breachers and 7% of controls testing abnormal), and slower LOS movement velocity (21% of breachers and 0% of controls testing abnormal) compared to controls.

Conclusion:

Our LOS test findings are like those previously reported for students in the military breacher training course and seem to indicate that while acute effects of blasts on sensory control of balance fade away, effects on postural LOS persist over time.
Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease
Authors: Smeijer J. David , Kohan Donald E. , Webb David J. , Dhaun Neeraj , Heerspink Hiddo J.L.
Published: May 2021

Purpose of review

To summarize new clinical findings of endothelin receptor antagonists (ERA) in various etiologies of kidney disease targeted in clinical trials.

Recent findings

Endothelin-1 is a multifunctional peptide with potential relevance to glomerular and tubulointerstitial kidney diseases. The phase 3 SONAR trial demonstrated a significant reduction in clinically relevant kidney outcomes for patients with diabetic kidney disease (DKD) after long-term treatment with the ERA, atrasentan, in addition to blockade of the renin-angiotensin-aldosterone system. Promising preclinical disease models and small clinical trials in non-DKD resulted in the initiation of phase 3 trials investigating the effects of long-term treatment with ERA in patients with immunoglobulin A (IgA) nephropathy and focal segmental glomeruloscelerosis (FSGS). The mechanisms by which ERA protects the kidneys have been extensively studied with evidence for the protection of tubule cells, podocytes, mesangial cells, the endothelial glycocalyx, and a reduction in glomerular perfusion pressure. The occurrence of fluid retention during ERA treatment, particularly in susceptible populations, necessitates strategies to support safe and effective treatment.

Treatment with ERA induces long-term kidney protection in DKD. Phase 3 trials are underway to investigate ERA effects in patients with IgA nephropathy and FSGS.
Interprofessional Healthcare Students' Attitudes, Skills, and Knowledge After Comprehensive Pain Assessment Training in Verbal and Nonverbal Patients
Authors: Cook Heather , Kaiser Karen Snow , Walker Kathryn A. , McPherson Mary Lynn
Published: May 2021

A comprehensive pain assessment is the first step in safe, effective pain management. Few studies have explored variations of strategies and measures for multidimensional pain assessment education in both verbal and nonverbal patients. In this retrospective cohort study, interprofessional health care students enrolled in a palliative care curriculum completed a pain assessment training, which taught the PQRSTA (“palliating factors, precipitating factors, previous treatments, quality, region, radiation, severity, temporal factors and associated symptoms”) mnemonic as a strategy for assessing pain in verbal patients and the Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures for nonverbal patients. The purpose of this study was to compare the change in attitudes, self-perceived skills, and knowledge regarding pain assessment before and after the training. Attitudes and self-perceived skills were assessed in the pretraining and posttraining survey, which was analyzed using χ2 test or Fisher exact test. Students' knowledge responses were analyzed using Wilcoxon signed rank test to assess accuracy of responses compared with the expert defined score. One hundred eighty-two students were included. Results showed a statistically significant improvement in attitudes related to applicability of pain measures and self-perceived skills. Overall, data did not support an increase in knowledge using the PQRSTA mnemonic, or Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures. Future pain trainings should consider training on only 1 nonverbal pain measure, incorporating bedside assessments, and integrating real-time feedback.
The Effect of Yoga Asana “Vrksasana (Tree Pose)” on Balance in Patients With Postmenopausal Osteoporosis
Authors: Solakoglu Ozge , Dogruoz Karatekin Bilinc , Yumusakhuylu Yasemin , Mesci Erkan , Icagasioglu Afitap
Published: May 2021

Objective

In this study, the effect of the add-on effect of the Tree Pose (Vrksasana) on the balance of patients with postmenopausal osteoporosis was investigated.

Design

Thirty-two patients with postmenopausal osteoporosis were randomly assigned to conservative exercise group (30 mins/d for 12 wks) or Tree Pose–added exercise group (30-min conventional exercise + 2-min Tree Pose/d for 12 wks) by Microsoft Excel randomization option. The balance of the patients was evaluated with Berg Balance Scale, Timed Up and Go Test, single-leg standing test, tandem walk test, tandem stance test, and Korebalance static&dynamic balance tests at baseline, sixth week, and third month of the exercise program.

Results

There was no statistically significant difference on baseline data between groups. There was a statistically significant difference between the two groups in the sixth-week measurement of single-leg stance (P < 0.05). In the Berg Balance Scale, static balance test, dynamic balance test, and tandem walk test, a statistically significant difference was found among baseline, sixth-week, and 12th week measurements in both the exercise group and the Tree Pose–added exercise group.

Conclusions

Gains in the static and dynamic balance of postmenopausal osteoporotic patients can be obtained by adding “Vrksasana” to conventional exercises.
Neuromuscular Ultrasound
Authors: Jorgensen Shawn P. , Cartwright Michael S. , Norbury John
Published: May 2021

Accurate assessment of neuromuscular disorders is critical to facilitate timely treatment and achieve the best outcomes. Historically, electrodiagnostic studies have filled this role, but recently, neuromuscular ultrasound is being used in the electrodiagnostic laboratory. This review discusses the uses of neuromuscular ultrasound in the electrodiagnostic laboratory that have strong evidence, emphasizing those that could be adopted in a typical electrodiagnostic laboratory with a reasonable level of equipment and training. The evidence currently supports using neuromuscular ultrasound to diagnose carpal tunnel syndrome and ulnar neuropathies at the elbow and as a supplementary test when electrodiagnostic studies are suspected to be falsely negative or in axonal nonlocalizing lesions. Neuromuscular ultrasound can identify the causes of focal mononeuropathies, which can change treatment in specific cases. It is sensitive at identifying fasciculations and providing complementary evidence of autoimmune demyelinating polyneuropathies. It is particularly helpful in assessing nerves after trauma. Neuromuscular ultrasound is likely to prove even more useful in the electrodiagnostic laboratory as the technology continues to advance.
Laboratory Reflex and Clinic-Based Point-of-Care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality Among People Living With HIV
Authors: Drain Paul K. , Galagan Sean R. , Govere Sabina , Krows Meighan , Thulare Hilary , Wallis Carole L. , Gosnell Bernadett I. , Moosa Mahomed-Yunus , Celum Connie , Bassett Ingrid V.
Published: May 2021

Introduction:

Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa.

Methods:

We conducted a prospective pre–post intervention study of adults presenting for HIV testing in Umlazi township, South Africa, over a 6-year period (2013–2019). Participants were enrolled during 3 phases of CrAg testing: CrAg testing ordered by a clinician (clinician-directed testing, 2013–2015); routine laboratory-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 (laboratory reflex testing, 2015–2017); and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine laboratory reflex testing among those with CD4 ≤100 cells/mm3 (clinic-based testing, 2017–2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK). We followed up participants for up to 14 months to compare associations between baseline CrAg positivity, antiretroviral therapy and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization, and mortality.

Results:

Three thousand one hundred five (39.4%) of 7877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in the analyses. Laboratory reflex and clinic-based testing increased CrAg screening (P < 0.001) and diagnosis of CrAg-positive PLHIV (P = 0.011). When compared with clinician-directed testing, clinic-based CrAg testing showed an increase in the number of PLHIV diagnosed with cryptococcal meningitis (4.5% vs. 1.5%; P = 0.059), initiation of fluconazole preemptive therapy (7.2% vs. 2.5%; P = 0.010), and initiation of antiretroviral therapy (96.8% vs. 91.3%; P = 0.012). Comparing clinic-based testing with laboratory reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% vs. 4.1%; P = 0.836) or mortality (8.1% vs. 9.9%; P = 0.557).

Conclusions:

Laboratory reflex and clinic-based CrAg testing facilitated the diagnosis of HIV-associated cryptococcosis and fluconazole initiation but did not reduce cryptococcal meningitis or mortality. In this nonrandomized cohort, clinical outcomes were similar between laboratory reflex testing and clinic-based POC CrAg testing.
Fracture Healing in Patients With HIV in South Africa: A Prospective Cohort Study
Authors: Graham Simon M. , Maqungo Sithombo , Laubscher Maritz , Ferreira Nando , Held Michael , Harrison William J. , Simpson A. Hamish , MacPherson Peter , Lalloo David G.
Published: May 2021

Background:

HIV reduces bone mineral density, mineralization, and turnover and may impair fracture healing.

Setting:

This prospective cohort study in South Africa investigated whether HIV infection was associated with impaired fracture healing after trauma.

Methods:

All adults with acute tibia and femur fractures who underwent intermedullary (IM) nailing for fracture fixation between September 2017 and December 2018, at 2 tertiary hospitals, were followed up for a minimum of 12 months postoperatively. The primary outcome was delayed bone union at 6 months (defined by the radiological union scoring system for the tibia score <9), and the secondary outcome was nonunion (defined as radiological union scoring system for the tibia score <9) at 9 months. Multivariable logistic regression models were constructed to investigate the associations between HIV status and impaired fracture healing.

Results:

In total, 358 participants, who underwent 395 IM nailings, were enrolled in the study and followed up for 12 months. Seventy-one of the 358 (19.8%) participants were HIV-positive [83/395 (21%) IM nailings]. HIV was not associated with delayed fracture healing after IM nailing of the tibia or femur (multivariable odds ratio: 1.06; 95% confidence interval: 0.50 to 2.22). HIV-positive participants had a statistically significant lower odds ratio of nonunion compared with HIV-negative participants (multivariable odds ratio: 0.17; 95% confidence interval: 0.01 to 0.92).

Conclusions:

Fractures sustained in HIV-positive individuals can undergo surgical fixation as effectively as those in HIV-negative individuals, with no increased risk of delayed union or nonunion.
Expression of the hippocampal PTCH during early abstinence is associated with drinking patterns in a rat model of voluntary alcohol intake
Authors: Peregud Danil , Stepanichev Mikhail , Gulyaeva Natalia
Published: May 2021

Perinatal alcohol exposure induces fetal alcohol syndrome partially through Sonic Hedgehog (SHH) impairment; however, the relationship between SHH signaling cascade and alcohol drinking pattern in adulthood remains obscure. We studied the expression of SHH and components of respective signaling cascade [PTCH receptor (Patched), SMO co-receptor (Smoothened) and downstream transcriptional factor Glioma-associated oncogene (GLI)] during early abstinence in brain regions of rats demonstrating different drinking patterns in intermittent access two-bottle choice paradigm (IA2BC). Male Wistar rats were subjected to twenty 24-h sessions of free access to two-bottle choice (water or 20% ethanol) with 24-h withdrawal periods (water only). Control animals had access to water only. Quantitative PCR and western blotting were used to assess transcript and protein levels in the brain, respectively. During the course of the IA2BC, one part of animals demonstrated gradual escalation from low to high alcohol intake and preference of alcohol over water (group I), while the other one consumed alcohol at stable high level (group II) (Peregud et al., 2021). Three days after the last drinking session, PTCH mRNA elevated in the hippocampus of group I rats as compared to the control group. However, SHH, SMO and GLI mRNA levels in the hippocampus did not change. The protein content of PTCH in the hippocampus of group I rats was higher as compared to both control and group II. PTCH elevation is a known marker of SHH cascade activity. Thus, activated hippocampal SHH signaling cascade is a hallmark of rats demonstrating gradual escalation of alcohol intake in the IA2BC procedure.
Continuous theta-burst stimulation over the right dorsolateral prefrontal cortex impairs visuospatial working memory performance in medium load task
Authors: Ngetich Ronald , Li Wenjuan , Jin Donggang , Zhang Junjun , Jin Zhenlan , Li Ling
Published: May 2021

Previous studies have shown that visuospatial working memory (VSWM) plays a key role in the encoding and processing of visuospatial information. More importantly, there is evidence suggesting the role of frontal and parietal cortical areas in VSWM and especially, the influence of the frontal cortex in regulating goal-directed behavior. However, the functional role of the right dorsolateral prefrontal cortex (rDLPFC) in visuospatial working memory is still unclear. Here, we noninvasively modulated the rDLPFC activity using continuous theta-burst stimulation (cTBS), with the vertex as the control site. Our study aimed to investigate the effects of cTBS over rDLPFC on working memory task (2- and 4-back) performance. Working memory performance was assessed at the baseline and after stimulation. We observed that the working memory performance as measured by discriminability index was impaired after cTBS over rDLPFC in 2-back task, whereas 4-back task performance was not significantly affected. More so, there was no effect on performance after cTBS over the vertex, suggesting a functional role of rDLPFC in VSWM. Our findings demonstrate the involvement of the rDLPFC in VSWM as well as the load-dependent effect of working memory performance. Taken together, our work constitutes a useful addition to the literature and underscores the effectiveness and efficiency of noninvasive brain stimulation in modulating neuro-cognitive activity.
Kaustia mangrovi gen. nov., sp. nov. isolated from Red Sea mangrove sediments belongs to the recently proposed Parvibaculaceae family within the order Rhizobiales
Authors: Sefrji Fatmah O. , Marasco Ramona , Michoud Grégoire , Seferji Kholoud A. , Merlino Giuseppe , Daffonchio Daniele
Published: May 2021

We isolated a novel strain, R1DC25T, described as Kaustia mangrovi gen. nov. sp. nov. from the sediments of a mangrove forest on the coast of the Red Sea in Saudi Arabia. This isolate is a moderately halophilic, aerobic/facultatively anaerobic Gram-stain-negative bacterium showing optimum growth at between 30 and 40 °C, at a pH of 8.5 and with 3–5 % NaCl. The genome of R1DC25T comprises a circular chromosome that is 4 630 536 bp in length, with a DNA G+C content of 67.3 mol%. Phylogenetic analyses based on the 16S rRNA gene sequence and whole-genome multilocus sequence analysis of 120 concatenated single-copy genes revealed that R1DC25T represents a distinct lineage within the family

Parvibaculaceae

in the order

Rhizobiales

within the class

Alphaproteobacteria

. R1DC25T showing 95.8, 95.3 and 94.5 % 16S rRNA gene sequence identity with

Rhodoligotrophos appendicifer

,

Rhodoligotrophos jinshengii

and

Rhodoligotrophos defluvii

, respectively. The predominant quinone was Q-10, and the polar lipids were phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, as well as several distinct aminolipids and lipids. The predominant cellular fatty acids were C19 : 0 cyclo ω8c, a combination of C18 : 1
ω7c and/or C18 : 1
ω6c and C16 : 0. On the basis of the differences in the phenotypic, physiological and biochemical characteristics from its known relatives and the results of our phylogenetic analyses, R1DC25T (=KCTC 72348T;=JCM 33619T;=NCCB 100699T) is proposed to represent a novel species in a novel genus, and we propose the name Kaustia mangrovi gen. nov., sp. nov. (Kaustia, subjective name derived from the abbreviation KAUST for King Abdullah University of Science and Technology; mangrovi, of a mangrove).
Dear Watch, Should I Get a COVID-19 Test? Designing deployable machine learning for wearables
Authors: Nestor Bret , Hunter Jaryd , Kainkaryam Raghu , Drysdale Erik , Inglis Jeffrey B. , Shapiro Allison , Nagaraj Sujay , Ghassemi Marzyeh , Foschini Luca , Goldenberg Anna
Published: May 2021

Commercial wearable devices are surfacing as an appealing mechanism to detect COVID-19 and potentially other public health threats, due to their widespread use. To assess the validity of wearable devices as population health screening tools, it is essential to evaluate predictive methodologies based on wearable devices by mimicking their real-world deployment. Several points must be addressed to transition from statistically significant differences between infected and uninfected cohorts to COVID-19 inferences on individuals. We demonstrate the strengths and shortcomings of existing approaches on a cohort of 32, 198 individuals who experience influenza like illness (ILI), 204 of which report testing positive for COVID-19. We show that, despite commonly made design mistakes resulting in overestimation of performance, when properly designed wearables can be effectively used as a part of the detection pipeline. For example, knowing the week of year, combined with naive randomised test set generation leads to substantial overestimation of COVID-19 classification performance at 0.73 AUROC. However, an average AUROC of only 0.55 ± 0.02 would be attainable in a simulation of real-world deployment, due to the shifting prevalence of COVID-19 and non-COVID-19 ILI to trigger further testing. In this work we show how to train a machine learning model to differentiate ILI days from healthy days, followed by a survey to differentiate COVID-19 from influenza and unspecified ILI based on symptoms. In a forthcoming week, models can expect a sensitivity of 0.50 (0-0.74, 95% CI), while utilising the wearable device to reduce the burden of surveys by 35%. The corresponding false positive rate is 0.22 (0.02-0.47, 95% CI). In the future, serious consideration must be given to the design, evaluation, and reporting of wearable device interventions if they are to be relied upon as part of frequent COVID-19 or other public health threat testing infrastructures.
Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses
Authors: Perez-Zsolt Daniel , Muñoz-Basagoiti Jordana , Rodon Jordi , Elousa Marc , Raïch-Regué Dàlia , Risco Cristina , Sachse Martin , Pino Maria , Gumber Sanjeev , Paiardini Mirko , Chojnacki Jakub , Erkizia Itziar , Muñiz Xabier , Ballana Ester , Riveira-Muñoz Eva , Noguera Marc , Paredes Roger , Trinité Benjamin , Tarrés-Freixas Ferran , Blanco Ignacio , Guallar Victor , Carrillo Jorge , Blanco Julià , Telenti Amalio , Heyn Holger , Segalés Joaquim , Clotet Bonaventura , Martinez-Picado Javier , Vergara-Alert Júlia , Izquierdo-Useros Nuria
Published: May 2021

COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.
Saturation variant interpretation using CRISPR prime editing
Authors: Erwood Steven , Bily Teija M.I. , Lequyer Jason , Yan Joyce , Gulati Nitya , Brewer Reid A. , Zhou Liangchi , Pelletier Laurence , Ivakine Evgueni A. , Cohn Ronald D.
Published: May 2021

Over the last decade, next generation sequencing has become widely implemented in clinical practice. However, as genetic variants of uncertain significance (VUS) are frequently identified, the need for scaled functional interpretation of such variants has become increasingly apparent. One method to address this is saturation genome editing (SGE), which allows for scaled multiplexed functional assessment of single nucleotide variants. The current applications of SGE, however, rely on homology-directed repair (HDR) to introduce variants of interest, which is limited by low editing efficiencies and low product purity. Here, we have adapted CRISPR prime editing for SGE and demonstrated its utility in understanding the functional significance of variants in the NPC1 gene underlying the lysosomal storage disorder Niemann-Pick disease type C1 (NPC). Additionally, we have designed a genome editing strategy that allows for the haploidization of gene loci, which permits isolated variant interpretation in virtually any cell type. By combining saturation prime editing (SPE) with a clinically relevant assay, we have functionally scored and interpreted 256 variants in NPC1 haploidized HEK293T cells. To further demonstrate the applicability of this strategy, we used SPE and cell model haploidization to functionally score 465 variants in the BRCA2 gene. We anticipate that our work will be translatable to any gene with an appropriate cellular assay, allowing for more rapid and accurate diagnosis and improved genetic counselling and ultimately precise patient care.
USING PHYLOGENETICS TO INFER HIV-1 TRANSMISSION DIRECTION BETWEEN KNOWN TRANSMISSION PAIRS
Authors: Villabona-Arenas Christian Julian , Hué Stéphane , Baxter James A. C. , Hall Matthew , Lythgoe Katrina A. , Bradley John , Atkins Katherine E.
Published: May 2021

Inferring the transmission direction between linked individuals living with HIV provides unparalleled power to understand the epidemiology that determines transmission. Phylogenetic ancestral state reconstruction approaches infer the transmission direction by identifying the individual in whom the most recent common ancestor of the virus populations originated. However, these methods vary in their accuracy but it is unclear why. To evaluate the performance of phylogenetic ancestral state reconstruction, we inferred the transmission direction for 112 HIV transmission pairs where transmission direction was known and detailed additional information was available. We then fit a statistical model to evaluate the extent to which epidemiological, sampling, genetic and phylogenetic factors influenced the outcome of the inference. We repeated the analysis under real-life conditions with only routinely-collected data. We found that the inference of transmission direction depends principally on the topology class and branch length characteristics of the phylogeny. Under real-life conditions, the probability of identifying the correct transmission direction increases from 52%—when a monophyletic-monophyletic or paraphyletic-polyphyletic tree topology is observed, when the sample size in both partners is small and when the tip closest to the root does not agree with the state at the root—to 93% when a paraphyletic-monophyletic topology is observed, when the sample size is large and when the tip closest to the root agrees with root state. Our results suggest that discordance between previous studies in inferring the transmission direction can be explained by differences in key phylogenetic properties that arise due to different evolutionary, epidemiological and sampling processes.

Significance Statement

Identifying the direction of infectious disease transmission between individuals provides unparalleled power to understand infectious disease epidemiology. With epidemiological and clinical information typically unable to distinguish the direction, phylogenetic analysis of pathogen sequence data is an alternative approach. However, when these phylogenetic methods have been implemented, their accuracy is highly variable, and the reasons for this discordance is unknown. Here we analyse sequence data from over 100 pairs of individuals for whom both the direction of transmission of HIV is known and detailed epidemiological and sampling information is available. We find that easily quantifiable phylogenetic characteristics discriminate whether a phylogenetically-inferred transmission direction is correct. Our analysis highlights that phylogenetic approaches are unsuitable for individual-level analysis such as forensic investigations.
Occupation and COVID-19 mortality in England: a national linked data study of 14.3 million adults
Authors: Nafilyan Vahé , Pawelek Piotr , Ayoubkhani Dan , Rhodes Sarah , Pembrey Lucy , Matz Melissa , Coleman Michel P , Allemani Claudia , Windsor-Shellard Ben , van Tongeren Martie , Pearce Neil
Published: May 2021

Objective

To estimate occupational differences in COVID-19 mortality, and test whether these are confounded by factors, such as regional differences, ethnicity and education or due to non-workplace factors, such as deprivation or pre-pandemic health.

Design

Retrospective cohort study

Setting

People living in private households England

Participants

14,295,900 people aged 40-64 years (mean age 52 years, 51% female) who were alive on 24 January 2020, living in private households in England in 2019, were employed in 2011, and completed the 2011 census.

Main outcome measures

COVID-19 related death, assessed between 24 January 2020 and 28 December 2020. We estimated age-standardised mortality rates per 100,000 person-years at risk (ASMR) stratified by sex and occupations. To estimate the effect of occupation due to work-related exposures, we used Cox proportional hazard models to adjust for confounding (region, ethnicity, education), as well as non-workplace factors that are related to occupation.

Results

There is wide variation between occupations in COVID-19 mortality. Several occupations, particularly those involving contact with patients or the public, show three-fold or four-fold risks. These elevated risks were greatly attenuated after adjustment for confounding and mediating non-workplace factors. For example, the hazard ratio (HR) for men working as taxi and cab drivers or chauffeurs changed from 4.60 [95%CI 3.62-5.84] to 1.47 [1.14-1.89] after adjustment. More generally, the overall HR for men working in essential occupations compared with men in non-essential occupations changed from 1.45 [1.34 - 1.56] to 1.22 [1.13 - 1.32] after adjustment. For most occupations, confounding and other mediating factors explained about 70% to 80% of the age-adjusted hazard ratios.

Conclusions

Working conditions are likely to play a role in COVID-19 mortality, particularly in occupations involving contact with COVID-19 patients or the public. However, there is also a substantial contribution from non-workplace factors, including regional factors, socio-demographic factors, and pre-pandemic health.
Chromatin state barriers enforce an irreversible mammalian cell fate decision
Authors: Blanco M. Andrés , Sykes David B. , Gu Lei , Wu Mengjun , Petroni Ricardo , Karnik Rahul , Wawer Mathias , Rico Joshua , Li Haitao , Jacobus William D. , Jambhekar Ashwini , Cheloufi Sihem , Meissner Alexander , Hochedlinger Konrad , Scadden David T. , Shi Yang
Published: May 2021

Stem and progenitor cells have the capacity to balance self-renewal and differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection. At what point along the spectrum of maturation do progenitors lose capacity for self-renewal and become irreversibly committed to differentiation? Using a system of conditional myeloid development that can be toggled between self-renewal and differentiation, we interrogated determinants of this ‘point of no return’ in differentiation commitment. Irreversible commitment is due primarily to loss of open regulatory site access and disruption of a positive feedback transcription factor activation loop. Restoration of the transcription factor feedback loop extends the window of cell plasticity and alters the point of no return. These findings demonstrate how the chromatin state enforces and perpetuates cell fate and identifies potential avenues for manipulating cell identity.

Highlights

There exists a point of irreversible commitment in granulocytic differentiation

Chromatin state dynamics establish the transition from self-renewal to differentiation commitment

Reduced chromatin accessibility underlies an irreversible loss of regulatory site access

Restoration of a transcription factor feedback loop alters the differentiation commitment point