bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplement (mis)use in adolescents
Authors: Tiwari Kritika
Published: June 2020

Purpose of review

Dietary supplement usage by adolescents has been on the rise in the last decade and is expected to continue to grow, although the evidence of their benefits in healthy individuals remains unclear. This review aims to spread awareness about the poorly regulated supplements and their effects on the health of adolescents to minimize medical hazards.

Recent findings

In this review, we have attempted to summarize some of the commonly consumed supplements, their alleged benefits, effects and side effects, along with the motivation that drives adolescents into consuming them.

The widespread use of dietary supplements among adolescents, in the background of lack of knowledge and medical guidance, predisposes adolescents to significant health risks. Although supplements may be necessary and safely consumed in certain specific situations, most healthy adolescents do not need them. The lack of regulation of supplements encourages contamination and ensures indiscriminate, easy access.
Treatment of cardiometabolic risk factors in patients with type 1 diabetes
Authors: Niechciał Elżbieta , Marcovecchio M. Loredana
Published: June 2020

Purpose of review

Individuals with type 1 diabetes (T1D) have excess cardiovascular risk and reduced life expectancy. Adolescence is the time when the first signs of vascular complications appear and a critical window for interventions. This article reviews recent evidence on cardiometabolic risk factors and their management in youth with T1D.

Recent findings

Adolescents with T1D show early signs of vascular complications, as a result of several cardiometabolic risk factors. Poor glycemic control is one of the main risk factors and the main target of treatment. However, only a minority of adolescents with T1D reaches recommended targets for glycemic control. Hypertension, dyslipidemia, smoking, alcohol use, obesity and insulin resistance are other common cardiometabolic risk factors in this age group. Recent data confirm that screening for these risk factors is suboptimal and use of pharmacological interventions for hypertension and dyslipidemia remains low. Data on adjunctive noninsulin agents to improve glycemic control and other cardiometabolic risk factors are still lacking in this age group.

Vascular complications and the associated mortality remain a major issue for youth with T1D. Better screening strategies for cardiometabolic risk factors and interventions are required to improve the long-term prognosis of youth with T1D.
Recent advances in precision medicine for individualized immunosuppression
Authors: Fu Shengyi , Zarrinpar Ali
Published: June 2020

Purpose of review

The current tools to proactively guide and individualize immunosuppression in solid organ transplantation are limited. Despite continued improvements in posttransplant outcomes, the adverse effects of over-immunosuppression or under-immunosuppression are common. The present review is intended to highlight recent advances in individualized immunosuppression.

Recent findings

There has been a great focus on genomic information to predict drug dose requirements, specifically on single nucleotide polymorphisms of CYP3A5 and ABCB1. Furthermore, biomarker studies have developed ways to better predict clinical outcomes, such as graft rejection.

The integration of advanced computing tools, such as artificial neural networks and machine learning, with genome sequencing has led to intriguing findings on individual or group-specific dosing requirements. Rapid computing allows for processing of data and discovering otherwise undetected clinical patterns. Genetic polymorphisms of CYP3A5 and ABCB1 have yielded results to suggest varying dose requirements correlated with race and sex. Newly proposed biomarkers offer precise and noninvasive ways to monitor patient's status. Cell-free DNA quantitation is increasingly explored as an indicator of allograft injury and rejection, which can help avoid unneeded biopsies and more frequently monitor graft function.
Autoimmune Hepatitis in Children
Authors: Cuarterolo Miriam L. , Ciocca Mirta , López Susana , Araujo María , Álvarez Fernando
Published: June 2020

Objective:

The aim of this study was to find the outcome and adverse effects of 2 initial treatments in children with autoimmune hepatitis, prednisone (PRED) plus azathioprine (AZA) versus cyclosporine (CsA).

Study Design:

Between December 2008 and February 2012, 50 consecutive patients were centrally randomized to 1 of 2 treatment arms. Group 1: PRED was indicated at a dose of 1 to 2 mg · kg−1 · day−1 (up to 60 mg/day) and AZA at a dose of 1 to 2 mg · kg−1 · day−1. Group 2: CsA was administered at a dose of 4 mg · kg−1 · day−1 orally divided into 2 doses. After remission, all patients were given a combination of PRED at 0.3 to 0.5 mg · kg−1 · day−1 and AZA at 1 to 2 mg · kg−1 · day−1. Children presenting liver failure were placed on a triple immunosuppressive regimen if this condition persisted after 1 week of treatment, after liver function normalization they were switched back to their initial scheme.

Results:

A total of 26 patients received PRED‐AZA and 24 CsA. Both treatments showed similar initial results in effectiveness and safety, although remission was achieved earlier with PRED‐AZA: 8.6 versus CsA: 13.6 weeks (P < 0.0081). All children recovered liver function in a mean time of 32 ± 26 days. Cushingoid syndrome was more frequently observed with PRED‐AZA (P < 0.001) and gingival hypertrophy with CsA (P < 0.001). A significant increase in body mass index was observed in all patients from initial treatment to remission, being greater with PRED‐AZA.

Conclusions:

Similar outcomes were obtained with PRED plus AZA or CsA treatments. Either therapeutic strategy could be used according to the particular characteristics of each patient. Triple immunosuppression was beneficial in patients with liver failure at onset.
Association of Clinical Nursing Work Environment with Quality and Safety in Maternity Care in the United States
Authors: Clark Rebecca R. S. , Lake Eileen T.
Published: June 2020

Purpose:

Maternal outcomes in the United States are the poorest of any high-income country. Efforts to improve the quality and safety of maternity care are frequently reported by individual hospitals, limiting generalizability. The purpose of this study is to describe maternity care quality and safety in hospitals in four states.

Study Design and Methods:

This cross-sectional study is a secondary analysis of the Panel Study of Effects of Changes in Nursing on Patient Outcomes data. Registered nurses reported on maternity unit quality, safety, and work environment. Descriptive statistics and clustered linear regressions were used. Results: The sample included 1,165 nurses reporting on 166 units in California, New Jersey, Pennsylvania, and Florida in 2015. One-third of nurses, on average, gave their units an overall safety grade of “excellent,” but this decreased to less than one-sixth of nurses in units with poor work environments. Overall, 65% of nurses reported that their mistakes were held against them. A good work environment, compared with poor, was significantly associated with fewer nurses grading safety as poor (β -35.6, 95% CI -42.9 – -28.3).

Clinical Implications:

Our research found that the nurses in the majority of hospitals with maternity units in four states representing a quarter of the nation's annual births felt their units do not provide excellent quality care and have a less than optimal safety climate.
Ending the HIV Epidemic: Contributions Resulting From Syphilis Partner Services
Authors: DiOrio Dawne , Collins Dayne , Hanley Shane
Published: June 2020

Background

There is a high level of coinfection with human immunodeficiency virus (HIV) among persons diagnosed with syphilis in the United States. Public health workers at state and local health departments help inform exposed partners to sexually transmitted disease (STD)/HIV infections to facilitate early testing and treatment (partner services). The federal initiative, Ending the HIV Epidemic (EHE), identifies 4 key strategies: diagnose, treat, prevent, and respond. This study describes the contributions of syphilis partner services to the EHE strategies in a county prioritized by the EHE plan.

Methods

A retrospective record review of reported early syphilis cases (less than 1 year's duration) between 2016 and 2018 in the Indianapolis area was conducted to determine the extent of new HIV diagnoses, retention in HIV care, and other evidence-based HIV prevention interventions occurring after provision of syphilis partner services.

Results

A total of 752 partners to early syphilis were attempted to be notified of exposure. There were 1,457 case patients and partners that received STD/HIV prevention counseling; 400 partners received STD treatment, 352 partners learned their HIV status, and 22 received new HIV diagnoses, with 68% retained in medical care and 60% virally suppressed. Two thirds of partner services were completed within 21 days. New HIV positivity among partners to HIV-negative syphilis case patients was 3.5% and 14% among HIV-positive syphilis case patients.

Conclusions

Partner services for syphilis was an effective method of addressing the EHE strategies, resulting in persons at risk tested, STD treatment provided, behavioral prevention counseling provided, and new HIV cases identified, leading to retention in medical care and viral suppression.
Facilitators and Barriers to Expedited Partner Therapy: Results From a Survey of Family Physicians
Authors: Wong Jason , Zakher Bernadette , Consolacion Theodora , Leong Jeffrey , Choi Alexandra , Prescott Cheryl , Ng Brian , Pawa Jasmine , Campbell Audrey
Published: June 2020

Background

Expedited partner therapy (EPT) can prevent transmission of sexually transmitted infections (STIs) and reinfection of the index patient. We surveyed family physicians (FPs) in British Columbia to understand their perceptions of barriers and facilitators to EPT use and explored how perceptions varied by demographic and practice characteristics.

Methods

Survey participants were recruited through the Divisions of Family Practice, which include greater than 90% of FPs in British Columbia. Common barriers and facilitators for EPT were identified using descriptive statistics. The association between each EPT barrier and facilitator and demographic and practice characteristics were tested using χ2 test.

Results

One hundred eighty-one FPs started the survey, of which 146 (80.7%) answered 10 questions or more and were analyzed. Overall, inaccurate information about sex partners (88 [60.3%] of 146) and medicolegal concerns (87 [59.6%] of 146) were the most common barriers reported. Family physicians in nonurban settings were more likely to identify insufficient time as a barrier compared with FPs in urban settings (P < 0.01). The most common facilitators were having a health care professional for follow-up after prescribing EPT (110 [75.3%] of 146), improved remuneration (93 [63.7%] of 146), clear clinical guidelines around EPT (87/146, 59.6%), and having a legal framework (92 [63.0%] of 146). Family physicians practicing for less than 9 years (the median) were more likely to identify the latter as facilitating EPT compared with FPs practicing for 9 years or longer (P < 0.05).

Conclusions

Ensuring patients have access to a health care professional for follow-up, improved remuneration, and development of clinical guidelines and a legal framework can support the implementation of EPT. Tools catered to different practice types and contexts may help increase EPT use.
Leveraging Crowdsourcing for Human Immunodeficiency Virus Testing Posters: A Visual Content Analysis and Cognitive Responses Among Chinese Men Who Have Sex With Men
Authors: Smith M. Kumi , Cao Bolin , Fu Rong , Zhao Yang , Liu Chuncheng , Lazard Allison J. , Tucker Joseph D.
Published: June 2020

Introduction

Extensive marketing and advertising research has informed a deep understanding of the link between visual design and consumer behaviors, providing a useful framework for assessing associations between human immunodeficiency virus (HIV)-related health posters and viewer responses.

Methods

Crowdsourced posters included finalist submissions from a series of nationwide crowdsourcing contests. Centers for Disease Control (CDC) images were sampled from an online poster database maintained by the National Center for acquired immune deficiency syndrome (AIDS). Once coded according to a set of 27 visual features, posters were shown to an online sample of Chinese men who have sex with men—a group currently experiencing the highest HIV incidence in China—to assess their viewer response.

Results

The CDC posters were more likely to use positive facial expressions (65%; 95% confidence interval [CI], 40.9–83.7] vs 12.5%; 95% CI, 2.2–4%) and an educational messaging style (85%; 95% CI, 61.1–96% vs 31.3%; 95% CI, 12.1–58.5). Crowdsourced posters exhibited better craftsmanship than CDC posters (more design simplicity, image diversity, color choice, design quality, and moderate use of text) used more visual metaphors (56.3%; 95% CI, 30.6–79.2 vs 5%; [95% CI, 0.2–26.9%]). Several differences in visual complexity were identified but these lacked statistical significance.

Conclusion

Crowdsourced posters were of higher craftsmanship, possibly due to their ability to recruit skills of professional designers. The CDC posters' use of positive visual reinforcement (smiling faces) and educational messaging may be a legacy of their role in the early days of the epidemic in disseminating basic HIV/AIDS knowledge and dispelling misinformation. Crowdsourcing posters' used more metaphors, suggesting better ability to leverage in-group codes and language.
Population Size Estimate of Men Who Have Sex With Men, Female Sex Workers, and People Who Inject Drugs in Mozambique: A Multiple Methods Approach
Authors: Sathane Isabel , Boothe Makini A.S. , Horth Roberta , Baltazar Cynthia Semá , Chicuecue Noela , Seleme Jessica , Raymond Henry F.
Published: June 2020

Background

Accurate estimates of key population size are necessary to design programs and policies to prevent and reduce new HIV infections and to monitor the dynamics of the epidemic. The first bio-behavioral surveillance surveys, with population size estimation activities, were conducted in Mozambique in 2010 to 2014.

Methods

We used multiple methods—sequential sampling, unique object, unique event, and service multipliers—to estimate the numbers of men who have sex with men (MSM), female sex workers (FSW), and people who inject drugs (PWID) living in major cities in Mozambique. Results were applied to population sizes to estimate the number of people living with HIV and those unaware of their status.

Results

Our results suggest that Maputo has 5182 MSM, which constitutes 1.0% of the adult male population (plausibility bounds, 0.5%–2.6%); Beira, 1796 (1.4%, 1.0%–2.2%); and Nampula, 874 (0.6%, 0.4%–1.6%). The number of FSW population is 1514 (0.6%; plausibility bounds, 0.4%–1.6% of adult female city population) in Maputo, 2616 (2.2%, 1.3%–6.0%) in Beira, and 2052 (1.4%, 0.8%–5.9%) in Nampula. The number of people who inject drugs is 2518 (0.4%; plausibility bounds, 0.3%–0.5% of adult male city population) in Maputo and 1982 (1.2%, 0.6%–1.9%) in Nampula. People living with HIV ranged from 25 to 497 MSM, 382 to 664 FSW, and 712 to 1340 PWID, whereas people living with HIV unaware of their HIV positive serostatus ranged from 24 to 486 MSM, 327 to 552 FSW, and 265 to 468 PWID.

Conclusions

Although estimates generally fell within the range of those from the literature, the triangulation of survey and programmatic data over time will increasingly refine population size estimates and support the optimal allocation of limited resources.
Lack of Sexually Transmitted Infection Treatment Accuracy When Relying on Syndromic Management in an Urgent Care Setting
Authors: Glasgow Kimberly E.
Published: June 2020

Background

Chlamydia and gonorrhea are 2 of the most common sexually transmitted infections, and patients are increasingly seeking care for them in urgent care clinics. Providers often rely on syndromic management because of prolonged test turnaround times, which can result in inappropriate treatment.

Methods

This study retrospectively evaluated chlamydia and gonorrhea treatment accuracy of adults, men and women, 18 years and older in 4 urgent cares in Northeast Iowa, using standard nucleic acid amplification test in a 6-month time frame through medical records review. Seven hundred twenty-two visits were evaluated.

Results

The proportion of patients who were treated at the time of their visit was 25.8% (n = 186/722), resulting in 68.8% (n = 128/186) overtreatment and 8.2% (n = 44/536) undertreatment. Logistic regression analysis found that treatment prescribed without diagnostic test results and the patient-collected vaginal swabs were predictors of inappropriate treatment. Patients who were treated in the clinic were significantly less likely to be treated appropriately compared with patients who were treated later based on test results (odds ratio, 0.04; confidence interval, 0.02–0.06). Patients who self-collected vaginal swabs had significantly lower odds of being treated appropriately (odds ratio, 0.04; confidence interval, 0.09–0.80).

Conclusions

Syndromic management leads to inaccurate treatment of chlamydia and gonorrhea at the time of the initial patient visit. Changes in practice in urgent care are needed to improve treatment accuracy by promoting antibiotic stewardship and decreasing forward disease transmission.
Dual-Plane Gluteal Myocutaneous Flap for Reconstruction of Ischial Tuberosity Pressure Wounds
Authors: Sinnott Catherine J. , Stavrides Steven , Boutros Christina , Kuruvilla Annet , Glickman Laurence T.
Published: June 2020

Purpose

Ischial tuberosity pressure wounds are the most common type of pressure wound and contribute to a large percentage of the total cost of surgical and nonsurgical management of pressure wounds. Gluteal myocutaneous and fascocutaneous flaps are well-documented methods of coverage for ischial pressure wounds. This study aimed to describe results using a novel dual-plane gluteal myocutaneous flap technique for reconstruction of ischial tuberosity pressure wounds.

Methods

A retrospective chart review was performed of all patients who underwent dual-plane gluteus maximus myocutaneous flap reconstruction for ischial tuberosity pressure wounds performed by a single surgeon from 2012 to 2018. Patient demographic, clinical, and operative characteristics were reviewed. Outcomes were assessed by analyzing complication rates including recurrence, need for revision surgery, dehiscence, necrosis, wound infection, seroma, and hematoma.

Results

Eight dual-plane gluteus maximus myocutaneous flaps were performed for reconstruction of ischial tuberosity pressure wounds in 7 male patients with a mean age of 49.1 ± 14.9 years (mean ± SD) and mean body mass index of 26.7 ± 6.4 kg/m2. All patients were nonambulatory secondary to spinal cord injury or congenital neurological disease. Two patients (28.6%) were diabetic, and 1 patient (14.3%) was an active smoker. The mean defect size after debridement of ischial pressure wounds was 60.7 ± 29.4 cm2. After a mean follow-up of 16.4 months, partial wound dehiscence occurred in 1 patient (14.3%) and was managed with local wound care only. Infection and recurrence occurred in another patient (14.3%) and required revision surgery.

Conclusions

The dual-plane gluteal myocutaneous flap is an effective method for reconstruction of ischial tuberosity pressure wounds. Partially elevating the cutaneous layer off the gluteus maximus muscle allows for greater mobility and rotation of the muscle flap into the ischial pressure wound defect and closure of the flap and donor site with the cutaneous layer.
Improving the Quality of Evaluation Data in Simulation-Based Healthcare Improvement Projects
Authors: Santomauro Chiara M. , Hill Andrew , McCurdie Tara , McGlashan Hannah L.
Published: June 2020

Summary Statement

Simulation is increasingly being used in healthcare improvement projects. The aims of such projects can be extremely diverse. Accordingly, the outcomes or participant attributes that need to be measured can vary dramatically from project-to-project and may include a wide range of nontechnical skills, technical skills, and psychological constructs. Consequently, there is a growing need for simulation practitioners to be able to identify suitable measurement tools and incorporate them into their work. This article provides a practical introduction and guide to the key considerations for practitioners when selecting and using such tools. It also offers a substantial selection of example tools, both to illustrate the key considerations in relation to choosing a measure (including reliability and validity) and to serve as a convenient resource for those planning a study. By making well-informed choices, practitioners can improve the quality of the data they collect, and the likelihood that their projects will succeed.
Military civilian partnerships: International proposals for bridging the Walker Dip
Authors: Jensen Guy , van Egmond Teun , Örtenwall Per , Peralta Ruben , Aboutanos Michel B. , Galante Joseph
Published: June 2020

The Walker Dip refers to the cycle of the improvement of care for the battle injured soldier over the course of a conflict, followed by the decline in the skills needed to provide this care during peacetime, and the requisite need to relearn those skills during the next conflict. As the operational tempo of the conflicts in Afghanistan and Iraq has declined, concerns have arisen regarding whether US military surgeons are prepared to meet the demands of future conflicts. This problem is not unique to the US military, and allied nations have taken creative steps to address the Walker Dip in their own surgical communities. A panel entitled “Military and Civilian Trauma System Integration: Where Have We Come; Where Are We Going and What Can We Learn from Our International Partners” at the 2018 American Association for the Surgery of Trauma meeting brought together a cadre of civilian and military surgeons with experience in this area. The efforts described involved the creation of a new trauma training program in Doha, Qatar, the military civilian partnership in the Netherlands, and the steps taken to address the deficit of penetrating trauma in Sweden. This article focuses on the lessons that can be learned from our allied partners to assure readiness for deployment among military surgeons.

LEVEL OF EVIDENCE

Economic and Value Based Evaluations, level V.
Tremor pathophysiology: lessons from neuroimaging
Authors: Madelein van der Stouwe A.M. , Nieuwhof Freek , Helmich Rick C.
Published: June 2020

Purpose of review

We discuss the latest neuroimaging studies investigating the pathophysiology of Parkinson's tremor, essential tremor, dystonic tremor and Holmes tremor.

Recent findings

Parkinson's tremor is associated with increased activity in the cerebello-thalamo-cortical circuit, with interindividual differences depending on the clinical dopamine response of the tremor. Although dopamine-resistant Parkinson's tremor arises from a larger contribution of the (dopamine-insensitive) cerebellum, dopamine-responsive tremor may be explained by thalamic dopamine depletion. In essential tremor, deep brain stimulation normalizes cerebellar overactivity, which fits with the cerebellar oscillator hypothesis. On the other hand, disconnection of the dentate nucleus and abnormal white matter microstructural integrity support a decoupling of the cerebellum in essential tremor. In dystonic tremor, there is evidence for involvement of both cerebellum and basal ganglia, although this may depend on the clinical phenotype. Finally, in Holmes tremor, different causal lesions map to a common network consisting of the red nucleus, internal globus pallidus, thalamus, cerebellum and pontomedullary junction.

The pathophysiology of all investigated tremors involves the cerebello-thalamo-cortical pathway, and clinical and pathophysiological features overlap among tremor disorders. We draw the outlines of a hypothetical pathophysiological axis, which may be used besides clinical features and cause in future tremor classifications.
Spectral entropy of early-life distress calls as an iceberg indicator of chicken welfare
Authors: Herborn Katherine A. , McElligott Alan G. , Mitchell Malcolm A. , Sandilands Victoria , Bradshaw Brett , Asher Lucy
Published: June 2020

Chicks (Gallus gallus domesticus) make a repetitive, high energy ‘distress’ call when stressed. Distress calls are a catch-all response to a range of environmental stressors, and elicit food calling and brooding from hens. Pharmacological and behavioural laboratory studies link expression of this call with negative affective state. As such, there is ana prioriexpectation that distress calls on farms indicate not only physical, but emotional welfare. Using whole-house recordings on 12 commercial broiler flocks (n= 25 090–26 510/flock), we show that early life (day 1–4 of placement) distress call rate can be simply and linearly estimated using a single acoustic parameter: spectral entropy. After filtering to remove low-frequency machinery noise, spectral entropy per minute of recording had a correlation of −0.88 with a manual distress call count. In videos collected on days 1–3, age-specific behavioural correlates of distress calling were identified: calling was prevalent (spectral entropy low) when foraging/drinking were high on day 1, but when chicks exhibited thermoregulatory behaviours or were behaviourally asynchronous thereafter. Crucially, spectral entropy was predictive of important commercial and welfare-relevant measures: low median daily spectral entropy predicted low weight gain and high mortality, not only into the next day, but towards the end of production. Further research is required to identify what triggers, and thus could alleviate, distress calling in broiler chicks. However, within the field of precision livestock farming, this work shows the potential for simple descriptors of the overall acoustic environment to be a novel, tractable and real-time ‘iceberg indicator’ of current and future welfare.
Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2In VitroVirus Neutralization in Convalescent Plasma
Authors: Salazar Eric , Kuchipudi Suresh V. , Christensen Paul A. , Eagar Todd N. , Yi Xin , Zhao Picheng , Jin Zhicheng , Long S. Wesley , Olsen Randall J. , Chen Jian , Castillo Brian , Leveque Christopher , Towers Dalton M. , Lavinder Jason , Gollihar Jimmy D. , Cardona Jose , Ippolito Gregory C. , Nissly Ruth H. , Bird Ian M. , Greenawalt Denver , Rossi Randall M. , Gontu Abinhay , Srinivasan Sreenidhi , Poojary Indira B. , Cattadori Isabella M. , Hudson Peter J. , Joselyn Nicole , Prugar Laura , Huie Kathleen , Herbert Andrew , Bernard David W. , Dye John , Kapur Vivek , Musser James M.
Published: June 2020

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two differentin vitroassays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, andin vitroVN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.
ClipKIT: a multiple sequence alignment-trimming algorithm for accurate phylogenomic inference
Authors: Steenwyk Jacob L. , Buida Thomas J. , Li Yuanning , Shen Xing-Xing , Rokas Antonis
Published: June 2020

Highly divergent sites in multiple sequence alignments, which stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Trimming methods aim to remove these sites before phylogenetic inference, but recent analysis suggests that doing so can worsen inference. We introduce ClipKIT, a trimming method that instead aims to retain phylogenetically-informative sites; phylogenetic inference using ClipKIT-trimmed alignments is accurate, robust, and time-saving.
A Deep Learning Semiparametric Regression for Adjusting Complex Confounding Structures
Authors: Mi Xinlei , Tighe Patrick , Zou Fei , Zou Baiming
Published: June 2020

Deep Treatment Learning (deepTL), a robust yet efficient deep learning-based semiparametric regression approach, is proposed to adjust the complex confounding structures in comparative effectiveness analysis of observational data, e.g. electronic health record (EHR) data, in which complex confounding structures are often embedded. Specifically, we develop a deep learning neural network with a score-based ensembling scheme for flexible function approximation. An improved semiparametric procedure is further developed to enhance the performance of the proposed method under finite sample settings. Comprehensive numerical studies have demonstrated the superior performance of the proposed methods as compared with existing methods, with a remarkably reduced bias and mean squared error in parameter estimates. The proposed research is motivated by a post-surgery pain study, which is also used to illustrate the practical application of deepTL. Finally, an R package, “deepTL”, is developed to implement the proposed method.
Multiplexed imaging of human tuberculosis granulomas uncovers immunoregulatory features conserved across tissue and blood
Authors: McCaffrey Erin F. , Donato Michele , Keren Leeat , Chen Zhenghao , Fitzpatrick Megan , Jojic Vladimir , Delmastro Alea , Greenwald Noah F. , Baranski Alex , Graf William , Bosse Marc , Ramdial Pratista K. , Forgo Erna , Van Valen David , van de Rijn Matt , Bendall Sean C. , Banaei Niaz , Steyn Adrie J.C. , Khatri Purvesh , Angelo Michael
Published: June 2020

Tuberculosis (TB) is an infectious disease caused byMycobacterium tuberculosisthat is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with T-cell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.
Stability of SARS-CoV-2 Phylogenies
Authors: Turakhia Yatish , Thornlow Bryan , Gozashti Landen , Hinrichs Angie S. , Fernandes Jason D. , Haussler David , Corbett-Detig Russell
Published: June 2020

The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse.

Foreword

We wish to thank all groups that responded rapidly by producing these invaluable and essential sequence data. Their contributions have enabled an unprecedented, lightning-fast process of scientific discovery---truly an incredible benefit for humanity and for the scientific community. We emphasize that most lab groups with whom we associate specific suspicious alleles are also those who have produced the most sequence data at a time when it was urgently needed. We commend their efforts. We have already contacted each group and many have updated their sequences. Our goal with this work is not to highlight potential errors, but to understand the impacts of these and other kinds of highly recurrent mutations so as to identify commonalities among the suspicious examples that can improve sequence quality and analysis going forward.
Information Content of Trees: Three-taxon Statements Inference Rules and Dependency
Authors: Rineau Valentin , Zaragüeta René , Bardin Jérémie
Published: June 2020

Abstract

The three-taxon statement is the fundamental unit of rooted trees in Cladistics, stating that for three terminal taxa, two are more related to each other than to a third. Because of their fundamental role in phylogenetics, three-taxon statements are present in methodological research of various disciplines in evolutionary biology, as in consensus methods, supertree methods, species-tree methods, distance metrics, and even phylogenetic reconstruction. However, three-taxon statements methods are subject to important flaws related to information redundancy. We aim to study the behavior of three-taxon statements and the interactions among them in order to enhance their performance in evolutionary studies. We show here how specific interactions between three-taxon statements are responsible of the emergence of redundancy and dependency within trees, and how they can be used for the improvement of weighting procedures. Our proposal is subsequently empirically tested in the supertree framework using simulations. We show that three-taxon statements using fractional weights perform drastically better than classical methods such as MRP or methods using unweighted statements. Our study shows that appropriate fractional weighting of three taxon statements is of critical importance for removing redundancy in any method using three-taxon statements, as in consensus, supertrees, distance metrics, and phylogenetic or biogeographic analyses.
Unravelling lactate-acetate conversion to butyrate by intestinalAnaerobutyricumandAnaerostipesspecies
Authors: Shetty Sudarshan A. , Boeren Sjef , Nam Bui Thi Phuong , Smidt Hauke , de Vos Willem M.
Published: June 2020

The D-and L-forms of lactate are important fermentation metabolites produced by intestinal bacteria but have been found to negatively affect mucosal barrier function and human health. Of interest, both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, includingAnaerobutyricumandAnaerostipesspp. This is a low energy yielding process with a partially unknown pathway inAnaerobutyricumandAnaerostipesspp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We focused onAnaerobutyricum soehngeniiand compared its growth on lactate with that on sucrose and sorbitol. Comparative proteomics revealed a unique active gene cluster that was abundantly expressed when grown on lactate. This active gene cluster,lctABCDEF, encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), along with a nickel-dependent racemase (lctE) and a lactate permease (lctF). Extensive search of available genomes of intestinal bacteria revealed this gene cluster to be highly conserved in onlyAnaerobutyricumandAnaerostipesspp. The present study demonstrates thatA. soehngeniiand several relatedAnaerobutyricumandAnaerostipesspp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.
Vascular Injury Changes Topology of Vessel Network to Adapt to Partition of Blood Flow for New Arteriovenous Specification
Authors: In Baek Kyung , Chang Shyr-Shea , Chang Chih-Chiang , Roustei Mehrdad , Ding Yichen , Wang Yixuan , Chen Justin , O’donnelle Ryan , Chen Hong , Ashby Julianne W. , Mack Julia J. , Xu Xiaolei , Cavallero Susana , Roper Marcus , Hsiai Tzung K.
Published: June 2020

Within vascular networks, wall shear stress (WSS) modulates endothelial cell proliferation and arteriovenous specification. Mechano-responsive signaling pathways enable vessels within a connected network to structurally adapt to properly partition blood flow between different parts of organ systems. Here, we study vascular regeneration in a zebrafish model system, performing tail amputation of the Dorsal Aorta (DA)-Posterior Cardinal Vein (PCV) embryonic circulatory loop (ECL) at 3 days post fertilization (dpf). Following severing the ECL, the topology of the micro-circular network is reorganized to engender local increase in blood flow and peak WSS in the closest Segmental Artery (SeA) to the amputation site. Remodeling of this artery increases its radius, and blood flow. These hemodynamic WSS cues activate post-angiogenic Notch-ephrinb2 signaling to guide network reconnection and restore microcirculation. Gain- and loss-of-function analyses of Notch and ephrinb2 pathways, manipulations of WSS by modulating myocardial contractility and blood viscosity directly implicate that hemodynamically activated post-angiogenic Notch-ephrinb2 signaling guides network reconnection and restore microcirculation. Taken together, amputation of the DA-PCV loop induces changes in microvascular topology to partition blood flow and increase WSS-mediated Notch-ephrinb2 pathway, driving the new DLAV-PCV loop formation for restoring local microcirculation.
Diffuse neural coupling mediates complex network dynamics through the formation of quasi-critical brain states
Authors: Müller Eli J. , Munn Brandon , Shine James M.
Published: June 2020

The biological mechanisms that allow the brain to balance flexibility and integration remain poorly understood. A potential solution to this mystery may lie in a unique aspect of neurobiology, which is that numerous brain systems contain diffuse synaptic connectivity. In this manuscript, we demonstrate that increasing diffuse cortical coupling within a validated biophysical corticothalamic model traverses the system through a quasi-critical regime in which spatial heterogeneities in input noise support transient critical dynamics in distributed sub-regions. We then demonstrate that the presence of quasi-critical states coincides with known signatures of complex, adaptive brain network dynamics. Finally, we demonstrate the presence of similar dynamic signatures in empirical whole brain human neuroimaging data. Together, our results establish that modulating the balance between local and diffuse synaptic coupling in a thalamocortical model subtends the emergence of quasi-critical brain states that act to flexibly transition the brain between unique modes of information processing.
Relative humidity predominantly determines long-term biocrust-forming lichen survival under climate change
Authors: Baldauf Selina , Porada Philipp , Raggio José , Maestre Fernando T. , Tietjen Britta
Published: June 2020

Manipulative experiments show a decrease in dryland biological soil crust cover and altered species composition under climate change. However, the underlying mechanisms are not fully understood, and long-term interacting effects of different drivers are largely unknown due to the short-term nature of the studies conducted so far.

We addressed this gap and successfully parameterized a process-based model for the biocrust-forming lichenDiploschistes diacapsisas a common and globally distributed representative of biocrust communities to quantify how changing atmospheric CO2, temperature, rainfall amount and relative humidity affect its photosynthetic activity and cover. We also mimicked a long-term manipulative climate change experiment to understand the mechanisms underlying observed patterns in the field.

The model reproduced observed experimental findings: warming reduced lichen cover whereas less rainfall had no effect. This warming effect was caused by the associated decrease in relative humidity and non-rainfall water inputs as major water sources for lichens. Warming alone, however, increased cover because higher temperatures promoted photosynthesis during the cool morning hours with high lichen activity. When combined, climate variables showed non-additive effects on lichen cover, and fertilization effects of CO2leveled off with decreasing levels of relative humidity.

Synthesis.Our results show that a decrease in relative humidity, rather than an increase in temperature may be the key factor for the survival of dryland lichens under climate change and that CO2fertilization effects might be offset by a reduction in non-rainfall water inputs in the future. Because of a global trend towards warmer and thus drier air, this will affect lichen-dominated dryland biocrust communities and their role in regulating ecosystem functions, worldwide.
Multiple types of navigational information are independently encoded in the population activities of the dentate gyrus neurons
Authors: Murano Tomoyuki , Nakajima Ryuichi , Nakao Akito , Hirata Nao , Amemori Satoko , Murakami Akira , Kamitani Yukiyasu , Yamamoto Jun , Miyakawa Tsuyoshi
Published: June 2020

The dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca2+imaging in freely moving mice and analysed this activity using machine learning. The activity patterns of populations of DG neurons enabled us to successfully decode position, speed, and motion direction in an open field as well as current and future location in a T-maze, and each individual neuron was diversely and independently tuned to these multiple information types. In αCaMKII heterozygous knockout mice, which present deficits in spatial remote and working memory, the decoding accuracy of position in the open field and future location in the T-maze were selectively reduced. These results suggest that multiple types of information are independently distributed in DG neurons.
Microbiota-derived short chain fatty acids promote Aβ plaque deposition
Authors: Colombo Alessio Vittorio , Sadler Rebecca K. , Llovera Gemma , Singh Vikramjeet , Roth Stefan , Heindl Steffanie , Monasor Laura Sebastian , Verhoeven Aswin , Peters Finn , Parhizkar Samira , Kamp Frits , de Agüero Mercedes Gomez , Macpherson Andrew J. , Winkler Edith , Herms Jochen , Benakis Corinne , Dichgans Martin , Steiner Harald , Giera Martin , Haass Christian , Tahirovic Sabina , Liesz Arthur
Published: June 2020

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome-brain interaction in AD, including the microbial mediators and their cellular targets in the brain, were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as key metabolites along the gut-brain axis in AD. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice was sufficient to increase the Aβ plaque load to levels of conventionally colonized animals. While Aβ generation was only mildly affected, we observed strong microglial activation and upregulation of ApoE upon the SCFA supplementation. Taken together, our results demonstrate that microbiota-derived SCFA are the key mediators along the gut-brain axis resulting in increased microglial activation, ApoE upregulation and Aβ deposition.
Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis
Authors: Liu Yong , Li Chao , Dong Lijin , Li Ping , Chen Xuewei , Fan Rong
Published: June 2020

Background

Colorectal cancer (CRC) is the third most lethal malignancy in the world, wherein colon adenocarcinoma (COAD) is the most prevalent type of CRC. Exploring biomarkers is important for the diagnosis, treatment, and prevention of COAD.

Methods

We used GEO2R and Venn online software for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software, real-time PCR and immunohistochemistry.

Results

In this study, we screened 323 common differentially expressed genes from four GSE datasets. Furthermore, four hub genes were selected for survival correlation analysis and expression level verification, three of which were shown to be statistically significant.

Conclusion

Our study suggests that SERPINE1, SPP1 and TIMP1 may be biomarkers closely related to the prognosis of CRC patients.