bluuebunny/crossref_metadata_2025 huggingface dataset:
Eating disorders in adolescent boys and young men: an update
Authors: Nagata Jason M. , Ganson Kyle T. , Murray Stuart B.
Published: June 2020

Purpose of review

To review the recent literature on eating disorders and disordered eating behaviors among adolescent boys and young men, including epidemiology, assessment, medical complications, treatment outcomes, and special populations.

Recent findings

Body image concerns in men may involve muscularity, and muscle-enhancing goals and behaviors are common among adolescent boys and young men. Recent measures, such as the Muscularity Oriented Eating Test (MOET) have been developed and validated to assess for muscularity-oriented disordered eating. Medical complications of eating disorders can affect all organ systems in male populations. Eating disorders treatment guidance may lack specificity to boys and men, leading to worse treatment outcomes in these population. Male populations that may have elevated risk of eating disorders and disordered eating behaviors include athletes and racial/ethnic, sexual, and gender minorities.

Eating disorders and disordered eating behaviors in boys and men may present differently than in girls and women, particularly with muscularity-oriented disordered eating. Treatment of eating disorders in boys and men may be adapted to address their unique concerns.
Obesity and insulin resistance in children
Authors: Tagi Veronica Maria , Chiarelli Francesco
Published: June 2020

Purpose of review

It is well known that obesity represents the main modifiable risk factor for insulin resistance in children and adolescents; obesity-induced insulin resistance in children is the most important risk factor for developing cardiovascular diseases and type 2 diabetes in adulthood. The mechanisms through which obesity causes insulin resistance are complex and not completely known to date.

Recent findings

In children, global adiposity is the main factor determining insulin resistance. Excessive fatty acids play a determinant role in the pathogenesis of insulin resistance in obese children, inducing an increased production of acetyl-CoA in the liver and enhancing inflammation in adipose tissue. The aetiology of insulin resistance in polycystic ovary syndrome is multifactorial and still debated.

The aim of this review is to present an updated frame and new insights of the numerous pathways involved in the development of insulin resistance in obese patients, focusing on the peculiarities of children and adolescents. Improving the knowledge of mechanisms through which obesity leads to insulin resistance is fundamental in order to recommend particular follow-up and possible treatment to specific categories of obese children and adolescents.
Precision transplant pathology
Authors: Wood-Trageser Michelle A. , Xu Qinyong , Zeevi Adriana , Randhawa Parmjeet , Lesniak Drew , Demetris Anthony J.
Published: June 2020

Purpose of review

Transplant pathology contributes substantially to personalized treatment of organ allograft recipients. Rapidly advancing next-generation human leukocyte antigen (HLA) sequencing and pathology are enhancing the abilities to improve donor/recipient matching and allograft monitoring.

Recent findings

The present review summarizes the workflow of a prototypical patient through a pathology practice, highlighting histocompatibility assessment and pathologic review of tissues as areas that are evolving to incorporate next-generation technologies while emphasizing critical needs of the field.

Successful organ transplantation starts with the most precise pratical donor–recipient histocompatibility matching. Next-generation sequencing provides the highest resolution donor–recipient matching and enables eplet mismatch scores and more precise monitoring of donor-specific antibodies (DSAs) that may arise after transplant. Multiplex labeling combined with hand-crafted machine learning is transforming traditional histopathology. The combination of traditional blood/body fluid laboratory tests, eplet and DSA analysis, traditional and next-generation histopathology, and -omics-based platforms enables risk stratification and identification of early subclinical molecular-based changes that precede a decline in allograft function. Needs include software integration of data derived from diverse platforms that can render the most accurate assessment of allograft health and needs for immunosuppression adjustments.
Does Intense Sexually Transmitted Infection Screening Cause or Prevent Antimicrobial Resistance in Sexually Transmitted Infections? It Depends on One's Underlying Epistemology. A Viewpoint
Authors: Kenyon Chris
Published: June 2020

Certain authors argue that intensive sexually transmitted infection (STI) screening is a crucial way to reduce STI prevalence and prevent the emergence and spread of antimicrobial resistance (AMR) in STIs. Others argue the opposite: intense screening in high STI prevalence populations has little effect on prevalence and is likely to select for AMR. In this viewpoint, I argue that these radical differences in outlook stem, in part, from different conceptual frameworks of the determinants of STI prevalence and AMR. In the absence of strong evidence from randomized controlled trials, our brains interpret the weaker evidence from other sources in different ways, depending on our underlying epistemologies. To illustrate the argument, I contrast a predominantly biomedical individualist conceptual framework with a more ecological conceptual framework. I argue that if one's conceptual framework is based in biomedical individualism, then one is more likely to think that screening reduces STI prevalence and less likely to appreciate the connection between screening, antimicrobial exposure, and AMR than perspectives grounded in ecological frameworks.
Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics
Authors: Raghavan Shyam S. , Saleem Atif , Wang Jennifer Y. , Rieger Kerri E. , Brown Ryanne A. , Novoa Roberto A.
Published: June 2020

Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the β-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer–binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with β-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of β-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and β-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with β-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.
Progress in Cancer Control in Maryland: 1985-2015
Authors: Brun Victoria , Platz Elizabeth A. , Nguyen Thuy , Valek Sara , Gugel Donna , Warmkessel Karen , Kanarek Norma F.
Published: June 2020

Purpose:

Maryland historically had a high cancer burden, which prompted the implementation of aggressive cancer control strategies. We examined the status of cancer in Maryland and work under the current and previous editions of the MD Comprehensive Cancer Control Plan.

Methods:

We examined the prevalence of cancer mortality, cancer incidence, and cancer-related behaviors in Maryland and the United States from 1985 to 2015 using publicly available data in the US Cancer Control PLANET, CDC WONDER, and Behavioral Risk Factor Surveillance System portals. We estimated the average annual cancer deaths avoided by triangulation.

Results:

In 1983-1987, Maryland had the highest age-adjusted cancer mortality rate of all 50 states, second only to Washington, District of Columbia. Today (2011-2015), Maryland's age-adjusted cancer mortality rate ranks 31st. Overall cancer mortality rates have declined 1.9% annually from 1990 to 2015, avoiding nearly 60 000 deaths over 3 decades. While the prevalence of healthy cancer-related behaviors in Maryland was qualitatively similar or higher than that of the United States in 2015, Maryland's 5-year (2011-2015) cancer incidence rate was significantly greater than that of the United States.

Conclusions:

Maryland's 30-year cancer mortality declines have outpaced other states. However, a reduction in mortality while incidence rates remain high indicates a need for enhanced focus on primary prevention.
A Required, Combined Neurology-Physical Medicine and Rehabilitation Clerkship Addresses Clinical and Health Systems Knowledge Gaps for Fourth-Year Medical Students
Authors: Curtis Caitrin M. , Eubanks James E. , Charles Stephen C. , Boyer Philip J. , Harrell Kelly M. , Markandaya Manjunath , Lawson Luan E. , Norbury John W.
Published: June 2020

This study evaluated the impact of a 4-wk mandatory neurology-physical medicine and rehabilitation advanced-core clerkship for fourth-year medical students. The combined clerkship encouraged an interdisciplinary and function-based approach to the management of common neurologic, musculoskeletal, and pain complaints. Seventy-three fourth-year medical students participated in the rotation over 1 yr. A survey assessing knowledge and skill set topics was conducted before and after the clerkship. Qualitative feedback regarding the rotation was provided by the students and analyzed. Significant gaps in knowledge and skill sets were identified before the clerkship and successfully addressed by combined teaching modalities. These data demonstrate that an integrated neurology-physical medicine and rehabilitation clerkship can improve students’ confidence in multiple domains. Integrating physical medicine and rehabilitation into core clerkships at other medical schools may provide an avenue to address curriculum gaps.
A Quality Improvement Initiative to Improve the Administration of Systemic Corticosteroids in the Pediatric Emergency Department
Authors: Sneller Hannah , Keenan Kaitlin , Hoppa Eric
Published: June 2020

Introduction:

Timely administration of corticosteroids improves asthma care in the pediatric emergency department (ED). Using the Model for Improvement, we aimed to decrease time to delivery of corticosteroids in patients presenting to the ED with an acute asthma exacerbation.

Methods:

This is a single-center, prospective, multidisciplinary quality improvement (QI) project targeting ED patients 1−18 years of age with an acute asthma exacerbation. We collected 5 months of baseline data from the arrival time of an ED patient with an asthma exacerbation with a Modified Pulmonary Index Score ≥5 to the time of administration of corticosteroids. A quality improvement project was launched in October 2017 involving multiple Plan-Do-Study-Act ramps. Improvement interventions continued for 9 months through June 2018, including reeducation of residents and nurses in the ED asthma order set and nursing treatment protocols, respectively, and changes to the electronic health record. Data were tacked for 15 additional months until September 2019. To promote the use of the nursing treatment protocol, we utilized real-time improvement feedback and continuing nursing education.

Results:

The mean percentage of patients receiving steroids within 60 minutes of arrival improved from 59.3% to 84.3% over the first 5 months. The mean time to the administration of steroids within 60 minutes of arrival improved from 71.4 to 48.1 minutes. There was no increase in ED return rates.

Conclusions:

Our project improved the percentage of patients with acute asthma exacerbations receiving steroids within 60 minutes of ED arrival and mean time to administration of steroids. We sustained improvement for 18 months after the implementation of our QI interventions.
Outcomes After Being Lost to Follow-up Differ for Pregnant and Postpartum Women When Compared With the General HIV Treatment Population in Rural South Africa
Authors: Etoori David , Gomez-Olive Francesc Xavier , Reniers Georges , Rice Brian , Renju Jenny , Kabudula Chodziwadziwa W. , Wringe Alison
Published: June 2020

Background:

Undetermined attrition prohibits full understanding of the coverage and effectiveness of HIV programs. Outcomes following loss to follow-up (LTFU) among antiretroviral therapy (ART) patients may differ according to their reasons for ART initiation.

Setting:

We compare the true outcomes of adult patients previously identified as LTFU by reason for ART initiation in 8 health facilities in north eastern South Africa.

Methods:

Adult HIV patient records were linked to health and demographic surveillance system (HDSS) data from 2014 to 2017. Outcomes of adults categorized as LTFU (>90 days late for the last scheduled clinic visit) were determined through clinic and routine tracing record reviews, consultation of HDSS data, and supplementary tracing. We calculated the proportion of patients per outcome category and performed competing risk survival analysis to estimate the cumulative incidence of death, transfer, migration, ART interruption, and re-engagement following LTFU.

Results:

Of 895/1017 patients LTFU with an outcome ascertained, 120 (13.4%) had died, 225 (25.1%) re-engaged, 50 (5.6%) migrated out of the HDSS, 75 (8.4%) were alive and not on treatment, and 315 (35.1%) transferred their treatment. These outcomes varied by sex and pregnancy status at ART initiation. Mortality was less likely among pregnant women, patients with higher baseline CD4, and more likely among older patients.

Conclusions:

Patient survival and transfers to other facilities are considerably higher than those suggested in earlier studies. Outcomes differ for women who were pregnant or postpartum when initiating ART, with this population less likely to have died and more likely to have migrated.
Ultrasound Vibroelastography for Evaluation of Secondary Extremity Lymphedema
Authors: Bustos Samyd S. , Zhou Boran , Huang Tony C. T. , Shao Juntao , Ciudad Pedro , Forte Antonio J. , Zhang Xiaoming , Manrique Oscar J.
Published: June 2020

Background

Lymphedema treatment is an ongoing challenge. It impacts quality of life due to pain, loss of range of motion of the extremity, and repeated episodes of cellulitis. Different modalities have been used to evaluate lymphedema; some are more error-prone and some are more invasive. However, these measurements are poorly standardized, and intrarater and interrater reliabilities are difficult to achieve. This pilot study aims to assess the feasibility of ultrasound vibroelastography for assessing patients with extremity lymphedema via measuring shear wave speeds of subcutaneous tissues.

Methods

Patients with clinical and lymphoscintigraphic diagnosis of secondary lymphedema in the extremities without prior surgical treatment were included. A 0.1-s harmonic vibration was generated at three frequencies (100, 150, and 200 Hz) by the indenter of a handheld shaker on the skin. An ultrasound probe was used for noninvasively capturing of wave propagation in the subcutaneous tissue. Wave speeds were measured in the subcutaneous tissues of both the control and affected extremities.

Results

A total of 11 female patients with secondary lymphedema in the extremities were enrolled in this study. The magnitudes of the wave speeds of the region of interest in the subcutaneous tissue at lymphedema sites in the upper extremity (3.9 ± 0.17 m/s, 5.96 ± 0.67 m/s, and 7.41 ± 1.09 m/s) were statistically higher than those of the control sites (2.1 ± 0.27 m/s, 2.93 ± 0.57 m/s, and 3.56 ± 0.76 m/s) at 100, 150, and 200 Hz (P < 0.05), and at 100 and 200 Hz (P < 0.05) between lymphedema (4.33 ± 0.35 m/s, 4.17 ± 1.00 m/s, and 4.56 ± 0.37 m/s) and controls sites (2.48 ± 0.43 m/s, 2.77 ± 0.55 m/s, and 3.06 ± 0.29 m/s) in the lower extremity.

Conclusions

These preliminary data suggest that ultrasound vibroelastography may be useful in the evaluation of secondary lymphedema and can be a valuable tool to noninvasively track treatment progress.
Telemedicine for Surgical Consultations – Pandemic Response or Here to Stay?
Authors: Sorensen Meredith J. , Bessen Sarah , Danford Julia , Fleischer Christina , Wong Sandra L.
Published: June 2020

Objective:

This study aims to determine the public's perception of telemedicine surgical consultations, during the COVID-19 pandemic and beyond.

Summary Background Data:

With rapid expansion and uptake of telemedicine during the pandemic, many have posited that virtual visits will endure even as in-person visits are reinstated. The public's perception of telemedicine for an initial surgical consultation has not been previously studied.

Methods:

A 43-question survey assessed respondents’ attitudes toward telemedicine for initial consultations with surgeons, both in the context of COVID-19 and during “normal circumstances.” Participants were recruited through Amazon Mechanical Turk, an online crowd-sourcing marketplace.

Results:

Based on 1827 analyzable responses, we found that a majority (86%) of respondents reported being satisfied (either extremely or somewhat) with telemedicine encounters. Interestingly, preference for in-person versus virtual surgical consultation reflected access to care, with preference for telemedicine decreasing from 72% to 33% when COVID-related social distancing ends. Preferences for virtual visits decreased with increasing complexity of the surgical intervention, even during the pandemic. A majority felt that “establishing trust and comfort” was best accomplished in person, and the vast majority felt it was important to meet their surgeons before the day of surgery.

Conclusions:

The public views telemedicine as an acceptable substitute for in-person visits, especially during the pandemic. However, it seems that an in-person interaction is still preferred when possible for surgical consultations. If telemedicine services are to persist beyond social distancing, further exploration of its impact on the patient-surgeon relationship will be needed.
Effect of scanning speed on texture-elicited vibrations
Authors: Greenspon Charles M. , McLellan Kristine R. , Lieber Justin D. , Bensmaia Sliman J.
Published: June 2020

To sense the texture of a surface, we run our fingers across it, which leads to the elicitation of skin vibrations that depend both on the surface and on exploratory parameters, particularly scanning speed. The transduction and processing of these vibrations mediate the ability to discern fine surface features. The objective of the present study is to characterize the effect of changes in scanning speed on texture-elicited vibrations to better understand how the exploratory movements shape the neuronal representation of texture. To this end, we scanned a variety of textures across the fingertip of human participants at a variety of speeds (10–160 mm s−1) while measuring the resulting vibrations using a laser Doppler vibrometer. First, we found that the intensity of the vibrations—as indexed by root-mean-square velocity—increases with speed but that the skin displacement remains constant. Second, we found that the frequency composition of the vibrations shifts systematically to higher frequencies with increases in scanning speed. Finally, we show that the speed-dependent shift in frequency composition accounts for the speed-dependent change in intensity.
Distortions of political bias in crowdsourced misinformation flagging
Authors: Coscia Michele , Rossi Luca
Published: June 2020

Many people view news on social media, yet the production of news items online has come under fire because of the common spreading of misinformation. Social media platforms police their content in various ways. Primarily they rely on crowdsourced ‘flags’: users signal to the platform that a specific news item might be misleading and, if they raise enough of them, the item will be fact-checked. However, real-world data show that the most flagged news sources are also the most popular and—supposedly—reliable ones. In this paper, we show that this phenomenon can be explained by the unreasonable assumptions that current content policing strategies make about how the online social media environment is shaped. The most realistic assumption is that confirmation bias will prevent a user from flagging a news item if they share the same political bias as the news source producing it. We show, via agent-based simulations, that a model reproducing our current understanding of the social media environment will necessarily result in the most neutral and accurate sources receiving most flags.
Reprograming of epigenetic mechanisms controlling host insect immunity and development in response to egg-laying by a parasitoid wasp
Authors: Özbek Rabia , Mukherjee Krishnendu , Uçkan Fevzi , Vilcinskas Andreas
Published: June 2020

Parasitoids are insects that use other insects as hosts. They sabotage host cellular and humoral defences to promote the survival of their offspring by injecting viruses and venoms along with their eggs. Many pathogens and parasites disrupt host epigenetic mechanisms to overcome immune system defences, and we hypothesized that parasitoids may use the same strategy. We used the ichneumon waspPimpla turionellaeas a model idiobiont parasitoid to test this hypothesis, with pupae of the greater wax mothGalleria mellonellaas the host. We found that parasitoid infestation involves the suppression of host immunity-related effector genes and the modulation of host genes involved in developmental hormone signalling. The transcriptional reprogramming of host genes following the injection of parasitoid eggs was associated with changes in host epigenetic mechanisms. The introduction of parasitoids resulted in a transient decrease in host global DNA methylation and the modulation of acetylation ratios for specific histones. Genes encoding regulators of histone acetylation and deacetylation were mostly downregulated in the parasitized pupae, suggesting that parasitoids can suppress host transcription. We also detected a strong parasitoid-specific effect on host microRNAs regulating gene expression at the post-transcriptional level. Our data therefore support the hypothesis that parasitoids may favour the survival of their offspring by interfering with host epigenetic mechanisms to suppress the immune system and disrupt development.
Depth moderates loss of marine foundation species after an extreme marine heatwave: could deep temperate reefs act as a refuge?
Authors: Giraldo-Ospina Ana , Kendrick Gary A. , Hovey Renae K.
Published: June 2020

Marine heatwaves (MHWs) have been documented around the world, causing widespread mortality of numerous benthic species on shallow reefs (less than 15 m depth). Deeper habitats are hypothesized to be a potential refuge from environmental extremes, though we have little understanding of the response of deeper benthic communities to MHWs. Here, we show how increasing depth moderates the response of seaweed- and coral-dominated benthic communities to an extreme MHW across a subtropical–temperate biogeographical transition zone. Benthic community composition and key habitat-building species were characterized across three depths (15, 25 and 40 m) before and several times after the 2011 Western Australian MHW to assess resistance during and recovery after the heatwave. We found high natural variability in benthic community composition along the biogeographic transition zone and across depths with a clear shift in the composition after the MHW in shallow (15 m) sites but a lot less in deeper communities (40 m). Most importantly, key habitat-building seaweeds such as
Ecklonia radiata
and
Syctothalia dorycarpa
which had catastrophic losses on shallow reefs, remained and were less affected in deeper communities. Evidently, deep reefs have the potential to act as a refuge during MHWs for the foundation species of shallow reefs in this region.
Ant cuticular hydrocarbons are heritable and associated with variation in colony productivity
Authors: Walsh Justin , Pontieri Luigi , d'Ettorre Patrizia , Linksvayer Timothy A.
Published: June 2020

In social insects, cuticular hydrocarbons function in nest-mate recognition and also provide a waxy barrier against desiccation, but basic evolutionary features, including the heritability of hydrocarbon profiles and how they are shaped by natural selection are largely unknown. We used a new pharaoh ant (Monomorium pharaonis) laboratory mapping population to estimate the heritability of individual cuticular hydrocarbons, genetic correlations between hydrocarbons, and fitness consequences of phenotypic variation in the hydrocarbons. Individual hydrocarbons had low to moderate estimated heritability, indicating that some compounds provide more information about genetic relatedness and can also better respond to natural selection. Strong genetic correlations between compounds are likely to constrain independent evolutionary trajectories, which is expected, given that many hydrocarbons share biosynthetic pathways. Variation in cuticular hydrocarbons was associated with variation in colony productivity, with some hydrocarbons experiencing strong directional selection. Altogether, this study builds on our knowledge of the genetic architecture of the social insect hydrocarbon profile and indicates that hydrocarbon variation is shaped by natural selection.
Extended parenting and the evolution of cognition
Authors: Uomini Natalie , Fairlie Joanna , Gray Russell D. , Griesser Michael
Published: June 2020

Traditional attempts to understand the evolution of human cognition compare humans with other primates. This research showed that relative brain size covaries with cognitive skills, while adaptations that buffer the developmental and energetic costs of large brains (e.g. allomaternal care), and ecological or social benefits of cognitive abilities, are critical for their evolution. To understand the drivers of cognitive adaptations, it is profitable to consider distant lineages with convergently evolved cognitions. Here, we examine the facilitators of cognitive evolution in corvid birds, where some species display cultural learning, with an emphasis on family life. We propose that extended parenting (protracted parent–offspring association) is pivotal in the evolution of cognition: it combines critical life-history, social and ecological conditions allowing for the development and maintenance of cognitive skillsets that confer fitness benefits to individuals. This novel hypothesis complements the extended childhood idea by considering the parents' role in juvenile development. Using phylogenetic comparative analyses, we show that corvids have larger body sizes, longer development times, extended parenting and larger relative brain sizes than other passerines. Case studies from two corvid species with different ecologies and social systems highlight the critical role of life-history features on juveniles’ cognitive development: extended parenting provides a safe haven, access to tolerant role models, reliable learning opportunities and food, resulting in higher survival. The benefits of extended juvenile learning periods, over evolutionary time, lead to selection for expanded cognitive skillsets. Similarly, in our ancestors, cooperative breeding and increased group sizes facilitated learning and teaching. Our analyses highlight the critical role of life-history, ecological and social factors that underlie both extended parenting and expanded cognitive skillsets.

This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.
COVID19 Real-World Data for the US and Lessons to Re-Open Business
Authors: Goldschmidt-Clermont Pascal J.
Published: June 2020

In March of 2020, the COVID19 pandemic had expanded to the United States of America (US). Companies designated as “essential” for the US had to maintain productivity in spite of the growing threat created by the SARS-CoV-2 virus. With this report, we present the response of one such company, the Lennar Corporation, a major homebuilder in the US. Within days, Lennar had implemented a morning health check via its enterprise resource planning system, to identify associates (employees) who were sick, or not in their “usual state of health”. With this survey, Lennar was able to ensure that no one sick would show up to work, and instead, would self-quarantine at home. Furthermore, with thorough contact tracking, associates exposed to COVID19 patients (suspected or RT-PCR test-confirmed), were also asked to self-quarantine. This survey, in addition to other safety measures, such as an overhaul of the company with nearly 50% of the company working from home, prolific communication, and many more measures, Lennar was able to function safely for its associates and successfully as an enterprise. The data that we present here are “real world data” collected in the context of working throughout a dreadful pandemic, and the lessons learned could be helpful to other companies that are preparing to return to work.
Impaired Th17 immunity in recurrent C. difficile infection is ameliorated by fecal microbial transplantation
Authors: Cook Laura , Rees William D. , Wong May Q. , Wang Xiaojiao , Peters Hannah , Oliveira Laura , Lau Torey , Mah Regan , Bressler Brian , Gomez Rebecca , Chow I-Ting , James Eddie A. , Kwok William W. , Levings Megan K. , Steiner Theodore S.
Published: June 2020

Background & Aims

Clostridioides difficile is a leading cause of infectious diarrhea and an urgent antimicrobial resistant threat. Symptoms are caused by its toxins, TcdA and TcdB, with many patients developing recurrent C. difficile infection (CDI), requiring fecal microbiota transplant (FMT). Antibody levels have not been useful in predicting patient outcomes, which is an unmet need. We aimed to characterize T cell-mediated immunity to C. difficile toxins and assess how these responses were affected by FMT.

Methods

We obtained blood samples from patients with newly acquired CDI, recurrent CDI (with a subset receiving FMT), inflammatory bowel disease with no history of CDI, and healthy individuals (controls). Toxin-specific CD4+ T cell responses were analysed using a whole blood flow cytometry antigen-induced marker assay. Serum antibodies were measured by ELISA. Tetramer guided mapping was used to identify HLA-II-restricted TcdB epitopes and DNA was extracted from TcdB-specific CD4+ T cells for TCR repertoire analysis by Sanger sequencing.

Results

CD4+ T cell responses to C. difficile toxins were functionally diverse. Compared to controls, individuals with CDI, or inflammatory bowel disease had significantly higher frequencies of TcdB-specific CD4+ T cells. Subjects with recurrent CDI had reduced proportions of TcdB-specific CD4+ Th17 cells, FMT reversed this deficit and increased toxin-specific antibody production.

Conclusions

These data suggest that effective T cell immunity to C. difficile requires the development of Th17 cells. In addition, they show that an unknown aspect of the therapeutic effect of FMT may be enhanced T and B cell-mediated immunity to TcdB.

GRAPHICAL ABSTRACT
Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes
Authors: Takahashi Takehiro , Wong Patrick , Ellingson Mallory K. , Lucas Carolina , Klein Jon , Israelow Benjamin , Silva Julio , Oh Ji Eun , Mao Tianyang , Tokuyama Maria , Lu Peiwen , Venkataraman Arvind , Park Annsea , Liu Feimei , Meir Amit , Sun Jonathan , Wang Eric Y. , Wyllie Anne L. , Vogels Chantal B.F. , Earnest Rebecca , Lapidus Sarah , Ott Isabel M. , Moore Adam J. , Casanovas-Massana Arnau , Cruz Charles Dela , Fournier John B. , Odio Camila D. , Farhadian Shelli , Grubaugh Nathan D. , Schulz Wade L. , Ko Albert I. , Ring Aaron M. , Omer Saad B. , Iwasaki Akiko ,   the Yale IMPACT research team.
Published: June 2020

A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1-4. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with mild to moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines and chemokines including IL-8, IL-18, and CCL5, along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients’ age and was predictive of worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide important basis for the development of sex-based approach to the treatment and care of men and women with COVID-19.
Inference and validation of an integrated regulatory network of autism
Authors: Ganji Maedeh , Emadi-Baygi Modjtaba , Malek Maryam , Nikpour Parvaneh
Published: June 2020

Autism is a complex neurodevelopmental disorder. Functional roles of several non-coding transcripts including long noncoding RNAs (lncRNAs) have been shown to influence the pathobiology of autism. We hypothesized that there are more autism-associated lncRNAs to be discovered. Here, we utilized a systems biology approach to identify novel lncRNAs that might play a role in the molecular pathogenesis of autism. Based on the data provided by the Simons Foundation Autism Research Initiative (SFARI), a three-component regulatory network comprising mRNAs, microRNAs (miRNAs) and lncRNAs was constructed. Functional enrichment analysis was performed to identify molecular pathways potentially mediated by components of the network. The potential association of four candidate lncRNAs with autism was investigated experimentally by developing and verifying a valproic acid (VPA)-exposed mouse model of autism. We composed a network of 33 mRNA, 25 miRNA and 4 lncRNA nodes associated with neurologically-relevant pathways and functions. We then verified the differential expression of four candidate lncRNAs:Gm10033,1500011B03Rik,A930005H10RikandGas5in the brain of VPA-exposed mice. We furthermore identified a novel splice variant ofGm10033, designated asGm10033-ΔEx2, which was expressed in various mouse tissues. The integrative approach, we utilized, combines the analysis of a three-component regulatory network with experimental validation of targets in an animal model of autism. As a result of the analysis, we prioritized a set of candidate autism-associated lncRNAs. These links add to the common understanding of the molecular and cellular mechanisms that are involved in disease etiology, specifically in the autism.
Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences
Authors: Priedigkeit Nolan , Ding Kai , Horne William , Kolls Jay K. , Du Tian , Lucas Peter C. , Blohmer Jens-Uwe , Denkert Carsten , Machleidt Anna , Ingold-Heppner Barbara , Oesterreich Steffi , Lee Adrian V.
Published: June 2020

Endocrine therapy resistance is a hallmark of advanced estrogen receptor (ER) positive breast cancer. In this study, we performed DNA/RNA hybrid-capture sequencing on 12 locoregional recurrences after long-term estrogen-deprivation along with each tumor’s matched primary. Despite being up to 7 years removed from the primary lesion, most recurrences harbored similar intrinsic transcriptional and copy number profiles. Only two genes,AKAP9andKMT2C, were found to have single nucleotide variant (SNV) enrichments in more than one recurrence. Enriched mutations in single cases included SNVs within transcriptional regulators such asARID1A, TP53, FOXO1, BRD1, NCOA1andNCOR2with one local recurrence gaining threePIK3CAmutations. In contrast to DNA-level changes, we discovered recurrent outlier mRNA expression alterations were common—including outlier gains inTP63(n=5 cases [42%]),NTRK3[n=5 [42%]),NTRK2(n=4 [33%]),PAX3(n=4 [33%]),FGFR4(n=3 [25%]) andTERT(n=3 [25%]). Recurrent losses involvedESR1(n=5 [42%]),RELN(n=5 [42%]),SFRP4(n=4 [33%]) andFOSB(n=4 [33%]).ESR1-depleted recurrences harbored shared transcriptional remodeling events including upregulation ofPROM1and other basal cancer markers. Taken together, this study defines acquired genomic changes in long-term, estrogen-deprived disease, highlights longitudinal RNA-profiling and identifies a common endocrine-resistant breast cancer subtype with basal-like transcriptional reprogramming.
Stable tug-of-war between kinesin-1 and cytoplasmic dynein upon different ATP and roadblock concentrations
Authors: Monzon Gina A. , Scharrel Lara , DSouza Ashwin , Santen Ludger , Diez Stefan
Published: June 2020

The maintenance of intracellular processes like organelle transport and cell division depend on bidirectional movement along microtubules. These processes typically require kinesin and dynein motor proteins which move with opposite directionality. Because both types of motors are often simultaneously bound to the cargo, regulatory mechanisms are required to ensure controlled directional transport. Recently, it has been shown that parameters like mechanical motor activation, ATP concentration and roadblocks on the microtubule surface differentially influence the activity of kinesin and dynein motors in distinct manners. However, how these parameters affect bidirectional transport systems has not been studied. Here, we investigate the regulatory influence of these three parameter using in vitro gliding motility assays and stochastic simulations. We find that the number of active kinesin and dynein motors determines the transport direction and velocity, but that variations in ATP concentration and roadblock density have no significant effect. Thus, factors influencing the force balance between opposite motors appear to be important, whereas the detailed stepping kinetics and bypassing capabilities of the motors have only little effect.
Ecology-guided prediction of cross-feeding interactions in the human gut microbiome
Authors: Goyal Akshit , Wang Tong , Dubinkina Veronika , Maslov Sergei
Published: June 2020

Understanding a complex microbial ecosystem such as the human gut microbiome requires information about both microbial species and the metabolites they produce and secrete. These metabolites are exchanged via a large network of cross-feeding interactions, and are crucial for predicting the functional state of the microbiome. However, till date, we only have information for a part of this network, limited by experimental throughput. Here, we propose an ecology-based computational method, GutCP, using which we predict hundreds of new experimentally untested cross-feeding interactions in the human gut microbiome. GutCP utilizes a mechanistic model of the gut microbiome with the explicit exchange of metabolites and their effects on the growth of microbial species. To build GutCP, we combined metagenomic and metabolomic measurements from the gut microbiome with optimization techniques from machine learning. Close to 65% of the cross-feeding interactions predicted by GutCP are supported by evidence from genome annotation; we provide these predictions for experimentally testing. Our method has the potential to greatly improve existing models of the human gut microbiome, as well as our ability to predict the metabolic profile of the gut.
Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses
Authors: Schmidt Fabian , Weisblum Yiska , Muecksch Frauke , Hoffmann Hans-Heinrich , Michailidis Eleftherios , Lorenzi Julio C. C. , Mendoza Pilar , Rutkowska Magdalena , Bednarski Eva , Gaebler Christian , Agudelo Marianna , Cho Alice , Wang Zijun , Gazumyan Anna , Cipolla Melissa , Caskey Marina , Robbiani Davide F. , Nussenzweig Michel C. , Rice Charles M. , Hatziioannou Theodora , Bieniasz Paul D.
Published: June 2020

The emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARS-CoV-2-specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.
The Identification of A ROS Responsive Motif that is regulated by snoRNP inArabidopsis
Authors: Cheng Han , Sun Mingan , Guo Dianjing
Published: June 2020

A GGGCC motif (site II like motif) was identified from the upstream sequences of reactive oxygen species (ROS) and light induced genes in Arabidopsis. This motif is highly enriched within the −50 to −250 bp region of the induced genes, and it is also specifically distributed in the same region in mouse and human genome. EMSA experiments revealed that several nuclear factors (NFs) bind to this motif, and the binding activities altered under H2O2treatment. Two C/D family snoRNP proteins, namely fibrillarin 2 and NOP56, were identified from the site II like motif binding NFs. Several C/D family snoRNA, including R63, U24a and Z15, were also cloned from the motif binding NFs. These data suggest new regulatory roles of snoRNP in Arabidopsis.
SARS-CoV-2 virus and antibodies in front-line Health Care Workers in an acute hospital in London: preliminary results from a longitudinal study
Authors: Houlihan Catherine F , Vora Nina , Byrne Thomas , Lewer Dan , Heaney Judith , Moore David A. , Matthews Rebecca , Adam Sajida , Enfield Louise , Severn Abigail , McBride Angela , Spyer Moira , Beale Rupert , Cherepanov Peter , Gaertner Kathleen , Edwards Sarah , Shahmanesh Maryam , Ng Kevin , Faulkner Nikhil , Cornish Georgina , Walker Naomi , Michie Susan , Manley Ed , Lorencatto Fabiana , Gilson Richard , Gandhi Sonia , Gamblin Steve , Kassiotis George , McCoy Laura E , Swanton Charles , Hayward Andrew , Nastouli Eleni
Published: June 2020

Background

Although SARS-CoV-2 infection in Healthcare Workers (HCWs) is a public health concern, there is little description of their longitudinal antibody response in the presence or absence of SARS-CoV-2 and symptoms. We followed HCWs in an acute London hospital to measure seroconversion and RNA detection at the peak of the pandemic.

Methods

We enrolled 200 patient-facing HCWs between 26 March and 8 April 2020 and collected twice-weekly self-administered nose and throat swabs, symptom data and monthly blood samples. Swabs were tested for SARS-CoV-2 by PCR, and serum for antibodies to spike protein by ELISA and flow cytometry.

Findings

During the first month, 42/200 (21%) HCWs were PCR positive in at least one nose and throat swab. Only 8/42 HCW (19%) who were PCR positive during the study period had symptoms that met current case definition. Of 181 HCWs who provided enrollment and follow-up blood samples, 82/181 (45.3%) were seropositive. In 33 HCWs who had positive serology at baseline but were PCR negative, 32 remained PCR negative. One HCW had a PCR positive swab six days after enrollment, likely representing waning infection.

Conclusion

The high seropositivity and RNA detection in these front-line HCWs brings policies to protect staff and patients into acute focus. Our findings have implications for planning for the ‘second wave’ and for vaccination campaigns in similar settings. The evidence of asymptomatic SARS-CoV-2 infection indicates that asymptomatic HCW surveillance is essential, while our study sets the foundations to answer pertinent questions around the duration of protective immune response and the risk of re-infection.
Long identical sequences found in multiple bacterial genomes reveal frequent and widespread exchange of genetic material between distant species
Authors: Sheinman Michael , Arkhipova Ksenia , Arndt Peter F. , Dutilh Bas E. , Hermsen Rutger , Massip Florian
Published: June 2020

Horizontal transfer of genomic elements is an essential force that shapes microbial genome evolution. Horizontal Gene Transfer (HGT) occurs via various mechanisms and has been studied in detail for a variety of systems. However, a coarse-grained, global picture of HGT in the microbial world is still missing. One reason is the difficulty to process large amounts of genomic microbial data to find and characterise HGT events, especially for highly distant organisms. Here, we exploit the fact that HGT between distant species creates long identical DNA sequences in genomes of distant species, which can be found efficiently using alignment-free methods. We analysed over 90 000 bacterial genomes and thus identified over 100 000 events of HGT. We further developed a mathematical model to analyse the statistical properties of those long exact matches and thus estimate the transfer rate between any pair of taxa. Our results demonstrate that long-distance gene exchange (across phyla) is very frequent, as more than 8% of the bacterial genomes analysed have been involved in at least one such event. Finally, we confirm that the function of the transferred sequences strongly impact the transfer rate, as we observe a 3.5 order of magnitude variation between the most and the least transferred categories. Overall, we provide a unique view of horizontal transfer across the bacterial tree of life, illuminating a fundamental process driving bacterial evolution.