bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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.
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

Abstract
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.
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

AbstractIn 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

ABSTRACTBackground & AimsClostridioides 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.MethodsWe 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.ResultsCD4+ 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.ConclusionsThese 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

AbstractA 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

AbstractAutism 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

ABSTRACTEndocrine 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.