bluuebunny/crossref_metadata_2025 huggingface dataset:
OGEE v3: Online GEne Essentiality database with increased coverage of organisms and human cell lines
Authors: Gurumayum Sanathoi , Jiang Puzi , Hao Xiaowen , Campos Tulio L , Young Neil D , Korhonen Pasi K , Gasser Robin B , Bork Peer , Zhao Xing-Ming , He Li-jie , Chen Wei-Hua
Published: September 2020

OGEE is an Online GEne Essentiality database. Gene essentiality is not a static and binary property, rather a context-dependent and evolvable property in all forms of life. In OGEE we collect not only experimentally tested essential and non-essential genes, but also associated gene properties that contributes to gene essentiality. We tagged conditionally essential genes that show variable essentiality statuses across datasets to highlight complex interplays between gene functions and environmental/experimental perturbations. OGEE v3 contains gene essentiality datasets for 91 species; almost doubled from 48 species in previous version. To accommodate recent advances on human cancer essential genes (as known as tumor dependency genes) that could serve as targets for cancer treatment and/or drug development, we expanded the collection of human essential genes from 16 cell lines in previous to 581. These human cancer cell lines were tested with high-throughput experiments such as CRISPR-Cas9 and RNAi; in total, 150 of which were tested by both techniques. We also included factors known to contribute to gene essentiality for these cell lines, such as genomic mutation, methylation and gene expression, along with extensive graphical visualizations for ease of understanding of these factors. OGEE v3 can be accessible freely at https://v3.ogee.info.
RADON MEASUREMENTS IN BIG BUILDINGS: PILOT STUDY IN RUSSIA
Authors: Vasilyev A , Yarmoshenko I , Onishchenko A , Hoffmann M , Malinovsky G , Marenny A , Karl L
Published: September 2020

Detailed analysis of indoor radon concentration distribution by floors was conducted in four children institutions, one office building and two residential houses in Russian cities to develop approaches to draw up a program of radon survey for big buildings. Higher variability of radon concentration was found in high geogenic radon potential (GRP) area when the soil is the main source of radon. No essential dependence of radon concentration on the floor in high-rise buildings was found in low GRP area. The number of required radon measurements is estimated using obtained characteristics of radon variability.
Neural mechanisms of predicting individual preferences based on group membership
Authors: Vijayakumar Suhas , Hartstra Egbert , Mars Rogier B , Bekkering Harold
Published: September 2020

Successful social interaction requires humans to predict others’ behavior. To do so, internal models of others are generated based on previous observations. When predicting others’ preferences for objects, for example, observations are made at an individual level (5-year-old Rosie often chooses a pencil) or at a group level (kids often choose pencils). But previous research has focused either on already established group knowledge, i.e. stereotypes, or on the neural correlates of predicting traits and preferences of individuals. We identified the neural mechanisms underlying predicting individual behavior based on learned group knowledge using fMRI. We show that applying learned group knowledge hinges on both a network of regions commonly referred to as the mentalizing network, and a network of regions implicated in representing social knowledge. Additionally, we provide evidence for the presence of a gradient in the posterior temporal cortex and the medial frontal cortex, catering to different functions while applying learned group knowledge. This process is characterized by an increased connectivity between medial prefrontal cortex and other mentalizing network regions and increased connectivity between anterior temporal lobe and other social knowledge regions. Our study provides insights into the neural mechanisms underlying the application of learned group knowledge.
Participant Recruitment in Social Work: A Social Media Approach
Authors: Jones Aubrey , Walters Jayme , Brown Aaron
Published: September 2020

With the widespread adoption of social media, researchers are finding new ways to conduct research involving human subjects. Health-related fields have begun to use social media for participant recruitment. However, the social work profession has been slow to adopt the use of social media recruitment techniques. This article describes experiences of a team of social work researchers who used social media to recruit participants for a national survey of social workers using four social media platforms to recruit participants: Facebook, LinkedIn, Twitter, and Reddit. After three weeks of recruitment, 1,757 participants from all 50 states and the District of Columbia had completed the survey. Facebook and LinkedIn were the most effective social media platforms for recruitment. Authors discuss these results in light of their limitations to provide implications for future research using social media within the fields of social work and related health professions.
Draft Genome Sequence of Cumin Blight Pathogen Alternaria burnsii
Authors: Feng Zhonghong , Hsiang Tom , Liang Xiaofei , Zhang Rong , Sun Guangyu
Published: September 2020

The fungal genus Alternaria consists of highly diverse species. They can be isolated readily from soil, water, and many plants, and even from animals and humans. Alternaria burnsii is a small-spored species of section Alternaria. It has been reported as a pathogen, an endophyte, and a saprophyte, and can also be found in indoor air. It causes cumin blight, a destructive disease on cumin (Cuminum cyminum), and also causes other serious diseases, such as pumpkin seed rot, date palm leaf spot, wheat leaf spot, and gray spot of Notopterygium incisum. In this study, we sequenced and assembled the first genome of A. burnsii isolate CBS 107.38. The draft genome can be used as a reference for the further study of related pathogens and comparative genomics of Alternaria species.
Molecular Mapping of a Novel Quantitative Trait Locus Conferring Adult Plant Resistance to Stripe Rust in Chinese Wheat Landrace Guangtoumai
Authors: Wu Yu , Wang Yuqi , Yao Fangjie , Long Li , Li Jing , Li Hao , Pu Zhien , Li Wei , Jiang Qiantao , Wang Jirui , Wei Yuming , Ma Jian , Kang Houyang , Qi Pengfei , Dai Shoufen , Deng Mei , Zheng Youliang , Jiang Yunfeng , Chen Guoyue
Published: September 2020

Stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici, is one of the most destructive diseases of wheat worldwide. Chinese wheat landrace Guangtoumai (GTM) exhibited a high level of resistance against predominant P. striiformis f. sp. tritici races in China at the adult plant stage. The objective of this research was to identify and map the major locus/loci for stripe rust resistance in GTM. A set of 212 recombinant inbred lines (RILs) was developed from a cross between GTM and Avocet S. The parents and RILs were evaluated in three field tests (2018, 2019, and 2020 at Chongzhou, Sichuan) with the currently predominant P. striiformis f. sp. tritici races for final disease severity and genotyped with the Wheat 55K single nucleotide polymorphism (SNP) array to construct a genetic map with 1,031 SNP markers. A major locus, named QYr.GTM-5DL, was detected on chromosome 5DL in GTM. The locus was mapped in a 2.75-cM interval flanked by SNP markers AX-109855976 and AX-109453419, explaining up to 44.4% of the total phenotypic variation. Since no known Yr genes have been reported on chromosome 5DL, QYr.GTM-5DL is very likely a novel adult plant resistance locus. Haplotype analysis revealed that the resistance allele displayed enhanced levels of stripe rust resistance and is likely present in 5.3% of the 247 surveyed Chinese wheat landraces. The derived cleaved amplified polymorphic sequence (dCAPS) marker dCAPS-5722, converted from a SNP marker tightly linked to QYr.GTM-5DL with 0.3 cM, was validated on a subset of RILs and 48 commercial wheat cultivars developed in Sichuan. The results indicated that QYr.GTM-5DL with its linked dCAPS marker could be used in marker-assisted selection to improve stripe rust resistance in breeding programs, and this quantitative trait locus will provide new and possibly durable resistance to stripe rust.
The Management of Acute Lumbar Stress Reactions of the Pedicle and Pars in Professional Athletes Playing Collision Sports
Authors: Vaccaro Alexander R. , Divi Srikanth N. , Kepler Christopher K. , Schroeder Gregory D. , Hecht Andrew C. , Dossett Andrew B. , Watkins Robert G. , Watkins Robert G. , Mansoori Shireen , Reid Jerome , Vaccaro Alexander R.
Published: September 2020

Acute stress reactions in the lumbar spine most commonly occur in athletes at the pars interarticularis followed by the pedicle. These reactions occur as a result of repetitive microtrauma from supraphysiological loads applied to the lumbar spine. Characteristic motions such as trunk extension and twisting are also thought to play a role and may be sport-specific. Other risk factors include increased lumbar lordosis, hamstring and thoracolumbar fascia tightness, and abdominal weakness. On physical examination, pain is typically reproduced with lumbar hyperextension. Currently, magnetic resonance imaging or nuclear imaging remain the most sensitive imaging modalities for identifying acute lesions. In the elite athlete, management of these conditions can be challenging, particularly in those playing collision sports such as American football, hockey, or rugby. Nonoperative treatment is the treatment of choice with rehabilitation programs focused on pain-free positioning and progressive strengthening. Operative treatment is rare, but may be warranted for patients symptomatic for >12 months. Specialized diagnosis protocols as well as treatment and return to play guidelines from 4 physicians treating elite athletes playing collision sports are presented and reviewed.
The Effect of ACDF or Arthroplasty on Cervicogenic Headaches
Authors: Lombardi Joseph M. , Vivas Andrew C. , Gornet Matthew F. , Lanman Todd H. , McConnell Jeffrey R. , Dryer Randall F. , Burkus J. Kenneth , Riew K. Daniel
Published: September 2020

Study Design:

This was a post hoc analysis of a prospective FDA-IDE study.

Objective:

The purpose of this study is to determine the effectiveness of a 2-level anterior cervical discectomy and fusion (ACDF) or cervical disk arthroplasty (CDA) at relieving headaches associated with cervical radiculopathy or myelopathy at 10 years postoperative.

Background:

To our knowledge, there is no large, prospective study that has examined the efficacy of cervical spine surgery for relieving headaches associated with radiculopathy or myelopathy at 10 years postoperative.

Materials and Methods:

This was a post hoc analysis of a prospective FDA-IDE study for the Prestige LP versus ACDF for radiculopathy or myelopathy due to 2 levels. Preoperatively and out to 10 years, their Neck Disability Index documented if they had headaches (0: no headaches; 1: infrequent slight; 2: infrequent moderate; 3: frequent moderate; 4: frequent severe; 5: nearly constant).

Results:

Three hundred ninety-seven patients were randomized to CDA (209) or ACDF (188). Preoperatively 86% had headaches and 55.9% (52.2% of CDA, 60.1% of ACDFs) had frequent moderate, severe, or nearly constant headache (grades 3–5). By 6 weeks postoperative, 64.4% had headaches and only 12.5% had grades 3–5 headaches (9.3% of CDA and 16% of ACDFs). The benefit lasted to the 10-year follow-up such that 60.3% had any headaches and 16.8% had grades 3–5 headaches (10.9% CDA; 24.3% ACDF).

Conclusions:

These results suggest that 86% of patients with radiculopathy or myelopathy complain of headaches preoperatively, with 55.9% having frequent or constant, moderate to severe headaches (grades 3–5). By 6 weeks postoperative, only 12.5% had grades 3–5 headaches. At 10-year follow-up, 16.8% had grades 3–5 headaches. Both arthroplasty and ACDF are often effective at alleviating headaches associated with radiculopathy or myelopathy.
Curvilinear Relations Between Parallel Multiple Jobs and Physical Activities Functioning/Mental Health Problems
Authors: Yuan Bocong , Huang Chulan , Liang Wenqi , Li Jiannan , Zhong Shuru
Published: September 2020

Objective:

The practice of parallel multiple jobs has increasingly become a global trend. However, the effects of parallel multiple jobs on physical and mental health have not been well understood.

Method:

Data come from China Health and Retirement Longitudinal Study published by CHARLS in 2015. The agricultural population aged 45 years old and above are selected through stratified random sampling (N = 10,118). Robust regression method is used to give robust estimation.

Results:

U-shape relations are found. The modest increase in the number of parallel multiple jobs can alleviate the difficulty in physical activities functioning and can reduce mental health problems. However, these beneficial effects could turn detrimental with the number of parallel multiple jobs beyond the modest level, leading to work overload.

Conclusion:

Parallel multiple jobs could be considered a double edge sword for physical and mental health.
Apolipoprotein L1: role in the evaluation of kidney transplant donors
Authors: Lentine Krista L. , Mannon Roslyn B.
Published: September 2020

Purpose of review

To summarize the current state of evidence regarding the role of apolipoprotein L1 (APOL1) genotyping in evaluating donors for kidney transplantation.

Recent findings

African ancestry is associated with an increased risk of kidney failure following living donation. Moreover, kidney transplants from African ancestry deceased donors have an increased risk of graft failure. Preliminary evidence suggests that APOL1 genotype may mediate at least a portion of this racial variation, with high-risk APOL1 genotypes defined by presence of two renal risk variants (RRVs). A pilot study 136 African ancestry living donors found that those with APOL1 high-risk genotypes had lower baseline kidney function and faster rates of kidney function decline after donation. To date, three retrospective studies identified a two-to-three times greater risk of allograft failure associated with kidneys from donors with high-risk APOL1 genotype. Active research initiatives seek to address unanswered questions, including reproducibility in large national samples, the role of ‘second hits’ injuries, and impact of recipient genotype, with a goal to build consensus on applications for policy and practice.

As evidence evolves, APOL1 genotyping may have applications for organ quality scoring in deceased donor kidney allocation, and for the evaluation and selection of living donor candidates.
Pancreatic Angiopathy Associated With Islet Amyloid and Type 2 Diabetes Mellitus
Authors: Ling Wei , Huang Yi , Huang Yan-Mei , Shen Jian , Wang Shan-Huan , Zhao Hai-Lu
Published: September 2020

Objectives

Type 2 diabetes (T2D) is histopathologically characterized by islet amyloid and is closely connected with vascular complications. Here, we explore the presence of pancreatic angiopathy (PA) associated with islet amyloid and T2D.

Methods

From a total of 172 autopsy cases who had a history of T2D diagnosis, we randomly selected 30 T2D autopsy cases with islet amyloid (DA+) in comparison with islet amyloid-free (DA−) 30 T2D cases and 60 nondiabetic (ND) controls. Amyloid deposits and PA including atherosclerosis of pancreatic interlobar arteries, arterial calcification, atheroembolism, hyaline arteriosclerosis of small arterioles, and islet capillary density were detected in all groups.

Results

Pancreatic angiopathy was found in 91.7% of patients with T2D and in 68.3% of ND controls (P < 0.01). Furthermore, 100% of DA+ patients and 83.3% of DA− subjects showed PA. The intraislet capillary density was significantly lower in DA+ subjects than DA− subjects (mean [standard deviation], DA+: 205 [82] count/mm2; DA−: 344 [76] count/mm2; ND: 291 [94] count/mm2; P < 0.01). Finally, interlobar arteriosclerosis (R = 0.603, P < 0.01) was linearly correlated with the severity of islet amyloid deposits.

Conclusions

Pancreatic angiopathy might be both a cause and a consequence of islet amyloid and T2D.
Prevalence of Hoarding Behavior Among Formerly Homeless Persons Living in Supported Housing
Authors: Greig Astrea , Tolin David , Tsai Jack
Published: September 2020

Hoarding disorder has become an official disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Hoarding disorder affects approximately 1.5% to 5% of the general population, and there is no known literature that has examined the prevalence of hoarding disorder among homeless populations or those living in supported housing, although hoarding problems can jeopardize their housing situation. This study used the Clutter Image Rating to estimate the prevalence of possible hoarding behavior among 660 adults living in supported housing. The results indicate that 18.5% of supported housing residents had hoarding behavior, which is more than three times the prevalence reported in the general population. These results suggest that hoarding behavior and possibly hoarding disorder may be more prevalent among those with histories of homelessness and housing instability, which may be of concern because it may affect both housing and health statuses.
A Mixed Methods Study of Symptom Experience in Patients With End-Stage Renal Disease
Authors: Ng Marques Shek Nam , Wong Cho Lee , Choi Kai Chow , Hui Yun Ho , Ho Eva Hau Sim , Miaskowski Christine , So Winnie Kwok Wei
Published: September 2020

Background

Patients with end-stage renal disease receiving dialysis experience a significant symptom burden. Identifying factors associated with this burden may improve symptom management. However, specific evidence about patients’ experiences is lacking.

Objectives

The aim of this study was to explore factors that are associated with patients’ symptom experiences.

Methods

The convergent parallel mixed methods design was used. In the quantitative component, the Dialysis Symptom Index was used to assess the symptom burden of 271 participants to examine its associations with patient characteristics using correlation coefficients and multivariate regression analyses. In the qualitative component, associated factors reported by 10 participants were identified through semistructured interviews using content analysis. Assessments were conducted at enrollment, 6 months, and 12 months. After separate data analyses, findings were integrated using side-by-side comparison and joint display.

Results

Several significant associations were identified between patient characteristics and symptom burden, and the participants described four categories of factors (i.e., treatment related, pathophysiological, situational, dietary) associated with a higher symptom burden during their interviews. Across both components of this study, three factors were consistent (i.e., employment, hyperphosphatemia, anemia). Participants described several factors not reported previously.

Discussion

This study explored subjective and objective factors influencing the symptom experiences of patients with end-stage renal disease using a mixed methods design. These risk factors can be used to identify high-risk patients. Our findings suggest that participants relied on laboratory results and treatments to explain their symptom experiences. These findings suggest that assessment of both subjective and objective factors is needed to explore patients’ symptom experiences.
Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children’s Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up
Authors: Jonat Brian , Gorelik Mark , Boneparth Alexis , Geneslaw Andrew S. , Zachariah Philip , Shah Amee , Broglie Larisa , Duran Juan , Morel Kimberly D. , Zorrilla Maria , Svoboda Leanne , Johnson Candace , Cheng Jennifer , Garzon Maria C. , Silver Wendy G. , Gross Margolis Kara , Neunert Cindy , Lytrivi Irene , Milner Joshua , Kernie Steven G. , Cheung Eva W.
Published: September 2020

Objectives:

The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome.

Data Sources:

The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods.

Data Synthesis:

Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay.

Conclusions:

This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.
Seventy-two-hour Return Initiative: Improving Emergency Department Discharge to Decrease Returns
Authors: Navanandan Nidhya , Schmidt Sarah K. , Cabrera Natasha , Topoz Irina , DiStefano Michael C. , Mistry Rakesh D.
Published: September 2020

Introduction:

Unscheduled return visits within 72 hours of discharge account for 4% of pediatric emergency department (ED) visits each year and are a quality indicator of ED care. This project aimed to reduce the unexpected 72-hour return visit rate for a network of ED and urgent cares (UC) by improving discharge processes.

Methods:

A multidisciplinary team conducted a quality improvement initiative in the EDs/UCs of a tertiary children’s hospital network. The team developed discharge interventions through successive Plan-Do-Study-Act cycles. They included standardization of the electronic health record discharge workflow and implementation of “mini-after care instructions” and teach-back education. The team used a statistical process control chart to follow the 72-hour return rate, and a chi-square test to compare the pre- and post-intervention 72-hour return rate.

Results:

The ED/UC network discharged 219,196 patients during the study, 12/2014–4/2016. The baseline 72-hour return rate was 3.5% before interventions. The team implemented discharge interventions from 12/14 to 9/15. After the implementation of mini-after care instructions (4/15), 8 consecutive points fell below the mean on the statistical process control chart, and there was an 8.2% reduction in the 72-hour return rate (P < 0.01). Admission rates of 72-hour return patients remained stable throughout the study (27% pre-intervention and 28% post-intervention). Improvements to the ED/UC discharge process resulted in the estimated prevention of 600 ED/UC visits annually throughout the network.

Conclusions:

Quality improvement methodology and multidisciplinary enhancement of discharge processes significantly decreased 72-hour return rates across a network of pediatric EDs and UCs.
Cross-Sectional and Longitudinal Associations Between Psychosocial Well-Being and Cardiometabolic Markers in European Children and Adolescents
Authors: Thumann Barbara F. , Börnhorst Claudia , Ahrens Wolfgang , Arvidsson Louise , Gwozdz Wencke , Iguacel Isabel , Mårild Staffan , Molnár Dénes , Rach Stefan , Russo Paola , Tornaritis Michael , Veidebaum Toomas , De Henauw Stefaan , Michels Nathalie ,   on behalf of the IDEFICS and I.Family consortia
Published: September 2020

Objective

Research examining aspects of positive mental health as potential predictors of cardiometabolic health in young populations is scarce. We investigated the associations between psychosocial well-being and waist circumference (WAIST), blood pressure (BP), the homeostasis model assessment for insulin resistance, triglycerides, and high-density lipoprotein cholesterol considering life-style factors as mediators.

Methods

Data of European children and adolescents participating in the baseline (2007/2008), first follow-up (FU1; 2009/2010) and second follow-up (FU2; 2013/2014) examinations of the IDEFICS/I.Family study were used (ncross-sectional= 6519;nlongitudinal= 1393). A psychosocial well-being score was calculated from 16 items on emotional well-being, self-esteem, and social relationships (0–48 points). Cardiometabolic markers were transformed to age- and sex-specific and, in case of BP, also height-specificzscores. Life-style factors included diet, physical activity, sleep, and electronic media use. Applying path analysis, we obtained unstandardized estimates of direct and indirect effects of well-being on cardiometabolic markers.

Results

Cross-sectionally, well-being score showed a negative direct and a negative indirect effect through life-style factors on WAISTzscore (estimate per 4-point increase, −0.051 [p= .001] and −0.014 [p< .001], respectively). Longitudinally, positive changes in well-being score between baseline and FU1 and between FU1 and FU2, respectively, demonstrated negative indirect effects through life-style factorsFU2on WAISTzscoreFU2. Both cross-sectionally and longitudinally, higher levels of well-being showed lowering indirect effects on homeostasis model assessment, BP, and triglyceridezscores and an increasing indirect effect on high-density lipoprotein cholesterolzscore through both life-style factors and WAISTzscore.

Conclusions

These results supported our hypothesis that a healthier life-style may be one mechanism through which higher well-being is linked with lower abdominal obesity and fewer other cardiometabolic disorders in young populations.

Trial Registration:Pan-European IDEFICS/I.Family children cohort, ISRCTN registry number: ISRCTN62310987 (http://www.isrctn.com/ISRCTN62310987).
Misdiagnosis of Third Nerve Palsy
Authors: Schroeder Richard M. , Stunkel Leanne , Gowder Mangayarkarasi Thandampallayam Ajjeya , Kendall Emerson , Wilson Bradley , Nagia Lina , Eggenberger Eric R. , Van Stavern Gregory P.
Published: September 2020

Background:

This study identifies the diagnostic errors leading to misdiagnosis of 3rd nerve palsy and to aid clinicians in making this diagnosis. The objective of this article is to determine the incidence of misdiagnosis of 3rd cranial nerve palsy (3rd nerve palsy) among providers referring to a tertiary care neuro-ophthalmology clinic and to characterize diagnostic errors that led to an incorrect diagnosis.

Methods:

This was a retrospective clinic-based multicenter cross-sectional study of office encounters at 2 institutions from January 1, 2014, to January 1, 2017. All encounters with scheduling comments containing variations of “3rd nerve palsy” were reviewed. Patients with a documented referral diagnosis of new 3rd nerve palsy were included in the study. Examination findings, including extraocular movement examination, external lid examination, and pupil examination, were collected. The final diagnosis was determined by a neuro-ophthalmologist. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was used to categorize the causes of misdiagnosis. Seventy-eight patients referred were for a new diagnosis of 3rd nerve palsy. The main outcome measure was the type of diagnostic error that led to incorrect diagnoses using the DEER criteria as determined by 2 independent reviewers. Secondary outcomes were rates of misdiagnosis, misdiagnosis rate by referring specialty, and examination findings associated with incorrect diagnoses.

Results:

Of 78 patients referred with a suspected diagnosis of 3rd nerve palsy, 21.8% were determined to have an alternate diagnosis. The most common error in misdiagnosed cases was failure to correctly interpret the physical examination. Ophthalmologists were the most common referring provider for 3rd nerve palsy, and optometrists had the highest overdiagnosis rate of 3rd nerve palsy.

Conclusions:

Misdiagnosis of 3rd nerve palsy was common. Performance and interpretation of the physical examination were the most common factors leading to misdiagnosis of 3rd nerve palsy.
Acute damage to the blood–brain barrier and perineuronal net integrity in a clinically-relevant rat model of traumatic brain injury
Authors: Vita Sydney M. , Grayson Bernadette E. , Grill Raymond J.
Published: September 2020

Closed-head, frontal impacts in which the brain undergoes both lateral and rotational acceleration comprise the majority of human traumatic brain injury (TBI). Here, we utilize a clinically relevant model to examine the effects of a single concussion on aspects of brain integrity: the blood–brain barrier, the perineuronal nets (PNNs), and diffuse axonal injury. Adult, male Sprague–Dawley rats received either a frontal, closed-head concussive TBI, or no injury and were evaluated at 1- or 7-day post-injury. Using immunolabeling for albumin, we observed a significant increase in the permeability of the blood–brain barrier at 1-, but not 7-day post-injury. Breakdown of the PNN, as measured by the binding of wisteria floribunda, was observed at 1-day post-injury in the dorsal, lateral, and ventral cortices. This difference was resolved at 7-day. Finally, axonal injury was identified at both 1- and 7-day post-injury. This preclinical model of closed-head, frontal TBI presents a useful tool with which to understand better the acute pathophysiology of a single, frontal TBI.
Joule's 1840 manuscript on the production of heat by voltaic electricity
Authors: Martins Roberto de Andrade
Published: September 2020

In 1840, James Prescott Joule submitted to the Royal Society a paper describing experimental research on the heat produced by electric currents in metallic conductors, and inferring that the effect was proportional to the resistance of the conductors and to the square of the intensity of the current. Only an abstract of this paper was published in the
Proceedings of the Royal Society
, although a full paper with a similar title was printed in the
Philosophical Magazine
in 1841. Several authors have assumed that the content of the 1841 publication was the same as the rejected 1840 paper; however, the unpublished manuscript has been found within the archives of the Royal Society and is published here for the first time, along with a detailed analysis and comparison with the 1841 paper. The unpublished version is much shorter, and is different in certain respects from the published article. A detailed comparison throws light on several shortcomings of the unpublished version. The present work also studies the assessment of Joule's paper by the Royal Society, and elucidates the roles of Peter Roget and Samuel Christie in this connection.
Drug REpurposing using AI/ML tools - for Rare Diseases (DREAM-RD): A case study with Fragile X Syndrome (FXS)
Authors: Agastheeswaramoorthy Kavitha , Sevilimedu Aarti
Published: September 2020

Drug repositioning is emerging as an increasingly relevant option for rare disease therapy and management. Various methods for identifying suitable drug candidates have been tried and range from clinical symptomatic repurposing to data driven strategies which are based on the disease-specific gene or protein expression, modification, signalling and physiological perturbation profiles. The use of Artificial Intelligence (AI) and machine learning algorithms (ML) allows one to combine diverse data sets, and extract disease-specific data profiles which may not be intuitive or apparent from a subset of data. In this case study with Fragile X syndrome and autism, we have used multiple computational methodologies to extract profiles, which are then combined to arrive at a comprehensive signature (disease DEG). This DEG was then used to interrogate the large collection of drug-induced perturbation profiles present in public databases, to find appropriate small molecules to reverse or mimic the disease-profiles. We have labelled this pipelineDrugRepurposing usingAI/ML tools - forRareDiseases (DREAM-RD). We have shortlisted over 100 FDA approved drugs using the aforementioned pipeline, which may potentially be useful to ameliorate autistic phenotypes associated with FXS.
A naturalistic environment to study natural social behaviors and cognitive tasks in freely moving monkeys
Authors: Jacob Georgin , Katti Harish , Cherian Thomas , Das Jhilik , KA Zhivago , Arun SP
Published: September 2020

Macaque monkeys are widely used to study the neural basis of cognition. In the traditional approach, the monkey is brought into a lab to perform tasks while it is restrained to obtain stable gaze tracking and neural recordings. This unnatural setting prevents studying brain activity during natural, social and complex behaviors. Here, we designed a naturalistic environment with an integrated behavioral workstation that enables complex task training with viable gaze tracking in freely moving monkeys. We used this facility to train monkeys on a challenging same-different task. Remarkably, this facility enabled a naïve monkey to learn the task merely by observing trained monkeys. This social training was faster primarily because the naïve monkey first learned the task structure and then the same-different rule. We propose that such hybrid environments can be used to study brain activity during natural behaviors as well as during controlled cognitive tasks.
Electronic cigarette vaping triggers lipid mediated vocal fold mucosal injury
Authors: Lungova Vlasta , Thibeault Susan L.
Published: September 2020

Electronic cigarettes (e-cigs) are nicotine delivery systems that have been touted as safer alternatives to smoking. A recently reported case of epiglottitis revealed a connection between vaping and swollen laryngeal and vocal fold (VF) structures that can lead to acute life-threatening airway obstruction. The clinical course and biopsy revealed direct epithelial injury and subsequent inflammatory reaction. Here we show that we were able to recapitulate this phenomenon in in vitro conditions. Exposure of engineered VF mucosae to 5% e-cig vapor extract for one week induced cellular damage in VF luminal epithelial cells, disrupting mucosal homeostasis and mucosal innate immune responses. Epithelial erosion was likely caused by the accumulation of solvents and lipid particles, most likely medium chain fatty acids, in the cytosol and intercellular spaces, which altered lipid metabolism and plasma membrane properties. In summary, vaping represents a threat to the VF mucosa health and airway protection.
Neurons learn by predicting future activity
Authors: Luczak Artur , McNaughton Bruce L. , Kubo Yoshimasa
Published: September 2020

Understanding how the brain learns may lead to machines with human-like intellectual capacities. However, learning mechanisms in the brain are still not well understood. Here we demonstrate that the ability of a neuron to predict its future activity may provide an effective mechanism for learning in the brain. We show that comparing a neuron’s predicted activity with the actual activity provides a useful learning signal for modifying synaptic weights. Interestingly, this predictive learning rule can be derived from a metabolic principle, where neurons need to minimize their own synaptic activity (cost), while maximizing their impact on local blood supply by recruiting other neurons. This reveals an unexpected connection that learning in neural networks could result from simply maximizing the energy balance by each neuron. We show how this mathematically derived learning rule can provide a theoretical connection between diverse types of brain-inspired algorithms, such as: Hebb’s rule, BCM theory, temporal difference learning and predictive coding. Thus, this may offer a step toward development of a general theory of neuronal learning. We validated this predictive learning rule in neural network simulations and in data recorded from awake animals. We found that in the sensory cortex it is indeed possible to predict a neuron’s activity ∼10-20ms into the future. Moreover, in response to stimuli, cortical neurons changed their firing rate to minimize surprise: i.e. the difference between actual and expected activity, as predicted by our model. Our results also suggest that spontaneous brain activity provides “training data” for neurons to learn to predict cortical dynamics. Thus, this work demonstrates that the ability of a neuron to predict its future inputs could be an important missing element to understand computation in the brain.
An optimal set of inhibitors for Reverse Engineering via Kinase Regularization
Authors: Rata Scott , Gruver Jonathan Scott , Trikoz Natalia , Lukyanov Alexander , Vultaggio Janelle , Ceribelli Michele , Thomas Craig , Gujral Taran Singh , Kirschner Marc W. , Peshkin Leonid
Published: September 2020

We present a comprehensive resource of 257 kinase inhibitor profiles against 365 human protein kinases using gold-standard kinase activity assays. We show the utility of this dataset with an improved version of Kinome Regularization (KiR) to deconvolve protein kinases involved in a cellular phenotype. We assayed protein kinase inhibitors against more than 70% of the human protein kinome and chose an optimal subset of 58 inhibitors to assay at ten doses across four orders of magnitude. We demonstrate the effectiveness of KiR to identify key kinases by using a quantitative cell migration assay and updated machine learning methods. This approach can be widely applied to biological problems for which a quantitative phenotype can be measured and which can be perturbed with our set of kinase inhibitors.
Road to ruin? Urbanization increases herbivory in a tropical wildflower but does not lead to the evolution of chemical defence traits
Authors: Rivkin L. Ruth , Moura Antonio
Published: September 2020

Urbanization is associated with numerous changes to the biotic and abiotic environment, many of which degrade the environment and lead to a loss of biodiversity. Cities often have elevated pollution levels that harm wildlife; however, the increased concentration of some pollutants can fertilize urban plants, leading to corresponding positive effects on herbivore populations. Increases in herbivory rates may lead to natural selection for greater defence phenotypes in plants. However, evidence supporting increased herbivory leading to the evolution of plant defence in urban environments is contradictory, and entirely absent from tropical regions of the world. To address these research gaps, we evaluated herbivory onTurnera subulata, a common urban wildflower, along an urbanization gradient in Joao Pessoa, Brazil. We predicted that higher rates of herbivory in urban areas would lead these populations to evolve cyanogenesis, a chemical defence found in a closely relatedTurneraspecies. We assessed herbivory and screened for cyanogenesis in 32 populations along the urbanization gradient, quantified by the Human Footprint Index. Our results show that urbanization is significantly associated with increased herbivory rates inT. subulatapopulations. Despite elevated herbivory, we found no evidence for the evolution of cyanongenesis in any of the populations, suggesting that the fitness effects of leaf herbivory are not extreme enough to select for the evolution of plant defence in these populations. Habitat loss, predator release, and nutrient enrichment likely act together to increase the abundance of herbivorous arthropods, influencing the herbivory patterns observed in our study.
Brief Report: High-Quality Masks Can Reduce Infections and Deaths in the US
Authors: Rosenstrom Erik , Oruc Buse Eylul , Ivy Julie , Keskinocak Pinar , Mayorga Maria E. , Swann Julie L.
Published: September 2020

Objectives

To evaluate the effectiveness of widespread adoption of masks or face coverings to reduce community transmission of the SARS-CoV-2 virus that causes Covid-19.

Methods

We employed an agent-based stochastic network simulation model, where Covid-19 progresses across census tracts according to a variant of SEIR. We considered a mask order that was initiated 3.5 months after the first confirmed Covid-19 case. We evaluated scenarios where wearing a mask reduces transmission and susceptibility by 50% or 80%; an individual wears a mask with a probability of 0%, 20%, 40%, 60%, 80%, or 100%.

Results

If 60% of the population wears masks that are 50% effective, this decreases the cumulative infection attack rate (CAR) by 25%, the peak prevalence by 51%, and the population mortality by 25%. If 100% of people wear masks (or 60% wear masks that are 80% effective), this decreases the CAR by 38%, the peak prevalence by 67%, and the population mortality by 40%.

Conclusions

After community transmission is present, masks can significantly reduce infections.
SARS-CoV-2 cell entry gene ACE2 expression in immune cells that infiltrate the placenta in infection-associated preterm birth
Authors: Lye Phetcharawan , Dunk Caroline E. , Zhang Jianhong , Wei Yanxing , Nakpu Jittanan , Hamada Hirotaka , Imperio Guinever E , Bloise Enrrico , Matthews Stephen G , Lye Stephen J
Published: September 2020

COVID-19 infection during pregnancy is associated with an increased incidence of preterm birth but neonatal infection is rare. We assessed pathways by which SARS-CoV-2 could access the placenta and contribute to fetal transmission. Placentas from pregnancies complicated with chorioamnionitis (ChA), exhibited increased expression of ACE2 mRNA. Treatment of 2nd trimester placental explants with LPS, induced an acute increase in cytokine expression followed by ACE2 mRNA. Placental ACE2 protein localized to syncytiotrophoblast, in fetal blood vessels and M1/M2 macrophage and neutrophils within the villous stroma. Increased numbers of M1 macrophage and neutrophils were present in the placenta of ChA pregnancies. Maternal peripheral immune cells (mainly granulocytes and monocytes) express the ACE2 mRNA and protein. These data suggest that in COVID19 positive pregnancies complicated by ChA, ACE2 positive immune cells have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.
The functional and phenotypic diversity of single T-cell infiltrates in human colorectal cancer as correlated with clinical outcome
Authors: Masuda Kazuya , Kornberg Adam , Lin Sijie , Ho Patricia , Secener Kerim , Suek Nathan , Bacarella Alyssa M. , Ingham Matthew , Rosario Vilma , Al-Masrou Ahmed M. , Lee-Kong Steven A. , Kiran P. Ravi , Yan Kelley S. , Stoeckius Marlon , Smibert Peter , Oberstein Paul E. , Sims Peter A. , Han Arnold
Published: September 2020

Although degree of T-cell infiltration in CRC was shown to correlate with a positive prognosis, the contribution of phenotypically and functionally distinct T cell subtypes within tumors remains unclear. We analyzed 37,931 single T cells with respect to transcriptome, TCR sequence and 23 cell surface proteins, from tumors and adjacent normal colon of 16 patients. Our comprehensive analysis revealed two phenotypically distinct cytotoxic T cell populations within tumors, including positively prognostic effector memory cells and non-prognostic resident memory cells. These cytotoxic T cell infiltrates transitioned from effector memory to resident memory in a stage-dependent manner. We further defined several Treg subpopulations within tumors. While Tregs overall were associated with positive clinical outcomes, CD38+peripherally-derived Tregs, phenotypically related to Th17 cells, correlated with poor outcomes independent of cancer stage. Thus, our data highlight the diversity of T cells in CRC and demonstrate the prognostic significance of distinct T cell subtypes, which could inform therapeutic strategies.
Evidence for associations between Rey-Osterrieth Complex Figure test and motor skill learning in older adults
Authors: VanGilder Jennapher Lingo , Lohse Keith R. , Duff Kevin , Wang Peiyuan , Schaefer Sydney Y.
Published: September 2020

Age-related declines in motor learning may be related to poor visuospatial function. Thus, visuospatial testing could evaluate older adults’ potential for motor learning, which has implications for geriatric motor rehabilitation. To this end, the purpose of this study was to identify which visuospatial test is most predictive of motor learning within older adults. Forty-five nondemented older adults completed six standardized visuospatial tests, followed by three weekly practice sessions on a functional upper-extremity motor task. Participants were re-tested one month later on the trained task and another untrained upper-extremity motor task to evaluate the durability and generalizability of motor learning, respectively. Principal component analysis first reduced the dimensions of the visuospatial battery to two principal components for inclusion in a mixed-effects model that assessed one-month follow-up performance as a function of baseline performance and the principal components. Of the two components, only one was related to one-month follow-up. Factor loadings and post hoc analyses suggested that of the six visuospatial tests, the Rey-Osterrieth test (visual construction and memory) was related to one-month follow-up of the trained and untrained tasks. Thus, it may be plausible that older adults’ long-term motor learning capacity could be evaluated using the Rey-Osterrieth test, which would be feasible to administer prior to motor rehabilitation to indicate risk of non-responsiveness to therapy.