bluuebunny/crossref_metadata_2025 huggingface dataset:
Sport disciplines and cardiac remodeling in elite university athletes competing in 2017 Taipei Summer Universiade
Authors: Adea Jose-Ernesto B. , Leonor Rona Marie L. , Lu Cheng-Hui , Lin Lung-Chun , Wu Michael , Lee Kuang-Tso , Lin Yu-Sheng , Chang Shang-Hung , Hung Kuo-Chun , Lin Fen-Chiung , Hsieh I-Chang , Chu Pao-Hsien , Wen Ming-Shien , Wu Victor Chien-Chia , Wang Chun-Li
Published: November 2020

Cardiac remodeling is common in the athletes. Little data is available regarding the cardiac remodeling on the recently proposed 4 sport disciplines among the elite university athletes.

A total of 7639 athletes participated in the 2017 Taipei Summer Universiade. Cardiac evaluation via history, ECG, and echocardiography were performed in 826 athletes who signed up for Check Up Your Heart. Athletes were grouped into one of 4 sport disciplines Skill, Power, Mixed, and Endurance.

After excluding 66 participants with missing demographic data, 13 missing echocardiographic data, and 24 inadequate echocardiographic images, a total number of 723 university athletes (mean age 23 ± 3 years, 419 males) from 99 countries engaging in 25 different sporting events were analyzed. Electrocardiograms showed that Endurance group had a slower heart rate and higher percentage of left ventricular (LV) hypertrophy (39%). Echocardiograms showed there were significant differences in LV mass index (P < .001), LV geometry (P < .001), left atrial (LA) dilatation (P = .026), right ventricular (RV) dilatation (P < .001), right atrial (RA) dilatation (P < .0001), and tricuspid annular plane systolic excurse (P = .006). LV ejection fraction, LV strain, RV strain, and LV diastolic function showed no difference in 4 sport disciplines.

Eccentric LV hypertrophy was the most common type of cardiac remodeling in the university athletes participated in 2017 Taipei Summer Universiade. Adaptive changes in chamber size were more commonly seen in Endurance sport. RA dilatation was the most sensitive to hemodynamic demand, followed by RV dilatation, LA dilatation, and LV dilatation.
Platelets as a prognostic marker for sepsis
Authors: Zhao Lina , Zhao Lijiao , Wang Yun ying , Yang Fei , Chen Zhuang , Yu Qing , Shi Hui , Huang Shiying , Zhao Xiaoli , Xiu Limei , Li Xiaolu , Li Yun
Published: November 2020

During sepsis, platelets dysfunction contributes to organ dysfunction. Studies on platelets dysfunction in the long-term prognosis of sepsis are lacking. The aim of this study was to assess the role of platelets in the long-term prognosis of sepsis patients.

A total of 4576 sepsis patients were extracted from MIMIC III Database. Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate cox analyses were performed to identify prognostic factors. Significant prognostic factors were combined to build a nomogram to predict 1 year overall survival (OS). The discriminative ability and predictive accuracy of the nomogram were evaluated using the receiver operating characteristic curve (ROC) analysis and calibration curves used for sepsis.

The more abnormal the platelet level, the worse prognosis of patients. After final regression analysis, age, blood urea nitrogen, platelets, international normalized ratio, partial thromboplastin time, potassium, hemoglobin, white blood cell count, organ failures were found to be independent predictors of 1 year OS of sepsis patient and were entered into a nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve of 0.752. The calibration curves for the probability of the prognosis of sepsis patients showed optimal agreement between the probability as predicted by the nomogram and the actual probability.

Platelet was an independent prognostic predictor of 1 year OS for patients with sepsis. Platelet-related nomogram that can predict the 1 year OS of sepsis patients. It revealed optimal discrimination and calibration, indicating that the nomogram may have clinical utility.
AML, ALL, and CML classification and diagnosis based on bone marrow cell morphology combined with convolutional neural network
Authors: Huang Furong , Guang Peiwen , Li Fucui , Liu Xuewen , Zhang Weimin , Huang Wendong
Published: November 2020

Leukemia diagnosis based on bone marrow cell morphology primarily relies on the manual microscopy of bone marrow smears. However, this method is greatly affected by subjective factors and tends to lead to misdiagnosis. This study proposes using bone marrow cell microscopy images and employs convolutional neural network (CNN) combined with transfer learning to establish an objective, rapid, and accurate method for classification and diagnosis of LKA (AML, ALL, and CML). We collected cell microscopy images of 104 bone marrow smears (including 18 healthy subjects, 53 AML patients, 23 ALL patients, and 18 CML patients). The perfect reflection algorithm and a self-adaptive filter algorithm were first used for preprocessing of bone marrow cell images collected from experiments. Subsequently, 3 CNN frameworks (Inception-V3, ResNet50, and DenseNet121) were used to construct classification models for the raw dataset and preprocessed dataset. Transfer learning was used to improve the prediction accuracy of the model. Results showed that the DenseNet121 model based on the preprocessed dataset provided the best classification results, with a prediction accuracy of 74.8%. The prediction accuracy of the DenseNet121 model that was obtained by transfer learning optimization was 95.3%, which was increased by 20.5%. In this model, the prediction accuracies of the normal groups, AML, ALL, and CML were 90%, 99%, 97%, and 95%, respectively. The results showed that the leukemic cell morphology classification and diagnosis based on CNN combined with transfer learning is feasible. Compared with conventional manual microscopy, this method is more rapid, accurate, and objective.
Effectiveness of modeling videos on psychological responses of patients following anterior cruciate ligament reconstruction
Authors: Rhim Hye Chang , Lee Seo Jun , Jeon Jin Sung , Kim Geun , Lee Kwang Yeol , Lee Jin Hyuck , Jang Ki-Mo
Published: November 2020

Background:

To date, much of the rehabilitation following anterior cruciate ligament reconstruction (ACLR) has centered on physical components. However, clinical outcomes including return to sport after ACLR depends on not only physical recovery but also psychological components. This study was performed to assess the feasibility of 6-month modeling video intervention on psychological responses following ACLR.

Methods:

Following the baseline assessment of psychological measures through Knee Self Efficacy Scale (K-SES), ACL-Return to Sport after Injury (ACL-RSI), and Tampa Scale of Kinesiophobia-11 (TSK-11), 32 patients scheduled for ACLR were randomly assigned to intervention (n = 10), placebo (n = 11), or control (n = 11) group. Six modeling videos and placebo videos were developed by the investigators. Intervention and placebo groups watched their respective videos during their follow-up visits while control group did not. All groups completed psychological assessments during hospitalization, at 2 weeks, at 6 weeks, at 3 months, and at 6 months following ACLR. Also, Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to evaluate symptoms and function of the knee at 3 and 6 months after surgery.

Results:

No significant changes in K-SES, ACL-RSI, and TSK-11 scores over 6-month period were observed among groups (P = .808, P = .574, P = .888, respectively). Compared with baseline, only the scores of K-SES improved with statistical significance in the intervention, placebo, and control groups (P = .05, .01, .00) at 6 months after ACLR. The KOOS subscale scores were not significantly different among the intervention, placebo, and control groups at 3 and 6 months.

Conclusion:

A modeling video intervention, although feasible, was not effective in addressing the psychological risk factors in patients undergoing ACLR.
High prevalence of multidrug-resistant gram-negative bacterial infection following pediatric liver transplantation
Authors: Phichaphop Chanita , Apiwattanakul Nopporn , Techasaensiri Chonnamet , Lertudomphonwanit Chatmanee , Treepongkaruna Suporn , Thirapattaraphan Chollasak , Boonsathorn Sophida
Published: November 2020

Bacterial infection has been identified as one of the most significant complications of liver transplantation (LT). Multidrug-resistant (MDR) gram-negative bacteria (GNB) infection remains problematic issue following LT in the adults. However, data in children are scarce. We aimed to examine the prevalence and associated factors of MDR-GNB infection among pediatric LT recipients.

We performed a single-center retrospectively study of 118 children who underwent LT between January 2010 and December 2018. Data on the prevalence, clinical characteristics, types, and sites of MDR-GNB infection within 3 months after LT as well as the treatment outcomes were collected. Multidrug resistance was defined as acquired non-susceptibility to at least 1 agent in 3 or more antibiotic classes.

In total, 64 (53.7%) patients developed 96 episodes of culture-proven bacterial infection with 93 GNB isolates. Moreover, there were 58 (62.4%) MDR-GNB isolates, with a predominance of Klebsiella pneumoniae (32.7%), Escherichia coli (31%), and Pseudomonas aeruginosa (10.3%). Interestingly, 10 (17.2%) isolates were determined to be carbapenem-resistant Enterobacteriaceae. The median time to MDR-GNB infection was 9 (interquartile range: 5–33) days. The most common type of infection was intra-abdominal infection (47.9%). In the multivariate analysis, the significant variables associated with post-LT MDR-GNB infection include exposure to third-generation cephalosporins (hazard ratio [HR]: 2.16, P = .023), operative time (hazard ratio [HR] 1.20, P = .009), and length of intensive care unit stay (HR 1.03, P = .049). With a focus on carbapenem-resistant Enterobacteriaceae infection, a pediatric end-stage liver disease score >21 was the only significant 6 variable in the multivariate analysis (HR 11.48, P = .024). The overall 3-month mortality rate was 6.8%.

This study has highlighted the high prevalence rate of MDR-GNB infection after pediatric LT. Therefore, caution on the emergence of MDR-GNB infection should be paid in at-risk children. Moreover, knowledge regarding the prevalence of MDR-GNB infection and resistant patterns is essential for guideline development to prevent and minimize the risk of MDR-GNB infection in this group of patients.
Early Inflammatory Markers are Associated With Inadequate Post‐Induction Infliximab Trough in Pediatric Crohn's Disease
Authors: Constant Brad D. , Khushal Salina , Jiang Jiji , Bost James E. , Chaisson Ellen , Conklin Laurie S.
Published: November 2020

Objectives:

In pediatric Crohn's disease, infliximab trough concentrations after standard weight‐based induction therapy are commonly below 7 μg/mL. Clinical treatment outcomes are associated with post‐induction infliximab trough concentration. Markers of inflammation are associated with low infliximab concentrations during maintenance dosing. We sought to determine if early markers of disease activity are associated with inadequate post‐induction infliximab trough concentrations in pediatric Crohn's disease.

Methods:

We performed a retrospective single‐center case‐control study of pediatric Crohn's disease patients to assess the association between baseline and week‐2 biomarkers (albumin, C‐reactive protein, and erythrocyte sedimentation rate) and inadequate post‐induction infliximab trough concentration (<7 μg/mL) in patients treated with standard 5 mg/kg dosing. Baseline and week‐2 biomarker values were coded as dichotomous variables at clinically useful thresholds. Univariable logistic regression was used to calculate odds ratios of developing an inadequate infliximab trough concentration for each threshold, as well as thresholds in combination.

Results:

Fifty‐five patients were evaluated. Early biomarker thresholds significantly associated with inadequate post‐induction infliximab trough concentrations included baseline C‐reactive protein >1 mg/dL (odds ratio [OR] 4.58; 95% confidence interval [CI] 1.24‐‐17.01), both baseline C‐reactive protein >0.5 mg/dL and albumin <3.5 g/dL (OR 8.31; 95% CI 1.99‐‐34.63), and week‐2 C‐reactive protein >0.5 mg/dL or albumin <3.5 mg/dL or erythrocyte sedimentation rate >25 mm/hour (OR 11.08; 95% CI 2.14‐‐57.22).

Conclusions:

Routine baseline and week‐2 markers of disease activity at clinically useful thresholds were associated with inadequate post‐induction infliximab trough concentration in pediatric Crohn's disease patients receiving standard weight‐based induction dosing.
Caregiver Decision‐making in Pediatric Intestinal Failure
Authors: Raghu Vikram Kalathur , Prathapan Krishnapriya M. , Hamm Megan E. , Rudolph Jeffrey A. , Norman Marie K.
Published: November 2020

Background:

Caregivers of children with intestinal failure (IF) face difficult decisions without a clear best alternative. Providers assist in decision‐making but often lack knowledge of caregiver perspectives. Using decision‐making around anemia treatment as a focal point, we explored how caregivers of children with IF prefer to make decisions. Our goal was to offer insight to guide providers as they assist in decision‐making.

Methods:

We conducted 12 half‐hour semistructured interviews with parents of children with IF. Interview questions addressed general decision‐making and specifics of iron supplementation, including key factors and stakeholders in decision‐making. Interviews were transcribed verbatim. Two investigators coded the transcripts and inductively derived themes.

Results:

Four themes were identified regarding decision‐making. They involved the search for reliable, accurate, and positive information; the role of caretakers on the medical team; the relationships between caretakers and the medical team; and effective communication. Themes around anemia treatment included: identification of anemia by bloodwork; proactive supplementation; individualized regimens; prioritizing safety and convenience.

Conclusions:

Understanding caregiver perspectives regarding anemia treatment in pediatric IF identifies opportunities for systematic quality improvement.
Clinical Hypnosis in Pediatric Crohn's Disease
Authors: Lee Amanda , Moulton Dedrick , Mckernan Lindsey , Russell Alexandra , Slaughter James C. , Acra Sari , Walker Lynn
Published: November 2020

Objective:

The aim of this study was to implement clinical hypnosis (CH) as an adjunctive therapy for adolescents with Crohn's disease (CD) and to assess the impact of CH on quality of life (QoL), abdominal pain, psychosocial measures, and disease activity compared with standard care.

Methods:

Forty adolescents with CD were randomized to a hypnosis intervention (HI) or waitlist control (WC) group. The intervention consisted of 1 in‐person CH session, self‐hypnosis education, and recordings for home practice. Data was collected at baseline, after the 8‐week intervention, and at week 16. The primary outcome was patient‐ and parent‐reported QoL; secondary outcomes were patient‐reported abdominal pain, depression, anxiety, and sleep; school absences; and disease activity by Pediatric Crohn's Disease Activity Index. Paired and independent t‐tests were used to compare differences from baseline to postintervention within and between groups.

Results:

Forty patients (50% girls, mean 15.8 years) were enrolled from February to May 2019. Seventy‐eight percent had inactive disease, and 55% had abdominal pain. Post intervention, significant improvements were noted in HI parent‐reported QoL compared with WC in total score (P = 0.05), social functioning (P = 0.01), and school functioning (P = 0.04) but patient‐reported QoL was unchanged. Abdominal pain severity significantly improved in HI compared with WC (P = 0.03). School absences decreased in significantly more intervention than control patients (P = 0.01). Patients who practiced self‐hypnosis consistently showed a trend toward greater QoL improvement than those who did not (P = 0.1).

Conclusions:

CH is an acceptable and feasible adjunct in CD and may improve psychosocial QoL and abdominal pain. Further research is warranted.
Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era
Authors: Ruderman Stephanie A. , Crane Heidi M. , Nance Robin M. , Whitney Bridget M. , Harding Barbara N. , Mayer Kenneth H. , Moore Richard D. , Eron Joseph J. , Geng Elvin , Mathews William C , Rodriguez B , Willig Amanda L. , Burkholder Greer A. , Lindström Sara , Wood Brian R. , Collier Ann C. , Vannappagari Vani , Henegar Cassidy , Van Wyk Jean , Curtis Lloyd , Saag Michael S. , Kitahata Mari M. , Delaney Joseph A. C.
Published: November 2020

Objectives:

Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.

Methods:

Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.

Results:

Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.

Conclusions:

There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.
Correlates of HIV Status Nondisclosure by Pregnant Women Living With HIV to Their Male Partners in Uganda: A Cross-Sectional Study
Authors: Bulterys Michelle A. , Sharma Monisha , Mugwanya Kenneth , Stein Gabrielle , Mujugira Andrew , Nakyanzi Agnes , Twohey-Jacobs Lorraine , Ware Norma C. , Heffron Renee , Celum Connie
Published: November 2020

Background:

HIV status disclosure by pregnant women living with HIV (PWLHIV) to their male partners is associated with improved maternal and infant outcomes. Understanding relationship factors associated with nondisclosure of HIV status by PWLHIV to their partners can inform the design of interventions to facilitate disclosure.

Methods:

We conducted a cross-sectional study using enrollment data from 500 PWLHIV unaware of their male partners' HIV status and participating in a randomized clinical trial assessing secondary distribution of HIV self-testing kits in Kampala, Uganda. The primary outcome was women's HIV status nondisclosure to their partners. We conducted univariate and multivariate binomial regressions to assess the association between baseline sociodemographic, HIV history, and relationship characteristics with HIV status nondisclosure.

Results:

68.2% of the 500 PWLHIV had not disclosed their HIV status to their partner(s). Factors associated with higher likelihood of nondisclosure included relationship duration <1 year [adjusted prevalence ratio (aPR = 1.25); 95% confidence interval (CI): 1.02 to 1.54], being in a polygamous relationship (aPR = 1.21; 95% CI: 1.07 to 1.36), unmarried (aPR = 1.20; 95% CI: 1.07 to 1.35), uncertainty about whether their partner had ever tested for HIV (aPR = 1.55; 95% CI: 1.28 to 1.88), and a lack of social support from people aware of their status (aPR = 1.32; 95% CI: 1.18 to 1.49).

Conclusion:

Relationship factors, including shorter-term, unmarried, and polygamous relationships and uncertainty about partner's HIV testing history, were associated with higher likelihood of pregnant women's nondisclosure of HIV status to their partner. Interventions that facilitate couples' HIV testing and disclosure, provide counseling to reduce relationship dissolution in serodiscordant couples, and offer peer support for women may increase disclosure.

ClinicaltrialsRegistration:

Clinicaltrials.gov ID number: NCT03484533.
Sexual Behavior Among Men Who Have Sex With Men: The Need for More Targeted Outreach to Men Who Also Have Sex With Cisgender Women
Authors: Mayer Megan E. , White Edward , Montano Michalina A. , Lama Javier R. , Sanchez Hugo , Cabello Robinson , Sanchez Jorge , Pasalar Siavash , Duerr Ann
Published: November 2020

Background:

In Peru, as in the Americas overall, men who have sex with men (MSM) are disproportionately affected by HIV. Most research focuses on practices between cisgender men, whereas many MSM report male and female partners, cisgender, transgender, or both.

Methods:

Data for these analyses were from a treatment-as-prevention study in Lima (the Sabes study). We compared demographics and behaviors of MSM who reported cisgender women partners in the past 3 months (MSMW) and MSM who reported both cisgender and transgender women partners (MSMW-T) to MSM who reported only male partners (MSMO). We calculated HIV incidence in each group during 2-year follow-up.

Results:

Compared with MSMO, MSMW and MSMW-T more often self-identify as heterosexual or bisexual and report insertive sex practices. MSMW reported condomless sex with cisgender women: vaginal (72%), anal sex (18%). One-third of MSMW reported condomless receptive anal sex with men in the past 3 months, with 24% of MSMW overall who reported both condomless receptive sex with men and condomless insertive vaginal or anal sex with cisgender women. Of these, 17% were HIV infected. HIV incidence did not differ significantly between groups.

Conclusion:

Most MSMW and MSMW-T report bisexual or heterosexual orientation and prefer insertive sex. MSMW and MSMW-T (47% and 29%, respectively) engage in receptive anal intercourse. In both groups, the majority who engaged in condomless receptive sex with men (76% MSMW, 85% MSMW-T) also engaged in condomless vaginal and/or anal sex with women, indicating need for intervention.
Simulation Innovation
Authors: Drake Hilary , Abbey Darin , Holmes Chelsea , Macdonald Anna , Mackinnon Laura , Slinn JoAnne , Baylis Jared
Published: November 2020

Summary Statement

The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory distress syndrome coronavirus 2, has spread globally and requires effective preparedness within healthcare institutions. The British Columbia Simulation Network COVID-19 Simulation Guide was created to disseminate information throughout the province of British Columbia, Canada, and to allow simulation educators, from novice to expert, to participate in COVID-19 simulations. As of July 15, 2020, the guide had been downloaded 465 times from the British Columbia Simulation Network website, with downloads in 41 countries around the world. The guide has been frequently updated and revised to reflect evolving guidelines as new knowledge about COVID-19 was established.
Host adaptation and microbial competition drive Ralstonia solanacearum phylotype I evolution in the Republic of Korea
Authors: Prokchorchik Maxim , Pandey Ankita , Moon Hayoung , Kim Wanhui , Jeon Hyelim , Jung Gayoung , Jayaraman Jay , Poole Stephen , Segonzac Cécile , Sohn Kee Hoon , McCann Honour C.
Published: November 2020

Bacterial wilt caused by the

Ralstonia solanacearum

species complex (RSSC) threatens the cultivation of important crops worldwide. We sequenced 30 RSSC phylotype I (

R. pseudosolanacearum

) strains isolated from pepper (Capsicum annuum) and tomato (Solanum lycopersicum) across the Republic of Korea. These isolates span the diversity of phylotype I, have extensive effector repertoires and are subject to frequent recombination. Recombination hotspots among South Korean phylotype I isolates include multiple predicted contact-dependent inhibition loci, suggesting that microbial competition plays a significant role in

Ralstonia

evolution. Rapid diversification of secreted effectors presents challenges for the development of disease-resistant plant varieties. We identified potential targets for disease resistance breeding by testing for allele-specific host recognition of T3Es present among South Korean phyloype I isolates. The integration of pathogen population genomics and molecular plant pathology contributes to the development of location-specific disease control and development of plant cultivars with durable resistance to relevant threats.
Multifunctional transcription factor CytR of Vibrio cholerae is important for pathogenesis
Authors: Das Suman , Chourashi Rhishita , Mukherjee Priyadarshini , Gope Animesh , Koley Hemanta , Dutta Moumita , Mukhopadhyay Asish K. , Okamoto Keinosuke , Chatterjee Nabendu Sekhar
Published: November 2020

Vibrio cholerae,the Gram-negative facultative pathogen, resides in the aquatic environment and infects humans and causes diarrhoeagenic cholera. Although the environment differs drastically,V. choleraethrives in both of these conditions aptly and chitinases play a vital role in their persistence and nutrient acquisition. Chitinases also play a role inV. choleraepathogenesis. Chitinases and its downstream chitin utilization genes are regulated by sensor histidine kinase ChiS, which also plays a significant role in pathogenesis. Recent exploration suggests that CytR, a transcription factor of the LacI family inV. cholerae,also regulates chitinase secretion in environmental conditions. Since chitinases and chitinase regulator ChiS is involved in pathogenesis, CytR might also play a significant role in pathogenicity. However, the role of CytR in pathogenesis is yet to be known. This study explores the regulation of CytR on the activation of ChiS in the presence of mucin and its role in pathogenesis. Therefore, we created a CytR isogenic mutant strain ofV. cholerae(CytR¯) and found considerably less β-hexosaminidase enzyme production, which is an indicator of ChiS activity. The CytR¯ strain greatly reduced the expression of chitinaseschiA1andchiA2in mucin-supplemented media. Electron microscopy showed that the CytR¯ strain was aflagellate. The expression of flagellar-synthesis regulatory genesflrB,flrCand class III flagellar-synthesis genes were reduced in the CytR¯ strain. The isogenic CytR mutant showed less growth compared to the wild-type in mucin-supplemented media as well as demonstrated highly retarded motility and reduced mucin-layer penetration. The CytR mutant revealed decreased adherence to the HT-29 cell line. In animal models, reduced fluid accumulation and colonization were observed during infection with the CytR¯ strain due to reduced expression ofctxB,toxTandtcpA. Collectively these data suggest that CytR plays an important role inV. choleraepathogenesis.
Use of an integrated pan-cancer oncology enrichment NGS assay to measure tumour mutational burden and detect clinically actionable variants
Authors: Pestinger Valerie , Smith Matthew , Sillo Toju , Findlay John M , Laes Jean-Francois , Martin Gerald , Middleton Gary , Taniere Phillipe , Beggs Andrew D
Published: November 2020

Introduction

The identification of tumour mutational burden (TMB) as a biomarker of response to PD-1 immunotherapy has necessitated the development of genomic assays to measure this. We carried out comprehensive molecular profiling of cancers using the Illumina TruSight Oncology panel (TSO500) and compared to whole genome sequencing.

Methods

Cancer samples derived from formalin fixed material were profiled on the TSO500 panel, sequenced on an Illumina NextSeq 500 instrument and processed through the TSO500 Docker Pipeline. Either FASTQ files (PierianDx) or VCF files (OncoKDM) were processed to understand clinical actionability

Results

In total, 108 samples (a mixture of colorectal, lung, oesophageal and control samples) were processed via the DNA panel. There was good correlation between TMB, SNV, indels and CNV as predicted by TSO500 and WGS (R2>0.9) and good reproducibility, with less than 5% variability between repeated controls. For the RNA panel, 13 samples were processed, with all known fusions observed via orthogonal techniques detected. For clinical actionability 72 Tier 1 variants and 297 Tier 2 variants were identified with clinical trials identified for all patients.

Conclusions

The TruSight Oncology 500 assay accurately measures TMB, MSI, single nucleotide variants, indels, copy number/structural variation and gene fusions when compared to whole genome sequencing and orthogonal technologies. Coupled with a clinical annotation pipeline this provides a powerful methodology for identification of clinically actionable variants.
Peeling Back the Layers: First Phylogenomic Insights into the Ledebouriinae (Scilloideae, Asparagaceae)
Authors: Howard Cody Coyotee , Crowl Andrew A. , Harvey Timothy S. , Cellinese Nico
Published: November 2020

The Ledebouriinae (Scilloideae, Asparagaceae) are a widespread group of bulbous geophytes found predominantly throughout seasonal climates in sub-Saharan Africa, with a handful of taxa in Madagascar, the Middle East, India, and Sri Lanka. Phylogenetic relationships within the group have been historically difficult to elucidate. Here, we provide the first phylogenomic perspective into the Ledebouriinae. Using the Angiosperms353 targeted enrichment probe set, we consistently recovered four major clades (i.e., twoLedebouriaclades,Drimiopsis, andResnova). The twoLedebouriaclades closely align with geography, either consisting almost entirely of sub-Saharan African taxa (LedebouriaClade A), or East African and non-African taxa (LedebouriaClade B). Our results suggest that the Ledebouriinae likely underwent a rapid radiation leading to rampant incomplete lineage sorting. We additionally find evidence for potential historical hybridization betweenDrimiopsisand a subclade withinLedebouriaClade A.
Disrupted visual cortical plasticity in early neurodegeneration
Authors: Papanikolaou Amalia , Rodrigues Fabio R. , Holeniewska Joanna , Phillips Keith , Saleem Aman B. , Solomon Samuel G.
Published: November 2020

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.

Highlights

Visual plasticity is disrupted at early stages of neurodegeneration in rTg4510 mice

Visual plasticity is reduced in older animals, particularly during neurodegeneration

Instinctive visual behaviours are reduced in neurodegeneration

Short-term visual plasticity is reduced in neurodegeneration
Multi-omics analysis of chromatin accessibility and interactions with transcriptome by HiCAR
Authors: Wei Xiaolin , Xiang Yu , Shan Ruocheng , Peters Derek T , Sun Tongyu , Lin Xin , Li Wei , Diao Yarui
Published: November 2020

The long-range interactions of cis-regulatory elements (cREs) play a central role in regulating the spatial-temporal gene expression program of multi-cellular organism. cREs are characterized by the presence of accessible (or open) chromatin, which can be identified at genome-wide scale with assays such as ATAC-seq, DHS-seq, and FAIRE-seq. However, it remains technically challenging to comprehensively identify the long-range physical interactions that occur between cREs, especially in a cost effective manner using low-input samples. Here, we report HiCAR (High-throughput Chromosome conformation capture on Accessible DNA with mRNA-seq co-assay), a method that enables simultaneous assessment of cis-regulatory chromatin interactions and chromatin accessibility, as well as evaluation of the transcriptome, which represents the functional output of chromatin structure and accessibility. Unlike immunoprecipitation-based methods such as HiChIP, PLAC-seq, and ChIA-PET, HiCAR does not require target-specific antibodies and thus can comprehensively capture the cis-regulatory chromatin contacts anchored at accessible regulatory DNA regions and associated with diverse epigenetic modifications and transcription factor binding. Compared to Trac-looping, another method designed to capture interactions between accessible chromatin regions, HiCAR produced a 17-fold greater yield of informative long-range cis- reads at a similar sequencing depth and required 1,000-fold fewer cells as input. Applying HiCAR to H1 human embryonic stem cells (hESCs) revealed 46,792 cis-regulatory chromatin interactions at 5kb resolution. Interestingly, we found that epigenetically poised, bivalent, and repressed cREs exhibit comparable spatial interaction activity to those transcriptionally activated cREs. Using machine learning approaches, we predicated 22 epigenome features that are potentially important for the spatial interaction activity of cREs in H1 hESC. Lastly, we also identified long-range cis-regulatory chromatin interactions in GM12878 and mouse embryonic stem cells with HiCAR. Our results demonstrate that HiCAR is a robust and cost-effective multi-omics assay, which is broadly applicable for simultaneous analysis of genome architecture, chromatin accessibility, and the transcriptome using low-input samples.
Human-in-the-Loop Weight Compensation in Upper Limb Wearable Robots Towards Total Muscles’ Effort Minimization
Authors: Nasiri Rezvan , Aftabi Hamidreza , Ahmadabadi Majid Nili
Published: November 2020

In this paper: (1) We present a novel human-in-the-loop adaptation method for whole arm muscles’ effort minimization by means of weight compensation in the face of an object with an unknown mass. (2) This adaptation rule can also be used as a cognitive model for the identification of mass value using EMG sensors. (3) This adaptation rule utilizes the activation (myoelectric) signal of only four muscles in the upper limb to minimize the whole muscles’ effort. We analytically discuss the stability, optimality, and convergence of the proposed method. The effectiveness of this method for whole muscles’ effort reduction is studied by simulations (OpenSim software) on a generic and realistic model of the human arm, a model with 7-DOF and 50 Hill-type-muscles. The simulation results show the presented method’s performance and applicability for weight compensation and mass estimation in upper limb assistive robots. In addition, the simulations in OpenSim completely support that the suggested set of mono-articular muscles are sufficient for whole muscles’ effort reduction.
Immune modulating drug MP1032 with SARS-CoV-2 antiviral activity in vitro: A potential multi-target approach for prevention and early intervention treatment of COVID-19
Authors: Schumann Sara , Kaiser Astrid , Nicoletti Ferdinando , Mangano Katia , Fagone Paolo , van Wijk Eduard , Yan Yu , Schulz Petra , Ludescher Beate , Niedermaier Michael , von Wegerer Joerg , Rauch Pia , Setz Christian , Schubert Ulrich , Brysch Wolfgang
Published: November 2020

At least since March 2020, the multiorgan disease COVID-19 has a firm grip on the world. Although most of the cases are mild, patients from risk populations could develop a cytokine storm, which is characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper will introduce the small molecule MP1032, describe its mode of action, and give rationale why it is a promising option for prevention/treatment of SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-pthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting antioxidant activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, immune-regulatory and PARP-1 modulating properties, coupled with antiviral effects against SARS-CoV-2 were shown in various cell models. Efficacy has been preclinically elucidated in LPS-induced endotoxemia, a model with excessively activated immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-months daily administrations, no serious adverse drug reactions occurred highlighting the outstanding safety profile of MP1032.
Cognitive Practice Effects Delay Diagnosis; Implications for Clinical Trials
Authors: Sanderson-Cimino Mark , Elman Jeremy A. , Tu Xin M. , Gross Alden L. , Panizzon Matthew S. , Gustavson Daniel E. , Bondi Mark W. , Edmonds Emily C. , Eglit Graham M.L. , Eppig Joel S. , Franz Carol E. , Jak Amy J. , Lyons Michael J. , Thomas Kelsey R. , Williams McKenna E. , Kremen William S. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2020

Objective

Practice effects on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). This reduces opportunities for slowing Alzheimer’s disease progression and can hinder clinical trials. Using a novel method, we assessed the ability of practice-effect-adjusted diagnoses to detect MCI earlier, and tested the validity of these diagnoses based on AD biomarkers.

Methods

Of 889 Alzheimer’s Disease Neuroimaging Initiative participants who were cognitively normal (CN) at baseline, 722 returned at 1-year-follow-up (mean age=74.9±6.8). Practice effects were calculated by comparing returnee scores at follow-up to demographically-matched individuals who had only taken the tests once, with an additional adjustment for attrition effects. Practice effects for each test were subtracted from follow-up scores. The lower scores put additional individuals below the impairment threshold for MCI. CSF amyloid-beta, phosphorylated tau, and total tau were measured at baseline and used for criterion validation.

Results

Practice-effect-adjusted scores increased MCI incidence by 26% (p<.001). Adjustment increased proportions of amyloid-positive MCI cases (+20%) and reduced proportions of amyloid-positive CNs (−6%) (ps<.007). With the increased MCI base rate, adjustment for practice effects would reduce the sample size needed for detecting significant drug treatment effects by an average of 21%, which we demonstrate would result in multi-million-dollar savings in a clinical trial.

Interpretation

Adjusting for practice effects on cognitive testing leads to earlier detection of MCI. When MCI is an outcome, this reduces recruitment needed for clinical trials, study duration, staff and participant burden, and can dramatically lower costs. Importantly, biomarker evidence also indicates improved diagnostic accuracy.
COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support
Authors: Shea Katriona , Borchering Rebecca K. , Probert William J.M. , Howerton Emily , Bogich Tiffany L. , Li Shouli , van Panhuis Willem G. , Viboud Cecile , Aguás Ricardo , Belov Artur , Bhargava Sanjana H. , Cavany Sean , Chang Joshua C. , Chen Cynthia , Chen Jinghui , Chen Shi , Chen YangQuan , Childs Lauren M. , Chow Carson C. , Crooker Isabel , Del Valle Sara Y. , España Guido , Fairchild Geoffrey , Gerkin Richard C. , Germann Timothy C. , Gu Quanquan , Guan Xiangyang , Guo Lihong , Hart Gregory R. , Hladish Thomas J. , Hupert Nathaniel , Janies Daniel , Kerr Cliff C. , Klein Daniel J. , Klein Eili , Lin Gary , Manore Carrie , Meyers Lauren Ancel , Mittler John , Mu Kunpeng , Núñez Rafael C. , Oidtman Rachel , Pasco Remy , Piontti Ana Pastore y , Paul Rajib , Pearson Carl A. B. , Perdomo Dianela R. , Perkins T Alex , Pierce Kelly , Pillai Alexander N. , Rael Rosalyn Cherie , Rosenfeld Katherine , Ross Chrysm Watson , Spencer Julie A. , Stoltzfus Arlin B. , Toh Kok Ben , Vattikuti Shashaank , Vespignani Alessandro , Wang Lingxiao , White Lisa , Xu Pan , Yang Yupeng , Yogurtcu Osman N. , Zhang Weitong , Zhao Yanting , Zou Difan , Ferrari Matthew , Pannell David , Tildesley Michael , Seifarth Jack , Johnson Elyse , Biggerstaff Matthew , Johansson Michael , Slayton Rachel B. , Levander John , Stazer Jeff , Salerno Jessica , Runge Michael C.
Published: November 2020

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.
Systematic errors in orthology inference: a bug or a feature for evolutionary analyses?
Authors: Natsidis Paschalis , Kapli Paschalia , Schiffer Philipp H , Telford Maximilian J.
Published: November 2020

Introductory paragraph

The availability of complete sets of genes from many organisms makes it possible to identify genes unique to (or lost from) certain clades. This information is used to reconstruct phylogenetic trees; to identify genes involved in the evolution of clade specific novelties; and for phylostratigraphy - identifying ages of genes in a given species. These investigations rely on accurately predicted orthologs. Here we use simulation to produce sets of orthologs which experience no gains or losses. We show that errors in identifying orthologs increase with higher rates of evolution. We use the predicted sets of orthologs, with errors, to reconstruct phylogenetic trees; to count gains and losses; and for phylostratigraphy. Our simulated data, containing information only from errors in orthology prediction, closely recapitulate findings from empirical data. We suggest published downstream analyses must be informed to a large extent by errors in orthology prediction which mimic expected patterns of gene evolution.
The same but different: setal arrays of anoles and geckos indicate alternative approaches to achieving similar adhesive effectiveness
Authors: Garner Austin M. , Wilson Michael C. , Wright Caitlin , Russell Anthony P. , Niewiarowski Peter H. , Dhinojwala Ali
Published: November 2020

The functional morphology of squamate fibrillar adhesive systems has been extensively investigated and has indirectly and directly influenced the design of synthetic counterparts. Not surprisingly, the structure and geometry of exemplar fibrils (setae) have been the subject of the bulk of the attention in such research, although variation in setal morphology along the length of subdigital adhesive pads has been implicated in the effective functioning of these systems. Adhesive setal field configuration has been described for several geckos, but that of the convergentAnolislizards, comprised of morphologically simpler fibrils, remains largely unexplored. Here we examine setal morphology along the proximodistal axis of the digits ofAnolis equestrisand compare our findings to those for a model gecko,Gekko gecko. Consistent with previous work, we found that the setae ofA. equestrisare generally thinner, shorter, and present at higher densities than those ofG. geckoand terminate in a single spatulate tip. Contrastingly, the setae ofG. geckoare hierarchically branched in structure and carry hundreds of spatulate tips. Although the splitting of contacts into multiple smaller tips is predicted to increase the adhesive performance of a fiber compared to an unbranched one, we posited that the adhesive performance ofG. geckoandA. equestriswould be relatively similar when the configuration of the setal fields of each was accounted for. We found that, as in geckos, setal morphology ofA. equestrisfollows a predictable pattern along the proximodistal axis of the pad, although there are several critical differences in the configuration of the setal fields of these two groups. Most notably, the pattern of variation in setal length ofA. equestrisis effectively opposite to that exhibited byG. gecko. This difference in clinal variation mirrors the difference in the direction in which the setal fields of anoles and geckos are peeled from the substrate, consistent with the hypothesis that biomechanical factors are the chief determinants of these patterns of variation. Future empirical work, however, is needed to validate this. Our findings introduceAnolislizards as an additional source of inspiration for bio-inspired design and set the stage for comparative studies investigating the functional morphology of these convergent adhesive apparatuses. Such investigations will lead to an enhanced understanding of the interactions between form, function, and environment of fibril-based biological adhesive systems.