bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic sclerosis pathogenesis: contribution of recent advances in genetics
Authors: Orvain Cindy , Assassi Servin , Avouac Jérôme , Allanore Yannick 
Published: August 2020

Purpose of review
To review susceptibility genes and how they could integrate in systemic sclerosis (SSc) pathophysiology providing insight and perspectives for innovative therapies.

Recent findings
SSc is a rare disease characterized by vasculopathy, dysregulated immunity and fibrosis. Genome-Wide association studies and ImmunoChip studies performed in recent years revealed associated genetic variants mainly localized in noncoding regions and mostly affecting the immune system of SSc patients. Gene variants were described in innate immunity (IRF5, IRF7 and TLR2), T and B cells activation (CD247, TNFAIP3, STAT4 and BLK) and NF-κB pathway (TNFAIP3 and TNIP1) confirming previous biological data. In addition to impacting immune response, CSK, DDX6, DNASE1L3 and GSDMA/B could also act in the vascular and fibrotic components of SSc.

Summary
Although genetic studies highlighted the dysregulated immune response in SSc, future research must focus on a deeper characterization of these variants with determination of their functional effects. Moreover, the role of these genes or others on specific vasculopathy and fibrosis would provide insight. Establishment of polygenic score or integrated genome approaches could identify new targets specific of SSc clinical features. This will allow physicians to propose new therapies to SSc patients.
Immunometabolism in the pathogenesis of systemic lupus erythematosus: an update
Authors: Romo-Tena Jorge , Kaplan Mariana J. 
Published: August 2020

Purpose of review
To provide an update on state-of-the-art evidence on the role of immunometabolism reprogramming in the pathogenesis of systemic lupus erythematosus (SLE).

Recent findings
Mitochondrial dysfunction and enhanced oxidative stress, along with specific defects in other metabolic pathways, can promote dysregulation of innate and adaptive immune responses in SLE. These abnormalities appear to be driven by genetic and epigenetic factors, modulated by stochastic events. In addition to extensive descriptions of abnormalities in immunometabolism of lupus lymphocytes, recent studies support the critical role of dysregulation of metabolic pathways in innate immune cells including neutrophils, macrophages and dendritic cells, in SLE pathogenesis. Recent abnormalities described in lipid metabolism have been associated with SLE disease activity and related damage. Promising therapeutic strategies that target these metabolic abnormalities have recently been described in SLE.

Summary
Fundamental new insights regarding the role of mitochondrial dysfunction in innate immune dysregulation in SLE pathogenesis have recently emerged. Defects in specific molecular pathways pertinent to immunometabolism in SLE have been described. New insights in translational medicine and promising therapeutic targets have been proposed based on these recent findings.
Mortality Rates in a Diverse Cohort of Mechanically Ventilated Patients With Novel Coronavirus in the Urban Midwest
Authors: Twigg Homer L. , Khan Sikandar H. , Perkins Anthony J. , Roberts Scott , Sears Catherine , Rahman Omar , Smith Joseph P. , Kapoor Rajat , Farber Mark O. , Ellender Timothy , Carlos Graham , Gilroy Grant , Buckley John , Bosslet Gabriel , Machado Roberto , Gao Sujuan , Khan Babar A. 
Published: August 2020

Objectives:
Differences in mortality rates previously reported in critically ill patients with coronavirus disease 2019 have increased the need for additional data on mortality and risk factors for death. We conducted this study to describe length of stay, mortality, and risk factors associated with in-hospital mortality in mechanically ventilated patients with coronavirus disease 2019.

Design:
Observational study.

Setting:
Two urban, academic referral hospitals in Indianapolis, Indiana.

Patients or Subjects:
Participants were critically ill patients 18 years old and older, admitted with coronavirus disease 2019 between March 1, 2020, and April 27, 2020.

Interventions:
None.

Measurements and Main Results:
Outcomes included in-hospital mortality, duration of mechanical ventilation, and length of stay. A total of 242 patients were included with mean age of 59.6 years (sd, 15.5 yr), 41.7% female and 45% African American. Mortality in the overall cohort was 19.8% and 20.5% in the mechanically ventilated subset. Patients who died were older compared with those that survived (deceased: mean age, 72.8 yr [sd, 10.6 yr] vs patients discharged alive: 54.3 yr [sd, 14.8 yr]; p < 0.001 vs still hospitalized: 59.5 yr [sd, 14.4 yr]; p < 0.001) and had more comorbidities compared with those that survived (deceased: 2 [0.5–3] vs survived: 1 [interquartile range, 0–1]; p = 0.001 vs still hospitalized: 1 [interquartile range, 0–2]; p = 0.015). Older age and end-stage renal disease were associated with increased hazard of in-hospital mortality: age 65–74 years (hazard ratio, 3.1 yr; 95% CI, 1.2–7.9 yr), age 75+ (hazard ratio, 4.1 yr; 95% CI, 1.6–10.5 yr), and end-stage renal disease (hazard ratio, 5.9 yr; 95% CI, 1.3–26.9 yr). The overall median duration of mechanical ventilation was 9.3 days (interquartile range, 5.7–13.7 d), and median ICU length of stay in those that died was 8.7 days (interquartile range, 4.0–14.9 d), compared with 9.2 days (interquartile range, 4.0–14.0 d) in those discharged alive, and 12.7 days (interquartile range, 7.2–20.3 d) in those still remaining hospitalized.

Conclusions:
We found mortality rates in mechanically ventilated patients with coronavirus disease 2019 to be lower than some previously reported with longer lengths of stay.
Tracheostomy for Coronavirus Disease 2019 Patients: Maintaining the Standard of Care
Authors: Bassily-Marcus Adel , Leibner Evan S. , Kohli-Seth Roopa 
Published: August 2020

Objectives:
To respond to the new recommendations for delaying tracheostomy for coronavirus disease 2019 patients to day 21 post-intubation to ensure viral clearance.

Design:
Prospective observational cohort from April 1, 2020, to April 30, 2020, with 60 days follow-up.

Setting:
Academic medical center with nine adult ICUs dedicated to caring for coronavirus disease 2019 patients requiring mechanical ventilation.

Patients:
Mechanically ventilated patients with coronavirus disease 2019 pneumonia requiring tracheostomy for prolonged ventilatory support.

Interventions:
Adherence to the standard of care for timing of tracheostomy as deemed necessary by the intensivist without delay and utilizing the existing tracheostomy team in performing the needed procedures within 1 day of the request.

Measurements and Main Results:
One hundred eleven patients with coronavirus disease 2019 received tracheostomy in the month of April 2020. Median time to tracheostomy was 11 days. All procedures were performed percutaneously at bedside under bronchoscopic guidance. Sixty-three percent of patients who received tracheostomy either weaned or discharged alive within 60 days of the procedure. Performing tracheostomy on these patients without delay did not lead to coronavirus disease 2019 viral transmission to the tracheostomy team as evident by lack of symptoms and negative antibody testing.

Conclusions:
Adherence to standard of care in timing of tracheostomy is safe. Recommending delaying the procedure may lead to harmful consequences from prolonging mechanical ventilation and sedation without apparent benefit.
Testing for Severe Acute Respiratory Syndrome–Coronavirus 2: Challenges in Getting Good Specimens, Choosing the Right Test, and Interpreting the Results
Authors: Tu Yuan-Po , O’Leary Timothy J. 
Published: August 2020

Objectives:
We explore ways to reduce errors in laboratory diagnosis of severe acute respiratory syndrome–coronavirus 2 infection by considering preanalytic, analytic, and postanalytic sources. To address preanalytic challenges, we first consider alternative anatomic sites for specimen collection, then discuss self-collection, alternative sampling devices, and transport media. Strengths and limitations of various analytic test systems are considered in the context of postanalytic challenges associated with making test results meaningful, specifically considering the complex relationship between “positive” test results and reproduction and shedding of intact virus. Finally, we provide recommendations regarding healthcare worker surveillance and release of patients with coronavirus disease 2019 from isolation.

Data Sources:
Material was derived from a Webinar available to the public, manufacturer’s websites, U.S. Food and Drug Administration, and Centers for Disease Control and Prevention websites and from both peer-reviewed papers identified by PubMed search and nonpeer-reviewed papers posted on Biorxiv and Medrxiv. Unpublished data came from the Washington State Department of Health.

Study Selection:
We included studies that compared diagnostic performance strategies without introducing bias due to use of an imperfect gold standard. Case series and case reports were included as necessary to illuminate the significance of results.

Data Extraction:
Data were extracted manually.

Data Synthesis:
Sensitivity, specificity, and CIs were computed from article data using a composite reference standard. Nucleic acid-based tests were assumed to perform at 100% specificity.

Conclusions:
Although sputum and bronchoalveolar lavage samples provide the highest diagnostic sensitivity for severe acute respiratory syndrome-coronavirus 2, nasopharyngeal, mid turbinate, and nasal specimens are suitable in most cases and require less use of personal protective equipment. When desired sampling materials are unavailable, alternatives may be substituted with no loss of performance. Both reverse transcriptase polymerase chain reaction tests and rapid nucleic acid-based tests offer good performance in most circumstances. Testing is not required to release most patients from isolation.
Association between age at arrival, duration of migration, and overweight/obesity in Chinese rural-to-urban migrants: the Yi migrant study
Authors: Wang Ye , Pan Li , Wan Shao-Ping , Yi Huo-Wu-Li , Yang Fang , He Hui-Jing , Li Zheng , Zhang Jia , Yong Zheng-Ping , Shan Guang-Liang 
Published: August 2020

Abstract

Background:
Urbanization in China is rapidly proceeding, but rural-to-urban migration and its association with overweight and obesity is not well studied. This study aimed to explore the age at arrival, duration of migration, and the corresponding association with overweight/obesity in Yi migrants in China.

Methods:
A cross-sectional study was conducted in rural and urban areas in 2015 in Sichuan province, China. Demographic characteristics, lifestyle factors, and anthropometry were collected. General linear regression models were used to assess the effect of duration of migration (1–10, 11–20, 21–30, and >30 years) on body mass index (BMI). Multi-variable logistic regression was used to examine the association between duration of migration and overweight/obesity (BMI ≥ 25 kg/m2).

Results:
A total of 3056 Yi people (1894 Yi farmers and 1162 Yi migrants) aged 20 to 80 years were enrolled. After adjusting for age, sex, and other potential confounders, Yi migrants had 1.71 kg/m2 (95% confidence interval [CI]: 1.36–2.06) higher BMI and a 2.13-fold (95% CI: 1.71–2.65) higher risk of overweight/obesity than Yi farmers. In Yi migrants, stratified by age at arrival, no significant association between duration of migration and overweight/obesity was observed in those who were 0 to 20 years old at arrival. In comparison, in migrants >20 years old at arrival, compared with the reference group (1–10 years), long-term migration (>30 years) was found to be associated with overweight/obesity after adjustment (odds ratio: 1.85, 95% CI: 1.04–3.29).

Conclusions:
Yi migrants were observed to have greater risk of overweight/obesity than Yi farmers. In Yi migrants, the risk of overweight/obesity increased according to the duration of migration, especially in those who were older upon their arrival.
Deep learning-based, computer-aided classifier developed with dermoscopic images shows comparable performance to 164 dermatologists in cutaneous disease diagnosis in the Chinese population
Authors: Wang Shi-Qi , Zhang Xin-Yuan , Liu Jie , Tao Cui , Zhu Chen-Yu , Shu Chang , Xu Tao , Jin Hong-Zhong 
Published: August 2020

Abstract

Background
Diagnoses of Skin diseases are frequently delayed in China due to lack of dermatologists. A deep learning-based diagnosis supporting system can facilitate pre-screening patients to prioritize dermatologists’ efforts. We aimed to evaluate the classification sensitivity and specificity of deep learning models to classify skin tumors and psoriasis for Chinese population with a modest number of dermoscopic images.

Methods
We developed a convolutional neural network (CNN) based on two datasets from a consecutive series of patients who underwent the dermoscopy in the clinic of the Department of Dermatology, Peking Union Medical College Hospital, between 2016 and 2018, prospectively. In order to evaluate the feasibility of the algorithm, we used two datasets. Dataset I consisted of 7192 dermoscopic images for a multi-class model to differentiate three most common skin tumors and other diseases. Dataset II consisted of 3115 dermoscopic images for a two-class model to classify psoriasis from other inflammatory diseases. We compared the performance of CNN with 164 dermatologists in a reader study with 130 dermoscopic images. The experts’ consensus was used as the reference standard except for the cases of basal cell carcinoma (BCC), which were all confirmed by histopathology.

Results
The accuracies of multi-class and two-class models were 81.49% ± 0.88% and 77.02% ± 1.81%, respectively. In the reader study, for the multi-class tasks, the diagnosis sensitivity and specificity of 164 dermatologists were 0.770 and 0.962 for BCC, 0.807 and 0.897 for melanocytic nevus, 0.624 and 0.976 for seborrheic keratosis, 0.939 and 0.875 for the “others” group, respectively; the diagnosis sensitivity and specificity of multi-class CNN were 0.800 and 1.000 for BCC, 0.800 and 0.840 for melanocytic nevus, 0.850 and 0.940 for seborrheic keratosis, 0.750 and 0.940 for the “others” group, respectively. For the two-class tasks, the sensitivity and specificity of dermatologists and CNN for classifying psoriasis were 0.872 and 0.838, 1.000 and 0.605, respectively. Both the dermatologists and CNN achieved at least moderate consistency with the reference standard, and there was no significant difference in Kappa coefficients between them (P > 0.05).

Conclusions
The performance of CNN developed with relatively modest number of dermoscopic images of skin tumors and psoriasis for Chinese population is comparable with 164 dermatologists. These two models could be used for screening in patients suspected with skin tumors and psoriasis respectively in primary care hospital.
Positive Cytosolic 5-Nucleotidase 1A Antibodies in Motor Neuron Disease
Authors: Assadi Rami-James K. , Manousakis Georgios 
Published: August 2020

Abstract
Inclusion body myositis (IBM) is the most common acquired myopathy in adults older than 50 years. Muscle biopsy remains the gold standard for diagnosis. Recently described serum antibodies against cytosolic 5-nucleotidase 1A (cN1A) are considered highly specific for IBM. However, positive cN1A antibodies in diseases other than IBM are recently reported. We review 2 cases in which serum antibodies were positive but ancillary testing revealed motor neuron disease. A 68-year-old man presented with asymmetric quadriceps and handgrip weakness prompting concern for IBM. However, electromyography showed purely chronic neurogenic abnormalities, and muscle biopsy was consistent with post-polio syndrome. A 60-year-old woman reported a history of progressive muscle weakness. Despite positive antibodies, examination and electromyography were indicative of amyotrophic lateral sclerosis. Serum cN1A antibodies are not 100% specific for the diagnosis of IBM. Careful clinical, electrophysiologic, and histopathologic correlation is required in workup of individuals with neuromuscular weakness and positive antibodies.
Wild-type Transthyretin Amyloid Myopathy With an Inclusion Body Myositis Phenotype
Authors: Huser Sara , Loavenbruck Adam , Manousakis Georgios 
Published: August 2020

AbstractSenile systemic amyloidosis (SSA), or wild-type transthyretin (wtATTR) amyloidosis, is associated most commonly with cardiomyopathy and carpal tunnel syndrome. SSA-associated skeletal myopathy is rare. We describe the case of a patient with SSA who exhibited asymmetric quadriceps and finger flexor weakness, a phenotype usually seen in inclusion body myositis.
Laing Myopathy: Report of 4 New Families With Novel MYH7 Mutations, Double Mutations, and Severe Phenotype
Authors: Alessi Catherine E. , Wu Qian , Whitaker Charles H. , Felice Kevin J. 
Published: August 2020

Abstract
Laing distal myopathy (LDM) is an autosomal dominant disorder caused by mutations in the slow skeletal muscle fiber myosin heavy chain (MYH7) gene on chromosome 14q11.2. The classic LDM phenotype—including early-onset, initial involvement of foot dorsiflexors and great toe extensors, followed by weakness of neck flexors and finger extensors—is well documented. Since the original report by Laing et al in 1995, the spectrum of MYH7-related myopathies has expanded to include congenital myopathies, late-onset myopathies, myosin storage myopathy, and scapuloperoneal myopathies. Most patients with LDM harbor mutations in the midrod domain of the MYH7 gene, but rare cases document disease-associated mutations in the globular head region. In this report, we add to the medical literature by describing the clinicopathological findings in 8 affected family members from 4 new LDM families—including 2 with novel MYH7 mutations (Y162D and A1438P), one with dual mutations (V39M and K1617del), and one family (E1508del) with severe early-onset weakness associated with contractures, respiratory insufficiency, and dilated cardiomyopathy. Our families highlight the ever-expanding clinical spectrum and genetic variation of the skeletal myopathies related to MYH7 gene mutations.
Persistent Postconcussion Symptoms: An Expert Consensus-Based Definition Using the Delphi Method
Authors: Lagacé-Legendre Corinne , Boucher Valérie , Robert Sébastien , Tardif Pier-Alexandre , Ouellet Marie-Christine , de Guise Elaine , Boulard Geneviève , Frémont Pierre , Émond Marcel , Moore Lynne , Le Sage Natalie 
Published: August 2020

Objective:
To provide an expert consensus definition of persistent postconcussion symptoms following a mild traumatic brain injury (mTBI).

Participants:
Canadian healthcare professionals caring for patients with mTBI.

Design:
Online Delphi process.

Main Measures:
A first Delphi round documented important dimensions or criteria to consider when defining persistent symptoms. Expert opinions were then resubmitted in 4 subsequent Delphi rounds and their relevance was rated using a 9-point Likert scale. An item with a median rating of 7 or more and a sufficient level of agreement were considered consensual.

Results:
After 5 rounds, consensus was reached on a set of criteria that can be summarized as follows: presence of any symptom that cannot be attributed to a preexisting condition and that appeared within hours of an mTBI, that is still present every day 3 months after the trauma, and that has an impact on at least one sphere of a person's life.

Conclusion:
This Delphi consensus proposes a set of criteria that support a more uniform definition of persistent symptoms in mild TBI among clinicians and researchers. This definition may help clinicians better identify persistent postconcussion symptoms and improve patient management.
CHOROIDAL VASCULARITY INDEX IN YOUNG CHOROIDEREMIA PATIENTS
Authors: Murro Vittoria , Mucciolo Dario Pasquale , Giorgio Dario , Passerini Ilaria , Cipollini Francesca , Virgili Gianni , Giansanti Fabrizio , Sodi Andrea 
Published: August 2020

Purpose:
To evaluate choroidal features in young patients affected by choroideremia (CHM).

Methods:
Young CHM patients and control subjects were recruited at the Eye Clinic in Florence. High-resolution choroidal imaging was obtained using swept-source optical coherence tomography with long optical coherence tomography scans (12 × 9 mm optical coherence tomography scans). We considered the subfoveal choroidal area within 9 mm of the optic disk in the horizontal plane and the subfoveal choroidal area within a 3-mm diameter centered over the fovea. The subfoveal choroidal thickness, total choroidal area, luminal area, stromal area, and choroidal vascularity index were assessed using the “ImageJ” software in both groups.

Results:
Eight patients (16 eyes; mean age, 19.3 ± 5.2 years) and seven control subjects (14 eyes; mean age, 19.0 ± 5.0 years) were included in this study. Best-corrected visual acuity was 20/20 in both eyes of seven CHM patients and in all control subjects and 20/25 in both eyes in one CHM patient. Mean subfoveal choroidal thickness did not differ between CHM patients and control subjects. Luminal area9mm, stromal area9mm, and total choroidal area9mm were reduced in patients compared with the control group. Luminal area3mm, stromal area3mm, and total choroidal area3mm did not differ between patients and control subjects. Choroidal vascularity index9mm and choroidal vascularity index3mm were not different between patients and control subjects.

Conclusion:
There are no differences in the choroidal vascularity index between young CHM patients and control subjects; this result suggests a simultaneous, proportional impairment of both the stromal and vascular components of the choroid in the early stages of the disease.
ASSOCIATION BETWEEN CHOROIDAL CHARACTERISTICS AND SYSTEMIC SEVERITY IN AMYLOIDOSIS
Authors: Mano Fukutaro , Dispenzieri Angela , Kusaka Shunji , Pavesio Carlos , Khalid Hagar , Keane Pearse A. , Pulido Jose S. 
Published: August 2020

Purpose:
This study aimed to describe the choroidal features of ocular amyloidosis using multimodal imaging, to correlate these findings with systemic involvement, and to propose a choroidal grading system.

Methods:
Eleven patients with systemic amyloidosis were reviewed retrospectively. Each case was assigned a grade according to the severity of choroidal findings as determined by both enhanced depth imaging optical coherence tomography and indocyanine green angiography. The severity of systemic amyloidosis was then correlated with the choroidal involvement.

Results:
On indocyanine green angiography, all patients exhibited hyperfluorescent spots in the late stage and were classified according to preexisting criteria. On enhanced depth imaging optical coherence tomography, hyperreflective foci were seen in the choriocapillaris and Sattler's layer in Grade 1, partial loss of Sattler's layer was additionally seen in Grade 2, and a dense hyperreflective Haller's layer was seen in Grade 3. Choroidal grading scores were significantly correlated with the systemic severity score (P = 0.0014, Pearson's correlation coefficient; ρ = 0.83).

Conclusion:
With ocular amyloidosis, evaluation of choroidal characteristics using multimodal imaging may serve as a biomarker for systemic involvement.