bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel compound heterozygous mutation in the arginase-1 gene identified in a Chinese patient with argininemia
Authors: Cui Dongqing , Liu Yanxia , Jin Liang , Hu Liping , Cao Lili 
Published: August 2020

Abstract

Introduction:
Arginineemia, also known as arginase deficiency, is a rare autosomal recessive metabolic disease. The diagnosis sometimes may be delayed due to atypical clinical manifestations. Confirmation of arginineemia depends on genetic testing.

Patient concerns:
We reported a Chinese male child presenting with hyperargininemia and progressive spastic diplegia, who has a novel compound heterozygous mutation in the arginase-1 (ARG1) gene (c.263-266delAGAA, p.K88Rfs∗45;c.674T>C,p.L216P), respectively, coming from his mother and father.

Diagnosis:
The patient was diagnosed with argininemia with a novel compound homozygous mutation of the ARG1 gene at the age of 12 years.

Interventions:
The patient had a low-protein diet (0.8 g/kg/day). Baclofen, eperisone hydrochloride, botulinum toxin, and rehabilitation training were used to improve his spastic diplegia symptoms for 3 months.

Outcomes:
The patient's blood arginine was still high after 3 months’ low-protein diet. His spastic diplegia symptoms had not aggravated after 3 months’ treatment.

Conclusions:
Argininemia should be considered in a patient with slowly progressive neurologic manifestations, especially spastic diplegia. This case also suggests that tandem mass spectrometry should be used as an effective tool in the validity of neonatal screening for early diagnosis.
Comparison of suture-button and screw fixation in the treatment of ankle syndesmotic injuries
Authors: Liu Xiaoning , Jin Guang , Piao Chengdong , Zhong Zhuan , Chang Fei , Huang Bingzhe 
Published: August 2020

Abstract

Background:
Syndesmotic injuries account for a significant number of ankle injuries. There is no consensus regarding the recommended method of treatment. The purpose of this study was to evaluate:

Methods:
This study was performed and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. The records of 200 patients with ankle fractures who had undergone surgical treatment in our clinics between January 2014 and January 2018 were retrospectively investigated. This retrospective cohort study was approved by the institutional review board in the 2nd Hospital of Jilin University. The primary outcome measure was the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and the Foot Function Index. Secondary outcome measures included visual analog scale score, complications, range of movement of ankle, reoperations, and radiologic outcomes. For statistical comparison of the clinical and radiologic findings between the 2 groups, we used SPSS, version 21.0 (SPSS, Chicago, IL), statistical software. P Values of < .05 were considered statistically significant.

Conclusion:
The hypothesis was that the SB technique would achieve better functional outcomes as compared to the syndesmotic screw technique after surgery.

Trial registration:
This study protocol was registered in Research Registry (researchregistry5793).
Vitamin D status is associated with hepcidin and hemoglobin concentrations in patients with severe traumatic injury
Authors: Apple Camille G. , Miller Elizabeth S. , Kannan Kolenkode B. , Stortz Julie A. , Cox Michael , Loftus Tyler J. , Parvataneni Hari K. , Patrick Matthew , Hagen Jennifer E. , Brakenridge Scott , Efron Philip A. , Mohr Alicia M. 
Published: August 2020

BACKGROUNDSevere traumatic injury leads to persistent injury-associated anemia that is associated with hypercatecholaminemia, systemic inflammation, increased hepcidin, and a functional iron deficiency. Vitamin D has been shown to reduce proinflammatory cytokines and hepcidin concentrations. This study aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia following blunt trauma.METHODSA prospective observational cohort study comparing blunt trauma patients (n = 45) with elective hip replacement patients (n = 22) and healthy controls (n = 8) was performed. Bone marrow ferroportin, transferrin receptor, and erythroferrone expression was measured using quantitative polymerase chain reaction (qPCR). Plasma was assessed for systemic inflammation, erythropoietin (EPO), iron regulation, and vitamin D (25-OH) concentrations using enzyme-linked immunosorbent assay. Hemoglobin was measured on the day of discharge.RESULTSCompared with hip replacement, trauma patients had higher plasma interleukin-6 (90.1 vs. 3.8 pg/mL), C-reactive protein (6,223 vs. 2,612 ng/mL), and hepcidin (79.3 vs. 21.2 ng/mL) concentrations. Trauma patients had lower vitamin D (25-OH) (12.8 vs. 18.1 ng/mL) and iron (23.5 vs. 59.9 μg/mL) levels compared with hip replacement patients. Despite the higher hepcidin EPO levels, bone marrow erythroferrone expression was increased 69% following trauma.CONCLUSIONFollowing elective hip replacement, patients did have anemia and impaired iron homeostasis without a significant change in inflammatory biomarkers, EPO, and vitamin D status. Vitamin D status did correlate with systemic inflammation, iron dysfunction, and persistent injury-associated anemia following severe blunt trauma. Further research is needed to determine whether supplementation with vitamin D in the trauma population could improve the persistent injury-associated anemia.LEVEL OF EVIDENCEProspective study, prognostic, level III.
The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation
Authors: Senda Atsushi , Morishita Koji , Kojima Mitsuaki , Doki Sanae , Taylor Beth , Yagi Masayuki , Watanabe Arisa , Kobayashi Tetsuyuki , Aiboshi Junichi , Coimbra Raul , Otomo Yasuhiro 
Published: August 2020

BACKGROUND
Intestinal ischemia caused by hemorrhagic shock is known to induce systemic inflammatory responses. Previous studies have shown that mesenteric lymph (ML) plays a crucial role in gut-mediated inflammation. Lipid mediators, such as lysophosphatidylcholines (LPCs), which contain polyunsaturated fatty acids (PUFAs), are present in the postshock ML. Exosomes are also present in the ML and act as transcellular carriers of lipids; however, their role in postshock systemic inflammation has not been revealed. Here, we aimed to identify changes in lipid mediators in ML exosomes after intestinal ischemia.

METHODS
Male Sprague-Dawley rats underwent laparotomy, followed by ML duct cannulation. Animals were subjected to 60 minutes of intestinal ischemia by superior mesenteric artery clamping, followed by 120 minutes of reperfusion. Mesenteric lymph was obtained before and after intestinal ischemia, and exosomes were isolated from ML by ultracentrifugation. The biological activity of ML exosomes was determined using the monocyte nuclear factor κB (NF-κB) activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry.

RESULTS
Mesenteric lymph exosome–induced NF-κB activation significantly increased after intestinal ischemia, and lipid analysis revealed a significant increase in the concentration of PUFA-containing LPCs. In addition, PUFA-containing LPCs also induced NF-κB activation.

CONCLUSION
Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.
Isolated low-grade solid organ injuries in children following blunt abdominal trauma: Is it time to consider discharge from the emergency department?
Authors: Plumblee Leah , Williams Regan , Vane Dennis , Zhang Jingwen , Jensen Aaron , Naik-Mathuria Bindi , Evans Lauren , Streck Christian J. 
Published: August 2020

INTRODUCTION
Acute intervention (AI) for solid organ injury (SOI) is rare in hemodynamically stable children. Pediatric guidelines recommend admission with follow-up laboratories, even for low-grade injuries.

METHODS
Data sets from two large multicenter prospective observational studies were used to analyze a cohort of children (age, <17 years) with grade I to III SOI following blunt abdominal trauma. Children with hollow viscus injuries were excluded. Patients were divided into (a) those with or without other major injuries (OMIs) (traumatic brain injury, hemothorax or pneumothorax, pelvic fracture, urgent orthopedic or neurosurgical operations) and (b) with grade I or II versus grade III injuries. Outcomes included AIs (transfusion, angiography, abdominal operation) and disposition (admission unit and length of stay).

RESULTS
There were 14,232 children enrolled in the two studies, and 791 patients had a SOI (5.6%). After excluding patients with hollow viscus injuries and higher-grade SOIs, 517 patients with a grade I to III SOI were included, and 262 of these had no OMI. Among patients with no OMI, none of 148 patients with grade I or II SOI underwent AI, while only 3 of 114 patients with grade III injuries underwent AI (3 transfusions/1 angioembolization). All three had hemoperitoneum; two of three had an additional organ with a grade II injury. Among grade I and II SOIs with no OMI, 28 (18.9%) of 148 were admitted to an intensive care unit, 110 (74.3%) of 148 to floor, and 7 (4.7%) of 148 discharged home from emergency department; median length of stay 2 days. Among grade III SOIs with no OMI, 38 (33.3%) of 114 were admitted to an intensive care unit and 61.4% to the floor; median length of stay was 4 days. Among 255 patients with a grade I to III SOI and other major organ system injuries, 31 (12.2%) underwent AI.

CONCLUSION
No patient with a grade I and II SOI and no OMI following blunt abdominal trauma received intervention, suggesting that patients with low-grade SOI without OMIs could be safely observed and discharged from the emergency department.

LEVEL OF EVIDENCE
Therapeutic study, level IV.
Gender Disparity and Potential Strategies for Improvement in Neurology and Clinical Neurophysiology
Authors: Galloway Gloria , Schmitt Sarah , Herman Susan T. , La Roche Suzette 
Published: August 2020

Summary:
Discrimination in the workplace when documented is illegal but is seen to still exist in some forms whether based on culture, race, or gender. Each of these disparities warrants further discussion and study because of their significant impacts on hiring decisions, career advancement, and compensation. In this article, the authors have focused their attention on gender disparity in the fields of neurology and clinical neurophysiology and shared the data currently available to them. At a time when the field of clinical neurophysiology has seen enormous growth, gender disparity in leadership and compensation remain. Despite the increasing number of women entering the fields of neurology and clinical neurophysiology, women remain underrepresented in national leadership positions. Many women physicians report experiencing gender discrimination despite increasing efforts by universities and medical centers to improve inclusivity and diversity. Equity and inclusivity are not the same and there is a disconnect between the increased numbers of women and their shared experiences in the workplace. Implicit bias undermines the ability of women to advance in their careers. For neurologists, data indicate that the latest gender pay gap is $56,000 (24%), increased from $37,000 in 2015, and is one of the largest pay gaps in any medical specialty. One third of the top 12 medical schools in the United States require that maternity leave be taken through disability coverage and/or sick benefits, and most family leave policies constrain benefits to the discretion of departmental leadership. The authors recommend strategies to improve gender disparity include institutional training to Identify and overcome biases, changes to professional organizations and national scientific meeting structure, transparency in academic hiring, promotion and compensation, and mentorship and sponsorship programs.
The Presence and Significance of A-Waves—A Retrospective Review of 679 Patients
Authors: Zhang WenWen , Roberts Leslie 
Published: August 2020

Purpose:
A-waves are late responses that have been reported in healthy individuals and patients with neurologic conditions. The mechanism(s) responsible for their generation and their clinical significance are not fully understood. The aim was to better characterize A-waves.

Methods:
A retrospective study was conducted in a high-volume Neurophysiology Department in a tertiary hospital in Melbourne, Australia. Consecutive neurophysiological tests including F-wave studies performed between July 2017 and September 2018 were reviewed to identify A-waves. Patients' characteristics and neurophysiological diagnoses were recorded.

Results:
A total of 679 patients were included in the analysis and a total of 2,730 nerves were studied. A-waves were most commonly found in tibial nerves, followed by peroneal, median, and ulnar nerves. A-waves were seen in 39.4% of individuals with otherwise normal nerve conduction studies and 39.1% of individuals with entrapment neuropathy. They were most seen in demyelinating neuropathy (85.7%), followed by mixed neuropathy (73.3%), anterior horn cell disease (66.7%), axonal neuropathy (61.2%), and radiculopathy (53.1%). Most patients with demyelinating neuropathy had multiple A-waves (61.9%), but these were also seen in 15.2% of individuals with otherwise normal nerve conduction studies and in 40% of those with other neurologic conditions. A-waves were more often seen in individuals older than 60 years.

Conclusions:
A-waves are commonly seen in symptomatic individuals with otherwise normal nerve conduction studies and individuals with various neurologic conditions but are more commonly found in nerves with otherwise abnormal electrophysiological testing. A-waves are most seen in tibial nerves. Multiple A-waves were more commonly seen in demyelinating neuropathy than other conditions.
Interim Results of a Phase II/III Multicenter Randomized Clinical Trial of AVIFAVIR in Hospitalized Patients with COVID-19
Authors: Ivashchenko Andrey A. , Dmitriev Kirill A. , Vostokova Natalia V. , Azarova Valeria N. , Blinow Andrew A. , Egorova Alina N. , Gordeev Ivan G. , Ilin Alexey P. , Karapetian Ruben N. , Kravchenko Dmitry V. , Lomakin Nikita V. , Merkulova Elena A. , Papazova Natalia A. , Pavlikova Elena P. , Savchuk Nikolay P. , Simakina Elena N. , Sitdekov Tagir A. , Smolyarchuk Elena A. , Tikhomolova Elena G. , Yakubova Elena V. , Ivachtchenko Alexandre V. 
Published: August 2020

ABSTRACTIn May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for the treatment of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR enabled SARS-CoV-2 viral clearance in 62.5% of patients within 4 days, and was safe and well-tolerated.
Therapeutic effectiveness of interferon alpha 2b treatment for COVID-19 patient recovery
Authors: Pereda R , González D , Rivero HB , Rivero JC , Pérez A , López LR , Mezquia N , Venegas R , Betancourt Julio Raul , Domínguez RE 
Published: August 2020

ABSTRACTBackgroundEffective antiviral treatments are required to contain the ongoing coronavirus disease 2019 (COVID-19) pandemic. A previous report in 814 patients COVID-19 positive in Cuba provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) from March 11 to April 14, 2020. This study, re-evaluates the contribution of IFN-α2b on the evolution of all patients, after 98 days of the epidemic, in a period from March 11 to June 17, 2020.MethodA prospective observational study was implemented to monitor a therapeutic intervention with IFN-α2b used in the national protocol for COVID-19 attending in Cuba. Were included patients with positive throat swab specimens by real time RT-PCR who gave informed consent and had no contraindications for IFN treatment. Patients received therapy as per the Cuban COVID protocol that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b The primary endpoint was the proportion of patients discharged from hospital, secondary was the case fatality rate and several outcomes related to time variables were also evaluated.ResultsFrom March 11th until June 17th, 2295 patients had been confirmed SARS-CoV-2 positive in Cuba, 2165 were treated with Heberon® Alpha R and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with non-IFN treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. The benefits of IFN were significantly supported by time variables analyzed.ConclusionsThis second report confirm the preliminary evidences from first for the therapeutic effectiveness of IFNα-2b for SARS-Cov-2 infection and postulated that Heberon® Alpha R is the main component within the antiviral triad used as a therapeutic intervention in the Cuban protocol COVID-19.
Efficacy of Connexin testing in detecting Non-syndromic Sensorineural Hearing Loss in an Indian cohort
Authors: Kurva Jagannath , Bhat Nalini , Shettigar Suresh , Tawade Harshada , Shaikh Shagufta , Ghosh Anu , Cherian Susan 
Published: August 2020

ABSTRACTHearing loss is one of the most common sensory disorder and approximately 466 million people have disabling hearing loss worldwide. This study was conducted to identify the mutations in the GJB2, GJB3, and GJB6 genes in an Indian cohort with non-syndromic sensorineural hearing loss and ascertain its use for genetic testing. 31 affected individuals with prelingual bilateral non-syndromic severe to profound sensorineural hearing loss were identified based on clinical evaluation and audiometric assessment. Sanger Sequencing method was used. Six out of 31 affected individuals showed pathogenic nonsense mutations in GJB2 gene, accounting to 19.3%. Of the 6 affected individuals, 5 were homozygous for c.71G>A(p.Trp24Ter) and one was compound heterozygous for c.71G>A and c.370C>T(p.Gln124Ter). Missense mutations [c.380G>A(p.Arg127His) and c.457G>A(p.Val153Ile)], and 3’ UTR variations were also identified in GJB2 gene. GJB3 and GJB6 genes showed only silent mutations and 3’ UTR variations. 19.3% of affected individuals showing pathogenic mutations in GJB2 gene in our cohort is comparable to other Indian studies (approximately 20%) and it is less as compared to Caucasian, Japanese, and Chinese studies (approximately 50%). Lower occurrence of pathogenic mutations in GJB2 gene in our cohort and other Indian studies as compared to other Caucasian, Japanese and Chinese studies, and absence of pathogenic mutations in GJB3 and GJB6 genes indicates that these genes may have a limited role in the Indian population. Hence there is a need to identify genes that play a major role in the Indian population so that they can be used for genetic testing for NHSL to aid in accurate and early diagnosis.
Plasma microRNA profiling for malaria disease: association with severity andP. falciparumbiomass
Authors: Gupta Himanshu , Rubio Mercedes , Sitoe Antonio , Varo Rosauro , Cisteró Pau , Madrid Lola , Cuamba Inocencia , Jimenez Alfons , Martiáñez-Vendrell Xavier , Barrios Diana , Pantano Lorena , Brimacombe Allison , Bustamante Mariona , Bassat Quique , Mayor Alfredo 
Published: August 2020

AbstractSevere malaria (SM) is a major public health problem in malaria-endemic countries. Sequestration ofPlasmodium falciparum(Pf) infected erythrocytes in vital organs and the associated inflammation leads to organ dysfunction. MicroRNAs (miRNAs), which are rapidly released from damaged tissues into the host fluids, constitute a promising biomarker for the prognosis of SM. This study applied next-generation sequencing to evaluate the differential expression of miRNAs in SM compared to uncomplicated malaria (UM). Six miRNAs were associated within vitro Pfcytoadhesion, severity in Mozambican children andPfbiomass. Relative expression of hsa-miR-4497 quantified by TaqMan-RT-qPCR, was higher in SM children plasmas compared to that of UM (p<0.048), and again correlated withPfbiomass (p=0.033). These findings suggest that different physiopathological processes in SM and UM lead to differential expression of miRNAs and pave the way to future studies aiming to assess the prognostic value of these miRNAs in malaria.
Analytical Model of COVID-19 for lifting non-pharmaceutical interventions
Authors: Jacyna Garry , Thompson James R. , Koehler Matt , Slater David M. 
Published: August 2020

AbstractIn the present work, we outline a set of coarse-grain analytical models that can be used by decision-makers to bound the potential impact of the COVID-19 pandemic on specific communities with known or estimated social contact structure and to assess the effects of various non-pharmaceutical interventions on slowing the progression of disease spread. This work provides a multi-dimensional view of the problem by examining steady-state and dynamic disease spread using a network-based approach. In addition, Bayesian-based estimation procedures are used to provide a realistic assessment of the severity of outbreaks based on estimates of the average and instantaneous basic reproduction number R0.
Atrial fibrillation and kidney function: A bidirectional Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Lee Yeonhee , Kang Min Woo , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki 
Published: August 2020

AbstractAimsTo investigate the causal effects between atrial fibrillation (AF) and kidney function.Methods and ResultsWe performed a bidirectional Mendelian randomization (MR) analysis implementing the results from large-scale genome-wide association study (GWAS) for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 1,046,070) and for AF (N = 588,190) to determine genetic instruments. A bidirectional two-sample MR based on summary-level data was performed. Inverse variance weighted method was the main MR method. For replication, an allele-score based MR was performed by individual-level data within the UK Biobank cohort of white British ancestry with eGFR values (N= 321,260).The genetical predisposition to AF was significantly associated with lower eGFR [beta - 0.002 (standard error 0.0005), P < 0.001] and higher risk of chronic kidney disease [beta 0.051 (0.012), P < 0.001], and the significance remained in various MR sensitivity analyses. The causal estimates were consistent when we limited the analysis to individuals of European ancestry. The genetically predicted eGFR did not show significant association with risk of AF [beta −0.189 (0.184), P = 0.305]. The results were similar in allele-score based MR, as allele-score for AF was significantly associated with lower eGFR [beta −0.069 (0.021), P < 0.001] but allele-score for eGFR did not show significant association with risk of AF [beta −0.001 (0.009), P = 0.907].ConclusionsOur study supports that genetical predisposition to AF is a causal risk factor for kidney function impairment. However, effect from kidney function on AF was not identified in this study.