bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features
Authors: Benincá Cristiane , Zanette Vanessa , Brischigliaro Michele , Johnson Mark , Reyes Aurelio , Valle Daniel Almeida do , J. Robinson Alan , Degiorgi Andrea , Yeates Anna , Telles Bruno Augusto , Prudent Julien , Baruffini Enrico , S. F. Santos Mara Lucia , R. de Souza Ricardo Lehtonen , Fernandez-Vizarra Erika , J. Whitworth Alexander , Zeviani Massimo 
Published: May 2020

BackgroundMitochondria provide ATP through the process of oxidative phosphorylation, physically located in the inner mitochondrial membrane (IMM). The mitochondrial contact site and organising system (MICOS) complex is known as the ‘mitoskeleton’ due to its role in maintaining IMM architecture. APOO encodes MIC26, a component of MICOS, whose exact function in its maintenance or assembly has still not been completely elucidated.MethodsWe have studied a family in which the most affected subject presented progressive developmental delay, lactic acidosis, muscle weakness, hypotonia, weight loss, gastrointestinal and body temperature dysautonomia, repetitive infections, cognitive impairment and autistic behaviour. Other family members showed variable phenotype presentation. Whole exome sequencing was used to screen for pathological variants. Patient-derived skin fibroblasts were used to confirm the pathogenicity of the variant found in APOO. Knockout models in Drosophila melanogaster and Saccharomyces cerevisiae were employed to validate MIC26 involvement in MICOS assembly and mitochondrial function.ResultsA likely pathogenic c.350T>C transition was found in APOO predicting an I117T substitution in MIC26. The mutation caused impaired processing of the protein during import and faulty insertion into the IMM. This was associated with altered MICOS assembly and cristae junction disruption. The corresponding mutation in MIC26 or complete loss was associated with mitochondrial structural and functional deficiencies in yeast and D. melanogaster models.ConclusionThis is the first case of pathogenic mutation in APOO, causing altered MICOS assembly and neuromuscular impairment. MIC26 is involved in the assembly or stability of MICOS in humans, yeast and flies.
Lower limb venous and arterial peripheral diseases and work conditions: systematic review
Authors: Huo Yung Kai Samantha , Ferrières Jean , Carles Camille , Turpin Marion , Lapébie François-Xavier , Dutheil Frederic , Bura-Rivière Alessandra , Esquirol Yolande 
Published: May 2020

ObjectivesThe individual peripheral vascular disease risk factors are well documented, but the role of work conditions remains equivocal. This systematic review aims to assess relationships between lower limb peripheral venous diseases (lower limb varicose veins (LLVV), venous thromboembolism (VTE) comprising deep vein thrombosis and pulmonary embolism), peripheral arterial disease (intermittent claudication, aortic dissection, aortic aneurysm) and occupational constraints among working adults.MethodsSeveral databases were systematically searched until February 2019 for observational studies and clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used for article selection. Quality assessment and risk of bias were evaluated using Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa scales.ResultsAmong the 720 screened articles, 37 remained after full-text evaluation. Among the 21 studies on LLVV, prolonged standing was significantly associated to a higher risk of varicose veins with a threshold probably around >3 to 4 hours/day but exposure duration in years was not sufficiently considered. Seated immobility was often observed in workers, with no sufficient evidence to prove that prolonged sitting at work is related to VTE. Carrying heavy loads, stress at work and exposure to high temperatures have emerged more recently notably in relation to varicose veins but need to be better explored. Only three studies discussed the potential role of work on peripheral arterial disease development.ConclusionsAlthough some observational studies showed that prolonged standing can be related to varicose veins and that seated immobility at work could be linked to VTE, very little is known about peripheral arterial disease and occupational constraints. Clinical trials to determine preventive strategies at work are needed.PROSPERO registration numberCRD42019127652.
Simple, fast and affordable triaging pathway for COVID-19
Authors: Eggleton Elizabeth Jane 
Published: May 2020

ABSTRACTCoronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.
The effect of head and neck per-cooling on neuromuscular fatigue following exercise in the heat
Authors: Gordon Ralph Joseph Frederick Hills , Tillin Neale Anthony , Tyler Christopher James 
Published: May 2020

The effect of localised head and neck per-cooling on central and peripheral fatigue during high thermal strain was investigated. Fourteen participants cycled for 60 min at 50% peak oxygen uptake on 3 occasions: thermoneutral control (CON; 18 °C), hot (HOT; 35 °C), and HOT with head and neck cooling (HOTcooling). Maximal voluntary force (MVF) and central activation ratio (CAR) of the knee extensors were measured every 30 s during a sustained maximal voluntary contraction (MVC). Triplet peak force was measured following cycling, before and after the MVC. Rectal temperatures were higher in HOTcooling (39.2 ± 0.6 °C) and HOT (39.3 ± 0.5 °C) than CON (38.1 ± 0.3 °C; P < 0.05). Head and neck thermal sensation was similar in HOTcooling (4.2 ± 1.4) and CON (4.4 ± 0.9; P > 0.05) but lower than HOT (5.9 ± 1.5; P < 0.05). MVF and CAR were lower in HOT than CON throughout the MVC (P < 0.05). MVF and CAR were also lower in HOTcooling than CON at 5, 60, and 120 s, but similar at 30 and 90 s into the MVC (P > 0.05). Furthermore, they were greater in HOTcooling than HOT at 30 s, whilst triplet peak force was preserved in HOT after MVC. These results provide evidence that central fatigue following exercise in the heat is partially attenuated with head and neck cooling, which may be at the expense of greater peripheral fatigue. Novelty Central fatigue was greatest during hyperthermia. Head and neck cooling partially attenuated the greater central fatigue in the heat. Per-cooling led to more voluntary force production and more peripheral fatigue.
Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk
Authors: Zhu Jingjing , Shu Xiang , Guo Xingyi , Liu Duo , Bao Jiandong , Milne Roger L. , Giles Graham G. , Wu Chong , Du Mengmeng , White Emily , Risch Harvey A. , Malats Nuria , Duell Eric J. , Goodman Phyllis J. , Li Donghui , Bracci Paige , Katzke Verena , Neale Rachel E. , Gallinger Steven , Van Den Eeden Stephen K. , Arslan Alan A. , Canzian Federico , Kooperberg Charles , Beane Freeman Laura E. , Scelo Ghislaine , Visvanathan Kala , Haiman Christopher A. , Le Marchand Loïc , Yu Herbert , Petersen Gloria M. , Stolzenberg-Solomon Rachael , Klein Alison P. , Cai Qiuyin , Long Jirong , Shu Xiao-Ou , Zheng Wei , Wu Lang 
Published: May 2020

Abstract

Background:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments.

Methods:
To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci.

Results:
We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of &lt; 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production.

Conclusions:
We identified 38 candidates of protein biomarkers for PDAC risk.

Impact:
This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.
AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer
Authors: McDaniel Nellie K. , Iida Mari , Nickel Kwangok P. , Longhurst Colin A. , Fischbach Samantha R. , Rodems Tamara S. , Kranjac Carlene A. , Bo Amber Y. , Luo Qianyun , Gallagher Meghan M. , Welke Noah B. , Mitchell Kaitlyn R. , Schulz Alison E. , Eckers Jaimee C. , Hu Rong , Salgia Ravi , Hong Seungpyo , Bruce Justine Y. , Kimple Randall J. , Wheeler Deric L. 
Published: May 2020

Abstract

Purpose:
Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment.

Experimental Design:
To study AXL signaling in the context of treatment-resistant HNSCC, we used patient-derived xenografts (PDXs) implanted into mice and evaluated the tumor response to AXL inhibition in combination with cetuximab or radiation treatment. To identify molecular mechanisms of how AXL signaling leads to resistance, three tyrosine residues of AXL (Y779, Y821, Y866) were mutated and examined for their sensitivity to cetuximab and/or radiation. Furthermore, reverse phase protein array (RPPA) was employed to analyze the proteomic architecture of signaling pathways in these genetically altered cell lines.

Results:
Treatment of cetuximab- and radiation-resistant PDXs with AXL inhibitor R428 was sufficient to overcome resistance. RPPA analysis revealed that such resistance emanates from signaling of tyrosine 821 of AXL via the tyrosine kinase c-ABL. In addition, inhibition of c-ABL signaling resensitized cells and tumors to cetuximab or radiotherapy even leading to complete tumor regression without recurrence in head and neck cancer models.

Conclusions:
Collectively, the studies presented herein suggest that tyrosine 821 of AXL mediates resistance to cetuximab by activation of c-ABL kinase in HNSCC and that targeting of both EGFR and c-ABL leads to a robust antitumor response.
Antimicrobial resistance in bacteria isolated from pigs with respiratory clinical signs in Brazil
Authors: Serpa Maysa , Nascimento Juliana Amália Fonte Bôa do , Alves Mirian Fátima , Guedes Maria Isabel Maldonado Coelho , Reis Adrienny Trindade , Heinemann Marcos Bryan , Lage Andrey Pereira , Lobato Zélia Inês Portela , Dorneles Elaine Maria Seles 
Published: May 2020

Antimicrobial resistance is a current and important issue to public health, and it is usually associated with the indiscriminate use of antimicrobials in animal production. This study aimed to evaluate the antimicrobial susceptibility profile in bacterial isolates from pigs with clinical respiratory signs in Brazil. One hundred sixty bacterial strains isolated from pigs from 51 pig farms in Brazil were studied. In vitro disk-diffusion method was employed using 14 antimicrobial agents: amoxicillin, penicillin, ceftiofur, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, oxytetracycline, tetracycline, erythromycin, tilmicosin, florfenicol, lincomycin, and sulfadiazine/trimethoprim. The majority of isolates were resistant to at least one antimicrobial agent (98.75%; 158/160), while 31.25% (50/160) of the strains were multidrug resistant. Streptococcus suis and Bordetella bronchiseptica were the pathogens that showed higher resistance levels. Haemophilus parasuis showed high resistance levels to sulfadiazine/trimethoprim (9/18=50%). We observed that isolates from the midwestern and southern regions exhibited four times greater chance of being multidrug resistant than the isolates from the southeastern region studied. Overall, the results of the present study showed a great level of resistance to lincomycin, erythromycin, sulfadiazine/trimethoprim, and tetracycline among bacterial respiratory pathogens isolated from pigs in Brazil. The high levels of antimicrobial resistance in swine respiratory bacterial pathogens highlight the need for the proper use of antimicrobials in Brazilian pig farms.
Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement
Authors: Strom Jordan B. , Faridi Kamil F. , Butala Neel M. , Zhao Yuansong , Tamez Hector , Valsdottir Linda R. , Brennan J. Matthew , Shen Changyu , Popma Jeffrey J. , Kazi Dhruv S. , Yeh Robert W. 
Published: May 2020

Background:
Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known.

Methods:
We linked adults ≥65 years of age in the HiR (US CoreValve Pivotal High Risk) and SURTAVI trials (Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients) to 100% Medicare inpatient claims, January 1, 2011, to December 31, 2016. Primary (eg, death and stroke) and secondary trial end points were compared across treatment arms (eg, transcatheter aortic valve replacement [TAVR] versus surgical aortic valve replacement [SAVR]) using trial-adjudicated outcomes versus outcomes derived from claims at 1 year (HiR) or 2 years (SURTAVI).

Results:

Among 600 linked HiR participants (linkage rate, 80.0%), the rate of the trial’s primary end point of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1 year by using both trial data (hazard ratio, 0.84 [95% CI, 0.65–1.09];
P
=0.33) and claims data (hazard ratio, 0.86 [95% CI, 0.66–1.11];
P
=0.34; interaction
P
value=0.80). Noninferiority of TAVR relative to SAVR was seen by using both trial- and claims-based outcomes (
P
noninferiority
<0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate, 60.5%), the trial’s primary end point was 12.9% for TAVR and 13.1% for SAVR using trial data (hazard ratio, 1.08 [95% CI, 0.79–1.48];
P
=0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (hazard ratio, 1.02 [95% CI, 0.73–1.41];
P
=0.58; interaction
P
value=0.89). TAVR was noninferior to SAVR when compared using both trial and claims (
P
non
inferiority
<0.001 for both). Rates of procedural secondary outcomes (eg, aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than nonprocedural outcomes (eg, stroke, bleeding, cardiogenic shock).

Conclusions:
In the HiR and SURTAVI trials, ascertainment of trial primary end points using claims reproduced both the magnitude and direction of treatment effect in comparison with adjudicated event data, but nonfatal and nonprocedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes but may be less suitable for other end points.
The Prosodic Models of Andalusi Hebrew Metrics
Authors: Martínez Delgado José 
Published: May 2020

Throughout the last two centuries, Hebrew metrics was studied by leading linguists and specialists in medieval Hebrew poetry. Nowadays, it has disappeared from the academic discussion such that it is sometimes even difficult to find scansions or the name of the meter in new editions of poems. This book aims to rectify this gap, helping readers to understand the metric structure of this poetry in order to facilitate the work of editing and cataloguing those samples still in manuscript form for future editors.
Delgado presents his view of Andalusi Hebrew metrics, as encountered in medieval manuals of Arabic and Hebrew metrics and scattered notes in the works of Andalusi Hebrew philologists. Whilst twentieth-century scholars spoke about the adaptation of Arabic metrics to Hebrew, he instead approaches these compositions by Andalusi Jews (10th-13th c.) as Arabic metrics written in Hebrew, thus emphasising how Hebrew poetry of the Andalusi Jews can help us to understand the general evolution of Arabic strophic poetry, and its experimental evolution, which is quite unlike classical and strophic Arabic poetry.
This method respects the Hebrew vowel system, and does not necessitate alteration of word morphology, leaving the guttural letters quiescent (unless required by metrical license); nor does it necessitate guesses about metres that are not in the classical catalogue. Although the author has not found each and every classical metre from Andalusi Hebrew poetry included in this manual, they are all catalogued, either in case someone finds them in future or because they help us to comprehend the metrical structures that are characteristic of strophic poetry. As such, this monograph will be of great interest to scholars of Hebrew metrics.
Perioperative Analgesia for Patients Undergoing Thyroidectomy and Parathyroidectomy: An Evidence-Based Review
Authors: Nguyen Brandon K. , Stathakios James , Quan Daniel , Pinto Jessica , Lin Hosheng , Pashkova Anna A. , Svider Peter F. 
Published: May 2020

Objective: To perform an evidence-based systematic review evaluating perioperative analgesia, including opioid alternatives, used for patients undergoing thyroidectomy and parathyroidectomy. Methods: A comprehensive literature search from 1997 to January 2018 of Pubmed, Cochrane, and EmBase libraries was performed for studies reporting analgesic administration following thyroid or parathyroid surgery. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were evaluated for level of evidence and given a Jadad score to assess for risk of bias. Outcomes gathered included postoperative pain scores, time to rescue analgesia, rescue analgesic consumption, and adverse events. Results: Thirty-eight randomized controlled trials met inclusion criteria. The GRADE criteria determined the overall evidence to be moderate-high. Studies utilizing NSAIDs reported reduced requirements for rescue analgesics. Acetaminophen studies presented with conflicting data on effectiveness. Gabapentinoid studies demonstrated lower pain scores and an increased time to rescue analgesic. Local anesthetics were effective at decreasing Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS) pain scores while also reducing rescue analgesic consumption. Ketamine was shown to increased postoperative nausea and vomiting. NSAIDs and local anesthetic studies had an aggregate grade of evidence A, while all others had grade B evidence. Conclusion: There is significant evidence supporting the use of NSAIDs and local anesthetics in the perioperative period for pain management for thyroid and parathyroid surgeries. Acetaminophen, gabapentinoid and ketamine have some supporting evidence and may serve as adequate alternatives. Further multi-institutional RCTs are warranted to delineate optimal analgesic regimens. Level of Evidence: NA
Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer’s disease evaluated by β-amyloid positron emission tomography imaging
Authors: Park Bok-Nam , Kim Jang-Hee , Lim Tae Sung , Park So Hyun , Kim Tae-Gyu , Yoon Bok Seon , Son Keoung Sun , Yoon Joon-Kee , An Young-Sil 
Published: May 2020

Objective: We evaluated the effects of bone marrow–derived mesenchymal stem cells in a model of Alzheimer’s disease using serial [18F]Florbetaben positron emission tomography. Methods: 3xTg Alzheimer’s disease mice were treated with intravenously injected bone marrow–derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and β-amyloid-reactive cells. Results: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow–derived mesenchymal stem cells–treated group ( n = 28). In contrast, there was no change in the ratio in control mice ( n = 25) at any time point. In addition, mice that received bone marrow–derived mesenchymal stem cell therapy also exhibited significantly better memory function and less β-amyloid-immunopositive plaques compared to controls. Conclusion: The therapeutic effect of intravenously injected bone marrow–derived mesenchymal stem cells in a mouse model of Alzheimer’s disease was confirmed by β-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.
Intermediate Input Imports, Domestic Input Use and Firm-level Outcomes: Evidence from Survey Data
Authors: Roy Suryadipta 
Published: May 2020

Imported intermediate inputs, that is, parts and materials sourced from abroad and used to make products either consumed domestically or in producing exported goods are a growing force in world trade. We test for the relative effect of imported intermediate inputs and domestic inputs in promoting foreign exports and various forms of domestic sales, using firm-level survey data. Imported intermediate inputs are found to be associated with higher overall sales, foreign exports and larger sales to multinational companies domiciled in the home country. On the other hand, domestic inputs are not found to have statistically significant positive effect on any firm-level outcomes. Since exporting firms are usually more productive than domestic firms, the results point towards the salience of outsourcing inputs in supporting firm productivity and the importance of policymaking in facilitating trade in intermediate inputs across countries. JEL: F10, F12, F23