bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel frameshift variant (c.409dupG) inSLC25A38is a common cause of congenital sideroblastic anaemia in the Indian subcontinent
Authors: Ravindra Niveditha , Athiyarath Rekha , S Eswari , S Sumithra , Kulkarni Uday , N A Fouzia , Korula Anu , Shaji Ramachandran V , George Biju , Edison Eunice Sindhuvi 
Published: June 2020

AimsCongenital sideroblastic anaemias (CSAs) are a group of rare disorders with the presence of ring sideroblasts in the bone marrow. Pathogenic variants are inherited in an autosomal recessive/X-linked fashion. The study was aimed at characterising the spectrum of mutations inSLC25A38andALAS2genes in sideroblastic anaemia patients, exploring the genotype-phenotype correlation and identifying the haplotype associated with any recurrent mutation.Patients and methodsTwenty probable CSA patients were retrospectively analysed for genetic variants inALAS2andSLC25A38genes by direct bidirectional sequencing. Real-time PCR was used to quantify gene expression in a case with promoter region variant inALAS2. Three single nucleotide polymorphisms were used to establish the haplotype associated with a recurrent variant in theSLC25A38gene.ResultsSix patients had causative variants inALAS2(30%) and 11 had variants inSLC25A38(55%). TheALAS2mutated cases presented at a significantly later age than theSLC25A38cases. A frameshift variant inSLC25A38(c.409dupG) was identified in six unrelated patients and was a common variant in our population exhibiting ‘founder effect’.ConclusionThis is the largest series of sideroblastic anaemia cases with molecular characterisation from the Indian subcontinent.
Embolus Retriever with Interlinked Cages (ERIC) versus conventional stent retrievers for thrombectomy: a propensity score-based analysis
Authors: Ducroux Célina , Renaud Nicolas , Bourcier Romain , Marnat Gaultier , Sibon Igor , Gory Benjamin , Richard Sébastien , Dargazanli Cyril , Arquizan Caroline , Eugene Francois , Vannier Stephane , Labreuche Julien , Walker Gregory , Blanc Raphaël , Obadia Mickael , Consoli Arturo , Lapergue Bertrand , Fahed Robert 
Published: June 2020

BackgroundThe Embolus Retriever with Interlinked Cages (ERIC) is one of the latest devices for thrombectomies. It has several architectural features that are supposed to enhance its ability to remove clots and prevent distal emboli. We aimed to compare ERIC with standard stent retrievers (SRs) using propensity score (PS) matching.MethodsThe clinical and radiological data of all consecutive patients treated with ERIC or standard FDA-approved stent retrievers were collected from a prospective multicenter registry. We compared procedural outcomes (recanalization rates according to the modified Thrombolysis In Cerebral Infarction (mTICI) score and procedural complications) and clinical outcomes (modified Rankin Scale (mRS) and mortality at 3 months). Matching of the populations with PS was performed to account for differences in baseline characteristics.ResultsA total of 1230 patients were included. In both the PS-matched cohort (195 ERIC patients, 630 SR patients) and the inverse probability of treatment weighting PS-adjusted cohort (206 ERIC patients, 1024 SR patients) there was no difference in terms of successful recanalization (modified TICI score ≥2b), good clinical outcome (mRS=0–2 or equal to pre-stroke mRS), or mortality at 3 months. Patients treated with first-line ERIC had a higher rate of complete recanalization (mTICI 3); however, they also required more passes and more frequent rescue therapy than the SR patient group.ConclusionIn a large multicenter registry with PS matching, the ERIC device provided equivalent angiographic and clinical results to conventional SRs.Clinical trial registrationURL:http://www.clinicaltrials.govUnique identifier:NCT03776877.
Sociodemographic and behavioural factors associated with testing for HIV and STIs in a US nationwide sample of transgender men who have sex with men
Authors: Antebi-Gruszka Nadav , Talan Ali J , Reisner Sari L , Rendina H Jonathon 
Published: June 2020

Objectives
Transgender men who have sex with men (TMSM) represent an understudied population in relation to screening for HIV and sexually transmitted infections (STIs). We examined HIV and STI testing prevalence among TMSM along with the factors associated with testing in a diverse US nationwide sample of TMSM.

Methods
Data from a cross-sectional online convenience sample of 192 TMSM were analysed using multivariable binary logistic regression models to examine the association between sociodemographic and behavioural factors and lifetime testing for HIV, bacterial STIs and viral STIs, as well as past year testing for HIV.

Results
More than two-thirds of TMSM reported lifetime testing for HIV (71.4%), bacterial STIs (66.7%), and viral STIs (70.8%), and 60.9% had received HIV testing in the past year. Engaging in condomless anal sex with a casual partner whose HIV status is different or unknown and having fewer than two casual partners in the past 6 months were related to lower odds of lifetime HIV, bacterial STI, viral STI and past year HIV testing. Being younger in age was related to lower probability of testing for HIV, bacterial STIs and viral STIs. Furthermore, TMSM residing in the South were less likely to be tested for HIV and viral STIs in their lifetime, and for HIV in the past year. Finally, lower odds of lifetime testing for viral STIs was found among TMSM who reported no drug use in the past 6 months.

Conclusions
These findings indicate that a notable percentage of TMSM had never tested for HIV and bacterial and viral STIs, though at rates only somewhat lower than among cisgender MSM despite similar patterns of risk behaviour. Efforts to increase HIV/STI testing among TMSM, especially among those who engage in condomless anal sex, are needed.
Neurocomputing approach to predict 2D ferromagnetic lattices by spin dynamics
Authors: Belayadi Adel , Bourahla Boualem , Mougari Ahmed , Mekideche-Chafa Fawzia 
Published: June 2020

An artificial neural networks modeling, based on spin dynamics, has been proposed to predict the 2D ferromagnetic crystals. The purpose is to establish an artificial neural network model (ANNM), which is able to predict the ordered magnetic surfaces. In crystal surfaces, Wood’s notation is used to describe different configurations. From the magnons dispersion curves and group velocity data of 2D spins crystallographic waveguide, we deduce the data used as an up input–output set to feed the ANNM. The input data are being given by the magnons modes over high symmetry points, or, by the group velocity of the magnon modes. However, the basis vectors of matrix notation and the rotation angle that aligns the unit cell of the reconstructed surface are giving the output data.The proposed neurocomputing model was capable of predicting the 2D crystals for the possible arrangements that the surface might take. In addition, the magnon excitations data were a useful approach for building a neural model which was able to predict and classify the magnetic surfaces of the crystals.
Circulating Tumor DNA is Prognostic and Potentially Predictive of Eryaspase Efficacy in Second-line in Patients with Advanced Pancreatic Adenocarcinoma
Authors: Bachet Jean-Baptiste , Blons Hélène , Hammel Pascal , Hariry Iman El , Portales Fabienne , Mineur Laurent , Metges Jean-Philippe , Mulot Claire , Bourreau Camille , Cain Jason , Cros Jérôme , Laurent-Puig Pierre 
Published: June 2020

Abstract

Purpose:
Eryaspase is composed of l-asparaginase encapsulated in erythrocytes and has demonstrated significant efficacy in a randomized phase II trial. We assessed the prognostic and predictive value of circulating tumor DNA (ctDNA) in patients, plasma included in this trial.

Experimental Design:
Samples prospectively collected pretreatment were centrally analyzed by next-generation sequencing. Prognostic values of baseline ctDNA and ctDNA early changes between day 0 and 28 were assessed in both arms combined on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS); three groups were defined: negative ctDNA (Neg), ctDNA responders (Resp), and ctDNA nonresponders (NResp). Predictive value of ctDNA for eryaspase efficacy was investigated.

Results:
ctDNA was positive at baseline in 77 patients of the 113 tested patients (68%). Detectable ctDNA was an independent negative prognostic factor for OS (4.6 vs. 8.8 months; P = 0.0025) and PFS (1.6 vs. 3.3 months; P = 0.00043). Early change in ctDNA levels was correlated with ORR (20%, 26%, 0%; P &lt; 0.04), PFS (3.7, 3.4, 1.6 months; P &lt; 0.0001), and OS (11.7, 6.5, 4.3 months; P &lt; 0.0001) according to the three defined groups (Neg, Res, NResp, respectively). In patients with ctDNA detectable at baseline, eryaspase was associated with better PFS [HR = 0.53; 95% confidence interval (CI): 0.3–0.94)] and OS (HR = 0.52; 95% CI: 0.29–0.91).

Conclusions:
We confirm from a prospective randomized trial that: (i) the presence of ctDNA at baseline is a major prognostic factor, (ii) the early change of ctDNA correlates with treatment outcome, and (iii) the ctDNA could be a predictive biomarker of eryaspase efficacy.
Multi-Ethnic Genome-Wide Association Study of Decomposed Cardioelectric Phenotypes Illustrates Strategies to Identify and Characterize Evidence of Shared Genetic Effects for Complex Traits
Authors: Baldassari Antoine R. , Sitlani Colleen M. , Highland Heather M. , Arking Dan E. , Buyske Steve , Darbar Dawood , Gondalia Rahul , Graff Misa , Guo Xiuqing , Heckbert Susan R. , Hindorff Lucia A. , Hodonsky Chani J. , Ida Chen Yii-Der , Kaplan Robert C. , Peters Ulrike , Post Wendy , Reiner Alex P. , Rotter Jerome I. , Shohet Ralph V. , Seyerle Amanda A. , Sotoodehnia Nona , Tao Ran , Taylor Kent D. , Wojcik Genevieve L. , Yao Jie , Kenny Eimear E. , Lin Henry J. , Soliman Elsayed Z. , Whitsel Eric A. , North Kari E. , Kooperberg Charles , Avery Christy L. 
Published: June 2020

Background:
We examined how expanding electrocardiographic trait genome-wide association studies to include ancestrally diverse populations, prioritize more precise phenotypic measures, and evaluate evidence for shared genetic effects enabled the detection and characterization of loci.

Methods:
We decomposed 10 seconds, 12-lead electrocardiograms from 34 668 multi-ethnic participants (15% Black; 30% Hispanic/Latino) into 6 contiguous, physiologically distinct (P wave, PR segment, QRS interval, ST segment, T wave, and TP segment) and 2 composite, conventional (PR interval and QT interval) interval scale traits and conducted multivariable-adjusted, trait-specific univariate genome-wide association studies using 1000-G imputed single-nucleotide polymorphisms. Evidence of shared genetic effects was evaluated by aggregating meta-analyzed univariate results across the 6 continuous electrocardiographic traits using the combined phenotype adaptive sum of powered scores test.

Results:

We identified 6 novels (
CD36, PITX2, EMB, ZNF592, YPEL2
, and
BC043580
) and 87 known loci (adaptive sum of powered score test
P
<5×10
−9
). Lead single-nucleotide polymorphism rs3211938 at
CD36
was common in Blacks (minor allele frequency=10%), near monomorphic in European Americans, and had effects on the QT interval and TP segment that ranked among the largest reported to date for common variants. The other 5 novel loci were observed when evaluating the contiguous but not the composite electrocardiographic traits. Combined phenotype testing did not identify novel electrocardiographic loci unapparent using traditional univariate approaches, although this approach did assist with the characterization of known loci.

Conclusions:
Despite including one-third as many participants as published electrocardiographic trait genome-wide association studies, our study identified 6 novel loci, emphasizing the importance of ancestral diversity and phenotype resolution in this era of ever-growing genome-wide association studies.
De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease
Authors: Boskovski Marko T. , Homsy Jason , Nathan Meena , Sleeper Lynn A. , Morton Sarah , Manheimer Kathryn B. , Tai Angela , Gorham Joshua , Lewis Matthew , Swartz Michael , Alfieris George M. , Bacha Emile A. , Karimi Mohsen , Meyer David , Nguyen Khanh , Bernstein Daniel , Romano-Adesman Angela , Porter George A. , Goldmuntz Elizabeth , Chung Wendy K. , Srivastava Deepak , Kaltman Jonathan R. , Tristani-Firouzi Martin , Lifton Richard , Roberts Amy E. , Gaynor J. William , Gelb Bruce D. , Kim Richard , Seidman Jonathan G. , Brueckner Martina , Mayer John E. , Newburger Jane W. , Seidman Christine E. 
Published: June 2020

Background:
De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown.

Methods:
We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network).

Results:

Two hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies (
P
=5.63×10
−12
). In 1268 patients (50.4%) who had surgical data available and underwent open-heart surgery exclusive of heart transplantation as their first operation, we analyzed transplant-free survival following the first operation. Median follow-up was 2.65 years. De novo variants were associated with worse transplant-free survival (hazard ratio, 3.51;
P
=5.33×10
−04
) and longer times to final extubation (hazard ratio, 0.74;
P
=0.005). As de novo variants had a significant interaction with extra-cardiac anomalies for transplant-free survival (
P
=0.003), de novo variants conveyed no additional risk for transplant-free survival for patients with these anomalies (adjusted hazard ratio, 1.96;
P
=0.06). By contrast, de novo variants in patients without extra-cardiac anomalies were associated with worse transplant-free survival during follow-up (hazard ratio, 11.21;
P
=1.61×10
−05
) than that of patients with no de novo variants. Using agnostic machine-learning algorithms, we identified de novo copy number variants at 15q25.2 and 15q11.2 as being associated with worse transplant-free survival and 15q25.2, 22q11.21, and 3p25.2 as being associated with prolonged time to final extubation.

Conclusions:
In patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01196182.
Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction
Authors: Gargiulo Giuseppe , Esposito Giovanni , Avvedimento Marisa , Nagler Michael , Minuz Pietro , Campo Gianluca , Gragnano Felice , Manavifar Negar , Piccolo Raffaele , Tebaldi Matteo , Cirillo Plinio , Hunziker Lukas , Vranckx Pascal , Leonardi Sergio , Heg Dik , Windecker Stephan , Valgimigli Marco 
Published: June 2020

Background:

Standard administration of newer oral P2Y
12
inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention.

Methods:

The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y
12
-naive patients with ST-segment–elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 μmol/L adenosine diphosphate.

Results:

At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5;
P
<0.001). Cangrelor or tirofiban were both superior to chewed prasugrel (IPA, 10.5±11.0;
P
<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4;
P
=0.47), despite yielding higher prasugrel active metabolite concentration (ng/mL; 62.3±82.6 versus 17.1±43.5;
P
=0.016).

Conclusions:
Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel, which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02978040; URL:
https://www.clinicaltrialsregister.eu
; EudraCT 2017-001065-24.
Retrospective Study of Risk Factors for Myocardial Damage in Patients With Critical Coronavirus Disease 2019 in Wuhan
Authors: Li Lingzhi , Zhang Shudi , He Bing , Chen Xiaobei , Zhao Qingyan 
Published: June 2020

BACKGROUND
The novel severe acute respiratory syndrome coronavirus 2 threatens human health, and the mortality rate is higher in patients who develop myocardial damage. However, the possible risk factors for myocardial damage in patients with coronavirus disease 2019 (COVID‐19) are not fully known.

METHODS AND RESULTS

Critical type patients were selected randomly from 204 confirmed COVID‐19 cases occurring in Renmin Hospital of Wuhan University from February 1, 2020 to February 24, 2020. Univariate analyses were used to compare the 2 groups: the myocardial damage group and the non–myocardial damage group. A total of 82 critical patients with COVID‐19 were recruited: 34 with myocardial damage and 48 without myocardial damage. A total of 30 patients died in the myocardial damage group, and 20 died in the non–myocardial damage group. In univariate analysis, the proportion of elderly patients (>70 years old, 70.59% versus 37.50%;
P
=0.003) and patients with cardiovascular disease (41.18% versus 12.50%;
P
=0.003) was higher among myocardial damage patients than among non–myocardial damage patients. Multivariate analysis showed that age >70 years old (hazard ratio [HR], 2.44; 95% CI, 1.01–5.40), CRP (C‐reactive protein) >100 mg/L (HR, 1.92; 95% CI, 0.94–3.92), lactate dehydrogenase >300 U/L (HR, 2.67; 95% CI, 1.03–6.90), and lactic acid >3 mmol/L (HR, 3.25; 95% CI, 1.57–6.75) were independent risk factors for myocardial damage in patients with COVID‐19.

CONCLUSIONS
Old age (>70 years old), CRP >100 mg/L, lactate dehydrogenase >300 U/L, and lactic acid >3 mmol/L are high‐risk factors related to myocardial damage in critical patients with COVID‐19.
The Medially-Invasive Cholesteatoma: An Aggressive Subtype of a Common Pathology
Authors: Casazza Geoffrey , Carlson Matthew L. , Shelton Clough , Gurgel Richard K. 
Published: June 2020

Objective: Describe the outcomes of treatment for patients with cholesteatomas that are medially invasive to the otic capsule, petrous apex, and/or skull base. Study Design: Retrospective case series Setting: Two tertiary care academic centers. Patients: Patients surgically managed for medially-invasive cholesteatoma at two tertiary care institutions from 2001 to 2017. Interventions: Surgical management of medially-invasive cholesteatomas. Main Outcome Measures: The presenting symptoms, imaging, pre- and post-operative clinical course, and complications were reviewed. Results: Seven patients were identified. All patients had pre-operative radiographic evidence of invasive cholesteatoma with erosion into the otic capsule beyond just a lateral semicircular canal fistula. Five patients had a complex otologic history with multiple surgeries for recurrent cholesteatoma including three with prior canal wall down mastoidectomy surgeries. Average age at the time of surgery was 41.3 years (range 20-83). Two patients underwent a hearing preservation approach to the skull base while all others underwent a surgical approach based on the extent of the lesion. Facial nerve function was maintained at the pre-operative level in all but one patient. No patient developed cholesteatoma recurrence. Conclusions: The medially-invasive cholesteatoma demonstrates an aggressive, endophytic growth pattern, invading into the otic capsule or through the perilabyrinthine air cells to the petrous apex. Surgical resection remains the best treatment option for medially-invasive cholesteatoma. When CSF leak is a concern, a subtotal petrosectomy with closure of the ear is often necessary.
Gazing into the World of Tattoos: An Invitation to Reconsider how we Conceptualize Religious Practices
Authors: Barras Amélie , Saris Anne 
Published: June 2020

Debates around the visibility of religious symbols – including whether and how to regulate them—have been quite vivid in recent years in Canada, and particularly in the province of Quebec. These discussions often focus on minority religious symbols and are based on the premise that symbols can be removed or modified. In fact, Saba Mahmood (2006, 2009) argues that using the term “symbol” precludes de-facto our ability to entertain the possibility that these symbols cannot be removed or modified. Drawing on 15 interviews with religiously tattooed individuals and tattoo artists in Montreal and Toronto, this article explores the practice of religious tattooing. Interestingly, this practice has been overlooked in debates on the regulation of religious symbols, as well as in the scholarly literature covering those debates. In this article, we are interested in thinking about why this is. We also argue that looking at the practice of religious tattooing helps give further credence to Mahmood’s criticism. It broadens our understanding of religious practices, including alerting us to the importance of the idea of ‘lived religion’ in comprehending how these practices can be an essential part of who someone is. While religious tattoos have largely escaped legal regulation, we conclude with a discussion of how they nonetheless remain the object of a regulatory gaze.