bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aromatic l-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies
Authors: Rossignoli Giada , Krämer Karolin , Lugarà Eleonora , Alrashidi Haya , Pope Simon , De La Fuente Barrigon Carmen , Barwick Katy , Bisello Giovanni , Ng Joanne , Counsell John , Lignani Gabriele , Heales Simon J R , Bertoldi Mariarita , Barral Serena , Kurian Manju A 
Published: March 2021

Abstract
Aromatic l-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Promising gene therapy approaches are emerging, though may not be either suitable or easily accessible for all patients. To characterize the underlying disease pathophysiology and guide precision therapies, we generated a patient-derived midbrain dopaminergic neuronal model of AADC deficiency from induced pluripotent stem cells. The neuronal model recapitulates key disease features, including absent AADC enzyme activity and dysregulated dopamine metabolism. We observed developmental defects affecting synaptic maturation and neuronal electrical properties, which were improved by lentiviral gene therapy. Bioinformatic and biochemical analyses on recombinant AADC predicted that the activity of one variant could be improved by l-3,4-dihydroxyphenylalanine (l-DOPA) administration; this hypothesis was corroborated in the patient-derived neuronal model, where l-DOPA treatment leads to amelioration of dopamine metabolites. Our study has shown that patient-derived disease modelling provides further insight into the neurodevelopmental sequelae of AADC deficiency, as well as a robust platform to investigate and develop personalized therapeutic approaches.
Endogenous Oscillations Time-Constrain Linguistic Segmentation: Cycling the Garden Path
Authors: Henke Lena , Meyer Lars 
Published: March 2021

AbstractSpeech is transient. To comprehend entire sentences, segments consisting of multiple words need to be memorized for at least a while. However, it has been noted previously that we struggle to memorize segments longer than approximately 2.7 s. We hypothesized that electrophysiological processing cycles within the delta band (&lt;4 Hz) underlie this time constraint. Participants’ EEG was recorded while they listened to temporarily ambiguous sentences. By manipulating the speech rate, we aimed at biasing participants’ interpretation: At a slow rate, segmentation after 2.7 s would trigger a correct interpretation. In contrast, at a fast rate, segmentation after 2.7 s would trigger a wrong interpretation and thus an error later in the sentence. In line with the suggested time constraint, the phase of the delta-band oscillation at the critical point in the sentence mirrored segmentation on the level of single trials, as indicated by the amplitude of the P600 event-related brain potential (ERP) later in the sentence. The correlation between upstream delta-band phase and downstream P600 amplitude implies that segmentation took place when an underlying neural oscillator had reached a specific angle within its cycle, determining comprehension. We conclude that delta-band oscillations set an endogenous time constraint on segmentation.
Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis Caused by Leishmania braziliensis
Authors: Lago Tainã , Carvalho Lucas P , Nascimento Mauricio , Guimarães Luiz H , Lago Jamile , Castellucci Léa , Carvalho Augusto M , Lago Alex , Carvalho Edgar M 
Published: March 2021

Abstract

Background
Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates &lt;60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response.

Methods
A total of 90 age-matched patients with CL were included (30 obese, 30 overweight, and 30 with normal body mass index [BMI]). CL was diagnosed through documentation of L. braziliensis DNA by polymerase chain reaction or identification of amastigotes in biopsied skin-lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (Sanofi-Aventis; 20 mg/kg/day) was administered for 20 days.

Results
Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After 1 course of antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (P &lt; .01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (P &lt; .05).

Conclusions
Obesity modifies the clinical presentation of CL and host immune response and is associated with greater failure to therapy.
Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study
Authors: Muzny Christina A , Schwebke Jane R , Nyirjesy Paul , Kaufman Gregory , Mena Leandro A , Lazenby Gweneth B , Van Gerwen Olivia T , Graves Keonte J , Arbuckle Janeen , Carter Belvia A , McMahon Connette P , Eder Scott , Shaw Jackie , Pandey Brajesh , Chavoustie Steven E 
Published: March 2021

AbstractBackgroundTrichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis.MethodsWomen with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6–12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups.ResultsBetween April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%–97.4%] vs 1.5% [95% CI: .0%–8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%–98.9%] vs 1.7% [95% CI: .0%–8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed.ConclusionsA single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV.Clinical Trials RegistrationNCT03935217.
Clinical efficacy and safety of angiogenesis inhibitors: sex differences and current challenges
Authors: Cignarella Andrea , Fadini Gian Paolo , Bolego Chiara , Trevisi Lucia , Boscaro Carlotta , Sanga Viola , Seccia Teresa Maria , Rosato Antonio , Rossi Gian Paolo , Barton Matthias 
Published: March 2021

AbstractVasoactive molecules, such as vascular endothelial growth factor (VEGF) and endothelins, share cytokine-like activities and regulate endothelial cell (EC) growth, migration, and inflammation. Some endothelial mediators and their receptors are targets for currently approved angiogenesis inhibitors, drugs that are either monoclonal antibodies raised towards VEGF, or inhibitors of vascular receptor protein kinases and signalling pathways. Pharmacological interference with the protective functions of ECs results in a similar spectrum of adverse effects. Clinically, the most common side effects of VEGF signalling pathway inhibition include an increase in arterial pressure, left ventricular dysfunction facilitating the development of heart failure, thromboembolic events including pulmonary embolism and stroke, and myocardial infarction. Sex steroids, such as androgens, progestins, and oestrogens and their receptors (ERα, ERβ, GPER; PR-A, PR-B; AR) have been identified as important modifiers of angiogenesis, and sex differences have been reported for anti-angiogenic drugs. This review article discusses the current challenges clinicians are facing with regard to angiogenesis inhibitor therapy, including the need to consider sex differences affecting clinical efficacy and safety. We also propose areas for future research taking into account the role of sex hormone receptors and sex chromosomes. Development of new sex-specific drugs with improved target- and cell-type selectivity likely will open the way to personalized medicine in men and women requiring anti-angiogenic therapy to reduce adverse effects and to improve therapeutic efficacy.
A case report: biventricular takotsubo cardiomyopathy with sequential ventricular recovery due to pulmonary hypertension
Authors: Agarwal Megha , Kardos Attila 
Published: March 2021

Abstract

Background
Biventricular Takotsubo cardiomyopathy (BTC) is estimated to occur in 25–42% of those with Takotsubo cardiomyopathy (TC). Little is known about which subset of patients are predisposed to having concomitant right ventricular (RV) involvement, or the pattern of recovery in BTC.

Case summary
We describe a 69-year-old woman who presented with dyspnoea and was subsequently diagnosed with BTC. We propose that this was triggered by an exacerbation of chronic obstructive pulmonary disease on a background of multiple predisposing factors including recent bereavement, previous excessive alcohol use, status as a current smoker, and anxiety. During her admission, she required non-invasive ventilation and inotropic support to manage her type two respiratory failure and acute heart failure. Serial echocardiograms during the admission allowed us to capture and present the sequential recovery of ventricular systolic function, with the left ventricular (LV) recovery preceding the right ventricle.

Discussion
Our patient fulfils the International Takotsubo Diagnostic criteria of transient LV dysfunction, emotional and physical triggers, electrocardiogram abnormalities, raised troponin and brain natriuretic peptide and no occlusive coronary artery disease. We hypothesize that pulmonary hypertension-related strain on the right ventricle due to lung disease, may have led to the observed delay in the recovery of RV function, despite the full recovery of LV function.
Lending Cycles and Real Outcomes: Costs of Political Misalignment
Authors: Bircan Çağatay , Saka Orkun 
Published: March 2021

Abstract
We document a strong political cycle in bank credit and industry outcomes in Turkey. In line with theories of tactical redistribution, state-owned banks systematically adjust their lending around local elections compared with private banks in the same province based on electoral competition and political alignment of incumbent mayors. This effect only exists in corporate lending and creates credit constraints for firms in opposition areas, which suffer drops in assets, employment and sales but not firm entry. Financial resources and factors of production are misallocated as more efficient provinces and industries suffer the greatest constraints, reducing aggregate productivity.
Comparison of shunt types in the neonatal Norwood procedure for single ventricle
Authors: Ono Masamichi , Kido Takashi , Wallner Marie , Burri Melchior , Lemmer Julia , Ewert Peter , Strbad Martina , Cleuziou Julie , Hager Alfred , Hörer Jürgen 
Published: March 2021

Abstract

OBJECTIVES
The ideal shunt for pulmonary blood flow, modified Blalock–Taussig shunt (MBTS) or right ventricular–pulmonary artery conduit (RVPAC) is yet to be determined. This study aimed to evaluate outcomes after the Norwood procedure according to the type of shunt.

METHODS
A total of 322 neonates with hypoplastic left heart syndrome and related anomalies who underwent the Norwood procedure at our institution between 2001 and 2019 were divided into MBTS and RVPAC groups and the outcomes after the Norwood procedure were compared between the groups with respect to mortality after each staged procedure.

RESULTS
We identified 322 consequent patients who underwent neonatal Norwood procedure for hypoplastic left heart syndrome (271 patients, 84.2%) and its variant (51 patients, 15.8%). RVPAC was performed in 163 (50.6%) patients and MBTS was performed in 159 (49.4%). There were no differences in the rate of early death (11.0% vs 12.6%, P = 0.69) or late death (7.4% vs 6.9%, P = 0.87) between the 2 groups after the Norwood procedure, and no significant difference in the number of patients who reached bidirectional cavopulmonary shunt (77.9% vs 76.1%, P = 0.69), and there was no difference in mortality after bidirectional cavopulmonary shunt (12.3% vs 7.5%, P = 0.15) or Fontan completion rate (54.0% vs 52.2%, P = 0.42) between the 2 groups. Survival at 0.5, 1, 3 and 6 years after the Norwood procedure was 81.0%, 73.8%, 67.9% and 67.0% in patients with RVPAC and 77.1%, 73.3%, 69.1% and 67.9% in patients with MBTS. There was no significant difference in the survival between the 2 groups during the median follow-up of 2.6 (interquartile ranges: 0.3–8.4, maximal 18.8) years (P = 0.97).

CONCLUSIONS
In neonates undergoing the Norwood procedure, our available data of maximal 18.8 years follow-up showed no significant difference in early mortality, inter-stage attritions, or overall survival, between MBTS and RVPAC.
Estimating the effective sample size in association studies of quantitative traits
Authors: Ziyatdinov Andrey , Kim Jihye , Prokopenko Dmitry , Privé Florian , Laporte Fabien , Loh Po-Ru , Kraft Peter , Aschard Hugues 
Published: March 2021

Abstract
The effective sample size (ESS) is a metric used to summarize in a single term the amount of correlation in a sample. It is of particular interest when predicting the statistical power of genome-wide association studies (GWAS) based on linear mixed models. Here, we introduce an analytical form of the ESS for mixed-model GWAS of quantitative traits and relate it to empirical estimators recently proposed. Using our framework, we derived approximations of the ESS for analyses of related and unrelated samples and for both marginal genetic and gene-environment interaction tests. We conducted simulations to validate our approximations and to provide a quantitative perspective on the statistical power of various scenarios, including power loss due to family relatedness and power gains due to conditioning on the polygenic signal. Our analyses also demonstrate that the power of gene-environment interaction GWAS in related individuals strongly depends on the family structure and exposure distribution. Finally, we performed a series of mixed-model GWAS on data from the UK Biobank and confirmed the simulation results. We notably found that the expected power drop due to family relatedness in the UK Biobank is negligible.
Novel Genetic Variant Predicts Surgical Recurrence Risk in Crohn’s Disease Patients
Authors: Wang Ming-Hsi , Friton Jessica J , Raffals Laura E , Leighton Jonathan A , Pasha Shabana F , Picco Michael F , Monroe Kelly , Nix Billy D , Newberry Rodney D , Faubion William A 
Published: March 2021

Abstract

Background
We aimed to identify a model of clinical and genetic risk factors through hypothesis-free search across genome that can predict the surgical recurrence risk after the first abdominal surgery in CD patients.

Materials and Methods
Two independent inflammatory bowel disease (IBD) cohort studies were used to derive and validate the genetic risk profile. The study subjects were genotyped using Illumina Immunochip custom genotyping array. Surgical recurrence was defined as having the second or more abdominal bowel resections after the first abdominal surgery at the time of study enrollment; nonsurgical recurrence was defined as having no further abdominal resection after the first abdominal surgery.

Results
Among 372 CD patients who had at least 1 abdominal surgery at the study enrollment, 132 (35.5%) had subsequent surgical recurrence after their first abdominal surgery, and 240 (64.5%) required no subsequent abdominal surgery at the end of follow up. Among clinical factors, multivariable analysis showed that history of immunomodulatory use (odds ratio [OR], 3.96; P = 0.002) and early era of CD first surgery (OR, 1.12; P = 1.01E-04) remained significant. Genotypic association tests identified a genome-wide significant locus rs2060886 in TCF4 at chr18q21.2 associated with surgical recurrence risk (OR, dom, 4.10 [2.37–7.11]; P = 4.58E-08).

Conclusions
Novel genetic locus rs2060886 in TCF4 was associated with surgical recurrence risk at genome-wide significance level among CD patients after their first abdominal surgery. Early era of CD first intestinal surgery predicts higher surgical recurrence risk. These results suggest that genetic variants may help guide the CD management strategy in patients at the highest risk of repeated abdominal surgeries.
Metazoan diversity and seasonality through eDNA metabarcoding at a Mediterranean long-term ecological research site
Authors: Di Capua Iole , Piredda Roberta , Mazzocchi Maria Grazia , Zingone Adriana 
Published: March 2021

Abstract
Metabarcoding of environmental DNA has provided striking insights into marine microbial diversity. With this approach, we assessed the diversity of metazoan assemblages and their temporal variations at the Long-Term Ecological Research site MareChiara (LTER-MC) in the Gulf of Naples (Mediterranean Sea). The Illumina sequencing of the V4-18S rRNA fragment from 48 surface samples collected from 2011 to 2013 produced a total of 5 011 047 marine metazoan reads. The normalized dataset was generally dominated by copepods (60.3%), followed by annelids (34.7%) mostly represented by the invasive benthic polychaete Hydroides elegans. Non-copepod holoplankton was mainly represented by siphonophores, rotifers, and appendicularians, with occasional mass occurrences of jellyfish. The rest of meroplankton (mainly molluscs, annelids, and anthozoans) showed a high diversity, covering all 11 zooplankton phyla, from Porifera to Craniata. A high number of copepod genera were identified, with seasonal recurrence matching patterns observed in 30 years of studies in the Gulf of Naples. Despite limitations related to the molecular marker resolution and reference dataset, the study provided valuable insights into diversity and seasonal patterns of the whole metazoan assemblage, expanding the knowledge on rare or hardly identifiable taxa and confirming DNA metabarcoding as a powerful approach to be integrated at LTER sites.
Learning from safety incidents in high-reliability organizations: a systematic review of learning tools that could be adapted and used in healthcare
Authors: Serou Naresh , Sahota Lauren M , Husband Andy K , Forrest Simon P , Slight Robert D , Slight Sarah P 
Published: March 2021

Abstract

Objective
A high-reliability organization (HRO) is an organization that has sustained almost error-free performance, despite operating in hazardous conditions where the consequences of errors could be catastrophic. A number of tools and initiatives have been used within HROs to learn from safety incidents, some of which have the potential to be adapted and used in healthcare. We conducted a systematic review to identify any learning tools deemed to be effective that could be adapted and used by multidisciplinary teams in healthcare following a patient safety incident.

Methods
This review followed the Preferred Reporting Items for Systematic Reviews and MetaAnalyses for Protocols reporting guidelines and was registered with the PROSPERO (CRD42017071528). A search of databases was carried out in January 2021, from the date of their commencement. We conducted a search on electronic databases such as Web of Science, Science Direct, MEDLINE in Process Jan 1950-present, EMBASE Jan 1974-present, CINAHL 1982-present, PsycINFO 1967-present, Scopus and Google Scholar. We also searched the grey literature including reports from government agencies, relevant doctoral dissertations and conference proceedings. A customized data extraction form was used to capture pertinent information from included studies and Critical Appraisal Skills Programme tool to appraise on their quality.

Results
A total of 5921 articles were identified, with 964 duplicate articles removed and 4932 excluded at the title (4055), abstract (510) and full-text (367) stages. Twenty-five articles were included in the review. Learning tools identified included debriefing, simulation, crew resource management and reporting systems to disseminate safety messages. Debriefing involved deconstructing incidents using reflective questions, whilst simulation training involved asking staff to relive the event again by performing the task(s) in a role-play scenario. Crew resource management is a set of training procedures that focus on communication, leadership and decision-making. Sophisticated incident-reporting systems provide valuable information on hazards and were widely recommended as a way of disseminating key safety messages following safety incidents. These learning tools were found to have a positive impact on learning if conducted soon after the incident with efficient facilitation.

Conclusion
Healthcare organizations should find ways to adapt to the learning tools or initiatives used in HROs following safety incidents. It is challenging to recommend any specific one as all learning tools have shown considerable promise. However, the way these tools or initiatives are implemented is critical, and so further work is needed to explore how to successfully embed them into healthcare organizations so that everyone at every level of the organization embraces them.