bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological Effective Dose as a Predictor of Hypopituitarism After Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis and Cohort Study of Patients Treated Using Contemporary Techniques
Authors: Graffeo Christopher S , Perry Avital , Link Michael J , Brown Paul D , Young William F , Pollock Bruce E 
Published: November 2020

AbstractBACKGROUNDHypopituitarism is the most frequent complication after pituitary adenoma stereotactic radiosurgery (SRS) and is correlated with increasing radiation to the pituitary gland. Biological effective dose (BED) is a dosimetric parameter that incorporates a time component to adjust for mechanisms of deoxyribonucleic acid repair activated during treatment.OBJECTIVETo assess mean gland BED as a predictor of post-SRS hypopituitarism, as compared to mean gland dose, in a contemporary cohort study of patients undergoing single-fraction SRS for pituitary adenoma.METHODSCohort study of 97 patients undergoing single-fraction SRS from 2007 to 2014. Eligible patients had no prior pituitary irradiation, normal pre-SRS endocrine function, and >24 mo of endocrine follow-up. Cox proportional hazards analysis was used to assess mean gland dose and BED as predictors of new post-SRS hypopituitarism.RESULTSMedian post-SRS follow-up was 48 mo (interquartile range [IQR], 34-68). A total of 27 patients (28%) developed new hypopituitarism at a median 22 mo (IQR, 12-36). Actuarial rates of new endocrinopathy were 17% at 2 yr (95% CI 10%-25%) and 31% at 5 yr (95% CI 20%-42%). On univariate analysis, sex (P = .02), gland volume (P = .03), mean gland dose (P < .0001), and BED significantly predicted new hypopituitarism (P < .0001). After adjusting for sex and gland volume, BED > 45 Gy2.47and mean gland dose > 10 Gy were significantly associated increased risk of hypopituitarism (hazard ratio [HR] = 14.32, 95% CI = 4.26-89.0,P < .0001; HR = 11.91, 95% CI = 3.54-74.0,P < .0001).CONCLUSIONBED predicted hypopituitarism more reliably than mean gland dose after pituitary adenoma SRS, but additional studies are needed to confirm these results.
Machine Learning-Driven Metabolomic Evaluation of Cerebrospinal Fluid: Insights Into Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage
Authors: Koch Matthew , Acharjee Animesh , Ament Zsuzsanna , Schleicher Riana , Bevers Matthew , Stapleton Christopher , Patel Aman , Kimberly W Taylor 
Published: November 2020

Abstract

BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high mortality and poor neurologic outcomes. The biologic underpinnings of the morbidity and mortality associated with aSAH remain poorly understood.

OBJECTIVE
To ascertain potential insights into pathological mechanisms of injury after aSAH using an approach of metabolomics coupled with machine learning methods.

METHODS
Using cerebrospinal fluid (CSF) samples from 81 aSAH enrolled in a retrospective cohort biorepository, samples collected during the peak of delayed cerebral ischemia were analyzed using liquid chromatography-tandem mass spectrometry. A total of 138 metabolites were measured and quantified in each sample. Data were analyzed using elastic net (EN) machine learning and orthogonal partial least squares-discriminant analysis (OPLS-DA) to identify the leading CSF metabolites associated with poor outcome, as determined by the modified Rankin Scale (mRS) at discharge and at 90 d. Repeated measures analysis determined the effect size for each metabolite on poor outcome.

RESULTS
EN machine learning and OPLS-DA analysis identified 8 and 10 metabolites, respectively, that predicted poor mRS (mRS 3-6) at discharge and at 90 d. Of these candidates, symmetric dimethylarginine (SDMA), dimethylguanidine valeric acid (DMGV), and ornithine were consistent markers, with an association with poor mRS at discharge (P = .0005, .002, and .0001, respectively) and at 90 d (P = .0036, .0001, and .004, respectively). SDMA also demonstrated a significantly elevated CSF concentration compared with nonaneurysmal subarachnoid hemorrhage controls (P = .0087).

CONCLUSION
SDMA, DMGV, and ornithine are vasoactive molecules linked to the nitric oxide pathway that predicts poor outcome after severe aSAH. Further study of dimethylarginine metabolites in brain injury after aSAH is warranted.
Efficacy and safety of multiple intra-articular corticosteroid injections for osteoarthritis—a systematic review and meta-analysis of randomized controlled trials and observational studies
Authors: Ayub Shazeen , Kaur Jaspreet , Hui Michelle , Espahbodi Shima , Hall Michelle , Doherty Michael , Zhang Weiya 
Published: November 2020

Abstract

Objectives
To investigate the efficacy and safety of multiple intra-articular corticosteroid (IACS) injections for the treatment of OA.

Methods
We conducted electronic searches of several databases for randomized controlled trials (RCTs) and observational studies. Standard mean difference was calculated for efficacy, whereas hazard ratio (HR) was used for adverse effects. Results were combined using the random effects model. Heterogeneity was measured using I2 statistics.

Results
Six RCTs were included for efficacy assessment. The use of multiple IACS appeared to be better than comparator (standard mean difference for pain −0.47, 95% CI −0.62, 0.31). However, there was considerable heterogeneity (I2 92.6%) and subgroup analysis by comparator showed no separation of regular IACS from placebo, though timing of pain assessments was questionable. Fourteen RCTs and two observational studies were assessed for the safety of multiple IACS. Minor local adverse events were similar in both groups. One RCT found that regular IACS every 3 months for 2 years caused greater cartilage loss compared with saline injection (−0.21 vs 0.10 mm). One cohort study found that multiple IACS injections associated with worsening of joint space narrowing (HR 3.02, 95% CI 2.25, 4.05) and increased risk of joint replacement (HR 2.54, 95% CI 1.81, 3.57).

Conclusion
Multiple IACS injections are no better than placebo for OA pain according to current evidence. The preliminary finding of a detrimental effect on structural OA progression warrants further investigation. Efficacy and safety of multiple IACS reflecting recommended best practice has yet to be assessed.
Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis
Authors: Roubille Camille , Coffy Amandine , Rincheval Nathalie , Dougados Maxime , Flipo René-Marc , Daurès Jean-Pierre , Combe Bernard 
Published: November 2020

Abstract

Objectives
To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA.

Methods
Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method.

Results
Among the 608 patients [480 women, mean age of 47.5  (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6–4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35).

Conclusion
The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes.

Trial registration
(ClinicalTrials.gov Identifier: NCT03666091).
Learning Speech Production and Perception through Sensorimotor Interactions
Authors: Shamma Shihab , Patel Prachi , Mukherjee Shoutik , Marion Guilhem , Khalighinejad Bahar , Han Cong , Herrero Jose , Bickel Stephan , Mehta Ashesh , Mesgarani Nima 
Published: November 2020

Abstract
Action and perception are closely linked in many behaviors necessitating a close coordination between sensory and motor neural processes so as to achieve a well-integrated smoothly evolving task performance. To investigate the detailed nature of these sensorimotor interactions, and their role in learning and executing the skilled motor task of speaking, we analyzed ECoG recordings of responses in the high-γ band (70–150 Hz) in human subjects while they listened to, spoke, or silently articulated speech. We found elaborate spectrotemporally modulated neural activity projecting in both “forward” (motor-to-sensory) and “inverse” directions between the higher-auditory and motor cortical regions engaged during speaking. Furthermore, mathematical simulations demonstrate a key role for the forward projection in “learning” to control the vocal tract, beyond its commonly postulated predictive role during execution. These results therefore offer a broader view of the functional role of the ubiquitous forward projection as an important ingredient in learning, rather than just control, of skilled sensorimotor tasks.
Neuroprotective effect of nerolidol in traumatic brain injury associated behavioural comorbidities in rats
Authors: Kaur Amandeep , Jaiswal Gagandeep , Brar Jasdeep , Kumar Puneet 
Published: November 2020

Abstract
Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to temporary/permanent secondary injuries, i.e. impairment of cognitive, physical, and psycho-social functions with altered consciousness. The leading mechanism responsible for neuronal damage following TBI is an increase in oxidative reactions initiated by free radicals generated by the injury along with various other mechanisms. Nerolidol is reported to have potent antioxidant and anti-neuroinflammatory properties. The present study was designed to explore the neuroprotective effect of nerolidol in weight-drop-induced TBI in rats. Animals were injured on the 1st day by dropping a free-falling weight of 200 gm from a height of 1 m through a guide pipe onto the exposed skull. After 14 days of injury, nerolidol (25, 50, and 100 mg/kg, i.p.) treatment was given for the next 14 days. Locomotor activity and motor coordination were evaluated using an actophotometer and rotarod, respectively. Cognitive impairment was observed through the Morris Water Maze and Object Recognition Test. On the 29th day, animals were sacrificed, and their brains were collected for the biochemical estimation. The weight drop model significantly decreased locomotor activity, motor coordination, increased Acetylcholinesterase (AChE) activity, oxidative stress, and induced cognitive deficits in TBI rats. Nerolidol significantly improved locomotor activity, reversed motor incoordination and cognitive impairment, and reduced the AChE activity and oxidative/nitrosative stress. The present study demonstrates the promising neuroprotective effects of nerolidol, which might improve the quality of life of TBI patients.
RDP5: a computer program for analyzing recombination in, and removing signals of recombination from, nucleotide sequence datasets
Authors: Martin Darren P , Varsani Arvind , Roumagnac Philippe , Botha Gerrit , Maslamoney Suresh , Schwab Tiana , Kelz Zena , Kumar Venkatesh , Murrell Ben 
Published: November 2020

AbstractFor the past 20 years, the recombination detection program (RDP) project has focused on the development of a fast, flexible, and easy to use Windows-based recombination analysis tool. Whereas previous versions of this tool have relied on considerable user-mediated verification of detected recombination events, the latest iteration, RDP5, is automated enough that it can be integrated within analysis pipelines and run without any user input. The main innovation enabling this degree of automation is the implementation of statistical tests to identify recombination signals that could be attributable to evolutionary processes other than recombination. The additional analysis time required for these tests has been offset by algorithmic improvements throughout the program such that, relative to RDP4, RDP5 will still run up to five times faster and be capable of analyzing alignments containing twice as many sequences (up to 5000) that are five times longer (up to 50 million sites). For users wanting to remove signals of recombination from their datasets before using them for downstream phylogenetics-based molecular evolution analyses, RDP5 can disassemble detected recombinant sequences into their constituent parts and output a variety of different recombination-free datasets in an array of different alignment formats. For users that are interested in exploring the recombination history of their datasets, all the manual verification, data management and data visualization components of RDP5 have been extensively updated to minimize the amount of time needed by users to individually verify and refine the program’s interpretation of each of the individual recombination events that it detects.
Joint Hypermobility Does Not Increase the Risk of Developing Hip Pain, Cartilage Defects, or Retirement in Professional Ballet Dancers Over 5 years
Authors: Mayes Susan , Smith Peter , Stuart Debbie , Cook Jill 
Published: November 2020

Objective:
This study aimed to evaluate the risk of developing hip pain, cartilage defects, and retirement in hypermobile ballet dancers over 5 years.

Design:
Prospective cohort study.

Setting:
Professional Ballet Company.

Participants:
Forty ballet dancers (57.5% women) were assessed at baseline and 21 dancers at 5 years.

Independent Variable:
Baseline evaluation of generalised joint hypermobility (GJH) (GJH = Beighton score ≥5/9).

Outcome Measures:
Cartilage defects on hip 3T magnetic resonance imaging and pain (the Copenhagen Hip and Groin Outcome Score: HAGOS) at baseline and follow-up, hip-related injury incidence, and retirement over 5 years.

Results:
Twelve dancers retired by follow-up, none due to hip injury or GJH. At baseline, 17 (42.5%) dancers were hypermobile, 18 (45%) had cartilage defects, and 15 (37.5%) reported hip pain (HAGOS pain <100). Cartilage defect prevalence was lower in GJH (n = 1) than non-GJH dancers (n = 17, P < 0.001). Beighton scores <5/9 were predictive of cartilage defect presence at baseline, independent of age and sex (P = 0.006). At follow-up, cartilage defects progressed in 2 dancers, one was hypermobile. Baseline and follow-up HAGOS pain scores were similar in GJH and non-GJH dancers (P > 0.05 for all). Hip-related injury over 5 years was reported by a similar number of GJH (n = 7) and non-GJH dancers (n = 6, P = 0.7). Hypermobility was more prevalent in active dancers (n = 12) than dancers who retired (n = 2), independent of age, rank, and sex (P = 0.03).

Conclusions:
Hypermobile dancers are at no greater risk of reporting hip pain and injury or retirement over 5 years, and cartilage defect prevalence was much lower in GJH than non-GJH dancers.
Evolutionary analysis of SARS-CoV-2 spike protein for its different clades
Authors: Pereson Matías J. , Flichman Diego M. , Martínez Alfredo P. , Baré Patricia , Garcia Gabriel H. , DI Lello Federico A. 
Published: November 2020

AbstractObjectiveThe spike protein of SARS-CoV-2 has become the main target for antiviral and vaccine development. Despite its relevance, there is scarce information about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches.MethodsTwo thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region.ResultsThe haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 x 10−3nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after nine months of pandemic was similar for each clade.ConclusionsIn conclusion, the present evolutionary analysis is relevant since the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail since re-infection by different phylogenetic clades has been reported.
Bile acid excess impairs thermogenic function in brown adipose tissue
Authors: Zhou Weinan , VanDuyne Philip , Zhang Chi , Riessen Ryan , Barragan Maribel , Rowitz Blair M. , Teran-Garcia Margarita , Boppart Stephen A. , Anakk Sayeepriyadarshini 
Published: November 2020

SUMMARYBile acids (BAs) not only facilitate fat digestion but also protect against obesity. Here, we show that a genetic mouse model for BA overload (Farnesoid X receptor; Small heterodimer double knockout (DKO)) exhibits mitochondrial dysfunction resulting in a thermogenic defect. By housing DKO mice at thermoneutrality, the poor mitochondrial function in brown fat protects them from diet-induced obesity. Compared to control, we find higher adipose BA levels with excess accumulation of taurocholic acid in the DKO mice. We report that the expression of genes responsible for BAde novosynthesis, conjugation and transporters and accumulation of BAs are present in both brown and white adipocytes. We determine that BA overload is sufficient to cause adipocyte mitochondrial dysfunction and induce the expression of cellular senescence genesin vitro. Taken together, we uncover that BA levels within the adipose tissue may modulate its overall function.HighlightsMouse model of BA overload exhibits adipose defects, which is partially restored by housing at thermoneutrality.BAs are present in detectable concentrations in both BAT and WAT.Adipocytes express genes responsible forde novosynthesis, conjugation and transport of BAs, and accumulate BAs.Pathological accumulation of BAs impairs mitochondrial function leading to thermogenic defect.
A pipeline to characterize local cortical folds by mapping them to human-interpretable shapes
Authors: Roy Arnab , McMillen Tyler , Beiler Donielle L , Snyder William , Patti Marisa , Troiani Vanessa 
Published: November 2020

BackgroundVariations in regional cortical folds across individuals have been examined using computationally-derived morphological measures, or by manual characterization procedures that map distinct variants of a regional fold to a set of human-interpretable shapes. Although manual mapping approaches have proven useful for identifying morphological differences of clinical relevance, such procedures are subjective and not amenable to scaling.New MethodWe propose a 3-step pipeline to develop computational models of manual mapping. The steps are: represent regional folds as feature vectors, manually map each feature vector to a shape-variant that the underlying fold represents, and train classifiers to learn the mapping.ResultsFor demonstration, we chose a 2D-problem of detecting within slice discontinuity of medial and lateral sulci of orbitofrontal cortex (OFC); the discontinuity may be visualized as a broken H-shaped pattern, and is fundamental to OFC-type-characterization. The classifiers predicted discontinuities with 86-95% test-accuracy.Comparison with Existing MethodsThere is no existing pipeline that automates a manualcharacterizationprocess. For the current demonstration problem, we conduct multiple analyses using existing softwares to explain our design decisions, and present guidelines for using the pipeline to examine other regional folds using conventional or non-conventional morphometric measures.ConclusionWe show that this pipeline can be useful for determining axial-slice discontinuity of sulci in the OFC and can learn structural-features that human-raters may rely on during manual-characterization.The pipeline can be used for examining other regional folds and may facilitate discovery of various statistically-reliable 2D or 3D human-interpretable shapes that are embedded throughout the brain.
Attitudes and Practices of Open Data, Preprinting, and Peer-review - a Cross Sectional Study on Croatian Scientists
Authors: Baždarić K , Vrkić I , Arh E , Mavrinac M , Gligora Marković M , Bilić-Zulle L , Stojanovski J , Malički M. 
Published: November 2020

AbstractAttitudes towards open peer review, open data and use of preprints influence scientists’ engagement with those practices. Yet there is a relatively small number of validated questionnaires that measure these attitudes. The goal of our study was to construct and validate such a questionnaire. Using a sample of Croatian scientists (N=541), from a wide range of disciplines, we developed a questionnaire titled Attitudes towards Open data sharing, preprinting, and peer-review (ATOPP). The questionnaire has 21 item with a four-factor structure (attitudes towards: open data, preprint servers, open peer-review and open peer-review in small scientific communities). Based on the questionnaire, the attitudes of Croatian scientists towards these topics were generally neutral, with a median of 3.3 out of 5 of the total attitude score. Croatian scientist attitudes were lowest for open peer-review in small scientific communities (Md 2.0) and highest for open data (Md 3.9).
Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model for Phospholamban R14del cardiomyopathy
Authors: Kamel S.M. , van Opbergen C.J.M. , Koopman C.D. , Verkerk A.O. , Onderwater Y. L. , Chocron S. , Polidoro Pontalti C. , Vos M.A. , de Boer T.P. , van Veen T.A.B. , Bakkers J. 
Published: November 2020

AbstractThe heterozygous phospholamban (PLN) p.Arg14del (R14del) mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. The PLN R14del mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+dynamics. Little is known about the physiological processes preceding PLN R14del induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we addressed these issues using a knock-in PLN R14del zebrafish model. Hearts from adult zebrafish with the R14del mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography revealed contractile pulsus alternans before overt structural changes occurred, which correlated at the cellular level with action potential duration (APD) alternans. These functional alterations are preceded by diminished Ca2+transient amplitudes in embryonic hearts. We found that istaroxime treatment ameliorates thein vivoCa2+dysregulation, rescues the cellular APD alternans, while it improves cardiac relaxation. Thus, we present novel insight into the pathophysiology ofPLNR14del cardiomyopathy and identify istaroxime as a potential novel drug for its treatment.