bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer – GRECCAR 15 trial protocol
Authors: Denost Quentin , Frison Eric , Salut Cécile , Sitta Remy , Rullier Anne , Harji Deena , Maillou‐Martinaud Helene , Rullier Eric , Smith Denis , Vendrely Veronique ,   on behalf the GRECCAR Group
Published: April 2021

AbstractAimTreatment strategies in locally recurrent rectal cancer (LRRC) are complex and need to be balanced against previous treatments received for the primary rectal cancer. Radiotherapy is an important component of treatment in LRRC. However, there is little high‐quality evidence on the role of reirradiation in this cohort. Therefore, the aim of this trial is to assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC.MethodGRECCAR 15 is a prospective, multicentre, open‐label, outcome assessor‐blinded, superiority randomized controlled phase III clinical trial comparing neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone in patients with LRRC previously irradiated for the primary cancer. Adult patients (>18 years old) with a histologically proven resectable LRRC, who have previously received pelvic radiotherapy for their primary rectal cancer at a dose of 25–50.4 Gy, and an Eastern Cooperative Oncology Group performance status of <2 will be eligible to participate. The pelvic reirradiation will consist of conformational intensity‐modulated external irradiation, delivering a dose of 30.6 Gy with concomitant chemotherapy using capecitabine. The primary outcome of this trial is the R0 resection rate. Overall, GRECCAR 15 aims to recruit 186 patients to detect an absolute difference of 20% in the R0 resection rate with 80% power and 5% two‐sided significance level.ConclusionThe GRECCAR 15 trial is the first, definitive, phase III trial to investigate reirradiation in LRRC. The results of this trial will inform definitively the neoadjuvant treatment strategy in previously irradiated patients and assess whether there is any associated benefit of reirradiation in combination with induction chemotherapy in improving R0 resection rates.
Determinants of kidney transplant candidates’ decision to accept organ donor intervention transplants and participate in post‐transplant research: A conjoint analysis
Authors: Gordon Elisa J. , Abt Peter , Lee Jungwha , Knopf Elizabeth , Phillips Caitlin , Bermudez Francisca , Krishnamurthi Lakshman , Karaca Huseyin S. , Veatch Robert , Knight Richard , Conway Paul T. , Dunn Sue , Reese Peter P. 
Published: April 2021

AbstractDeceased organ donor intervention research aims to increase organ quality and quantity for transplantation. We assessed the proportion of kidney transplant candidates who would accept “intervention organs,” participate in organ intervention research, and factors influencing acceptance. Kidney transplant candidates were presented 12 hypothetical scenarios, which varied three attributes, donor age, predicted waiting time to receive another organ offer, and research risk to the organ. Candidates were also randomly assigned to one of two conditions varying recipient risk. For each scenario, candidates agreed to accept the intervention organ or remain waitlisted. We fit a multivariable logit model to determine the association between scenario attributes and the acceptance decision. Of 249 participants, most (96%) accepted intervention organs under some or all conditions. Factors independently associated with candidates’ greater likelihood of accepting an intervention organ included: low risk to the kidney from the intervention (OR 20.53 [95% Confidence Interval (CI), 13.91‐30.29]); younger donor age (OR 3.72 [95% CI, 2.83‐4.89]), longer time until the next organ offer (OR 3.48 [95% CI, 2.65‐4.57]), and greater trust in their transplant physician (OR 1.03 [95% CI, 1.00‐1.06]). Candidates with a lower likelihood of acceptance had been waitlisted longer (OR 0.97 per month [95% CI, 0.96‐0.99]) and were Black (OR 0.21 [95% CI, 0.08‐0.55]). Most candidates would accept an intervention organ, which should encourage transplant leaders to conduct deceased donor organ intervention trials.
Multiple myxoid cellular neurothekeomas in a patient with systemic lupus erythematosus
Authors: Lau Sean K. , Cassarino David S. , Koh Stephen S. 
Published: April 2021

AbstractCellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal‐based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60‐year‐old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S‐100, SOX‐10, epithelial membrane antigen, desmin, smooth muscle actin, glial fibrillary acid protein, and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions.
A practitioner's guide to understanding equine infectious disease diagnostics in the United Kingdom. Part 1: How to optimise sampling approaches and a guide to agent detection testing methods
Authors: Whitlock F. M. , Newton J. R. 
Published: April 2021

SummaryDiagnostic testing is routinely performed by the equine clinician when dealing with suspected infectious disease cases and outbreaks. Optimal sample timing, choice and handling are fundamental to attain an accurate diagnosis, and a good understanding of laboratory‐based sample analysis techniques, and their validation is necessary for effective diagnostic test result interpretation. This two‐part series highlights the importance of interpreting results bearing testing limitations and specific clinical findings in mind, and on these foundations, the treating clinician should always be well placed to deal with equine infectious diseases. Part 1 in this series will provide a treating clinician with an overview of the importance of testing horses in infectious disease outbreaks and how this is achieved. The different laboratory testing options available for agent detection and their methods will also be discussed. Part 2 will summarise serological (antibody) testing techniques, sample processing (including how tests are performed and validated) and result interpretation.
The dystrophia myotonica WD repeat‐containing protein DMWD and WDR20 differentially regulate USP12 deubiquitinase
Authors: Olazabal‐Herrero Anne , Bilbao‐Arribas Martin , Carlevaris Onintza , Sendino Maria , Varela‐Martinez Endika , Jugo Begoña M. , Berra Edurne , Rodriguez Jose Antonio 
Published: April 2021

Despite its potential clinical relevance, the product of the DMWD (dystrophia myotonica, WD repeat containing) gene is a largely uncharacterized protein. The DMWD amino acid sequence is similar to that of WDR20, a known regulator of the USP12 and USP46 deubiquitinases (DUBs). Here, we apply a combination of in silico and experimental methods to investigate several aspects of DMWD biology. Molecular evolution and phylogenetic analyses reveal that WDR20 and DMWD, similar to USP12 and USP46, arose by duplication of a common ancestor during the whole genome duplication event in the vertebrate ancestor lineage. The analysis of public human gene expression datasets suggests that DMWD expression is positively correlated with USP12 expression in normal tissues and negatively correlated with WDR20 expression in tumors. Strikingly, a survey of the annotated interactome for DMWD and WDR20 reveals a largely nonoverlapping set of interactors for these proteins. Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct coimmunoprecipitation of epitope‐tagged proteins. We found that DMWD and WDR20 share the same binding interface in USP12, suggesting that their interaction with the DUB may be mutually exclusive. Finally, we show that both DMWD and WDR20 promote USP12 enzymatic activity, but they differentially modulate the subcellular localization of the DUB. Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires.
Drivers of native and non‐native freshwater fish richness across North America: Disentangling the roles of environmental, historical and anthropogenic factors
Authors: Anas M. U. Mohamed , Mandrak Nicholas E. 
Published: April 2021

AbstractAimA better understanding of native and non‐native species responses to environmental conditions, historical processes, and human pressures is crucial in the face of global environmental changes affecting biodiversity. Here, we evaluate the relative roles of environmental, historical and anthropogenic factors in influencing species richness of native and non‐native freshwater fishes in watersheds across North America.LocationNorth America (exclusive of Mexico).Time periodRecent.Major taxa studiedFreshwater fishes.MethodsWe compiled an extensive dataset of native and non‐native fish richness in 2,993 watersheds across North America, together with corresponding data for environmental (climatic, geographic), historical and anthropogenic factors. We used variance partitioning and hierarchical partitioning to quantify the relative importance of environmental, historical and anthropogenic factors in explaining richness variation in native and non‐native [overall, and by geographic origin (foreign/translocated) and pathway (authorized/unauthorized)] fishes, while accounting for correlations among explanatory variables and spatial autocorrelation.ResultsOverall importance of environmental and anthropogenic factors was greater than historical factors in explaining both native and non‐native richness. Precipitation‐related factors were more important in explaining native richness, whereas non‐native richness was largely associated with temperature‐related factors. However, richness related to authorized introductions was less constrained by temperature than unauthorized introductions. Dam density, road density and urbanization gradient were major anthropogenic factors related to non‐native richness, yet their relative importance varied among origin‐ and pathway‐based categories.ConclusionsOur findings indicate different environmental drivers influence native and non‐native fish richness patterns in North America. The accumulation of non‐native species in watersheds depends on the interaction between environmental conditions and anthropogenic‐based processes related to introduction history including geographic origin, introduction pathway, and propagule pressure, where the latter likely plays a major role. Warmer regions with high human population densities and more impoundments are more prone to fish invasions, mostly via unauthorized introductions.
Gastric granulomas and Helicobacter pylori: An incidental relationship
Authors: Turner Kevin O. , Lindberg Guy M. , Genta Robert M. 
Published: April 2021

Abstract
AimsStudies investigating the relationship between granulomatous gastritis (GG) and Helicobacter pylori infection have been largely inconclusive. This study was designed to determine whether the analysis of a very large number of patients would provide clearer answers evaluate the association between H. pylori infection and gastric granulomas.MethodsWe used a large national database of clinicopathological data to extract 1,673,086 patients who underwent esophagogastroduodenoscopy with gastric biopsies between 2008 and 2020. In a case‐control study, we evaluated the occurrence of H. pylori infection in patients with and without gastric granulomas. We also explored other clinical and histopathological associations.ResultsH. pylori infection was present in 44 of 496 (8.9%) patients with gastric granulomas, compared to 158,949 (9.5%) in the control group (OR = 0.93, 95% CI = 0.68–1.26). Of the 129 patients with gastric granulomas, 50 had documented inflammatory bowel disease.ConclusionsThe results of this study show that the prevalence of H. pylori infection in patients with gastric granulomas is essentially identical to that of controls with no evidence of granulomas or granulomatous disease. When patients with and without a plausible‐known association for gastric granulomas were analyzed separately, the prevalence of H. pylori infection remained remarkably similar in GG patients and controls. Considering the very large numbers of patients with gastric biopsies analyzed in this study, we submit that there is no basis for suggesting that H. pylori is etiologically related to GG.
Methodology for determining design rules for helical channels in glass components produced by selective laser sintering
Authors: Nissen Joseph , Sassaman Douglas M. , Lee Susanne M. , Desjardins Joseph A. , Beaman Joseph J. , Kovar Desiderio 
Published: April 2021

AbstractThe ability to accurately produce geometric features is one of the main hurdles in advancing additive manufacturing for the production of functional parts. Design rules can be found for parts produced using selective laser sintering for polymers with simple features such as thin walls and through‐holes; however, these rules have not been studied for more complex features such as helical channels produced from glass or ceramic materials. In this study, feature resolution for helical channels is quantified for successful production of both green and final parts after debinding and sintering. We found the ability to clear loose powder was a major factor in determining whether a particular channel/part geometry could be produced. Our experiments suggest a linear relationship between the scaled diameter and tortuosity for successful clearing of channels. Using this, we propose a design rule that can predict success and failure in accurately forming internal helical channels. The proposed methodology was experimentally validated for parts created via indirect selective laser sintering from mixtures of glass and nylon powders.
Contextualizing the Impact of Legal Representation on Juvenile Delinquency Outcomes: A Review of Research and Policy
Authors: Kokkalera Stuti S. , Tallas Annmarie , Goggin Kelly 
Published: April 2021

AbstractThis study examines the empirical research on legal representation in delinquency proceedings and situates it in the broader investigation of how states provide legal assistance to juvenile defendants. Our review of empirical studies found that attorney presence was an aggravating factor in dispositional decisions. After closely examining state statutory provisions on legal representation in juvenile delinquency proceedings, we suggest that the penalty effect of attorney presence is an artifact of the variation in state laws governing access and oversight of juvenile counsel. We conclude with suggestions for future research, policy, and practice.
On the Role of the Collateral Constraint Friction in the North–South Transmission of the 2008–2009 Financial Crisis
Authors: Nguyen Ha M. 
Published: April 2021

AbstractThis paper assesses the role of a popular collateral constraint–based transmission mechanism in the North–South transmission of the 2008–2009 financial crisis. Theoretically, in the presence of collateral constraints, depressed asset prices caused by a negative shock in a large creditor country generate feedback cycles in a smaller debtor country, in which the decline in borrowing capacity and the collapses of investment and output reinforce each other. I find that although the mechanism has appealing qualitative features and is consistent with the data, quantitative results from the model can only account for a very small part of the actual output declines.
Feasibility of assessing progression of transthyretin amyloid polyneuropathy using nerve conduction studies: Findings from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
Authors: Waddington‐Cruz Márcia , Ando Yukio , Amass Leslie , Kiszko Jan , Chapman Doug , Sekijima Yoshiki ,   THAOS investigators
Published: April 2021

AbstractPatients with transthyretin amyloid polyneuropathy (ATTR‐PN) show decreased motor and sensory nerve amplitudes and conduction. Electrophysiological changes over time may be sensitive indicators of progression. This analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS) assessed longitudinal changes in nerve conduction as signals of neurologic disease progression in patients with hereditary ATTR (ATTRv) amyloidosis. Patients with ATTRv in THAOS with recorded nerve conduction values were included (data cut‐off: January 6, 2020); changes in nerve amplitude and velocity over time were assessed. Patients (n = 1389) were 45.0% male; 80.4% were the Val30Met (p.Val50Met) genotype. Mean (SD) age at enrollment was 43.6 (14.5) years; duration of symptoms was 9.3 (6.4) years. Median (10th, 90th percentile) sural nerve amplitude and velocity was 18.0 (4.9, 35.0) μV and 50.7 (41.0, 57.9) m/s; peroneal conduction was 13.0 (4.4, 27.0) μV and 51.0 (41.7, 59.7) m/s, respectively. Median (10th, 90th percentile) percentage change from baseline in sural nerve amplitude was variable, but generally decreased over time from −7.4 (−43.2, 52.4) at year 1 to −14.4 (−76.9, 46.7) at year 8. Percent change from baseline in sural nerve velocity declined similarly: −0.1 (−14.5, 15.3) at year 1 and − 6.4 (−21.3, 10.5) at year 8. The decline was more pronounced in patients with greater disability at baseline. Similar patterns were observed for the peroneal nerve. These data show an association between nerve amplitudes and velocities and disease severity, suggesting progressive deterioration in nerve conduction may be an indicator of ATTRv amyloidosis disease progression.
Melatonin synthesis genes N‐acetylserotonin methyltransferases evolved into caffeic acid O‐methyltransferases and both assisted in plant terrestrialization
Authors: Zhao Dake , Yao Zhengping , Zhang Jiemei , Zhang Renjun , Mou Zongmin , Zhang Xue , Li Zonghang , Feng Xiaoli , Chen Suiyun , Reiter Russel J. 
Published: April 2021

AbstractTerrestrialization is one of the most momentous events in the history of plant life, which leads to the subsequent evolution of plant diversity. The transition species, in this process, had to acquire a range of adaptive mechanisms to cope with the harsh features of terrestrial environments compared to that of aquatic habitat. As an ancient antioxidant, a leading regulator of ROS signaling or homeostasis, and a presumed plant master regulator, melatonin likely assisted plants transition to land and their adaption to terrestrial ecosystems. N‐acetylserotonin methyltransferases (ASMT) and caffeic acid O‐methyltransferases (COMT), both in the O‐methyltransferase (OMT) family, catalyze the core O‐methylation reaction in melatonin biosynthesis. How these two enzymes with close relevance evolved in plant evolutionary history and whether they participated in plant terrestrialization remains unknown. Using combined phylogenetic evidence and protein structure analysis, it is revealed that COMT likely evolved from ASMT by gene duplication and subsequent divergence. Newly emergent COMT gained a significantly higher ASMT activity to produce greater amounts of melatonin for immobile plants to acclimate to the stressful land environments after evolving from the more environmentally‐stable aquatic conditions. The COMT genes possess more conserved substrate‐binding sites at the amino acid level and more open protein conformation compared to ASMT, and getting a new function to catalyze the lignin biosynthesis. This development directly contributed to the dominance of vascular plants among the Earth's flora and prompted plant colonization of land. Thus, ASMT, together with its descendant COMT, might play key roles in plant transition to land. The current study provides new insights into plant terrestrialization with gene duplication contributing to this process along with well‐known horizontal gene transfer.
Mathematics Interventions for Adolescents with Mathematics Difficulties: A Meta‐Analysis
Authors: Myers Jonté A. , Brownell Mary T. , Griffin Cynthia C. , Hughes Elizabeth M. , Witzel Bradley S. , Gage Nicolas A. , Peyton David , Acosta Kelly , Wang Jun 
Published: April 2021

AbstractWe quantitatively synthesized findings of quasi‐experimental and randomized control studies of interventions designed to improve the mathematics achievement of secondary school students with mathematics difficulties (MD). We identified 45 studies (49 interventions) published between 1978 and 2020 and classified interventions into five categories: technology‐based interventions (TBI), schema‐based interventions (SBI), use of visual representations, cognitive‐based instruction, and other. We used robust variance estimation (RVE) to address dependency in effect sizes (ESs). The cumulative effect size across 139 outcomes was moderately large (g = 0.52), with a substantial amount of between‐study heterogeneity. A multiple meta‐regression analysis showed several significant moderators of interventions' effectiveness, such as content domain, intervention length, and dependent measure. We discuss limitations and implications for research and classroom practice.