bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-center evaluation of prognostic factors for thymoma treated by surgery: a retrospective study
Authors: Kamata Satoshi , Ishida Itaru , Suzuki Yuyo , Oura Hiroyuki 
Published: January 2021

Abstract
Background
This study aimed to retrospectively evaluate the clinical, pathological, and treatment-related factors associated with survival in patients with surgically treated thymomas.

Methods
Sixty patients with thymomas who underwent treatment at our institution between 2004 and 2015 were included. Survival analysis was performed based on curves that were obtained using the Kaplan–Meier method. The Wilcoxon test was used for all comparisons, and p < 0.05 was considered statistically significant.

Results
Forty-seven, four, three, four, and two patients presented tumor stages I, II, III, IVa, and IVb (according to the Masaoka classification), respectively, while six, 14, 11, 22, and seven patients had type A, AB, B1, B2, and B3 thymomas, respectively. Furthermore, 53 and eight patients underwent complete resection and required additional resection of adjacent organs, respectively, and no patients died from surgery-related complications. The five-year survival and recurrence-free survival (RFS) rates were 96 and 86%, respectively. The five-year survival rate for all stages was 100% except for those with stage IVb tumors (Masaoka classification); the survival rate for those patients was 0%. Separately, the five-year RFS rates for tumor stages I, II, III, IVa, and IVb were 100, 91, 91, 81, and 71%, respectively. Finally, the five-year survival rates in cases with complete and incomplete resections were 100 and 71%, respectively, indicating that the latter group had a significantly poorer prognosis (p < 0.001).

Conclusions
These findings suggest that complete resection and the Masaoka pathological stage are significant predictors of prognosis in patients with thymomas. Surgery should aim to achieve complete resection; however, advanced cases may require multimodality therapy.
Induction of autophagy mitigates TDP-43 pathology and translational repression of neurofilament mRNAs in mouse models of ALS/FTD
Authors: Kumar Sunny , Phaneuf Daniel , Cordeau Pierre , Boutej Hejer , Kriz Jasna , Julien Jean-Pierre 
Published: January 2021

Abstract
Background
TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile also remains unknown.

Methods
Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used Ribotag with microarray and proteomic analysis to determine the neuronal translational profile in the mice model of ALS/FTD.

Results
Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-ĸB) essential modulator (NEMO), induced autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive impairment, reduced gliosis in the brain of ALS/FTD mouse models. With the Ribotrap method, we investigated the impact of TDP-43 proteinopathy and IMS-088 treatment on the translation profile of neurons of one-year old hTDP-43A315T mice. TDP-43 proteinopathy caused translational dysregulation of specific mRNAs including translational suppression of neurofilament mRNAs resulting in 3 to 4-fold decrease in levels type IV neurofilament proteins. Oral administration of IMS-088 rescued the translational defects associated with TDP-43 proteinopathy and restored the synthesis of neurofilament proteins, which are essential for axon integrity and synaptic function.

Conclusions
Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies.
Traditional and biomedical care pathways for mental well‐being in rural Nepal
Authors: Pham Tony V. , Koirala Rishav , Kohrt Brandon A. 
Published: January 2021

AbstractBackgroundThere is increasing access to mental health services in biomedical settings (e.g., primary care and specialty clinics) in low- and middle-income countries. Traditional healing continues to be widely available and used in these settings as well. Our goal was to explore how the general public, traditional healers, and biomedical clinicians perceive the different types of services and make decisions regarding using one or both types of care.MethodsWe conducted in-depth interviews using a pilot tested semi-structured protocol around the subjects of belief, traditional healers, and seeking care. We conducted 124 interviews comprising 40 traditional healers, 79 general community members, and five physicians. We then performed qualitative analyses according to a grounded theoretical approach.ResultsA majority of the participants endorsed belief in both supernatural and medical causes of illness and sought care exclusively from healers, medical practitioners, and/or both. Our findings also revealed several pathways and barriers to care that were contingent upon patient-, traditional healer-, and medical practitioner-specific attitudes. Notably, a subset of community members duplicated care across multiple, equally-qualified medical providers before seeing a traditional healer and vice versa. In view of this, the majority of our participants stressed the importance of an efficient, medically plural society. Though participants desired a more collaborative model, no consistent proposal emerged on how to bridge traditional and biomedical practices. Instead, participants offered suggestions which comprised three broad categories: (1) biomedical training of traditional healers, (2) two-way referrals between traditional and biomedical providers, and (3) open-dialogue to foster mutual understanding among traditional and biomedical providers.ConclusionParticipants offered several approaches to collaboration between medical providers and traditional healers, however if we compare it to the history of previous attempts, education and understanding between both fields may be the most viable option in low- and middle-income contexts such as Nepal. Further research should expand and investigate opportunities for collaborative learning and/or care across not only Nepal, but other countries with a history of traditional and complimentary medicine.
Multitasking behaviors and provider outcomes in emergency department physicians: two consecutive, observational and multi-source studies
Authors: Augenstein Tobias , Schneider Anna , Wehler Markus , Weigl Matthias 
Published: January 2021

AbstractBackgroundMultitasking is a key skill for emergency department (ED) providers. Yet, potentially beneficial or debilitating effects for provider functioning and cognition are underexplored. We therefore aimed to investigate the role of multitasking for ED physicians’ work stress and situation awareness (SA).MethodsTwo consecutive, multi-source studies utilizing standardized expert observations in combination with physicians’ self-reports on stress and SA were set out in an academic ED. To control for ED workload, measures of patient acuity, patient counts, and ED staff on duty were included. Regression analyses estimated associations between observed proportion of time spent in multitasking with matched ED physicians’ reports on stress (study 1) and SA (study 2).ResultsED physicians engaged between 18.7% (study 1) and 13.0% (study 2) of their worktime in multitasking. Self-reported as well as expert-observed multitasking were significantly associated. This confirms the internal validity of our observational approach. After controlling for ED workload, we found that physicians who engaged more frequently in multitasking perceived higher work stress (Beta = .02, 95%CI .001–.03;p = .01). In study 2, ED physicians with more frequent multitasking behaviors reported higher SA (B = .08, 95%CI .02–.14;p = .009).ConclusionsMultitasking is often unavoidable in ED care. Our findings suggest that ED physicians’ multitasking increases stress experiences, yet, may facilitate professional’s experiences of situation awareness. Our results warrant further investigation into potentially ambivalent effects of ED providers’ multitasking in effectively sharing time between competing demands while maintaining performance and safety.
Molecular screening of PROKR2 gene in girls with idiopathic central precocious puberty
Authors: Aiello Francesca , Cirillo Grazia , Cassio Alessandra , Di Mase Raffaella , Tornese Gianluca , Umano Giuseppina R. , Miraglia del Giudice Emanuele , Grandone Anna 
Published: January 2021

Abstract
Background
Prokineticin receptor 2 (PROKR2) loss of function mutations have been described as cause of hypogonadotropic hypogonadism. In 2017, a first case of central precocious puberty (CPP) caused by PROKR2 heterozygous gain of function mutation was described in a 3.5 years-old girl. No other cases have been reported yet. This study performs a molecular screening in girls with early onset CPP (breast budding before 6 years of age) to identify possible alterations in PROKR2.

Methods
We analysed DNA of 31 girls with idiopathic CPP diagnosed via basal LH levels > 0.3 IU/L or peak-LH > 5 IU/L after stimulation, without any MKRN3 mutations. The Fisher exact test was used to compare polymorphism allele frequency to corresponding ones in genome aggregation database (gnomAD).

Results
No rare variants were identified. Five polymorphisms were found (rs6076809, rs8116897, rS3746684, rs3746682, rs3746683). All except one (i.e. rs3746682) had a minor allele frequency (MAF) similar to that reported in literature. rs3746682 presented a MAF higher than that described in the gnomAD (0.84 in our cohort vs 0.25 from gnomAD).

Conclusions
As for other G protein-coupled receptors (i.e. GPR54), mutations in PROKR2 do not seem to be a frequent cause of CPP in girls.
Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer
Authors: Sanchez Katherine , Kim Isaac , Chun Brie , Pucilowska Joanna , Redmond William L. , Urba Walter J. , Martel Maritza , Wu Yaping , Campbell Mary , Sun Zhaoyu , Grunkemeier Gary , Chang Shu Ching , Bernard Brady , Page David B. 
Published: January 2021

AbstractBackgroundThe H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents.MethodsSerial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power.ResultsmIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p < .001). Hierarchical linear modeling resulted in more precise estimates of treatment-related increases in sTIL, PD-L1, and other metrics such as CD8+ tumor nest infiltration. Statistical precision was dependent on adequate tissue sampling, with at least 15 high-powered fields recommended per specimen. Compared to conventional t-testing of means, hierarchical linear modeling was associated with substantial reductions in enrollment size required (n = 25➔n = 13) to detect the observed increases in sTIL/PD-L1.ConclusionmIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials.Trial registrationNCT02950259.
An integrated multi-omics approach to identify regulatory mechanisms in cancer metastatic processes
Authors: Ghaffari Saba , Hanson Casey , Schmidt Remington E. , Bouchonville Kelly J. , Offer Steven M. , Sinha Saurabh 
Published: January 2021

Abstract
Background
Metastatic progress is the primary cause of death in most cancers, yet the regulatory dynamics driving the cellular changes necessary for metastasis remain poorly understood. Multi-omics approaches hold great promise for addressing this challenge; however, current analysis tools have limited capabilities to systematically integrate transcriptomic, epigenomic, and cistromic information to accurately define the regulatory networks critical for metastasis.

Results
To address this limitation, we use a purposefully generated cellular model of colon cancer invasiveness to generate multi-omics data, including expression, accessibility, and selected histone modification profiles, for increasing levels of invasiveness. We then adopt a rigorous probabilistic framework for joint inference from the resulting heterogeneous data, along with transcription factor binding profiles. Our approach uses probabilistic graphical models to leverage the functional information provided by specific epigenomic changes, models the influence of multiple transcription factors simultaneously, and automatically learns the activating or repressive roles of cis-regulatory events. Global analysis of these relationships reveals key transcription factors driving invasiveness, as well as their likely target genes. Disrupting the expression of one of the highly ranked transcription factors JunD, an AP-1 complex protein, confirms functional relevance to colon cancer cell migration and invasion. Transcriptomic profiling confirms key regulatory targets of JunD, and a gene signature derived from the model demonstrates strong prognostic potential in TCGA colorectal cancer data.

Conclusions
Our work sheds new light into the complex molecular processes driving colon cancer metastasis and presents a statistically sound integrative approach to analyze multi-omics profiles of a dynamic biological process.
Membranes for bioethanol production by pervaporation
Authors: Peng Ping , Lan Yongqiang , Liang Lun , Jia Kemeng 
Published: January 2021

Abstract
Background
Bioethanol as a renewable energy resource plays an important role in alleviating energy crisis and environmental protection. Pervaporation has achieved increasing attention because of its potential to be a useful way to separate ethanol from the biomass fermentation process.

Results
This overview of ethanol separation via pervaporation primarily concentrates on transport mechanisms, fabrication methods, and membrane materials. The research and development of polymeric, inorganic, and mixed matrix membranes are reviewed from the perspective of membrane materials as well as modification methods. The recovery performance of the existing pervaporation membranes for ethanol solutions is compared, and the approaches to further improve the pervaporation performance are also discussed.

Conclusions
Overall, exploring the possibility and limitation of the separation performance of PV membranes for ethanol extraction is a long-standing topic. Collectively, the quest is to break the trade-off between membrane permeability and selectivity. Based on the facilitated transport mechanism, further exploration of ethanol-selective membranes may focus on constructing a well-designed microstructure, providing active sites for facilitating the fast transport of ethanol molecules, hence achieving both high selectivity and permeability simultaneously. Finally, it is expected that more and more successful research could be realized into commercial products and this separation process will be deployed in industrial practices in the near future.

Graphical abstract
New World screwworm (Cochliomyia hominivorax) myiasis in feral swine of Uruguay: One Health and transboundary disease implications
Authors: Altuna Martín , Hickner Paul V. , Castro Gustavo , Mirazo Santiago , Pérez de León Adalberto A. , Arp Alex P. 
Published: January 2021

AbstractBackgroundFeral swine (Sus scrofa) are highly invasive and threaten animal and human health in the Americas. The screwworm (Cochliomyia hominivorax) is listed by the World Organization for Animal Health as a notifiable infestation because myiasis cases affect livestock, wildlife, and humans in endemic areas, and outbreaks can have major socioeconomic consequences in regions where the screwworm has been eradicated. However, a knowledge gap exists on screwworm infestation of feral swine in South America, where the screwworm is endemic. Here, we report screwworm infestation of feral swine harvested in Artigas Department (Uruguay), where the Republic of Uruguay shares borders with Brazil and Argentina.MethodsMyiasis caused by the larvae of screwworm were identified in feral swine with the support and collaboration of members of a local feral swine hunting club over a 3-year period in the Department of Artigas. Harvested feral swine were examined for the presence of lesions where maggots causing the myiasis could be sampled and processed for taxonomic identification. The sites of myiasis on the body of infested feral swine and geospatial data for each case were recorded. The sex and relative size of each feral swine were also recorded. Temperature and precipitation profiles for the region were obtained from public sources.ResultsMyiases caused by screwworms were recorded in 27 of 618 the feral swine harvested. Cases detected in males weighing > 40 kg were associated with wounds that, due to their location, were likely caused by aggressive dominance behavior between adult males. The overall prevalence of screwworm infestation in the harvested feral swine was associated with ambient temperature, but not precipitation. Case numbers peaked in the warmer spring and summer months.ConclusionsThis is the first report on myiasis in feral swine caused by screwworm in South America. In contrast to myiasis in cattle, which can reach deep into host tissues, screwworms in feral swine tended to cause superficial infestation. The presence of feral swine in screwworm endemic areas represents a challenge to screwworm management in those areas. Screwworm populations maintained by feral swine may contribute to human cases in rural areas of Uruguay, which highlights the importance of the One Health approach to the study of this invasive host species–ectoparasite interaction.Graphical Abstract
Echinococcus multilocularis and other cestodes in red foxes (Vulpes vulpes) of northeast Italy, 2012–2018
Authors: Citterio Carlo Vittorio , Obber Federica , Trevisiol Karin , Dellamaria Debora , Celva Roberto , Bregoli Marco , Ormelli Silvia , Sgubin Sofia , Bonato Paola , Da Rold Graziana , Danesi Patrizia , Ravagnan Silvia , Vendrami Stefano , Righetti Davide , Agreiter Andreas , Asson Daniele , Cadamuro Andrea , Ianniello Marco , Capelli Gioia 
Published: January 2021

Abstract
Background
Echinococcus multilocularis is a small tapeworm affecting wild and domestic carnivores and voles in a typical prey-predator life cycle. In Italy, there has been a focus of E. multilocularis since 1997 in the northern Italian Alps, later confirmed in red foxes collected from 2001 to 2005. In this study, we report the results of seven years of monitoring on E. multilocularis and other cestodes in foxes and describe the changes that occurred over time and among areas (eco-regions) showing different environmental and ecological features on a large scale.

Methods
Eggs of cestodes were isolated from feces of 2872 foxes with a sedimentation/filtration technique. The cestode species was determined through multiplex PCR, targeting and sequencing ND1 and 12S genes. Analyses were aimed to highlight variations among different eco-regions and trends in prevalence across the study years.

Results
Out of 2872 foxes, 217 (7.55%) samples resulted positive for cestode eggs at coproscopy, with differences of prevalence according to year, sampling area and age class. Eight species of cestodes were identified, with Taenia crassiceps (2.65%), Taenia polyacantha (1.98%) and E. multilocularis (1.04%) as the most represented. The other species, Mesocestoides litteratus, Taenia krabbei, T. serialis, T. taeniaeformis and Dipylidium caninum, accounted for < 1% altogether. Echinococcus multilocularis was identified in foxes from two out of six eco-regions, in 30 fecal samples, accounting for 1.04% within the cestode positives at coproscopy. All E. multilocularis isolates came from Bolzano province. Prevalence of cestodes, both collectively and for each of the three most represented species (T. crassiceps, T. polyacantha and E. multilocularis), varied based on the sampling year, and for E. multilocularis an apparent increasing trend across the last few years was evidenced.

Conclusions
Our study confirms the presence of a focus of E. multilocularis in red foxes of northeast Italy. Although this focus seems still spatially limited, given its persistence and apparent increasing prevalence through the years, we recommend research to be conducted in the future on the ecological factors that, on a smaller scale, allow this zoonotic species to persist. On the same scale, we recommend a health education campaign to inform on the measures to prevent this zoonosis, targeted at people living in the area, especially hunters, dog owners, forestry workers and other potentially exposed categories.