bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Lactated Ringers Solution Compared With Normal Saline Is Associated With Shorter Length of Stay in Pediatric Acute Pancreatitis
Authors: Farrell Peter R. , Farrell Leslie M. , Hornung Lindsey , Abu-El-Haija Maisam 
Published: March 2020

Objective
The aim of the study was to evaluate lactated ringers (LR) versus normal saline (NS) in pediatric acute pancreatitis (AP).

Methods
This retrospective study used Pediatric Health Information System database of primary AP patients, 2013 to 2017.

Results
The study included 1581 first time AP patients with exclusive use of a single fluid (111 LR, 1470 NS) for the first 48 hours. The LR cohort had a significantly shorter length of stay (P < 0.001) compared with NS. A multivariable logistic regression analysis suggests use of NS in the first 48 hours (after controlling for total parenteral nutrition, operation, and infection during the admission) had a significantly increased likelihood of requiring a hospitalization for 4 days or more compared with the LR group (odds ratio, 3.31; 95% confidence interval, 1.95–5.62). The overall cost was significantly less in the LR group. There was no statistical difference observed in risk factors for AP, intensive care transfer, organ dysfunction, or mortality.

Conclusions
This represents the first large data set analysis of LR versus NS in pediatric AP. The use of LR was associated with a shorter length of stay and reduced cost compared with NS. Future randomized trials will help determine the ideal fluid choice for pediatric AP.
The State of Mentorship and Pancreatic Research Among Trainees in Pancreatology
Authors: Tsen Adrianne , Han Samuel , Moreau Christopher , Akshintala Venkata S. , Yazici Cemal , Archibugi Livia , Hopson Puanani , Gougol Amir , Jin David , Paragomi Pedram , Kamal Ayesha , Valverde-López Francisco , Papachristou Georgios I. , Park Walter G. , Lee Peter J. 
Published: March 2020

Objectives
The recent decrease seen in pancreatic research and young investigator involvement may reflect inadequate mentorship. This study aimed to describe the current state of mentorship in pancreatic research and evaluate how mentorship is associated with research productivity.

Methods
In this prospective study, a survey addressing mentorship and research was distributed to trainees worldwide. Survey responses were analyzed using descriptive statistics and logistic regression was used to describe the association between mentorship and trainee research productivity.

Results
A total of 137 trainees from 16 countries participated. Although two-thirds of trainees expressed interest in pancreatic research and had identified a mentor in the field, only 34.8% had published a manuscript. Barriers to pancreatic research included lack of research opportunities (58.3%), limited mentorship (23.3%), and inadequate institutional support (15%). Although having a single mentor was not associated with research productivity (odds ratio, 1.43; 95% confidence interval, 0.74–2.76), having a local mentor was significantly associated with publishing (odds ratio, 4.57; 95% confidence interval, 1.95–10.74).

Conclusions
Although many trainees interested in pancreatology have access to a mentor, barriers including lack of research opportunities, mentorship, and institutional support hinder trainee productivity. Opportunities for mentorship, collaboration, and networking are needed.
Landscape of Health-Related Quality of Life in Patients With Early-Stage Pancreatic Cancer Receiving Adjuvant or Neoadjuvant Chemotherapy
Authors: Macarulla Teresa , Hendifar Andrew E. , Li Chung-Pin , Reni Michele , Riess Hanno , Tempero Margaret A. , Dueck Amylou C. , Botteman Marc F. , Deshpande Chinmay G. , Lucas Eleanor J. , Oh Do-Youn 
Published: March 2020

Objectives
Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC).

Methods
Databases/registries (through January 24, 2019) and conference abstracts (2014–2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] – Pancreatic Cancer [PAN26]).

Results
Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage–all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26.

Conclusions
In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.
Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein
Authors: Diao Bo , Wen Kun , Chen Jian , Liu Yueping , Yuan Zilin , Han Chao , Chen Jiahui , Pan Yuxian , Chen Li , Dan Yunjie , Wang Jing , Chen Yongwen , Deng Guohong , Zhou Hongwei , Wu Yuzhang 
Published: March 2020

SummaryBACKGROUNDNucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed. Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis.METHODSWe included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard.RESULTSWe developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes. 100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method. In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients.CONCLUSIONSThose findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.
Mortality of COVID-19 is Associated with Cellular Immune Function Compared to Immune Function in Chinese Han Population
Authors: Zeng Qiang , Li Yong-zhe , Huang Gang , Wu Wei , Dong Sheng-yong , Xu Yang 
Published: March 2020

AbstractIn December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in Chinese Han population is limited. Our objective is to describe the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in the Chinese Han population. In this case series of 752 patients, the full spectrum of cases is described. Fever was present in 86-90% of the patients. The second most common symptom was cough (49.1-51.0%), fatigue (25.2-27.1%), sputum (20.0-23.1%), and headache (9.8-11.1%). the mortality rate is 4.6% in Wuhan, 1.9% in Beijing, and 0.9% in Shanghai. Our findings showed that the levels of lymphocytes were 0.8(IQR, 0.6-1.1)109/L in Wuhan, 1.0(IQR, 0.7-1.4)109/L in Beijing, and 1.1 (IQR, 0.8-1.5) 109/L in Shanghai before admission to hospitals, respectively, indicating that cellular immune function might relate to the mortality. Based on the reference ranges of normal Chinese Han population and the data of the critically ill patients we have observed, it is recommended that reference ranges of people at high risk of COVID-19 infection are CD3+ lymphocytes below 900 cells/mm3, CD4+ lymphocytes below 500 cells/mm3, and CD8+ lymphocytes below 300 cells/mm3.
CryoSIM: super resolution 3D structured illumination cryogenic fluorescence microscopy for correlated ultra-structural imaging
Authors: Phillips Michael A. , Harkiolaki Maria , Susano Pinto David Miguel , Parton Richard M. , Palanca Ana , Garcia-Moreno Manuel , Kounatidis Ilias , Sedat John W. , Stuart David I. , Castello Alfredo , Booth Martin J. , Davis Ilan , Dobbie Ian M. 
Published: March 2020

AbstractRapid cryo-preservation of biological specimens is the gold standard for visualising cellular structures in their true structural context. However, current commercial cryo-fluorescence microscopes are limited to low resolutions. To fill this gap, we have developed cryoSIM, a microscope for 3D super-resolution fluorescence cryo-imaging for correlation with cryo electron microscopy or cryo soft X-ray tomography. We provide the full instructions for replicating the instrument mostly from off-the-shelf components and accessible, user-friendly open source Python control software. Therefore, cryoSIM democratises the ability to detect molecules using super-resolution fluorescence imaging of cryo-preserved specimens for correlation with their cellular ultrastructure.
Control of Mycobacterium tuberculosis Infection in Lungs is Associated with Recruitment of Antigen-Specific Th1 and Th17 cells Co-expressing CXCR3 and CCR6
Authors: Shanmugasundaram Uma , Bucsan Allison N , Ganatra Shashank R. , Ibegbu Chris , Quezada Melanie , Blair Robert V , Alvarez Xavier , Velu Vijayakumar , Kaushal Deepak , Rengarajan Jyothi 
Published: March 2020

AbstractMycobacterium tuberculosis(Mtb)-specific T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a non-human primate (NHP) aerosol model, we studied the kinetics, phenotypes and functions of Mtb antigen-specific T cells in peripheral and lung compartments of Mtb-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage (BAL), for up to 24 weeks post-infection. We found significantly higher frequencies of Mtb-specific effector and memory CD4 and CD8 T cells producing IFN-γ in the airways compared to peripheral blood, which were maintained throughout the study period. Moreover, Mtb-specific IL-17+ and IL-17/IFN-γ double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17responses are associated with LTBI. The majority of Mtb-specific CD4 T cells that homed to the airways expressed the chemokine receptor CXCR3 and co-expressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and non-granulomatous regions of the lung and inversely correlated with Mtb burden. Our findings provide novel insights into antigen-specific T cell responses associated with asymptomatic Mtb infection that are relevant for developing better strategies to control TB.
Stiffness of Nanoparticulate Mineralized Collagen Scaffolds Triggers Osteogenesis via Mechanotransduction and Canonical Wnt Signaling
Authors: Zhou Qi , Lyu Shengyu , Bertrand Anthony A. , Hu Allison C. , Chan Candace H. , Ren Xiaoyan , Dewey Marley J. , Tiffany Aleczandria S. , Harley Brendan A.C. , Lee Justine C. 
Published: March 2020

AbstractThe ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. We previously described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducingin vivoskull regeneration approaching 60% of the biomechanical properties of native calvarium without exogenous growth factors orex vivoprogenitor cell-priming, suggesting promise as a first-generation material for skull regeneration. Here, we evaluated the contribution of titrating stiffness to osteogenicity by comparing non-crosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. While both materials were osteogenic, MC demonstrated an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials were capable of autogenously activating the canonical bone morphogenetic protein receptor (BMPR) signaling pathway with phosphorylation of Smad1/5 (small mothers against decapentaplegic-1/5). However, unlike NX-MC, hMSCs cultured on MC demonstrated significant elevations in the major mechanotransduction mediators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) expression coincident with β-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduced osteogenic marker expression, mineralization, and β-catenin activation in MC with a much lesser of an effect on NX-MC. YAP/TAZ inhibition also resulted in a reciprocal increase in Smad1/5 phosphorylation as well as BMP2 expression. Our results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated in a manner independent of mechanical cues.
Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma
Authors: Ma Chao , Luo Huan , Cao Jing 
Published: March 2020

AbstractBackgroundLung adenocarcinoma (LUAD) is the most common primary lung cancer, and increasing evidence indicates the clinical importance of the microenvironment in LUAD. Tumor-infiltrating immune cells play an important role in promoting or inhibiting tumor growth. This study aimed to identify immune-related prognostic genes that were associated with the LUAD microenvironment.MethodsWe used the “estimate” R package to calculate the immune/stromal scores of each sample of GSE72094 based on the ESTIMATE algorithm. Then we looked up relationships between patients’ characteristics and immune/stromal scores. After that, we divided the samples into two groups: high and low scores, identified the common differentially expressed genes (DEGs), and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) on the common DEGs. After conducting the overall survival analysis of the common DEGs, prognostic genes were harvested. Then we constructed the protein-protein interaction network and performed the enrichment of GO and KEGG for the prognostic genes. Crucial prognostic genes were obtained after validating in two independent data sources (GSE68465 and TIMER). Finally, we investigated the immune correlates of the crucial prognostic genes based on the TIMER.ResultsImmune scores did not vary with gender, age, smoking history, tumor stage, and EGFR status, but vary with the status of KRAS, STK11, and TP53. For the stromal scores, only the status of STK11 and TP53 mattered. Reduced immune score predicted poor prognosis of LUAD. 357 common DEGs were found, of which 108 were identified as prognostic genes after overall survival analysis. GO and KEGG analysis found that common DEGs and prognostic genes were both mainly involved in immune-related items. After validation in two independent data sources, 12 genes were validated to be crucial prognostic genes linked to prognosis. After investigated the TIMER, all 12 genes were correlated with the main immune cell types.Conclusion12 immune-related prognostic genes were discovered relating to the microenvironment in LUAD. These findings suggest that the composition of the tumor microenvironment affects the clinical outcomes of LUAD, and it may provide a basis for the development of novel prognostic biomarkers and immunotherapy for LUAD.
Embryo-like features in developingBacillus subtilisbiofilms
Authors: Futo Momir , Opašić Luka , Koska Sara , Čorak Nina , Široki Tin , Ravikumar Vaishnavi , Thorsell Annika , Kifer Domagoj , Domazet-Lošo Mirjana , Vlahoviček Kristian , Mijaković Ivan , Domazet-Lošo Tomislav 
Published: March 2020

AbstractCorrespondence between evolution and development has been discussed for more than two centuries1. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity2–10. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes6, 10–12. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure13–16. For instance, it has been increasingly recognized that multicellular behaviour underlies biofilm formation in bacteria13, 14, 17–19. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes14–16, 18, 20. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed towards later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos11, 21. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants and fungi. Given that most cells on Earth reside in the form of biofilms22and that biofilms represent the oldest known fossils23, we anticipate that the widely-adopted vision of the first life as a single-cell and free-living organism needs rethinking.
Evidence fromAmphioxusfor acquisition of alternative mRNA splicing of NCoR corepressor after its duplication and divergence during vertebrate evolution
Authors: Privalsky Martin L. 
Published: March 2020

ABSTRACTNCoR-1 and NCoR-2 are transcriptional corepressors encoded in vertebrates by two interrelated loci and play distinct, though overlapping, roles in development, differentiation, and homeostasis. In contrast NCoR is encoded by a single locus in cephalochordates, urochordates, hemichordates, and echinoderms, with vertebrate NCoR-1 and NCoR-2 thought to be the products of a gene duplication originating near the beginning of vertebrate evolution. The structures, molecular properties, and functions of extant NCoR-1 and NCoR-2 are each substantially further diversified by alternative mRNA splicing; however it is unresolved as to whether the alternative-splicing observed in current day vertebrates reflects patterns present in the ancestral common gene or instead arose after the NCoR duplication event. This manuscript reports thatAmphioxus, a cephalochordate considered representative of the organisms that gave rise to the vertebrate lineage, lacks the alternative NCoR splicing events characteristic of vertebrates. This, together with prior taxonomic comparisons, suggests that the patterns of corepressor splicing found in existing vertebrates arose exclusively after the NCoR duplication event. Further, given that alternative-splicing of NCoR-1 and NCoR-2 appears to have arisen by a mix of convergent and divergent evolution, it is likely that both common and distinct selective pressures were operative on these corepressor paralogs after their divergence.
Rapid, direct detection of bacterial Topoisomerase 1-DNA adducts by RADAR/ELISA
Authors: Sinha Devapriya , Kiianitsa Kostantin , Sherman David R. , Maizels Nancy 
Published: March 2020

AbstractTopoisomerases are proven drug targets, but antibiotics that poison bacterial Topoisomerase 1 (Top1) have yet to be discovered. We have developed a rapid and direct assay for quantification of Top1-DNA adducts that is suitable for high throughput assays. Adducts are recovered by “RADAR fractionation”, a quick, convenient approach in which cells are lysed in chaotropic salts and detergent and nucleic acids and covalently bound adducts then precipitated with alcohol. Here we show that RADAR fractionation followed by ELISA immunodetection can quantify adducts formed by wild-type and mutant Top1 derivatives encoded by two different bacterial pathogens,Y. pestisandM. tuberculosis, expressed inE. coliorM. smegmatis, respectively. For both enzymes, quantification of adducts by RADAR/ELISA produces results comparable to the more cumbersome classical approach of CsCl density gradient fractionation. The experiments reported here establish that RADAR/ELISA assay offers a simple way to characterize Top1 mutants and analyze kinetics of adduct formation and repair. They also provide a foundation for discovery and optimization of drugs that poison bacterial Top1 using standard high-throughput approaches.
Mitochondria-mitochondria interaction networks show altered topological patterns in Parkinson’s disease
Authors: Zanin Massimiliano , Santos Bruno F. R. , Antony Paul M.A. , Berenguer-Escuder Clara , Larsen Simone B. , Hanss Zoé , Barbuti Peter , Baumuratov Aidos S. , Grossmann Dajana , Capelle Christophe , Weber Joseph , Balling Rudi , Ollert Markus , Krüger Rejko , Diederich Nico J. , He Feng Q. 
Published: March 2020

SUMMARYMitochondrial dysfunction is linked to pathogenesis of Parkinson’s disease (PD). However, individual-mitochondria-based analyses do not show a uniform feature in PD patients. Since mitochondria interact with each other, we hypothesize that PD-related features might exist in topological patterns of mitochondria-mitochondria interaction networks (MINs). Here we showed that MINs form non-classical scale-free supernetworks in colonic ganglia both from healthy controls and PD patients, however, altered topological patterns are observed in PD patients. These patterns highly correlate with PD clinical scores and a machine-learning approach based on the MIN features accurately distinguish between patients and controls with an area-under-curve value of 0.989. The MINs of midbrain dopaminergic neurons (mDANs) derived from several genetic PD patients also display specific changes. CRISPR/CAS9-based genome correction of alpha-synuclein point mutations reverses the changes in MINs of mDANs. Our MIN network analysis opens a new dimension for a deeper characterization of various complex diseases with mitochondrial dysregulation.