bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frailty is a useful predictive marker of postoperative complications after pancreaticoduodenectomy
Authors: Nakano Yutaka , Hirata Yuki , Shimogawara Tatsuya , Yamada Toru , Mihara Koki , Nishiyama Ryo , Nishiya Shin , Taniguchi Hideki , Egawa Tomohisa 
Published: August 2020

Abstract
Background
Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF).

Methods
This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study.

Results
Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy.

Conclusions
Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.
Individualized prediction of survival benefit from primary tumor resection for patients with unresectable metastatic colorectal cancer
Authors: Yang Yi , Lu Yujie , Jiang Wen , Zhu Jinzhou , Yan Su 
Published: August 2020

AbstractBackgroundThe impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not.MethodsPatients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA).ResultsBased on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700–0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application.ConclusionsThese practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.
32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma
Authors: Liu Xiaoyu , Gao Fang , Jiang Longwei , Jia Meng , Ao Lei , Lu Ming , Gou Liming , Ho Mitchell , Jia Shaochang , Chen Fei , Gao Wei 
Published: August 2020

Abstract
Background
Treatment of hepatocellular carcinoma (HCC) using antibody-based targeted therapies, such as antibody conjugates and chimeric antigen receptor T (CAR-T) cell therapy, shows potent antitumor efficacy. Glypican-3 (GPC3) is an emerging HCC therapeutic target; therefore, antibodies against GPC3 would be useful tools for developing immunotherapies for HCC.

Methods
We isolated a novel human monoclonal antibody, 32A9, by phage display technology. We determined specificity, affinity, epitope and anti-tumor activity of 32A9, and developed 32A9-based immunotherapy technologies for evaluating the potency of HCC treatment in vitro or in vivo.

Results
32A9 recognized human GPC3 with potent affinity and specificity. The epitope of 32A9 was located in the region of the GPC3 protein core close to the modification sites of the HS chain and outside of the Wnt-binding site of GPC3. The 32A9 antibody significantly inhibited HCC xenograft tumor growth in vivo. We then pursued two 32A9-based immunotherapeutic strategies by constructing an immunotoxin and CAR-T cells. The 32A9 immunotoxin exhibited specific cytotoxicity to GPC3-positive cancer cells, while 32A9 CAR-T cells efficiently eliminated GPC3-positive HCC cells in vitro and caused HCC xenograft tumor regressions in vivo.

Conclusions
Our study provides a rationale for 32A9 as a promising GPC3-specific antibody candidate for HCC immunotherapy.
Fat mass affects nutritional status of ICU COVID-19 patients
Authors: De Lorenzo Antonino , Tarsitano Maria Grazia , Falcone Carmela , Di Renzo Laura , Romano Lorenzo , Macheda Sebastiano , Ferrarelli Anna , Labate Demetrio , Tescione Marco , Bilotta Federico , Gualtieri Paola 
Published: August 2020

Abstract
Background
Obesity and steatosis are associated with COVID-19 severe pneumonia. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese population unrecognized. The aim is to evaluate the relationship between Percentage of Fat Mass (FM%) and immune-inflammatory response, after 10 days in Intensive Care Unit (ICU).

Methods
Prospective observational study of 22 adult patients, affected by COVID-19 pneumonia and admitted to the ICU and classified in two sets: (10) lean and (12) obese, according to FM% and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day.

Results
Obese have steatosis, impaired hepatic function, compromise immune response and higher inflammation. In addition, they have a reduced prognostic nutritional index (PNI), nutritional survival index for ICU patients.

Conclusion
This is the first study evaluating FM% in COVID-19 patient. We underlined obese characteristic with likely poorly prognosis and an important misclassification of obesity. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese. Is fundamental personalized patients nutrition basing on disease phases.
A consideration of publication-derived immune-related associations in Coronavirus and related lung damaging diseases
Authors: Geifman Nophar , Whetton Anthony D. 
Published: August 2020

Abstract
Background
The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of the recent COVID-19 pandemic affecting, to date, over 14 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets.

Methods
Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with COVID-19, Coronavirus in general, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research.

Results
Cytokine and cell-type associations captured from Medical Subject Heading (MeSH) terms linked to thousands of PubMed records, has identified differing patterns of associations between the four corpuses of publications (COVID-19, Coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of Coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of Coronavirus, SARS, and H5N1.

Conclusion
Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.
Musculoskeletal pain distribution in 1,000 Danish schoolchildren aged 8–16 years
Authors: Fuglkjær Signe , Vach Werner , Hartvigsen Jan , Dissing Kristina Boe , Junge Tina , Hestbæk Lise 
Published: August 2020

Abstract
Background
Knowledge about the occurrence and distribution of musculoskeletal problems in early life is needed. The objectives were to group children aged 8 to 16 according to their distribution of pain in the spine, lower- and upper extremity, determine the proportion of children in each subgroup, and describe these in relation to sex, age, number- and length of episodes with pain.

Method
Data on musculoskeletal pain from about 1,000 Danish schoolchildren was collected over 3 school years (2011 to 2014) using weekly mobile phone text message responses from parents, indicating whether their child had pain in the spine, lower extremity and/or upper extremity. Result are presented for each school year individually.

Results
When pain was defined as at least 1 week with pain during a school year, Danish schoolchildren could be divided into three almost equally large groups for all three school years: Around 30% reporting no pain, around 40% reporting pain in one region, and around 30% reporting pain in two or three regions. Most commonly children experienced pain from the lower extremities (~ 60%), followed by the spine (~ 30%) and the upper extremities (~ 23%). Twice as many girls reported pain in all three sites compared to boys (10% vs. 5%) with no other statistically significant sex or age differences observed. When pain was defined as at least 3 weeks with pain during a schoolyear, 40% reported pain with similar patterns to those for the more lenient pain definition of 1 week.

Conclusion
Danish schoolchildren often experienced pain at more than one pain site during a schoolyear, and a significantly larger proportion of girls than boys reported pain in all three regions. This could indicate that, at least in some instances, the musculoskeletal system should be regarded as one entity, both for clinical and research purposes.
Insulator-based loops mediate the spreading of H3K27me3 over distant micro-domains repressing euchromatin genes
Authors: Heurteau Alexandre , Perrois Charlène , Depierre David , Fosseprez Olivier , Humbert Jonathan , Schaak Stéphane , Cuvier Olivier 
Published: August 2020

Abstract
Background
Chromosomes are subdivided spatially to delimit long-range interactions into topologically associating domains (TADs). TADs are often flanked by chromatin insulators and transcription units that may participate in such demarcation. Remarkably, single-cell Drosophila TAD units correspond to dynamic heterochromatin nano-compartments that can self-assemble. The influence of insulators on such dynamic compartmentalization remains unclear. Moreover, to what extent heterochromatin domains are fully compartmentalized away from active genes remains unclear from Drosophila to human.

Results
Here, we identify H3K27me3 micro-domains genome-wide in Drosophila, which are attributed to the three-dimensional spreading of heterochromatin marks into euchromatin. Whereas depletion of insulator proteins increases H3K27me3 spreading locally, across heterochromatin borders, it concomitantly decreases H3K27me3 levels at distant micro-domains discrete sites. Quantifying long-range interactions suggests that random interactions between heterochromatin TADs and neighbor euchromatin cannot predict the presence of micro-domains, arguing against the hypothesis that they reflect defects in self-folding or in insulating repressive TADs. Rather, micro-domains are predicted by specific long-range interactions with the TAD borders bound by insulator proteins and co-factors required for looping. Accordingly, H3K27me3 spreading to distant sites is impaired by insulator mutants that compromise recruitment of looping co-factors. Both depletions and insulator mutants significantly reduce H3K27me3 micro-domains, deregulating the flanking genes.

Conclusions
Our data highlight a new regulatory mode of H3K27me3 by insulator-based long-range interactions controlling distant euchromatic genes.
Laboratory colonization and maintenance of Anopheles atroparvus from the Ebro Delta, Spain
Authors: Birnberg Lotty , Aranda Carles , Talavera Sandra , Núñez Ana I. , Escosa Raúl , Busquets Núria 
Published: August 2020

AbstractBackgroundHistorically,Anopheles atroparvushas been considered one of the most important malaria vectors in Europe. Since malaria was eradicated from the European continent, the interest in studying its vectors reduced significantly. Currently, to better assess the potential risk of malaria resurgence on the continent, there is a growing need to update the data on susceptibility of indigenousAnophelespopulations to importedPlasmodiumspecies. In order to do this, as a first step, an adequate laboratory colony ofAn. atroparvusis needed.MethodsAnopheles atroparvusmosquitoes were captured in rice fields from the Ebro Delta (Spain). Field-caught specimens were maintained in the laboratory under simulated field-summer conditions. Adult females were artificially blood-fed on fresh whole rabbit blood for oviposition. First- to fourth-instar larvae were fed on pulverized fish and turtle food. Adults were maintained with a 10% sucrose solutionad libitum.ResultsAnAn. atroparvuspopulation from the Ebro Delta was successfully established in the laboratory. During the colonization process, feeding and hatching rates increased, while a reduction in larval mortality rate was observed.ConclusionsThe present study provides a detailed rearing and maintenance protocol forAn. atroparvusand a publicly available reference mosquito strain within the INFRAVEC2 project for further research studies involving vector-parasite interactions.
Fermented soy supplementation improves indicators of quality of life: a randomized, placebo-controlled, double-blind trial in adults experiencing heartburn
Authors: Fatani Asmaa , Vaher Kadi , Rivero-Mendoza Daniela , Alabasi Karima , Dahl Wendy J. 
Published: August 2020

Abstract
Objective
To determine if fermented soy supplementation relieves heartburn and improves gastrointestinal symptoms and quality of life, a randomized, double-blind parallel study was conducted with adults experiencing mild or moderate heartburn. Participants consumed up to 3, 1 g sachets of flavored, Lactobacillus delbrueckii fermented with soy flour (n = 23) or placebo (maltodextrin) (n = 27) sachets per heartburn incident as needed for 3 weeks. Symptom intensity at 5, 15, and 30 min post-administration was assessed using a Likert-like scale. The Gastrointestinal Symptoms Rating Scale (GSRS) and Gastro-esophageal Reflux Disease Quality of Life Questionnaire (GERD-QOL) were administered at baseline, post-intervention and following a 1-week washout.

Results
No significant differences between groups were seen for heartburn severity or frequency, GSRS syndromes, or GERD-QOL domains. However, individual QOL items related to inconvenience of taking medications, fear of eating, inability to concentrate at work, and disturbance of after-meal activities and rest improved with fermented soy compared to placebo. Frequency of heartburn, diarrhea, and bloating improved during washout vs. baseline for the fermented soy group compared to placebo. Lactobacillus delbrueckii fermented soy supplementation improved QOL indicators and may decrease heartburn occurrence over time vs. an acute effect; efficacy of daily intake and longer duration requires investigation.
Chronic cortisol exposure in early development leads to neuroendocrine dysregulation in adulthood
Authors: Hartig Ellen I. , Zhu Shusen , King Benjamin L. , Coffman James A. 
Published: August 2020

Abstract
Objective
Chronic early life stress can affect development of the neuroendocrine stress system, leading to its persistent dysregulation and consequently increased disease risk in adulthood. One contributing factor is thought to be epigenetic programming in response to chronic cortisol exposure during early development. We have previously shown that zebrafish embryos treated chronically with cortisol develop into adults with constitutively elevated whole-body cortisol and aberrant immune gene expression. Here we further characterize that phenotype by assessing persistent effects of the treatment on cortisol tissue distribution and dynamics, chromatin accessibility, and activities of glucocorticoid-responsive regulatory genes klf9 and fkbp5. To that end cortisol levels in different tissues of fed and fasted adults were measured using ELISA, open chromatin in adult blood cells was mapped using ATAC-seq, and gene activity in adult blood and brain cells was measured using qRT-PCR.

Results
Adults derived from cortisol-treated embryos have elevated whole-body cortisol with aberrantly regulated tissue distribution and dynamics that correlate with differential activity of klf9 and fkbp5 in blood and brain.
Isolation and whole-genome sequencing of Pseudomonas sp. RIT 623, a slow-growing bacterium endowed with antibiotic properties
Authors: Steiner KayLee K. , Parthasarathy Anutthaman , Wong Narayan H. , Cavanaugh Nicole T. , Chu Jonathan , Hudson André O. 
Published: August 2020

Abstract
Objective
There is an urgent need for the discovery and/or development of novel antibiotics. We report an exploration of “slow”-growing bacteria, which can be difficult to isolate using rich media as they are usually outcompeted by “fast”-growing bacteria, as potential sources of novel antimicrobials.

Results
Pseudomonas sp. RIT 623 was isolated using pond water agar from a pond located on the campus of the Rochester Institute of Technology (RIT). The genome was sequenced and analyzed for potential secondary metabolite gene clusters. Bioinformatics analysis revealed 14 putative gene clusters predicted to encode pathways for the anabolism of secondary metabolites. Ethyl acetate extracts from spent growth medium of Pseudomonas sp. RIT 623 were tested against two Gram-negative (E. coli ATCC 25922 and P. aeruginosa ATCC 27853) and two Gram-positive (B. subtilis BGSC 168 and S. aureus ATCC 25923) type strains to assess antibiotic activity. The antibiotic assays demonstrated that extracts of Pseudomonas sp. RIT 623 were able to inhibit the growth of the four strains. The active compound was separated using diethyl ether in a multi-solvent extraction and reverse phase chromatography. The bioactive compound/s were subsequently eluted in two consecutive fractions corresponding to approximately 16–22% acetonitrile, indicative of polar compound/s.
Alleviation of acute radiation-induced bone marrow failure in mice with human fetal placental stromal cell therapy
Authors: Volinsky Evgenia , Lazmi-Hailu Astar , Cohen Nerel , Adani Boaz , Faroja Mohammad , Grunewald Myriam , Gorodetsky Raphael 
Published: August 2020

Abstract
Purpose
Selected placental mesenchymal stromal cells isolated from the fetal mesenchymal placental tissues (f-hPSCs) were tested as cell therapy of lethal acute radiation syndrome (ARS) with bone marrow regeneration and induced extramedullary hematopoiesis.

Methods and materials
f-hPSCs were isolated from the chorionic plate of human placentae and further expanded in regular culture conditions. 2 × 106 f-hPSCs were injected on days 1 and 4 to 8-Gy total body irradiated (TBI) C3H mice, both intramuscularly and subcutaneously. Pre-splenectomized TBI mice were used to test the involvement of extramedullary spleen hematopoiesis in the f-hPSC-induced hematopoiesis recovery in the TBI mice. Weight and survival of the mice were followed up within the morbid period of up to 23 days following irradiation. The role of hematopoietic progenitors in the recovery of treated mice was evaluated by flow cytometry, blood cell counts, and assay of possibly relevant growth factors.

Results and conclusions
The survival rate of all groups of TBI f-hPSC-treated mice at the end of the follow-up was dramatically elevated from < 10% in untreated to ~ 80%, with a parallel regain of body weight, bone marrow (BM) recovery, and elevated circulating progenitors of blood cell lineages. Blood erythropoietin levels were elevated in all f-hPSC-treated mice. Extramedullary splenic hematopoiesis was recorded in the f-hPSC-treated mice, though splenectomized mice still had similar survival rate. Our findings suggest that the indirect f-hPSC life-saving therapy of ARS may also be applied for treating other conditions with a failure of the hematopoietic system and severe pancytopenia.