bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventive procedure for stenosis after esophagojejunostomy using a circular stapler and transorally inserted anvil (OrVil™) following laparoscopic proximal gastrectomy and total gastrectomy involving reduction of anastomotic tension
Authors: Nomura Eiji , Kayano Hajime , Seki Takatoshi , Abe Rin , Yoshii Hisamichi , Uda Shuji , Kazuno Akihito , Izumi Hideki , Yamamoto Soichiro , Mukai Masaya , Makuuchi Hiroyasu 
Published: January 2021

Abstract
Background
Recently, due to increasing reports of stenosis after esophagojejunostomy created using circular staplers and a transorally inserted anvil (OrVil™) following laparoscopic proximal gastrectomy (LPG) and total gastrectomy (LTG), linear staplers are being used instead. We investigated our preventive procedure for esophagojejunostomy stenosis following use of circular staplers.

Methods
Since the anastomotic stenosis is considered to be mainly caused by tension in the esophageal and jejunal stumps at the anastomotic site, we have been performing procedures to relieve this tension, by cutting off the rubber band and pushing the shaft of the circular stapler toward the esophageal side, since July 2015. We retrospectively compared the incidence of anastomotic stenosis in cases of LPG and LTG performed before July 2015 (early phase, 30 cases) versus those performed after this period (later phase, 22 cases).

Results
Comparison of the incidence of anastomotic stenosis according to the type of surgery, LPG or LTG, and between the two time periods versus all cases, indicated a significantly lower incidence in the later phase than in the early phase (4.5 vs. 26.7%, p < 0.05), especially for LPG (0 vs. 38.5%, p < 0.05).

Conclusions
It is possible to use a circular stapler during laparoscopic esophagojejunostomy, as with open surgery, if steps to reduce tension on the anastomotic site are undertaken. These procedures will contribute to the spread of safe and simple laparoscopic anastomotic techniques.
In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study
Authors: Grant Rebecca , Fléchelles Olivier , Tressières Benoît , Dialo Mama , Elenga Narcisse , Mediamolle Nicolas , Mallard Adeline , Hebert Jean-Christophe , Lachaume Noémie , Couchy Elvire , Hoen Bruno , Fontanet Arnaud 
Published: January 2021

Abstract
Background
In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas.

Methods
We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition.

Results
Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions.

Conclusion
In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age.

Trial registration
ClinicalTrials.gov, NCT02810210. Registered 20 June 2016.
Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
Authors: Karolak Justyna A. , Gambin Tomasz , Szafranski Przemyslaw , Stankiewicz Paweł 
Published: January 2021

AbstractBackgroundThe epithelial-mesenchymal signaling involving SHH-FOXF1, TBX4-FGF10, and TBX2 pathways is an essential transcriptional network operating during early lung organogenesis. However, precise regulatory interactions between different genes and proteins in this pathway are incompletely understood.MethodsTo identify TBX2 and TBX4 genome-wide binding sites, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in human fetal lung fibroblasts IMR-90.ResultsWe identified 14,322 and 1,862 sites strongly-enriched for binding of TBX2 and TBX4, respectively, 43.95% and 18.79% of which are located in the gene promoter regions. Gene Ontology, pathway enrichment, and DNA binding motif analyses revealed a number of overrepresented cues and transcription factor binding motifs relevant for lung branching that can be transcriptionally regulated by TBX2 and/or TBX4. In addition, TBX2 and TBX4 binding sites were found enriched around and withinFOXF1and its antisense long noncoding RNAFENDRR,indicating that the TBX4-FGF10 cascade may directly interact with the SHH-FOXF1 signaling.ConclusionsWe highlight the complexity of transcriptional network driven by TBX2 and TBX4 and show that disruption of this crosstalk during morphogenesis can play a substantial role in etiology of lung developmental disorders.
Comparison between 3-dimensional and 2-dimensional endoscopic thyroidectomy for benign and malignant lesions: a meta-analysis
Authors: Huang Zigao , Qin Haiquan , Liao Jiankun , Meng Linghou , Qin Yongjie , Li Baojia , Lai Hao , Mo Xianwei 
Published: January 2021

Abstract
Background
The use of 3-dimensional (3D) endoscopic thyroidectomy (ET) has been increasing, but its feasibility and safety have not been well documented for thyroidectomy. Hence, to systematically investigate the comparative outcomes during 3D-ET and 2-dimensional (2D) ET for benign and malignant lesions, we conducted this meta-analysis.

Methods
Based on the PRISMA guidelines, a systematic database search of the PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases was performed. The eligible studies were published in English and Chinese up to October 2020. The major endpoints evaluated were procedure time, blood loss, postoperative drainage, postoperative hospitalization, postoperative complications, total number of lymph node dissections (LNDs), and total cost.

Results
A total of 15 relevant studies including 1190 patients (583 for 3D-ET and 607 for 2D-ET) compared the application of 3D and 2D laparoscopic systems in thyroid surgery, of which 8 were endoscopic benign thyroidectomy (EBT) and 7 were endoscopic malignant thyroidectomy (EMT). Our meta-analysis indicated that 3D-ET generally had advantages over 2D-ET in terms of procedure time (P = 0.000), blood loss (P = 0.000), postoperative drainage (P = 0.000), postoperative complications (P = 0.000), and LNDs (P = 0.006). However, there were no significant differences between the two systems in terms of total cost (P = 0.245) or postoperative hospitalization (P = 0.068). Subgroup analysis showed consistency of the overall outcomes in each subset, but a shorter postoperative hospitalization in 3D-EBT was revealed.

Conclusions
Compared to 2D-ET, 3D endoscopic thyroidectomy is an efficient, safe, and reliable method with better depth perception and stereoscopic vision, and an equally satisfactory outcome. More clinical RCTs with long-term follow-up are required to reproduce these promising results.
Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer
Authors: Qian Jin , Gong Zi-chen , Zhang Yi-na , Wu Hong-hua , Zhao Jing , Wang Li-ting , Ye Li-juan , Liu Da , Wang Wei , Kang Xia , Sheng Jun , Xu Wei , Liu Xi-lin , Wu Juan , Zheng Wei 
Published: January 2021

Abstract
Background
To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors.

Methods
The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts.

Results
LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate.

Conclusion
LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC.
Slit/Robo signaling regulates Leydig cell steroidogenesis
Authors: Martinot Emmanuelle , Boerboom Derek 
Published: January 2021

Abstract
Background
First identified as a regulator of neuronal axon guidance, Slit/Robo signaling has since been implicated in additional physiologic and pathologic processes, such as angiogenesis, organogenesis and cancer progression. However, its roles in the regulation of testis function have been little explored.

Methods
Immunohistochemistry and RT-qPCR analyses were performed to detect the expression of Slit/Robo signaling effectors in the adult mouse testis. To identify the roles and mechanisms of Slit/Robo signaling in the regulation of steroidogenesis, RT-qPCR, immunoblotting and hormone measurements were carried out using Leydig cells (primary cultures and the MA10 cell line) treated with exogenous SLIT ligands, and testes from Robo1-null mice.

Results
Slit1, -2 and -3 and Robo1 and -2 expression was detected in the adult mouse testis, particularly in Leydig cells. In vitro treatment of Leydig cells with exogenous SLIT ligands led to a decrease in the expression of the steroidogenic genes Star, Cyp11a1, and Cyp17a1. SLIT2 treatment decreased the phosphorylation of the key steroidogenic gene regulator CREB, possibly in part by suppressing AKT activity. Furthermore, SLIT2 treatment reduced the responsiveness of MA10 cells to luteinizing hormone by decreasing the expression of Lhcgr. Consistent with these in vitro results, an increase in testicular Star mRNA levels and intra-testicular testosterone concentrations were found in Robo1-null mice. Finally, we showed that the expression of the Slit and Robo genes in Leydig cells is enhanced by testosterone treatment in vitro, by an AR-independent mechanism.

Conclusion
Taken together, these results suggest that Slit/Robo signaling represents a novel mechanism that regulates Leydig cell steroidogenesis. It may act in an autocrine/paracrine manner to mediate negative feedback by testosterone on its own synthesis.
COVID-19 and healthcare system in China: challenges and progression for a sustainable future
Authors: Sun Shuangyi , Xie Zhen , Yu Keting , Jiang Bingqian , Zheng Siwei , Pan Xiaoting 
Published: January 2021

AbstractWith the ongoing COVID-19 outbreak, healthcare systems across the world have been pushed to the brink. The approach of traditional healthcare systems to disaster preparedness and prevention has demonstrated intrinsic problems, such as failure to detect early the spread of the virus, public hospitals being overwhelmed, a dire shortage of personal protective equipment, and exhaustion of healthcare workers. Consequently, this situation resulted in manpower and resource costs, leading to the widespread and exponential rise of infected cases at the early stage of the epidemic. To limit the spread of infection, the Chinese government adopted innovative, specialized, and advanced systems, including empowered Fangcang and Internet hospitals, as well as high technologies such as 5G, big data analysis, cloud computing, and artificial intelligence. The efficient use of these new forces helped China win its fight against the virus. As the rampant spread of the virus continues outside China, these new forces need to be integrated into the global healthcare system to combat the disease. Global healthcare system integrated with new forces is essential not only for COVID-19 but also for unknown infections in the future.
Medical unfitness for work at sea: causes and incidence rate over a 12-year period in France
Authors: Loddé Brice , Megard Marie-Fleur , Le Goff Nicolas , Misery Laurent , Pougnet Richard , Dewitte Jean-Dominique , Lucas David , Sauvage Thierry 
Published: January 2021

Abstract
Background
The purposes of the study were first to determine the incidence rate of medical unfitness for work at sea among French seafarers, second to identify the conditions (diseases or accidents) causing such incapacity so as to set up prevention measures where possible and third to ascertain whether there were any overrepresentations of diseases according to category of unfit seafarers (fishers, merchant seafarers, shellfish farmers and professional sailors).

Methods
An exhaustive, observational, descriptive, retrospective epidemiological and nosological study was carried out based on the medical coding of files stored in the Aesculapius® national database, which registers all medical data regarding seafarers presenting at the French seafarers’ health services. The increasing rate of permanent medical unfitness for work at sea was calculated in relation to the annual number of registered seafarers. A 12-year span was chosen in an attempt to ascertain the different sociodemographic categories associated with incapacity.

Results
In all, 2392 seafarers were declared unfit for work at sea. This represents a permanent medical unfitness for work at sea incidence rate of below 1% for all French seafarers examined for medical fitness between 2005 and 2016.
The average age of the population of unfit seafarers was 48. The average time spent at sea before being declared unfit for work at sea was 15.5 years. Sixty-seven percent of the seafarers declared unfit had been working in the fishing sector.
The main reasons for deciding permanent unfitness for work at sea were: rheumatological conditions associated specifically with the spine; injuries relating to accidents or other external causes, mostly affecting the upper limbs; mental and behavioural disorders, including mood disorders and particularly addictions; and diseases of the circulatory system, namely coronopathies. The incidence rate of medical unfitness for work at sea was seen to increase between 2005 and 2016, but a decrease due to the dilution effect was noted in 2015.

Conclusions
Permanent unfitness seldom occurs among French professional seafarers. Prevention measures must be focused on musculoskeletal disorders, psychiatric affections and coronary conditions as well as on combatting maritime accidents, especially in the professional fishing sector, where such affections and accidents are overrepresented.
Individualized quality of life benefit and cost-effectiveness estimates of proton therapy for patients with oropharyngeal cancer
Authors: Brodin N. Patrik , Kabarriti Rafi , Schechter Clyde B. , Pankuch Mark , Gondi Vinai , Kalnicki Shalom , Garg Madhur K. , Tomé Wolfgang A. 
Published: January 2021

Abstract
Background
Proton therapy is a promising advancement in radiation oncology especially in terms of reducing normal tissue toxicity, although it is currently expensive and of limited availability. Here we estimated the individual quality of life benefit and cost-effectiveness of proton therapy in patients with oropharyngeal cancer treated with definitive radiation therapy (RT), as a decision-making tool for treatment individualization.

Methods and materials
Normal tissue complication probability models were used to estimate the risk of dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis for 33 patients, comparing delivered photon intensity-modulated RT (IMRT) plans to intensity-modulated proton therapy (IMPT) plans. Quality-adjusted life years (QALYs) lost were calculated for each complication while accounting for patient-specific conditional survival probability and assigning quality-adjustment factors based on complication severity. Cost-effectiveness was modeled based on upfront costs of IMPT and IMRT, and the cost of acute and/or long-term management of treatment complications. Uncertainties in all model parameters and sensitivity analyses were included through Monte Carlo sampling.

Results
The incremental cost-effectiveness ratios (ICERs) showed considerable variability in the cost of QALYs spared between patients, with median $361,405/QALY for all patients, varying from $54,477/QALY to $1,508,845/QALY between individual patients. Proton therapy was more likely to be cost-effective for patients with p16-positive tumors ($234,201/QALY), compared to p16-negative tumors ($516,297/QALY). For patients with p16-positive tumors treated with comprehensive nodal irradiation, proton therapy is estimated to be cost-effective in ≥ 50% of sampled cases for 8/9 patients at $500,000/QALY, compared to 6/24 patients who either have p16-negative tumors or receive unilateral neck irradiation.

Conclusions
Proton therapy cost-effectiveness varies greatly among oropharyngeal cancer patients, and highlights the importance of individualized decision-making. Although the upfront cost, societal willingness to pay and healthcare administration can vary greatly among different countries, identifying patients for whom proton therapy will have the greatest benefit can optimize resource allocation and inform prospective clinical trial design.
Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
Authors: Chen Zhiqiang , Lin Tong , Liao Xiaozhong , Li Zeyun , Lin Ruiting , Qi Xiangjun , Chen Guoming , Sun Lingling , Lin Lizhu 
Published: January 2021

Abstract
Background
Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma.

Methods
By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods.

Results
32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions.

Conclusions
As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.