bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo porcine model study on the treatment outcomes of scissor-type knife versus needle-type knife in endoscopic submucosal dissection performed by trainees
Authors: Ichijima Ryoji , Esaki Mitsuru , Yamakawa Shun , Minoda Yosuke , Suzuki Sho , Kusano Chika , Ikehara Hisatomo , Gotoda Takuji 
Published: November 2020

AbstractBackgroundEndoscopic submucosal dissection (ESD) for gastrointestinal neoplasms can be technically difficult for trainee endoscopists. Presently, there is no consensus for trainees to select the endo-knife type in ESD. Therefore, we conducted a comparison study of treatment outcomes between scissors-type and needle-type knives in ESD performed by trainees in an ex vivo porcine model.MethodsThis study was conducted on trainee endoscopists who participated in ESD hands-on seminars held in August 2018 and September 2019. A total of 22 trainees from 13 institutions were divided into two groups according to their endoscopic experience. Under expert supervision, each trainee performed two ESDs in porcine models, namely, scissor-type knife (ESD-S) and needle-type knife (ESD-N). The efficacy and safety, including the procedure time and rates of self-completion, en bloc resection, and complications, were compared between ESD-S and ESD-N. In subgroup analysis, we also investigated the predictors associated with the difficulty of ESD for trainees using multivariate logistic regression analysis.ResultsEight trainees had an experience of over 1000 endoscopies (senior trainee: S-Trainee), whereas the others had an experience of less than 1000 endoscopies (junior trainee: J-Trainee). Among the S-Trainees, no significant differences were observed in any treatment outcome between ESD-S and ESD-N. Among the J-Trainees, the total procedure and mucosal incision times were significantly shorter in ESD-S than in ESD-N [total procedure time: 16.5 min (range 10.0–31.0) vs. 22.3 min (range 10.0–38.0), P = 0.018; circumferential incision time: 10.0 min (range 6–16) vs. 17.0 min (range 5.0–31.5); P = 0.019]. Regarding complications, muscular injury occurred in two patients during ESD-N performed by J-Trainees; however, no muscular injury occurred during ESD-S. In subgroup analysis, ESD-N was an independent predictive factor of difficult ESD (odds ratio 5.28, 95% confidence interval 1.25–22.30;P = 0.024).ConclusionsThis study revealed that trainees, particularly those who have experienced less than 1000 endoscopies, should opt for the scissor-type knife to perform ESD.
Laparoscopic resection of a primary diaphragmatic schwannoma: a case report and literature review
Authors: Kamiya Ayako , Yamagata Yukinori , Yoshida Hiroshi , Ishizu Kenichi , Wada Takeyuki , Hayashi Tsutomu , Otsuki Sho , Yoshikawa Takaki , Katai Hitoshi 
Published: November 2020

Abstract
Background
Schwannomas are nerve sheath tumors that commonly originate from the stomach and small intestine. A primary schwannoma of the diaphragm is rare and does not show any symptoms until it grows to a certain size. Hence, it is extremely rare that it was found at a size that allowed resection under videoscopic surgery.

Case presentation
A 77-year-old woman was referred to our department for surgical treatment of a tumor located near the gastric fornix. She underwent a routine esophagogastroduodenoscopy 2 years and 7 months prior to the referral. It was suspected that she had a submucosal tumor measuring 10 mm, located in the fornix, and was then referred to her previous physician. During her follow-up, endoscopic ultrasonography (EUS) revealed that the cystic structure had continued to grow toward the gastric wall, and she was then referred to the endoscopy division of our hospital. She continued to be followed-up, and it was noted that the tumor was gradually increasing in size. Therefore, she requested surgical resection, and was finally referred to our division. Since the tumor was rather small, we planned a laparoscopic surgery. An initial examination during the operation revealed that the tumor was located on the left diaphragm. Since the tumor was relatively small and visibility was good, we decided to continue with the laparoscopic surgery. Partial diaphragmectomy with complete inclusion of the tumor was performed, and the defect of the diaphragm was directly closed by a running suture. Pathological examination revealed a benign schwannoma that had originated from the diaphragm. To support our findings, we also reviewed the scientific literature on diaphragmatic schwannoma cases reported up to April 2020.

Conclusions
In this extremely rare case, we successfully resected the diaphragmatic schwannoma using laparoscopic surgery.
The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells
Authors: Kim Mi Ju , Park Ki-Su , Kim Kyoung-Tae , Gil Eun Young 
Published: November 2020

Abstract
Background
Fascin is an actin-binding protein and highly expressed in ovarian cancer cells. It is associated with metastasis of cancer and may be a useful prognostic factor. Anticancer activity of curcumin is related to its effect on several signaling mechanisms. Although there have been many reports regarding the anticancer properties of curcumin, its inhibitory effects on migration and invasion of ovarian cancer cells, particularly in the context of fascin expression, have not been reported. The purpose of this study was to investigate the effect of curcumin on fascin expression in ovarian cancer cells and to propose a possible mechanism for the anticancer activity of curcumin through reduced fascin expression.

Methods
SKOV3, human epithelial ovary cancer cell line, was cultured with curcumin at various dose and duration. The fascin was quantified using cell viability test and Western blot. To determine the effect of curcumin on the upstream pathway of fascin expression, the signal transducer and activator of transcription 3 (STAT3) was analyzed by sandwich-ELISA. Attachment assay, migration assay and invasion assay were analyzed to approve the change of cellular invasiveness of ovary cancer after curcumin. To determine the morphological changes of ovarian cancer cells by curcumin, immunofluorescence was performed.

Results
MTS assays showed that cell viability was different at various concentration of curcumin, and as concentration increased, cell viability tended to decrease. Curcumin appears to suppress fascin expression, even with a minimal concentration and short exposure time. Also, curcumin may suppress fascin expression in ovarian cancer cells through STAT3 downregulation. The attachment assay, migration assay and invasion assay of the ovarian cancer cells exhibited a statistically significant decrease. Immunofluorescence revealed a change of cell shape from a typical form of uninfluenced cells to a more polygonal appearance, with a significant reduction in filopodia formation.

Conclusions
Curcumin reduces fascin expression through JAK/STAT3 pathway inhibition, which interferes with the cellular interactions essential for the metastasis and recurrence of ovarian cancer cells. Higher curcumin concentrations and longer exposure times concomitantly decreased fascin expression.
Is lymph node dissection mandatory among early stage endometrial cancer patients? A retrospective study
Authors: Zhang Guangmin , Chen Hongyou , Liu Yanying , Niu Liyan , Jin Liming , Li Dong , Song Lihua , Shang Lifei , Lin Xiangya , Wang Fei , Li Fengtong , Zhang Xinyu , Zhang Xiaoyu , Gao Yan , Qiu Dongyu , Zhang Yunpu , Na Ren , Su Riguge 
Published: November 2020

Abstract
Background
Whether routine lymph node dissection for early endometrial cancer is beneficial to survival is still controversial. However, surgeons usually perform lymph node dissection on all patients with early endometrial cancer. This study aimed to prove that the risk of lymph node metastasis, as defined by our standard, is very low in such patients and may change the current surgical practice.

Methods
36 consecutive patients who had staged surgery for endometrial cancer were collected. All eligible patients meet the following very low risk criteria for lymph node metastasis, including: (1) preoperative diagnosis of endometrial cancer (preoperative pathological diagnosis), (2) tumors confined to the uterine cavity and not beyond the uterine body, (3) PET-MRI lymph node metastasis test is negative. PET-MRI and pathological examination were used to assess the extent and size of the tumor, the degree of muscular invasion, and lymph node metastasis.

Results
The median age at diagnosis was 52 years (range 35–72 years). The median tumor size on PET-MRI was 2.82 cm (range 0.66–6.37 cm). Six patients underwent robotic surgery, 20 underwent laparoscopic surgery, 8 underwent Laparoscopic-assisted vaginal hysterectomy, and 2 underwent vaginal hysterectomy. 23% (63.9%) patients had high-grade (i.e. 2 and 3) tumors. Among the 36 patients who underwent lymph node sampling, the median number of lymph nodes retrieved was 32 (range 9–57 nodules). No patient (0%) was diagnosed with lymph node metastasis. According to the policy of each institution, 8 patients (22.2%) received adjuvant therapy, and half of them also received chemotherapy (4 patients; 50%).

Conclusions
None of the patients who met the criteria had a pathological assessment of lymph node metastasis. Omitting lymph node dissection may be reasonable for patients who meet our criteria.
“Who is watching the watchdog?”: ethical perspectives of sharing health-related data for precision medicine in Singapore
Authors: Lysaght Tamra , Ballantyne Angela , Xafis Vicki , Ong Serene , Schaefer Gerald Owen , Ling Jeffrey Min Than , Newson Ainsley J. , Khor Ing Wei , Tai E. Shyong 
Published: November 2020

Abstract
Background
We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal research.

Methods
We conducted seven focus groups with 62 participants in Singapore from May to July 2019. They were conducted in three languages (English, Mandarin and Malay) and analysed with qualitative content and thematic analysis.

Results
Four key themes emerged: nuanced understandings of data security and data sensitivity; trade-offs between data protection and research benefits; trust (and distrust) in the public and private sectors; and governance and control options. Participants were aware of the inherent risks associated with data sharing for research. Participants expressed conditional support for data sharing, including genomic sequence data and information contained within electronic medical records. This support included sharing data with researchers from universities and healthcare institutions, both in Singapore and overseas. Support was conditional on the perceived social value of the research and appropriate de-identification and data security processes. Participants suggested that a data sharing oversight body would help strengthen public trust and comfort in data research for PM in Singapore.

Conclusion
Maintenance of public trust in data security systems and governance regimes can enhance participation in PM and data sharing for research. Contrary to themes in much prior research, participants demonstrated a sophisticated understanding of the inherent risks of data sharing, analysed trade-offs between risks and potential benefits of PM, and often adopted an international perspective.
The nSMase2/Smpd3 gene modulates the severity of muscular dystrophy and the emotional stress response in mdx mice
Authors: Matsuzaka Yasunari , Tanihata Jun , Ooshima Yoshiko , Yamada Daisuke , Sekiguchi Masayuki , Miyatake Shouta , Aoki Yoshitsugu , Terumitsu Mika , Yashiro Ryu , Komaki Hirofumi , Ishiyama Akihiko , Oya Yasushi , Inoue Yukiko U. , Inoue Takayoshi , Takeda Shin’ichi , Hashido Kazuo 
Published: November 2020

Abstract
Background
Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder and cognitive dysfunction caused by mutations in the dystrophin gene. It is characterized by excess inflammatory responses in the muscle and repeated degeneration and regeneration cycles. Neutral sphingomyelinase 2/sphingomyelin phosphodiesterase 3 (nSMase2/Smpd3) hydrolyzes sphingomyelin in lipid rafts. This protein thus modulates inflammatory responses, cell survival or apoptosis pathways, and the secretion of extracellular vesicles in a Ca2+-dependent manner. However, its roles in dystrophic pathology have not yet been clarified.

Methods
To investigate the effects of the loss of nSMase2/Smpd3 on dystrophic muscles and its role in the abnormal behavior observed in DMD patients, we generated mdx mice lacking the nSMase2/Smpd3 gene (mdx:Smpd3 double knockout [DKO] mice).

Results
Young mdx:Smpd3 DKO mice exhibited reduced muscular degeneration and decreased inflammation responses, but later on they showed exacerbated muscular necrosis. In addition, the abnormal stress response displayed by mdx mice was improved in the mdx:Smpd3 DKO mice, with the recovery of brain-derived neurotrophic factor (Bdnf) expression in the hippocampus.

Conclusions
nSMase2/Smpd3-modulated lipid raft integrity is a potential therapeutic target for DMD.
ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis
Authors: Charmsaz Sara , Doherty Ben , Cocchiglia Sinéad , Varešlija Damir , Marino Attilio , Cosgrove Nicola , Marques Ricardo , Priedigkeit Nolan , Purcell Siobhan , Bane Fiona , Bolger Jarlath , Byrne Christopher , O’Halloran Philip J. , Brett Francesca , Sheehan Katherine , Brennan Kieran , Hopkins Ann M. , Keelan Stephen , Jagust Petra , Madden Stephen , Martinelli Chiara , Battaglini Matteo , Oesterreich Steffi , Lee Adrian V. , Ciofani Gianni , Hill Arnold D. K. , Young Leonie S. 
Published: November 2020

Abstract
Background
Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets.

Methods
Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis.

Results
Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis.

Conclusion
ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.
Forest malaria in Cambodia: the occupational and spatial clustering of Plasmodium vivax and Plasmodium falciparum infection risk in a cross-sectional survey in Mondulkiri province, Cambodia
Authors: Sandfort Mirco , Vantaux Amélie , Kim Saorin , Obadia Thomas , Pepey Anaïs , Gardais Soazic , Khim Nimol , Lek Dysoley , White Michael , Robinson Leanne J. , Witkowski Benoit , Mueller Ivo 
Published: November 2020

Abstract
Background
After a marked reduction in malaria burden in Cambodia over the last decades, case numbers increased again in 2017–2018. In light of the national goal of malaria elimination by 2025, remaining pockets of high risk need to be well defined and strategies well-tailored to identify and target the persisting burden cost-effectively. This study presents species-specific prevalence estimates and risk stratification for a remote area in Cambodia.

Methods
A cross-sectional survey was conducted in 17 villages in the high-incidence province Mondulkiri in the dry season (December 2017 to April 2018). 4200 randomly selected participants (2–80 years old) were tested for Plasmodium infection by PCR. Risk of infection was associated with questionnaire-derived covariates and spatially stratified based on household GPS coordinates.

Results
The prevalence of PCR-detectable Plasmodium infection was 8.3% (349/4200) and was more than twice as high for Plasmodium vivax (6.4%, 268) than for Plasmodium falciparum (3.0%, 125, p < 0.001). 97.8% (262/268) of P. vivax and 92.8% (116/125, p < 0.05) of P. falciparum infections were neither accompanied by symptoms at the time of the interview nor detected by microscopy or RDT. Recent travels to forest sites (aOR 2.17, p < 0.01) and forest work (aOR 2.88, p < 0.001) were particularly strong risk factors and risk profiles for both species were similar. Large village-level differences in prevalence of Plasmodium infection were observed, ranging from 0.6% outside the forest to 40.4% inside. Residing in villages at the forest fringe or inside the forest compared to outside was associated with risk of infection (aOR 2.14 and 12.47, p < 0.001). Villages inside the forest formed spatial hotspots of infection despite adjustment for the other risk factors.

Conclusions
Persisting pockets of high malaria risk were detected in forested areas and in sub-populations engaging in forest-related activities. High levels of asymptomatic infections suggest the need of better case detection plans and the predominance of P. vivax the implementation of radical cure. In villages inside the forest, within-village exposure was indicated in addition to risk due to forest activities. Village-level stratification of targeted interventions based on forest proximity could render the elimination efforts more cost-effective and successful.
Spatial Anopheles arabiensis (Diptera: Culicidae) insecticide resistance patterns across malaria-endemic regions of Botswana
Authors: Buxton Mmabaledi , Wasserman Ryan J. , Nyamukondiwa Casper 
Published: November 2020

AbstractBackgroundSince the advent of the Green Revolution, pesticides have played an important role in the global management of invertebrate pests including vector mosquitoes. Despite optimal efficacy, insects often display insensitivity to synthetic insecticides owing to prolonged exposure that may select for resistance development. Such insecticide insensitivity may regress national and regional coordination in mosquito vector management and indeed malaria control. In Botswana, prolonged use of synthetic insecticides against malaria vectors have been practiced without monitoring of targeted mosquito species susceptibility status.MethodsHere, susceptibility status of a malaria vector (Anopheles arabiensis), was assessed against World Health Organization-recommended insecticides, across three malaria endemic districts. Adult virgin female mosquitoes (2–5 days old) emerging from wild-collected larvae were exposed to standardized insecticide-impregnated papers with discriminating doses.ResultsThe results showed resistance dynamics were variable in space, presumably as a result of spatial differences in insecticide use across malaria endemic districts and the types of insecticides used in the country. Overall, there was a reduced susceptibility ofAn. arabiensisfor the pyrethroid lambda-cyhalothrin and for dichloro diphenyl trichloroethane [DDT], which have similar modes of action and have been used in the country for many years. The Okavango district exhibited the greatest reduction in susceptibility, followed by Ngamiland and then Bobirwa, reflective of national intervention strategy spraying intensities. Vector mosquitoes were, however, highly susceptible to carbamates and organophosphates irrespective of region.ConclusionsThese results provide important findings of vector susceptibility to insecticides recommended for vector control. The results highlight the need to implement insecticide application regimes that more effectively including regionally integrated resistance management strategies for effective malaria control and elimination.
Nerve growth factor is closely related to glucose metabolism, insulin sensitivity and insulin secretion in the second trimester: a case–control study in Chinese
Authors: Tang Mengyang , Luo Mingjuan , Lu Wenqian , Zhang Rong , Liang Wei , Gu Jianfen , Yu Xuemei , Zhang Xueli , Hu Cheng 
Published: November 2020

Abstract
Objective
Inflammation-related factors have been shown to play a significant role throughout pregnancy. In this study, we aimed to explore the relationships between selected inflammatory cytokines and gestational diabetes (GDM) in Chinese pregnant women.

Design and methods
This was a 1:1 matched case–control study that included 200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester. Serum levels of nerve growth factor (NGF), Interleukin-6 (IL-6), leptin, Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) were measured by enzyme immunoassay. The associations of these inflammatory factors with metabolic parameters were analysed.

Results
In the second trimester, GDM patients had higher NGF levels and lower IL-8 levels than did normal controls (P < 0.001 and P = 0.015, respectively). However, in the third trimester, only lower leptin levels were observed in the GDM group (P = 0.031). Additionally, in the second trimester, NGF levels were not only positively associated with fasting, 1-h and 2-h glucose levels and the area under curve of glucose, but also positively related to insulin sensitivity and secretion, as suggested by fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment index of β-cell secretion (HOMA-β) (all P < 0.05). Moreover, IL-6 and leptin levels were positively correlated with HOMA-IR and HOMA-β, and TNF-α levels were positively related to HOMA-IR (all P < 0.05). Except for the relationships between NGF and HOMA-β and TNF-α and HOMA-IR, the other correlations still existed even after adjusting for confounding factors (all P < 0.05).

Conclusion
In addition to the positive associations of IL-6 and leptin with insulin resistance and secretion, NGF was higher in the GDM patients and strongly linked to glucose metabolism, insulin resistance and pancreatic β cell function in Chinese pregnant women in the second trimester.