bluuebunny/crossref_metadata_2025 huggingface dataset:
The Study the Influence of Overlapping on the Microstructure, Tensile, and Creep Strength after Performing FSP on AZ91 (Numerical and Experimental)
Authors: Amini Hoda , Arab Bani , Gollo Hoseinpour , Nami Bahram
Published: February 2020

In this paper, the effect of multi-pass friction stir processing on the mechanical properties of AZ91 alloy has been studied. For the numerical investigation, this process has been simulated with the three-dimensional numerical modeling based on the ABAQUS/Explicit. This simulation involves the Johnson-Cook models for defining the material behavior during this intense plastic deformation and investigating the fracture criterion. The tool plunging and stirring phases in the two-pass process has been simulated. To prevent too much distortion of elements during modeling, the Arbitrary Lagrangian-Eulerian technique for automatically re-meshing of distorted elements has been used. The model was calibrated using the experimental results from the previous works. This model can predict the transient temperature distribution and residual stress field during FSP on AZ91. The results show that the maximum temperature in the advancing-side region is more than that in the retreating-side region. In addition, numerical results show that at the end position of the process, the tool during the lift-up leaves the keyhole region in the compressive stress state. The experimental results investigated the effect of multi-pass FSP on the microstructure, microhardness, tensile and creep properties of AZ91 magnesium alloy. The FSP is performed by applying 50% overlapping. The tensile, and creep tests are conducted at several temperatures from 25 to 210 °C. The optical microscopy and scanning electron micrograph (SEM) were used to study the microstructure of the samples after performing multi-pass friction stir processing. The experimental results indicate that on average, the tensile strength, microhardness, and creep strength of the processed samples increased by about 29, 23, and 38 %, respectively compared to the unprocessed ones.
Research on the Visualization of Ocean Big Data Based on the Cite-Space Software
Authors: Wu Jiajing , Jia Dongning , Wei Zhiqiang , Dou Xin
Published: February 2020

Ocean big data is the scientific practice of using big data technology in the marine field. Data from satellites, manned spacecraft, space stations, airship, unmanned aerial vehicles, shore-based radar and observation stations, exploration platforms, buoys, underwater gliders, submersibles, and submarine observation networks are seamlessly combined into the ocean’s big data. Increasing numbers of scholars have tried to fully analyze the ocean’s big data. To explore the key research technology knowledge graphs related to ocean big data, articles between 1990 and 2020 were collected from the “Web of Science”. By comparing bibliometric software and using the visualization software Cite-Space, the pivotal literature related to ocean big data, as well as countries, institutions, categories, and keywords, were visualized and recognized. Journal co-citation analysis networks can help determine the national distribution of core journals. Co-citation analysis networks for documents show authors who are influential at key technical levels. Key co-occurrence analysis network keywords can determine research hot spots and research frontiers. The three supporting elements of marine big data research are shown in the co-citation network. These elements are author, institution, and country. By examining the co-occurrence of keywords, the key technology research directions for future marine big data were determined.
Collaboration with community connectors to improve primary care access for hardly reached people: a case comparison of rural Ireland and Australia
Authors: Wallace Carolyn , Farmer Jane , White Carolynne , McCosker Anthony
Published: February 2020

Background: This study presents a way for health services to improve service access for hardly reached people through an exploration of how staff can find and collaborate with citizens (referred to as connectors) who span socio-cultural boundaries in their community. The study explored the local socio-cultural contexts of connectors’ boundary spanning activities and if they are health related; boundary spanning occurring between connectors and health professionals at the interface of health systems and community; and the opportunities and barriers to actively seeking out and collaborating with community connectors to access marginalised and hardly reached people. Methods: We conducted a qualitative case comparison from rural Ireland and Australia. Following purposive snow-ball sampling techniques to recruit participants, semi-structured interviews were conducted with 34 community informants, 21 healthcare staff and 32 connectors. Transcripts were coded and analysed using an inductive approach to ascertain categories and overall themes. Results: We found a diverse sample of connectors relating to heterogenous, small and locally distinct groups of hardly reached people. Overall 26 connectors were active at the interface between health services and the community, with variation in how this occurred between cases. The majority (21) described one or more health related activities with hardly reached people. All connectors expressed a willingness to develop a relationship with local health services on issues they identified as relevant. Barriers to collaborations between connectors and health services related to bureaucracy, workload, and burnout. Conclusions: Collaborating with connectors has potential as one strategy to improve access to health services for hardly reached people. To enact this, health staff need to identify local socio-cultural boundaries and associated connectors, facilitate two-way connections at the boundary between health services and community and enable collaboration by attending to activities in the community, at the interface between health services and community, and within the health system.
Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function
Authors: Wu Jingtao , He Caimei , Bu Jie , Luo Yue , Yang Shuyuan , Ye Chengyan , Yu Silei , He Binsheng , Yin Yulong , Yang Xiaoping
Published: February 2020

Background：The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model. Results: The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1µg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription- polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.
Cross-cultural adaptation and validation of the Slovenian version of the Core Outcome Measures Index for Low back pain
Authors: Topolovec Matevž , Vozlič David , Plohl Nejc , Vengust Rok , Vodičar Miha , Mannion Anne Frances
Published: February 2020

Background: To conduct a cross-cultural adaptation and validation of the Core Outcome Measures Index (COMI) in the Slovenian language, for use in patients with low back pain.
Methods: The English version of COMI was translated into Slovene following established guidelines. 353 patients with chronic low back pain were recruited from the Orthopedic clinic department of a tertiary care teaching institution. Data quality, construct validity, responsiveness, and test-retest reliability of the COMI were assessed.
Results: The questionnaire was generally well accepted with no missing values. The majority of items exhibited only mild floor and ceiling effects. Correlations with Oswestry Disability Index (ODI) were high (ρ = 0.76 between overall COMI and ODI scores), suggesting that the Slovene version of COMI had high construct validity. Additionally, the Slovene version of COMI successfully captured surgical patients’ improvement in their low back problem (indicator of responsiveness) and showed acceptable test-retest reliability (ICC = 0.86).
Conclusions: The Slovene version of COMI showed good psychometric properties, comparable to those of previously tested language versions. It represents a valuable instrument for the use in future domestic and multicenter clinical studies.
Keywords Cross-cultural adaptation ‧ Validation ‧ Core outcome measures index ‧ Low back pain ‧ Slovenian
Gap analysis of acoustic tracking data reveals spatial and temporal segregation in sympatric reef sharks
Authors: Williamson Michael J. , Tebbs Emma J , Dawson Terrence P , Curnick David J , Ferretti Francesco , Carlisle Aaron B , Chapple Taylor K , Schallert Robert J , Tickler David M , Block Barbara A , Jacoby David MP
Published: February 2020

Background
There are now a wide array of field and laboratory techniques available for gaining insight into the movement and behaviour of sharks. Although acoustic telemetry may lack the fine-scale resolution of some satellite technologies, the low cost and longer battery life make it a powerful tool for investigating elasmobranch behaviour. Here, we develop a novel approach to analysing acoustic telemetry data, using detection gaps to infer movement patterns to and from monitored reef habitats, to investigate spatial and temporal segregation between two sympatric shark species in a large remote MPA.

Methods
A total of 102 grey reef sharks (Carcharhinus amblyrhynchos) and 76 silvertip sharks (Carcharhinus albimarginatus) were fitted with long-term acoustic transmitters and tracked inside a large acoustic array of reef-based receivers in the British Indian Ocean Territory MPA, between 2014 and 2018. From the resulting dataset (768,081 detections), movements between receivers and recursive loops to the same receiver were identified. Using the durations of inter-receiver movements (i.e. detection gaps), individual behaviours were classified into ‘restricted’ or potential wider ‘out of range’ movements. Drivers of these movements were identified using network analysis, GLMMs and multi-model inference starting from an a priori set of explanatory variables.

Results
In general, silvertip sharks were more likely to undertake ‘out of range’ movements than grey reef sharks. ‘Out of range’ movements were more common at night compared to during the day, and during the wet season compared to the dry season. In addition, the difference in ‘out of range’ movements between the two species increased at night. These results suggest spatial and temporal segregation of movements between the two species.

Conclusions
We present a novel analysis of detection gaps from acoustic telemetry data to infer differential movement patterns and describe how species organise in space and time. Furthermore, this approach shows that acoustic telemetry gap analysis can be used for comparative studies, or combined, with other research techniques to better understand the functional role of sharks in reef ecosystems, moving towards more informed strategies for the conservation and management of the marine environment.
Tissue Adhesive for Wound Closure in enhanced-recovery Total Hip Arthroplasty: A Prospective, Randomized and Controlled Study
Authors: Kong Xiangpeng , Yang Minzhi , Cao Zheng , Chen Jiying , Chai Wei , Wang Yan
Published: February 2020

Background: We aimed to present our experience of adopting tissue adhesive as adjunct to standard wound closure in total hip arthroplasty (THA) and evaluate its performance.Methods: From September 2019 to November 2019, we prospectively enrolled consecutive patients who underwent simultaneous bilateral THA in this randomized and controlled study. Standard wound closure was applied on one side of hip and additional tissue adhesive on the other side at random. We collected and analyzed patients’ information, including age, gender, body mass index (BMI), diagnosis, postoperative length of stay (LOS), dressing changes, wound evaluation scores, wound-related cost and complications. Results: Thirty patients with simultaneous bilateral THA were enrolled in this study. During the hospital stay, the dressing change in hips with tissue adhesive was significantly less than that in the other hips (p=0.000). However, the wound-related cost in hips with tissue adhesive was significantly higher (p=0.000). At one-month follow up, patient-reported wound measurement of hips with tissue adhesive was significantly better than the other hips (p=0.004). Seventeen patients preferred tissue adhesive and only five patients preferred standard wound closure. Conclusions: Tissue adhesive could significantly reduce wound drainage and increase patient satisfaction, which can be an ideal adjunct to standard wound closure in enhanced-recovery THA.
Influence of the treatment used in inflammatory bowel disease on the level of protease activity
Authors: Dudzińska Ewa , Strachecka Aneta , Gil-Kulik Paulina , Kocki Janusz , Bogucki Jacek , Shemedyuk Natalya , Gryzinska Magdalena
Published: February 2020

Introduction: There is growing evidence that intestinal proteases have a role in the pathogenesis of gastrointestinal inflammatory diseases. IBD, which includes Crohn's disease (CD) and ulcerative colitis (UC), has an additional source of proteases represented by infiltrated and activated inflammatory cells. The aim of our study was to determine proteolytic system activity in patients with CD and UC. We limited the number of proteases tested by determining proteases active in acidic, neutral and alkaline pH.Material and methods: The study included 40 patients with IBD – 20 CD patients and 20 UC patients. Among the 20 CD patients, 17 were treated with aminosalicylates, 14 with azathioprine, and 4 with corticosteroids, while 8 patients were undergoing biological treatment. Among the 20 UC patients, 19 were treated with aminosalicylates, 8 with azathioprine, and 3 with corticosteroids. The optimal pH in which the enzymes were active was determined in acidic, neutral, and alkaline buffer environments. We prepared buffers of defined pH from 2.2 to 12.8, separated by 0.2 intervals and then determined proteolytic activity against substrates (gelatine, haemoglobin, ovalbumin, albumin, cytochrome C, and casein). Results: A decrease was observed in the activity of acid proteases (pH 5), alkaline proteases (pH 7), and neutral proteases (pH 7.6 and 8.6) in the groups of CD patients in remission in comparison with the active phase. In the group of patients with CD treated biologically, acid protease activity (pH 5.0) was lower than in CD patients not receiving biological treatment.Activity of neutral (pH 7.0) and alkaline (pH 7.6 and 8.6) proteases in the plasma of patients with UC in remission were lower in comparison to the active phase.Activity of acid (pH 5.0) and alkaline (8.6) protease inhibitors was higher in CD patients in the active phase in comparison to remission. In UC patients with exacerbation of the disease, the activity of alkaline (pH 8.6) protease inhibitors was increased compared to remission.Conclusions: 1. Our research may suggest that the immunomodulatory treatment used in IBD, aimed at reducing the level of leukocytes, may contribute to a reduction in protease activity.2. The decrease in the level of proteases in patients with CD and UC in remission may be a marker suggesting the patients’ response to the treatment.
Synthesis of CVD Diamond nanoparticles and Cytotoxicity evaluation in murine metastatic melanoma cells
Authors: Wachesk Cristiane Costa , Hurtado Carolina Guimarães , Falcão Rebeca , Tada Dayane Batista , Vasconcelos Getulio , Corat Evaldo José , Airoldi Vladimir Jesus Trava
Published: February 2020

Diamond nanoparticles (DNPs) have showed in vitro and in vivo biomedical applicability due to their low toxicity and biocompatibility. Recent studies have focused on the potential use of (DNPs) as suitable vehicles for improving drug delivery in cancer treatment. The advantages of DNPs lies in their high stability and small size compared to other carbon-based nanomaterials. In this work, CVD-diamond nanoparticles (CVD-DNPs) were synthesized and evaluated regarding their application as a new drug delivery platform for metastatic melanoma therapy. A new synthesis technique developed DNPs from CVD diamond thin film. This type of diamond has the same physical and chemical properties as a natural diamond: extreme hardness, excellent thermal conductivity, low coefficient of friction, biocompatibility, chemically inert for temperatures below 800 0 C, among others. The main objective of this study was to produce CVD-DNPs by laser ablation and to evaluate their cytotoxicity. A pulsed, ytterbium-doped fiber (Yb) was used to form DNPs in the pure aqueous medium (Milli-Q). The final suspension was obtained at high concentration of the CVD-DNPs and it was used to evaluate the cytotxicity in murine metastatic melanoma B16-F10 cells by using colorimetric assays. The characterization by FT-IR, X-Ray, DLS, RAMAN, SEM, and TEM demonstrated the successful synthesis of CVD-DNPs with a hydrodynamic diameter of 57 and 54 nm. In vitr o studies performed for 24h and 48h resulted in viability of 70-80% of cells incubated with CVD-DNPs at 250 μg/mL, which demonstrated a insignificant cytotoxic effect. Thus, these results suggest a potential use of CVD-DNPs as a drug delivery platform for antitumoral therapy.
Determination of water quality, trace elements contamination in Oreochomis niloticus and Clarias gariepinus reared in 2 types of ponds and health risk assessment in Cameroon
Authors: Ntsama Isabelle Sandrine Bouelet , Tambe Betrand Ayuk , Biyegue Christine Fernande Nyangono , Pouokam Guy , Mentho Hélène Claudia , Takadong Julie Judith Tsafack , Nama Gabriel Medoua , Serratosa Jordi , Kansci Germain
Published: February 2020

Background: Fish farming in Cameroon is growing very rapidly and fish available in the markets is mostly coming from fish farms, but domestic fish production is still low to meet demand. Intensification of production could lead to the occurrence of various types of contaminants that can affect the sanitary quality of farmed fish and consumer health. This study aimed to assess the quality of farmed fish collected in fish farms located in four regions of Cameroon (Center, South, West, Littoral).Results: Concentrations of arsenic, cadmium, lead, chromium, cobalt, and nickel were determined in pond water and muscles of Oreochromis niloticus and Clarias gariepinus raised in concrete and earthen ponds to evaluate health risk for consumers. Trace elements were determined using Inductively Coupled Plasma Optical Emission spectrometry (ICP-OES). Heavy metals in water for concrete and earthen ponds shows there are no significant differences (p<0.05) between the rearing systems except for cobalt and nickel. Heavy metals concentrations in water were lower when compared to the WHO recommended limits except for cadmium in all the ponds. For concrete ponds, heavy metal concentrations decreased in water in the sequence of Cd > As > Co > Ni > Cr > Pb. For earthen ponds the concentrations decreased as Cd > Co > As > Ni > Cr > Pb.Conclusion: Concentrations recorded in the muscles of the 2 species were above the safety limits recommended by FAO/WHO. The target hazard quotient of As was highest compared to other metals and higher than the acceptable limits according to US Environmental Protection Agency guidelines in all fish species. the level of each investigated metal, highlighted a very low health risk for consumers.
Influence of cement-augmented pedicle screws with different volumes of polymethylmethacrylate in osteoporotic lumbar vertebrae over the adjacent segments: A 3D finite element analysis
Authors: Guo Hui-zhi , Zhang Shun-cong , Guo Dan-qing , Ma Yan-huai , yuan Kai , Li Yong-xian , Peng Jian-cheng , Li Jing-lan , Liang De , Tang Yong-chao
Published: February 2020

Background: Polymethylmethacrylate (PMMA) is commonly used for cement-augmented pedicle screw instrumentation (CAPSI) to improve the fixation stability and reduce the risk of screw loosening in the osteoporotic thoracolumbar spine. Biomechanical researches have shown that various dose of cement (1-3ml) can be injected to enhance screw stability. To date, there have been no studies on the relationship between adjacent segment degeneration and the volume of PMMA. This study aimed to explore the influence of CAPSI with different volumes of PMMA in osteoporotic lumbar vertebrae over adjacent segments by using finite element analysis.Methods: Seven different finite element models were reconstructed and simulated under different loading conditions, including (1) an intact model, (2) three single-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml), and (3) three double-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml). To improve the accuracy of the finite element analysis, the models of the injectable pedicle screw and bone cement were created by using a three-dimensional scanning machine and the CAPSI patient’s CT data, respectively. The range of motion (ROM), the stress of intervertebral discs, and the stress of facet in the adjacent segment were comparatively analysed among the different models.Results: The ROMs of the different segments were compared with experimental data, with good agreement under the different load conditions. Compared with the intact model, the ROM, disc stresses, and facet stress in adjacent segments were found to be higher in the six operative models. Otherwise, with a larger volume of PMMA injected, the ROM, disc stresses, and facet stress slightly increased at the adjacent segment. However, the differences among the augmented models were insignificant for all loading cases.Conclusions: CAPSI could increase the incidence of disk degeneration in the adjacent segment, while within a certain range, different volumes of PMMA provided an approximate impact over the adjacent segment degeneration.
Outcomes of a retrospective study on sustained release betamethasone for transient radicular symptoms in patients after Transforaminal Lumbar Interbody Fusion operation
Authors: Haojie Li , Wang Yang , Ma Weihu , Xu Dingli
Published: February 2020

Background:Transforaminal lumbar interbody fusion(TLIF) operation is a commonly treatment for Lumbar disc herniation(LDH). but some patients had transient radicular symptoms after surgery.At present, some studies believes that the application of steroids is effective in radiculopathy caused by LDH.
Method: The patients who with single-level LDH underwent TLIF operation were retrospectively analyzed from March 2017 to July 2019. Patients were divided into observation group（a gelatin sponge with a mixture of 1 ml betamethasone injection + 2 ml 2% lidocaine placed around the spinal nerve roots after decompression） and control group 1（1 ml betamethasone injection + 2ml 2% lidocaine placed around the spinal nerve roots after decompression）、group 2（a gelatin sponge with 3 ml normal saline placed around the spinal nerve roots after decompression）group 3（no anything was placed）. Clinical data such as lasegue sign, postoperative hospital stays, VAS score of leg pain, ODI index, Effective standard and therapeutic effect were collected.Results: A total of 186 patients were finally included,the observation group 46 cases, control group 1: 53 cases, group 2:45 cases, and group 3:42 cases. VAS score of postoperative legs pain in the observation group at the postoperative 1-5 day were significantly lower than those in the control groups (P<0.05). The recovery of Lasegue sign in the observation group were significantly better than the control groups (P<0.05). The average of postoperative hospital stay in the observation was significantly shorter than the control groups. In addition,the unmeration of leukocyte in the four groups postoperative were significantly higher than before operation (P<0.05). the rate of complications in observation group and control groups has no significant difference.The patients in the four groups had basically the same satisfaction with the final efficacy (> 90%) .Conclusion：the use of gelatin sponge sustained-release steroids and other mixed solutions can significantly relieve transient radicular symptoms after TLIF operation,and does not influence the occurrence of postoperative complications.
Significant Symptoms and Non-Symptom-Related Factors for Malaria Diagnosis in Endemic Regions of Indonesia
Authors: Bria Yulianti Paula , Yeh Chung-Hsing , Bedingfield Susan
Published: February 2020

Background: In rural areas of Indonesia, where parasitological tests are not always available, a knowledge of significant symptoms and non-symptom-related factors is crucial for clinical diagnosis of malaria in order to take appropriate actions for treatment. Malaria diagnosis at early stages can avoid a progression in severity of the conditions and possible transmission of the disease. With insufficient knowledge of significant malaria symptoms and non-symptom-related factors for clinical diagnosis of malaria, medical doctors may presumptively treat febrile patients, which leads to an increase in resistance to antimalarial drugs.Methods: The study involves five stages. First, medical records are collected from patients suffering from malaria and other febrile diseases such as dengue fever, typhoid fever, respiratory tract infection, dyspepsia, pneumonia, common cold and gastritis. The records are obtained from two public hospitals in endemic regions in Indonesia’s East Nusa Tenggara Province, East Sumba and Lembata. Second, interviews with eight Indonesian medical doctors are conducted to understand the symptoms and non-symptom-related factors they use for clinical diagnosis of malaria. Third, symptoms and non-symptom-related factors from 472 collected medical records are selected and ranked using the correlation matrix method. Fourth, the 17 feature sets extracted from the ranked features are used to develop and compare various malaria classifiers using three machine-learning techniques, including logistic regression, support vector machines and k-nearest neighbors. Fifth, the most significant symptoms and non-symptom-related factors are identified for malaria diagnosis using the malaria classifiers developed. In addition, further experiments and comparisons are conducted to examine the performance of malaria classifiers using various feature sets.Results: (a) Out of 17 features identified from medical records, six significant symptoms (duration of fever, headache, nausea and vomiting, heartburn, pain and severe symptoms), and two non-symptom-related factors (history of malaria and age) contribute most to malaria diagnosis. These significant features can be used for malaria diagnosis with an average 85% accuracy. (b) As a symptom, duration of fever is more significant than temperature or fever for distinguishing malaria from other febrile diseases. (c) Trios malaria symptoms (fever, shivering and sweating) are shown to be less significant than other symptoms in endemic regions.Conclusions: The findings of this study can be used to raise the public awareness of significant malaria symptoms and non-symptom-related factors within societies vulnerable to malaria. These findings can also be used for helping unexperienced medical doctors with clinical diagnosis of malaria especially in rural areas, where the availability of parasitological tests is scarce.
The chemotherapy and radiation in low-grade myofibroblastic sarcoma: is there a role?
Authors: Xu Yao , Xu Guijun , Wang Xin , Mao Min , Wu Haixiao , Baklaushev Vladimir P. , Chekhonin Vladimir P. , Peltzer Karl , Wang Guowen , Zhang Chao
Published: February 2020

Background: Low-grade myofibroblastic sarcoma (LGMS) is a rare entity with a predilection in the head and neck. There are still no optimal treatment strategies for LGMS. We aimed to investigate the role of chemotherapy and radiation treatment for LGMS. Survival estimate was performed and prognostic factors were identified.Methods: Based on the Surveillance, Epidemiology, and End Result (SEER) database, LGMS patients diagnosed between 2001 and 2015 were involved in our study. Kaplan-Meier curves and log-rank tests were used to estimate overall survival. Cox proportional hazard regression model was performed to identify prognostic factors.Results: A total of 96 eligible patients with LGMS were included, among which 86 (89.6%) received surgical treatment. Twenty-eight (29.2%) patients received radiation treatment while chemotherapy was offered to 20 (10.4%) patients. The median age was 55.0 years old with 22 cases occurred in head and neck region. The mean OS was 125.2 (95%CI 106.3-144.2) months while 1-, 3-, 5- and 10-year OS rates were 88%, 77%, 70% and 59%, respectively. Age older than 60 years, positive nodal status and no surgical treatment were independent prognostic factors for patients with LGMS. Chemotherapy and radiation were not independent prognostic factors for LGMS.Conclusions: Several prognostic factors for LGMS were revealed in this study. Surgical resection is the main therapy while chemotherapy and radiation showed limited effects on survival improvement. Thus, chemotherapy and/or radiation should not be routinely performed in LGMS.
A single oral fixed - dose praziquantel-miltefosine nanocombination for effective control of experimental Schistosomiasis mansoni
Authors: Eissa Maha Mohamed , El-Azzouni Mervat , El-Khordagui Labiba Khalil , Bary Amany Abdel , El-Moslemany Riham Mohamed , Salam Sara Ahmed Abdel
Published: February 2020

Background: Schistosomiasis control has been centered to date on praziquantel, with shortcomings involving ineffectiveness against immature worms, reinfection and emergence of drug resistance. Strategies based on drug repurposing and/or praziquantel combination therapy proved effective, though with some limitations. Combining such strategies with nanotechnology would further augment therapeutic benefits. Nanocarrier-mediated delivery of multiple drugs in schistosomiasis control has not been documented to date. Our objective was to combine drug repurposing, combinational therapy and nanotechnology for the development of a single oral fixed dose nanocombination to improve praziquantel therapeutic profile. This was based on praziquantel and an antischistosomal repurposing candidate miltefosine, co-loaded into lipid nanocapsules in reduced doses. Methods: Two fixed dose lipid nanocapsule formulations were prepared at two concentration levels of praziquantel and miltefosine. Their antischistosomal activity in comparison with control singly loaded lipoid nanocapsules was assessed in Schistosoma mansoni- infected mice. Single oral dos of 250mg praziquantel-20mg miltefosine/kg and 125mg praziquantel-10mg miltefosine/kg were administered on the initial day of infection, 21st and 42nd days post infection. Scanning electron microscopy, parasitological and histopathological studies were used for assessment. In vivo data were subjected to analysis of variance and post hoc test (Tukey) was used for pairwise comparisons. Results: Lipid nanocapsules showed a mean diameter of 58 nm and high entrapment efficiency of both drugs (>95%). Compared to singly loaded lipid nanocapsules, the larger dose praziquantel-miltefosine nanocombination exerted high antischistosomal efficacy in terms of % reduction of worm burden, particularly when given against invasive and juvenile worms, and amelioration of hepatic granulomas. Scanning electron microscopy revealed extensive tegumental damage with noticeable deposition of nanostructures. Conclusions: A fixed dose praziquantel-miltefosine nanocombination offers great potential as a novel single dose oral antischistosomal therapy offering multistage activity and protection against hepatic pathology. The novel drug repurposing/combination therapy/nanotechnology multiple approach has the potentials of improving the therapeutic profile of praziquantel, achieving radical cure, hindering resistance to the component drugs, and simplifying praziquantel chemotherapy. Key words: Praziquantel, miltefosine, lipid nanocapsules, Schistosoma mansoni, nanocombination, multistage activity, tegumental targeting, scanning electron microscopy. ​ [LE1] [LE1]
MiR-877-5p down-regulation of PDK-1 involving in aspirin-induced gastric epithelial cells damage
Authors: jiang zongdan , Dan Ran , Jianjun Zou , Zhibing Wang , Zhi Wang , Chao Li , Zhenyu Zhang , Weihao Sun
Published: February 2020

It has been found that the expression of miR-877-5p is increased in serum of patients taking NSAIDs drugs. However, whether miR-877-5p play a role in aspirin-induced gastrointestinal mucosal erosion remains largely unknown. In this study, we investigated the effects of miR-877-5p on gastric epithelial cells (GES-1) proliferation and apoptosis in vitro. MiR-877-5p mimic/inhibitor and their oligonucleotides were transfected into GES-1 cells, then GES-1 cells were treated with different concentrations of aspirin (1.25, 2.5, 5 and 10 mmol/L). The bioinformatics software and dual-luciferase reporter assay were used to predict and verify the target gene of miR-877-5p. qRT-PCR and Western Blotting were employed to assess gene and protein expression, and CCK-8 assay and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. qRT-PCR data showed that miR-877-5p level was significantly increased in aspirin incubated GES-1 cells. The proliferation of GES-1 cells were markedly inhibited and apoptosis was significantly induced in the miR-877-5p mimic groups compared to control groups. Using PITA, Targetscan and miRWalk database, the three databases indicated that PDK1 was a target gene of miR-miR-877-5p. Dual luciferase reporter assay confirmed that the existence of a direct interaction between miR-877-5p and PDK1 mRNA. Importantly, miR-877-5p knockdown resulted in a significant upregulation of PDK1 mRNA and its encoded protein in GES-1 cells. miR-877-5p plays a role in aspirin-induced gastrointestinal mucosal erosion, which may via down-regulation of targeting PDK1 gene.
Prevalence of fosfomycin resistance and gene mutations in clinical isolates of methicillin-resistant Staphylococcus aureus
Authors: Lee Yi-Chien , Chen Pao-Yu , Wang Jann-Tay , Chang Shan-Chwen
Published: February 2020

Background: Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the genetic mechanisms of fosfomycin resistance.Methods: All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates.Results: A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, 12 harbored the fosB gene, and expression of murA, uhpT, and glpT mutations was noted in 11, 59, and 66 isolates, respectively. Combination of mutations of uhpT and glpT genes (58 isolates) was the most prevalent resistant mechanism. The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002.Conclusions: An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.
Assessing inequalities and regional disparities in child nutrition outcomes in India using MANUSH—a more sensitive yardstick
Authors: Jain Ayushi , Agnihotri Satish Balram
Published: February 2020

Background: India is strongly committed to reducing the burden of child malnutrition, which has remained a persistent issue. Findings from recent surveys indicate co-existence of child undernutrition, micronutrient deficiency and overweight/obesity, i.e. the triple burden of malnutrition in children below five years. While considerable efforts are being made to address this challenging issue, and several composite indices are being explored to inform policy actions, the methodology used for creating such indices, i.e., linear averaging, has its limitations. Briefly put, it could mask the uneven improvement across different indicators by discounting the ‘lagging’ indicators, signifying negative implications on policy discourse for improved nutrition. To address this gap, we attempt to develop a composite index for estimating the triple burden of malnutrition in India, using a more sensitive measure, MANUSH.Methodology: Data from publicly available nation-wide surveys - National Family Health Survey (NFHS) and Comprehensive National Nutrition Survey (CNNS), was used for this study. First, we addressed the robustness of MANUSH method of composite indexing over conventional aggregation methods. Second, using MANUSH scores, we assessed the triple burden of malnutrition at the subnational level over different periods NHFS- 3(2005-06), NFHS-4 (2015-16) and CNNS (2106-18). Through the use of maps and spatial tools, we gauged the existence of neighbourhood dependency, the formation of clusters, within and across states.Result: MANUSH method succeeds over its counterparts – linear aggregation and geometric mean, by fulfilling additional conditions of Shortfall and Hiatus Sensitivity, implicitly penalising when, improvement in worst-off dimension is less or not proportionate to improvement in best-off dimension, or when, even with overall improvement, the gap between dimensions remain same. MANUSH scores helped in revealing the changing paradigm in the improvement of nutrition outcomes and the rising inequalities within and across states and districts in India. Significant clusters (p<0.05) of high burden and low burden districts were found, revealing geographical heterogeneities and sharp regional disparities. The usefulness of MANUSH index in context-specific planning and prioritising actions is also brought out using the case of the National Nutrition Mission.Conclusion: MANUSH indexing depicts balanced development effectively, hence finds relevance in bringing out inequality in a diverse and developing economy like India.
Determination of Median Lethal Concentrations (Lc50) of Pathogenic Antigens and Their Applications in Vaccine Development
Authors: Saganuwan Saganuwan Alhaji
Published: February 2020

Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used for determination of antigen concentration and parasites inoculums that would kill 50% of test animals (LC50).Results: Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103 (sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. N is the number of vaccine dose that could neutralize the LC50.Titre index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. Hence, parasite inoculum of 103 to 1011 could be used as basis for median lethal dose (LD50), LC50 and median bacterial concentrations (BC50) determination, pathogenic dose for immune stimulation should be sought at concentrations less than LC10.
Psychosocial needs of the parents of children with mental disorder
Authors: Zangeneh Zahra , Jalali Amir , Jalali Rostam , Daryoushi Hooman
Published: February 2020

Background In addition to the major problems that a child with mental disorder, the family, and society are faced with, mental disorders in children cause several problems and care pressure on the parents in particular. While the parents suffer the highest damages by their child’ disease, they tend to hide their pains, sufferings, and needs from others. The present study is an attempt to elaborate on psychosocial needs in the parents of children with mental disorder. Methods The study was carried out as a qualitative study using content analysis method. To this end, 21 parents of children with mental disorder at age range 10-18 years took part in the study. The participants were selected through purposeful sampling and after signing an informed letter of consent, deep semi-structured interviews were conducted with them. The interviews were recorded with the consent of the participants and the data was analyzed using conventional content analysis. Results Analysis of the interviews revealed 302 codes, 16 subcategories, seven categories, and two themes. The theme “psychological needs” was comprised of categories the need for assurance, the need for emotional support, and the need for being accepted. The theme “social needs” was comprised of categories the need for social support, the need for welfare, the need for information support, and the need for family support. Conclusion Given the changes in their lives caused the disease of their children, parents of children with mental disorders deal with several needs and challenges. The needs categorized in mental and emotional fields and social and information supports were the main needs.
Two immune-enhanced molecular subtypes differ in inflammation, immune checkpoints, mutations and outcome in Stage I-II colonic carcinoma.
Authors: Tang Dongxin , Huang Wei , Yang Zhu , Wu Xin , Sang Xianan , Wang Kuilong , Cao Gang , Hao Min
Published: February 2020

Background: The purpose of this paper is to investigate the immune function of the tumor microenvironment and its clinical correlation with colonic carcinoma.
Methods : Immune genes were downloaded from the The Cancer Genome Atlas （TCGA）database. Five subtypes are obtained by cluster screening based on immune gene expression data.
Results: The C3 and C4 subtypes show stronger immune activity. In addition, the C4 subtype has the largest number of gene mutations and the worst prognosis. Most of the immune signatures are upregulated in the C4 subtype, while most of the immune infiltration-related cells are upregulated in the C3 and C4 subtypes.
Conclusions: The different immune microenvironments between these subtypes may provide new ideas for immunotherapy strategies in colon carcinoma.
Male castration alters the gut microbiota, leading to increased serum levels of branched-chain amino acids and adiposity
Authors: Whon Tae Woong , Kim Hyun Sik , Shin Na-Ri , Jung Eun Sung , Tak Euon Jung , Sung Hojun , Jung Mi-Ja , Jeong Yun-Seok , Hyun Dong-Wook , Kim Pil Soo , Jang Yu Kyung , Lee Choong Hwan , Bae Jin-Woo
Published: February 2020

Background : Testosterone deficiency is positively correlated with fat accumulation and obesity-related comorbidities, such as metabolic syndrome. Castration of young males is widely used in the cattle industry to improve meat quality. However, the mechanism linking hypogonadism and host metabolism is not clear. We aimed to evaluate the effect of male hypogonadism on the gut microbiota and serum metabolites, and the contribution of the altered microbiota to the host metabolic phenotype during hypogonadism.Results : We used metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. We then used a male mouse castration model to evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. After pubescence, the CtM cattle harbored distinct ileal microbiota dominated by the family Peptostreptococcaceae , and exhibited distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. Castration of male mice phenocopied both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model further revealed that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals.Conclusions : We demonstrated altered gut microbial profiles in the hypogonadal animals, with a negative feedback between the serum testosterone levels and the ileal abundance of Peptostreptococcaceae , and a distinct metabolic phenotype, with an enhanced amino acid metabolism. These findings suggest targeting the gut microbiota as a potential therapeutic strategy for the treatment of both hypogonadism and obesity.
Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma
Authors: Liu Fangxian , Pan Qijin , Wang Liangliang , Yi Shijiang , Liu Peng , Huang Wenjun
Published: February 2020

Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.