bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological and Molecular Evidence of Brucella Species in the Rapidly Growing Pig Sector in Kenya
Authors: Akoko James Miser , Pelle Roger , Kivali Velma , Schelling Esther , Shirima Gabriel , Machuka Eunice , Mathew Coletha , Fèvre Eric M. , Kyallo Victoria , Falzon Laura C. , Lukambagire AbdulHamid S. , Halliday Jo E.B. , Bonfoh Bassirou , Kazwala Rudovick , Ouma Collins
Published: March 2020

Background: Brucellosis is an emerging yet neglected zoonosis that has been reported in Kenya. Epidemiological data on brucellosis in ruminants is readily accessible; however, reports on brucellosis in pigs remain limited. This study sought to detect Brucella infection in pig serum by both serological and molecular techniques. Serum from 700 pigs randomly collected at a centralized abattoir in Nairobi region, Kenya were screened in parallel, using both Rose Bengal Test (RBT) and competitive Enzyme-Linked Immuno-sorbent Assay (cELISA) for antibodies against Brucella spp. All sera positive by RBT and 16 randomly selected negative samples were further tested using conventional PCR targeting bcsp31 geneand real-time PCR (RT-PCR) assays targeting IS711 and bcsp31 genes. Results: A prevalence of 0.57% (n = 4/700) was estimated using RBT; none of these samples was positive on cELISA. All RBT positive sera were also positive by both PCRs, while two sero-negative samples also tested positive on RT-PCR (n = 6/20). Brucella abortus was detected in four out of the six PCR positive samples through a real-time multiplex PCR. Conclusion: The detection of antibodies against Brucella spp. and DNA in serum from slaughterhouse pigs confirm the presence of Brucella in pigs. Therefore, investigation of the epidemiology and role of pigs in the transmission of brucellosis in Kenya is needed. Further targeted studies would be useful to systematically quantify and identify the spp. of Brucella in pigs.
Experiences and views of different key stakeholders on the feasibility of treating cancer-related fatigue
Authors: Canella Claudia , Mikolasek Michael , Rostock Matthias , Guckenberger Matthias , Jenewein Josef , Linka Esther , Six Claudia , Stoll Sarah , Stupp Roger , Witt Claudia M.
Published: March 2020

Background: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, therapy remains a challenge. Treatment programs are more likely to be effective if the needs and interests of the persons involved are well represented. This can be achieved by stakeholder engagement.
In this paper, different key stakeholders' experiences and views on the feasibility of treating CRF in the context of supportive care in hospital environments are analyzed.
Method: In a qualitative study with the aim of developing an integrative treatment program for CRF, a total of 22 stakeholders (6 medical oncologists, 5 nurses, 9 patients, 1 patient family member, 1 representative of the Swiss Cancer League) were interviewed either in a face-to-face (n=12) or focus group setting (n=2). For data analyses, the method of qualitative content analysis was used.
Results: The stakeholders referred to different contextual factors when talking about the feasibility of treating CRF in the context of supportive care in hospital environments. These included assessment, reporting and information; treatability; attitude; infrastructure, time-management, costs and affordability; and integrative approach.
Conclusions: Key factors of a feasible treatment approach to CRF are a coherent, cost effective integrative treatment program facilitated by an interdisciplinary team of health care providers. Furthermore, the treatment approach should be patient orientated, adopting an individualized approach. The major challenges of making the integrative treatment program feasible for CRF are resources and interprofessional collaboration.
Rare homozygous mutation in TUBB8 associated with oocyte maturation defect-2 in a consanguineous mating family
Authors: Xing Qiong , Wang Ruyi , Chen Beili , Li Lin , Pan Hong , Li Tengyan , Ma Xu , Cao Yunxia , Wang Binbin
Published: March 2020

Purpose: Variations in many genes may lead to the occurrence of oocyte maturation defects. To investigate the genetic basis of oocyte maturation defects, we performed clinical and genetic analysis of a pedigree.
Methods: The proband with oocyte maturation defect-2 receiving ovulation induction therapy and her parents were selected for clinical detection, whole exome sequencing and Sanger sequencing. One unrelated healthy woman received ovulation induction therapy as control. Mutations were assessed after frequency screening of public exome databases. Then homozygous variants shared by the proband and her parents were selected.
Results: Arrest of oocytes maturation was observed. A new missense mutation in TUBB8 (TUBB8: NM_177987: exon 2: c. C161T: p. A54V) was identified, which was shown to be rare compared with public databases. The variant was highly conserved among primates, and was suggested to be deleterious by online software prediction.
Conclusions: The homozygote of this variant (TUBB8: NM_ 177987: exon 2:c.C161T: p.A54V) might affect spindle assembly, cause arrest of oocyte maturation and lead to oocyte maturation defect-2.
The Effect of Posterior Capsule Repair in Total Hip Arthroplasty：A Systematic Review and Meta-Analysis
Authors: Sun Xiaobo , Zhu Xingyang , Zeng Yuqing , Zhang Haitao , Zeng Jianchun , Feng Wenjun , Li Jie , Zeng Yirong
Published: March 2020

Background: Prior studies have compared the posterior capsule repair group in primary total hip arthroplasty by posterior approach with the control group without posterior capsule repair suggesting that the posterior capsule repair group had better clinical outcomes. However, it is still a controversy which treatment is more helpful for hip diseases. The purpose of our article is to obtain the postoperative outcomes between the 2 procedures. Methods: We performed a systematic search by browsing the MEDLINE, EMBASE, Cochrane Library. There is no restriction on the date of publication. Before we submit our manuscript, we have re-searched the literatures again, including the articles which directly compared the postoperative outcomes of the 2 procedures. Results: A total of 8 comparative studies were included in our meta-analysis. The posterior capsule repair group showed less dislocation rate, higher HHS, and even less postoperative bleeding volume. Meanwhile, there is no significant difference in ROM between 2 groups. Conclusion: In conclusion, according to current evidences, repairing posterior capsule during primary THA may have better functional outcomes, less dislocation incidence, and less loss of blood.
Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma
Authors: Ma Bingqi , Meng Huijuan , Tian Ye , Wang Yingying , Song Tianqiang , Zhang Ti , Wu Qiang , Cui Yunlong , Li Huikai , Zhang Wei , Li Qiang
Published: March 2020

Background: Isocitrate dehydrogenase 1/2 (IDH1/2), BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in intrahepatic cholangiocarcinoma (ICC), and their relationships with clinicopathological features and prognosis were researched in this study.
Methods: We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or immunohistochemical methods, and histological subtype of ICCs was determined by hematoxylin-eosin, Alcian blue and S100P staining.
Results: IDH1/2 mutation was related to decreased preoperative serum total bilirubin (P=0.039), ferritin (P=0.000) and higher histological differentiation (P=0.024), and was associated with prolonged disease-free surviva l (P=0.009) and a trend toward increased overall survival (P=0.126) in small duct type of ICCs. Immunohistochemical staining results of MsMab-1 were generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ= 0.691). Only BAP1 expression loss was correlated to prolonged disease-free survival (P=0.031) and overall survival (P=0.041) in large duct type of ICCs.
Conclusions : IDH1/2 mutation is a favorable predictor and may be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct type ICCs, while it is not necessary in large duct of ICCs. MsMab-1 is a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was correlated with improved prognosis only in large duct type ICCs.
Time-dependent changes in FT4 and FT3 levels measured using mass spectrometry after an acute ingestion of excess levothyroxine in a case with hypothyroidism
Authors: Ito Yuko , Suzuki Satoru , Matsumoto Yoshiko , Ohkouchi Chiyo , Suzuki Satoshi , Iwadate Manabu , Midorikawa Sanae , Yokoya Susumu , Suzuki Shinichi , Shimura Hiroki
Published: March 2020

Background: Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined.
Case presentation: We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed three hours after the last ingestion showed that the patient’s free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional four days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and two days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the two days. The FT3/FT4 ratios were revealed to be low, accounting for the patient’s benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect.
Conclusion: It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.
Effect of Corneal Cross-linking on Endothelial Cell Density and Morphology in the Peripheral Cornea.
Authors: Goukon Hiroyasu , Kamiya Kazutaka , Takahashi Masahide , Shoji Nobuyuki
Published: March 2020

BACKGROUND: To compare the endothelial cell density and morphology in the peripheral cornea before and after corneal cross-linking (CXL).METHODS: This study evaluated thirty-one eyes of 31 patients who were treated with standard CXL for progressive keratoconus. Preoperatively and 6 months postoperatively, we compared the corneal endothelial cell density (ECD), the coefficient of variation in cell size (CV), and the percentage of hexagonal cells (HEX), in the peripheral regions of the cornea, using a non-contact specular microscope (EM-3000, Tomey).RESULTS: All keratoconic eyes in this series were measurable in the peripheral regions. No significant differences were found in the peripheral ECD preoperatively and 6 months postoperatively at each point (Wilcoxon signed-rank test, superior, p=0.16, nasal superior, p=0.12, temporal superior, p= 0.17, inferior, p=0.37, nasal inferior, p=0.28, temporal inferior, p=0.17). The mean percentage of the ECD loss was 1.3%, 1.3%, 1.0%, 1.4%, 0.7%, and 1.4%, respectively. No significant differences in the peripheral CV or HEX were found preoperatively and 6 months postoperatively at each point.CONCLUSIONS: Standard CXL does not cause significant changes in endothelial cell density, polymegethism, or polymorphism, in the peripheral regions of the cornea. It is suggested that CXL is a minimally invasive surgical approach for progressive keratoconus, even in terms of peripheral endothelial cells.
A feasibility study to investigate the utility of a home–based exercise intervention during and after neo-adjuvant chemotherapy for oesophago-gastric cancer – the ChemoFit study protocol
Authors: Chmelo Jakub , Phillips Alexander William , Greystoke Alastair , Charman Sarah Jane , Avery Leah , Hallsworth Kate , Welford Jenny , Sinclair Rhona Catherine France
Published: March 2020

Background
Treatment of locally advanced oesophago-gastric adenocarcinoma usually entails neo-adjuvant chemotherapy (NAC), and surgery. Surgery is associated with high morbidity and mortality. Cardiopulmonary reserve of patients having major surgery is related to postoperative outcomes. Complications are associated with poorer quality of life and may affect prognosis. Preventing complications may be beneficial to both of these and have cost implications. Prehabilitation may improve recovery from surgery by increasing a patients’ fitness before surgery. Designing a potentially cost and resource effective regimen which improves cardiopulmonary reserve may have a beneficial impact on patient outcomes after surgery.
Methods
The ChemoFit study is a non-randomised, single-arm and single-centre pilot study designed to investigate the feasibility of a home-based prehabilitation exercise intervention for patients receiving neoadjuvant treatment prior to oesophago-gastric surgery. Forty patients will be recruited at a single high-volume centre. The simple, home-based exercise intervention involves patients increasing their daily step-count during and after NAC and in the weeks leading up to surgical resection of the cancer. Additionally, quality of life assessments (QLQ-C30 and QLQ-OG25), oncological treatment delivery and participant perceptions of the study assessed by focus groups and questionnaires will be performed. The primary outcomes are to assess feasibility of the exercise intervention. The secondary outcomes will evaluate changes in cardiopulmonary reserve, sarcopenia and fat composition.
Discussion
It is anticipated that during an important teachable moment, the diagnosis and treatment of cancer, our patients will be open to the possibility of improving their fitness during chemotherapy and before major cancer surgery. It is possible that the negative impact of NAC on cardiopulmonary fitness could be prevented by implementing a home-based prehabilitation programme during and after NAC, prior to surgery for oesophago-gastric adenocarcinoma.
Trial registration
This study has been approved by the Health Research Authority (REC 18/WA/0427). Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH) will act as the study sponsor and the work is funded by a grant awarded by The Jon Moulton Charitable Foundation, supported by a research post funded by the Sir Bobby Robson Foundation. Trial registration: Clinicaltrials.gov, NCT04194463. Registered 11 th December 2019 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04194463.
Real-world use of ACEI/ARB in diabetic hypertensive patients before the initial diagnosis of obstructive coronary artery disease: patient characteristics and long-term follow-up outcome
Authors: Zhang Yue , Ding Xiaosong , Hua Bing , Liu Qingbo , Chen Hui , Zhao Xue-Qiao , Li Weiping , Li Hongwei
Published: March 2020

Background: Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI) /angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. Methods: A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. Results: Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p<0.05), smaller infarct size in patients with AMI (pTNI: 5.7 vs. 6.8 ng/ml, p<0.05; pCKMB: 21.7 vs. 28.7 ng/ml, p<0.05), better heart function (LVEF: 60.0 vs. 58.5%, p<0.05), and lower incidences of non-fatal stroke (2.4% vs. 4.6%, p<0.05) and composite MACCE (23.1% vs. 29.7%, p<0.05). No prior ACEI/ARB therapy was significantly and independently associated with non-fatal stroke and composite MACCE. Conclusions: In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration: retrospectively registered.
Enhanced production of recombinant proteins in Corynebacterium glutamicum by construction a bicistronic gene expression system
Authors: Sun Manman , Gao Xiong , Zhao Zihao , Li An , Wang Yali , Yang Yankun , Liu Xiuxia , Bai Zhonghu
Published: March 2020

Background: Corynebacterium glutamicum is a traditional food-grade industrial microorganism， in which an efficient endotoxin-free recombinant protein expression factory is under developing in recent years. However, the intrinsic disadvantage of low recombinant protein expression level is still difficult to be solved. Here, according to the bacteria-specific polycistronic feature that multiple proteins can be translated in one mRNA, efforts have been made to insert a leading peptide gene upstream of target genes as an expression enhancer, and it is found that this can remarkably improve the expression level of proteins under the control of inducible tac promoter in C. glutamicum. Results: In this research, the Escherichia coli ( E. coli ) tac promoter combined with 24 different fore-cistron sequences were constructed in a bicistronic manner in C. glutamicum. Three strong bicistronic expression vectors were isolated and exhibited high efficiency under different culture conditions. The compatibility of these bicistronic vectors was further validated using six model proteins- aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), RamA (regulator of acetate metabolism), Bovine interferon-a (BoIFN-a), glycoprotein D protein (gD) of infectious bovine rhinotracheitis virus (IBRV) and procollagen type I N-terminal peptide (PINP). All examined proteins were highly expressed compared with the original vector with tac promoter. Large-scale production of PINP was also performed in fed-batch cultivation, and the highest PINP production level was 1.2 g/L. Conclusion: In this study, the strength of the inducible tac promoter for C. glutamicum was improved by screening and inserting fore-cistron sequences in front of the target genes. Those vectors with bicistronic expression patterns have strong compatibility for expressing various heterogeneous proteins in high yield. This new strategy could be used to further improve the performance of inducible promoters, achieving double competence of inducible control and high yield.
Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency
Authors: Nakajima Tomoyuki , Uehara Takeshi , Iwaya Mai , Kobayashi Yukihiro , Maruyama Yasuhiro , Ota Hiroyoshi
Published: March 2020

Background: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC). Methods: In 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and β-catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by the RNAscope assay in tissue microarrays. Results: LGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases (P=0.0033). Nuclear β-catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases (P=0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.6796, P<0.001). Even in MMR-D and MMR-P cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.7180, P<0.0085 and r=0.6574, P<0.003, respectively). MMR-D CRC cases showed low expression of LGR5, which may be due to low activation of the Wnt/β-catenin signaling pathway. Conclusions: Our results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.
Serum Fetuin-A levels were increased and associated with insulin resistance in women with polycystic ovary syndrome
Authors: Liu Sha , Hu Wenjing , He Yirui , Li Ling , Liu Hua , Gao Lin , Yang Gangyi , Liao Xin
Published: March 2020

Background: Insulin resistance (IR) is a common characteristic of women with polycystic ovary syndrome (PCOS). It has been reported that circulating Fetuin-A levels were associated with IR and type 2 diabetes mellitus (T2DM). However, previous reports on changes in circulating Fetuin-A concentrations in women with PCOS have been inconsistent.Methods: 207 subjects were screened for PCOS according to the diagnostic guideline of the Rotterdam consensus criterion. Serum Fetuin-A levels were measured using an ELISA kit. An independent t-test or Nonparametric test was used to detect differences between PCOS and control groups. The association of the serum Fetuin-A with other parameters was examined by spearman’s correlation analysis.
Results: Our findings show that circulating Fetuin-A concentration ranged from 196.6 to 418.2 µg/L for most women without PCOS (95 %). Women with PCOS have higher circulating Fetuin-A levels than healthy women (437.9 ± 119.3 vs. 313.8 ± 60.5 μg/L; p < 0.01). Serum Fetuin-A was positively correlated with BMI, WHR, TG, TC, LDL-C, HOMA-IR, LH, T, and DHEA-S. Multivariate regression analysis showed that WHR, TG, HOMA-IR, and DHEA-S were independent predictors of the levels of circulating Fetuin-A. Binary logistic regression revealed that serum Fetuin-A was associated with the .occurrence of PCOS. In addition, our ROC curve analysis found that the cutoff values for Fetuin-A to predict PCOS and IR were 366.3 and 412.6 µg/L.Conclusion: Blood Fetuin-A may be a useful biomarker for screening women for PCOS and IR.
High-throughput profiling of diapause regulated genes from Trichogramma dendrolimi, an important egg parasitoid
Authors: Author) Xue Zhang(Former Corresponding , Du Wenmei , Zhang Junjie , Zou Zhen , New Changchun Ruan
Published: March 2020

Background The parasitoid insect Trichogramma dendrolimi can successfully enter diapause at the prepupal stage. Thus, diapause is an efficient preservation method during the mass production of T. dendrolimi . Previous studies on diapause have focused mostly on ecological characteristics, so the molecular mechanism of diapause in T. dendrolimi is mostly unknown. In this study, we compared transcriptomes of diapause and non-diapause T. dendrolimi to identify genes involved in the development of diapause. Results Transcriptome sequencing was performed using different samples, including diapause prepupae, pupae after diapause, normal prepupae, and pupae. This initially yielded a total of 87,022 unigenes with an average length of 1,604 bp. By removing redundant sequences and those without significant BLAST hits, a non-redundant dataset was generated, containing 7,593 sequences with an average length of 3351 bp. Among the differentially expressed genes, 1,204 were specifically expressed during the diapause stage, and 820 were significantly up-regulated. The result of GO enrichment analysis revealed that binding, oxidation−reduction process, and ribosome biogenesis were significantly affected. Ten genes were selected for validation using a quantitative real-time PCR (qPCR). The changes showed the same trend between the qPCR and RNA-Seq results. Based on previous studies and our data, several genes were identified to be involved in diapause, including UDP-glucuronosyltransferase ; Glutathione-S-transferase , ATGs , zinc finger protein genes, cell cycle-related genes, Trehalase , trehalose transporter , hsp68 , p53, and DNA damage-regulated gene 1 ( pdrg1 ), and genes related to lipid metabolism were also included. Conclusions In this study, we generated a great amount of transcriptome data from T. dendrolimi , providing a resource for gene function research. The diapause-related genes that we identified establish a valuable basis for future studies on the molecular mechanisms of diapause, not only for T. dendrolimi, but for other species as well.
In vitro synergistic potentials of novel antibacterial combination therapies against Salmonella enterica serovar Typhimurium
Authors: Hossain Md. Akil , Park Hae-Chul , Lee Kwang-jick , Park Sung-Won , Park Seung-Chun , Kang JeongWoo
Published: March 2020

Background: The antibiotics generally used in farm animals are rapidly losing their effectiveness all over the world as bacteria develop antibiotic resistance. Like some other pathogenic bacteria multidrug-resistant strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) are also frequently found in animals and humans which poses a major public health concern. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. Thus, this study aimed to increase the efficacy of existing antibiotics against S. Typhimurium by combining them with the opportunistic phenolic compounds gallic acid (GA), epicatechin, epicatechin gallate, epigallocatechin and hamamelitannin. Fractional inhibitory concentration indexes (FICI) of phenolic compound-antibiotic combinations against S. Typhimurium were determined. Based on the FICI and clinical importance, 1 combination (GA and ceftiofur) was selected to evaluate its effects on the virulence factors of this bacterium. Viability of Rattus norvegicus (IEC-6) cell in presence of this antibacterial combination was evaluated.Results: Minimum inhibitory concentrations (MICs) of GA, epigallocatechin and hamamelitannin found against different strains of S. Typhimurium were 256, (512–1024), and (512–1024) μg/mL, respectively. Synergistic antibacterial effect was obtained from the combination of erythromycin-epicatechin gallate (FICI: 0.50) against S. Typhimurium. Moreover, additive effects (FICI: 0.502–0.750) were obtained from 16 combinations against this bacterium. The time-kill assays and ultrastructural morphology showed that GA-ceftiofur combination more efficiently inhibited the growth of S. Typhimurium compared to individual antimicrobials. Biofilm viability and swimming and swarming motilities of S. Typhimurium in presence of GA-ceftiofur combination were more competently inhibited than individual antimicrobials. Viabilities of IEC-6 cells were significantly enhanced by GA-ceftiofur combinations than these antibacterials alone.Conclusions: This study suggest that GA-ceftiofur combination can be potential medication to treat S. Typhimurium-associated diarrhea and prevent S. Typhimurium-associated blood-stream infections (e.g.: fever) in farm animals, and ultimately its transmission from animal to human. Further in vivo study to confirm these effects and safety profiles in farm animal should be undertaken for establishing these combinations as medications.
Contribution of the simulation in the training of the 7th grade medical students in the insertion of the interval intra-uterine device
Authors: Kiemtoré Sibraogo , Ouédraogo Issa , Sib Rodrigue Sansan , Komboigo Evelyne , Kaboré Wendyam Charles Paulin Didier , Ouédraogo Ali , Bonané Blandine
Published: March 2020

Introduction A simulation laboratory has been set up in the Department of Obstetrics and Gynaecology at Yalgado Ouedraogo Teaching Hospital. The objective of this study was to evaluate the role of the simulation in training of 7th grade students on interval IUD insertion. Material and method This was an evaluation study of skills before and after training that included 38 students of 7th grade medicine. Pre-training knowledges and skills were compared to those based on training using the paired Student test with a 5% significance level. Perceptions and suggestions for improvement of training made by students were collected. Results The sex of the study participants was 1.1. Their average age was 26.8 ± 0.9 years. The training increased the average knowledges score from 48.2% to 93.0% (p<0.001). The average skills score increased from 34.4% to 92.8% (p<0.001). The 7th grade medicine students had a good perception of this training. Conclusion The training of 7th grade medicine students in IUD insertion using simulation had a positive impact on their knowledges and skills and was well appreciated.
HIV patients dying on anti-tuberculosis treatment: are undiagnosed infections still a problem in French Guiana?
Authors: nacher mathieu , Adenis Antoine , Abboud Philippe , Djossou Felix , Demar Magalie , Epelboin Loïc , Couppié Pierre
Published: March 2020

Objective
Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana’s HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients.
Results
There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n=347) did not have a final diagnosis of tuberculosis (n=93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying.
Clinical and cost effectiveness of staff training in the delivery of positive behaviour support (PBS) for adults with intellectual disabilities, autism spectrum disorder and challenging behaviour - randomised trial
Authors: Strydom André , Bosco Alessandro , Vickerstaff Victoria , Hunter Rachael , Hassiotis Angela
Published: March 2020

Background: Although Positive Behaviour Support (PBS) is a widely usedintervention for ameliorating challenging behaviour (CB), evidence for its use in adults with intellectual disability (ID) and comorbid autism (ASD) is lacking. We report a planned subsidiary analysis of adults with both ASD and ID who participated in a randomised trial of PBS delivered by health professionals.Methods: The study was a multicentre, cluster randomised trial conducted in 23 community ID services in England, participants were randomly allocated to either the delivery of PBS (n=11 clusters) or to treatment as usual (TAU; n=12). One-hundred and thirteen participants (46% of all participants in the trial) had a diagnosis of ID, autism spectrum disorder and CB (ASD+); (47 allocated to the intervention arm, and 66 to the control). CB (primary outcome) was measured with the Aberrant Behaviour Checklist total score (ABC-CT). Secondary outcomes included mental health status, psychotropic medication use, health and social care costs and quality adjusted life years (QALYs) over 12 months.Results: There were no statistically significant differences in ABC-CT between ASD+ groups randomised to the two arms over 12 months (adjusted mean difference = -2.10, 95% CI: -11.3 7.13, p =0.655) or other measures. The mean incremental cost of the intervention per participant was £628 (95% CI -£1004 to £2013). There was a difference of 0.039 (95% CI -0.028 to 0.103) for QALYs and a cost per QALY gained of £16,080.Conclusions: Results suggest lack of clinical effectiveness for PBS delivered by specialist ID clinical teams. Further evidence is needed from larger trials, and development of improved interventions.Trial registrationClinicalTrials.gov: NCT01680276
Further Development of the 12-item EDE-QS: Identifying a Cut-Off for Screening Purposes
Authors: Prnjak Katarina , Mitchison Deborah , Griffiths Scott , Mond Jonathan , Gideon Nicole , Serpell Lucy , Hay Phillipa
Published: March 2020

Background The Eating Disorder Examination – Questionnaire Short (EDE-QS) was developed as a 12-item version of the Eating Disorder Examination Questionnaire (EDE-Q) with a 4-point response scale that assesses eating disorder (ED) symptoms over the preceding 7 days. It has demonstrated good psychometric properties at initial testing. The purpose of this brief report is to determine a threshold score that could be used in screening for probable ED cases in community settings. Methods Data collected from Gideon et al. (2016) were re-analyzed. In their study, 559 participants (80.86% female; 9.66% self-reported ED diagnosis) completed the EDE-Q, EDE-QS, SCOFF, and Clinical Impairment Assessment (CIA). Discriminatory power was compared between ED instruments using receiver operating characteristic (ROC) curve analyses. Results A score of 15 emerged as the threshold that ensured the best trade-off between sensitivity (.83) and specificity (.85), and good positive predictive value (.37) for the EDE-QS, with discriminatory power comparable to other ED instruments. Conclusion The EDE-QS appears to be an instrument with good discriminatory power that could be used for ED screening purposes.
lncRNA CRNDE promotes the proliferation and metastasis by acting as sponge miR-539-5p to regulate POU2F1 expression in HCC
Authors: Li Zhixi , Wu Gang , Li Jie , Wang Youyu , Ju Xueming , Jiang Wenjun
Published: March 2020

Background This article focuses on the roles and mechanism of lncRNA CRNDE on the progression of HCC. Methods We used qRT-PCR to detect the expression of lncRNA CRNDE in HCC cells, normal cells and clinical tissues. MTT assay, FCM analysis, Transwell migration and invasion assay were used to detect the effects of lncRNA CRNDE on cell viability, apoptosis, migration and invasion of HCC cells. The expression of apoptosis-related proteins Bcl-2, Bax, Cleaved Caspase 3, Cleaved Caspase 9, EMT epithelial marker E-cadherin and mesothelial marker Vimentin were analyzed by Western blot. Online prediction software was used to predict the binding sites between lncRNA CRNDE and miR-539-5p, or miR-539-5p and POU2F1 3’UTR. Dual luciferase reporter assay, qRT-PCR and RNA pulldown were used to detect target-relationship between lncRNA CRNDE and miR-539-5p. Dual luciferase reporter assay, qRT-PCR, Western blot and Immunofluorescence were used to detect target-relationship between miR-539-5p and POU2F1. qRT-PCR was used to detect the expression of miR-539-5p and POU2F1 in clinical tissues. Rescue experiments was used to evaluate the association among lncRNA CRNDE, miR-539-5p and POU2F1. Finally, we used Western blot to detect the effects of lncRNA CRNDE, miR-539-5p and POU2F1 on NF-κB and AKT pathway. Results lncRNA CRNDE was highly expressed in HCC cells and HCC tissues compared with normal cells and the corresponding adjacent normal tissues. lncRNA CRNDE promoted the cell viability, migration and invasion of HCC cells, while inhibited the apoptosis and promoted the EMT process of HCC cells. lncRNA CRNDE adsorbed miR-539-5p acts as a competitive endogenous RNA to regulate POU2F1 expression indirectly. In HCC clinical tissues, miR-539-5p expression decreased and POU2F1 increased compared with the corresponding adjacent normal tissues. lncRNA CRNDE/miR-539-5p/POU2-
F1 participated the NF-κB and AKT pathway in HCC. Conclusion lncRNA CRNDE promotes the expression of POU2F1 by adsorbing miR-539-5p, thus promoting the progression of HCC.
Keywords : HCC, lncRNA CRNDE, miR-539-5p, POU2F1, ceRNA
Putting together the pieces of the puzzle – Part II - Assessing harbour porpoise (Phocoena phocoena) carcasses potentially subjected to grey seal (Halichoerus grypus) predation
Authors: Neer Abbo van , Gross Stephanie , Kesselring Tina , Grilo Miguel L. , Ludes-Wehrmeister Eva , Roncon Giulia , Siebert Ursula
Published: March 2020

The authors have withdrawn this preprint from Research Square.
Anatomical Variation of the Psoas Valley: A Scoping Review
Authors: Kuroda Yuichi , Rai Ankit , Saito Masayoshi , Khanduja Vikas
Published: March 2020

Background: This scoping review aimed to investigate the literature on the anatomy of the psoas valley, an anterior depression on the acetabular rim, and propose a unified definition of the anatomical structure, describe its dimensions, anatomical variations and clinical implications. Methods: A systematic computer search of EMBASE, PubMed and Cochrane for literature related to the psoas valley was undertaken using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Clinical outcome studies, prospective/retrospective case series, case reports and review articles that described the psoas valley and its synonyms were included. Studies on animals as well as book chapters were excluded. Results: Of the 313 articles, the filtered literature search identified 14 papers describing the psoas valley and its synonyms such as iliopsoas notch, a notch between anterior inferior iliac spine and the iliopubic eminence, Psoas-U and anterior wall depression. Most of these were cross-sectional studies that mainly analyzed normal skeletal hips. In terms of anatomical variation, 4 different configurations of the anterior acetabular rim have been identified and it was found that the curved type was the most frequent while the straight type may be nonexistent. Additionally, the psoas valley tended to be deeper in males as compared with females. Several papers established the psoas valley, or Psoas-U in a consistent location at approximately 3 o'clock on the acetabular rim which may have implications with labral pathology. Conclusion: This review highlights the importance of the anatomy of the psoas valley which is a consistent bony landmark. The anatomy and the anatomical variations of the psoas valley need to be well-appreciated by surgeons involved in the management of young adults with hip pathology and also joint replacement surgeons to ensure appropriate seating of the acetabular component.
Weakly-supervised Convolutional Neural Networks of Renal Tumor Segmentation in Abdominal CTA Images
Authors: Yang Guanyu , Wang Chuanxia , Yang Jian , Chen Yang , Tang Lijun , Shao Pengfei , Dillenseger Jean-Louis , Shu Huazhong , Luo Limin
Published: March 2020

Background: Renal cancer is one of the ten most common cancers in human beings. The laparoscopic partial nephrectomy (LPN) is an effective way to treat renal cancer. Localization and delineation of the renal tumor from pre-operative CT Angiography (CTA) is an important step for LPN surgery planning. Recently, with the development of the technique of deep learning, deep neural networks can be trained to provide accurate pixel-wise renal tumor segmentation in CTA images. However, constructing the training dataset with a large amount of pixel-wise annotations is a time-consuming task for the radiologists. Therefore, weakly-supervised approaches attract more interest in research. Methods: In this paper, we proposed a novel weakly-supervised convolutional neural network (CNN) for renal tumor segmentation. A three-stage framework was introduced to train the CNN with the weak annotations of renal tumors, i.e. the bounding boxes of renal tumors. The framework includes pseudo masks generation, group and weighted training phases. Clinical abdomina CT angiographic images of 200 patients were applied to perform the evaluation. Results: Extensive experimental results show that the proposed method achieves a higher dice coefficient (DSC) of 0.826 than the other two existing weakly-supervised deep neural networks. Furthermore, the segmentation performance is close to the fully supervised deep CNN. Conclusions: The proposed strategy improves not only the efficiency of network training but also the precision of the segmentation.
A comparison among PCNL, Miniperc and Ultraminiperc for lower calyceal stones between 1 and 2 cm: A multicenter experience
Authors: Bozzini Giorgio , Aydogan Tahsin B , Sighinolfi Maria Chiara , Besana Umberto , Calori Alberto , Lorenzo Berti , Govorov Alexander , Pushkar Dmitry Y , Pini Giovannalberto , Pastore Antonio Luigi , Romero-Otero Javier , Rocco Bernardo , Buizza Carlo
Published: March 2020

Background Conventional Percutaneous Lithotripsy (PCNL) has been an effective, successful and easy approach for lower calyceal stones however risks of complications and nephron loss are inevitable. Our aim is to compare the efficacy and safety of PCNL, MiniPerc(MP) and UltraMiniPerc(UMP) for lower calyceal stones between 1 and 2 cm with a multicenter prospective randomized study. Methods Patients with single lower calyceal stone were enrolled. Exclusion criteria were the presence of coagulation impairments, age of <18 or >75, presence of infection or serious comorbidities. Patients were randomized in three groups; A: PCNL; B: MP; C: UMP. Patients were controlled with abdomen X-ray and computerized tomography scan after 3 months. A negative X-ray or an asymptomatic patient with stone fragments < 3 mm size were the criteria to assess the stone-free status. Patient characteristics, stone free rates (SFR)s, complications and re-treatment rates were analyzed. Results Between January 2015 and June 2018, 132 consecutive patients were enrolled. 44 patients for the Group A, 47 for Group B and 41 for Group C. The mean stone size were 16.38, 17.82 and 15.23mm respectively in Group A, B and C(p=0.34). The overall SFR was significantly higher in Group A(86.3%) and B(82.9%) as compared to Group C(78%)(p<0.05).The re-treatment rate was significantly higher in Group C(12.1%) and complication rates was higher in Group A (13.6%) as compared to others(p<0.05). Conclusions PCNL and MP were more effective than UMP to obtain a better SFR. Auxiliary and re-treatment rates were higher in UMP. On the other hand for such this kind of stones PCNL had more complications. Overall evaluation favors MP as a better indication in stones 1-2 cm size.
Slope Mass Rating-based Analysis to Assess Rockfall Hazard on Yogyakarta Southern Mountain, Indonesia
Authors: Triana Karlina , Hermawan Koko
Published: March 2020

The main road to the Parangtritis Beach tourism site in the southern Yogyakarta Province, Indonesia, has full of local and economic activities. The road was made mainly by karst mountains cutting and resulting in almost vertical long and high slopes by its side. Rockfall is being the most potential hazards occurred in this area. The purpose of this study is to determine the rockfalls hazard assessment along the main road using Slope Mass Rating (SMR) analysis. Parameters used in rockfall hazard assessment are SMR with additional valuation from the slope height and the block size. The necessary data of each parameter obtained by direct measurement and the uniaxial compressive strength test in the laboratory. Geomechanics analysis, stereographic projection analysis, and hazard parameters weighting are needed to produce research results in form Rockfall Hazard Zonation Map in the research location. The results showed that the largest percentage of rockfalls hazard class is very low class, with 83,83% of the total hazard classes, associated with normal SMR score (51,66 – 51,75), slope height between 2,85 – 4,57 m, and block size 0,2 – 0,3 m. Followed by intermediate class with 7,16% of the total hazard classes with very bad to bad SMR score (5,82 – 38,15), slope height between 4,26 – 8,96 m, and block size 0,3 – 1,0 m. In the third position followed by a low class with 4,28% of the total hazard classes with bad to normal SMR score (31,17 – 53,03), slope height between 3,52 – 5,28 m, and block size 0,2 – 0,7 m. The last position was taken by high class with 4,19% of the total hazard classes with very bad to bad SMR score (18,31 – 36,50), slope height between 3,62 – 7,82 m, and block size 0,7 – 1,3 m. The SMR analysis also identified the influence of rock types with the rockfall occurrence. Hazard zonation map verification showed a congeniality with the results of rockfalls quantity inventory in the research area.
Construct validity of the Functional Status Score for the Intensive Care Unit: a prospective observational study using actigraphy in mechanically-ventilated patients
Authors: Camus-Molina Agustín , González-Seguel Felipe , Castro-Ávila Ana Cristina , Leppe Jaime
Published: March 2020

Background The Functional Status Score for the Intensive Care Unit (FSS-ICU) is a widely used instrument, designed to measure the mobility of critically ill patients that is available in English, Portuguese, Turkish and Spanish. The lack of a gold standard for measuring mobility limits the validation of outcome measures. However, actigraphy, from which measures movement intensity can be derived, is a potential alternative in the intensive care unit (ICU). Thus, this study aimed to assess the construct validity (hypotheses testing) of the FSS-ICU using continuous actigraphy from ICU admission to ICU discharge. Methods This prospective observational study included mechanically-ventilated patients selected from a 12-bed academic medical-surgical ICU. The Chilean-Spanish version of the FSS-ICU was used to evaluate its correlation with activity counts, activity time (>99 counts per minute) and inactivity time (0-99 counts per minute) measured by actigraphy ( GT9X Link ActiGraph). The FSS-ICU was assessed on awakening and at ICU discharge, while actigraphy variables were recorded from ICU admission to ICU discharge. Results Of 92 patients screened, 30 were analysed. The median FSS-ICU was 19 (IQR 10–26) points on awakening and 28.5 (IQR 22–32) at ICU discharge. There was no floor/ceiling effect of the FSS-ICU at awakening (0%/0%) and only a ceiling effect at ICU discharge that was acceptable (0%/10%). Less activity time was associated with better mobility on the FSS-ICU at both awakening (rho = -0.62, P<0.001) and ICU discharge (rho = -0.79, P<0.001). Activity counts and activity time were not correlated as expected with the FSS-ICU. Conclusions The FSS-ICU had a strong correlation with inactivity time during the ICU stay. These findings enhance the available clinimetric properties of the FSS-ICU.