bluuebunny/crossref_metadata_2025 huggingface dataset:
Male Breast Cancer with Ureteral Metastasis: A Case Report
Authors: Yanbo Chen , Jiannan Wu , Tingting Hu , Juanjuan Wang , Fengxi Su
Published: August 2020

Background: Breast cancer is rare in men and there is no report of male breast cancer (MBC) with ureteral metastasis. In this study, we report the first case of MBC with ureteral metastasis. Case presentation: A 60-year-old man was diagnosed with triple negative breast cancer (TNBC) with lymph nodes metastasis. After surgery, chemotherapy and radiotherapy he was diagnosed with ureter metastasis because of hematuria. This patient took a Precitype gene test (immune index and PAM50) after several lines of treatment and the result indicated that this was a Luminal A subtype case, which was quite different from his immunohistochemical staining. We adjusted his therapeutic regimen according to the genetic test but there was no obvious efficacy and he passed away five months later. Conclusions: MBC patients with urinary symptoms should be considered for the possibility of metastasis although urinary metastasis in breast cancer is rare. We still need more research and evidence of treatment recommendations for MBC.
Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma
Authors: Shen Rui , Meng Xiangying , Li Jianyi , Yu Tengbo , Xu Kuishuai
Published: August 2020

Background
Sarcomas is a group of heterogeneous malignant tumors originated from mesenchymal tissue and different types of sarcomas have disparate outcomes. The present study aims to identify the prognostic value of immune-related genes (IRGs) in sarcoma and establish a prognostic signature based on IRGs.
Methods
We collected the expression profile and clinical information of 255 soft tissue sarcoma samples from The Cancer Genome Atlas (TCGA) database and 2498 IRGs from the ImmPort database. The LASSO algorithm and Cox regression analysis were used to identify the best candidate genes and construct a signature. The prognostic ability of the signature was evaluated by ROC curves and Kaplan-Meier survival curves and validated in an independent cohort. Besides, a nomogram based on the IRGs and independent prognostic clinical variables was developed.
Results
A total of 19 IRGs were incorporated into the signature. In the training cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.938, 0.937 and 0.935, respectively. The Kaplan-Meier survival curve indicated that high-risk patients were significantly worse prognosis(P < 0.001). In the validation cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.730, 0.717 and 0.647, respectively. The Kaplan-Meier survival curve also showed significant distinct survival outcome between two risk groups. Furthermore, a nomogram based on the signature and four prognostic variables showed great accuracy in whole sarcoma patients and subgroup analyses. More importantly, the results of the TF regulatory network and immune infiltration analysis revealed the potential molecular mechanism of IRGs.
Conclusions
In general, we identified and validated an IRG-based signature, which can be used as an independent prognostic signature in evaluating the prognosis of sarcoma patients and provide potential novel immunotherapy targets.
PVT1 Assumes Signifying Capacity in Cervical Cancer Diagnosis.
Authors: Cao Shuangqing , Zheng Lei
Published: August 2020

Background: Cervical cancer (CC) is the second most prevalent malignancy among women, which severely threatens patients’ health. The study was conducted to determine the diagnostic role of plasmacytoma variant translocation 1 (PVT1) in CC to improve patients outcomes.Methods: The qRT-PCR was used to determine the expression level of PVT1 mRNA in CC samples and healthy controls. Chi-square test was used to determine the clinical effects of patients’ features on PVT1 expression. The receiver operating characteristics (ROC) curve with the area under the curve (AUC) was used as a tool for assessing the diagnostic role of PVT1 expression in CC.Results: The PVT1 mRNA level was significantly higher in CC samples than healthy controls (P<0.0001). Large tumor size (P=0.006), positive uterus infiltration (P=0.031) and advanced FIGO stages (P=0.011) were contributed to the elevated expression of PVT1 level. However, there was no close relationship between PVT1 expression and other clinical parameters, including age (P=0.205), family history (P=0.073), positive HPV infection (P=0.155 and histological type (P=0.159). The ROC curve showed the optimal cutoff point for PVT1 was 2.325, providing the sensitivity and specificity of 85.84% and 72.15%, respectively. Moreover, the AUC was 0.856, suggesting PVT1 level could be regarded as a diagnostic biomarker in CC (P<0.0001, 95%CI= 0.803-0.909).Conclusion: In summary, the level of PVT1 mRNA was significantly increased in CC samples and the up-regulation of PVT1 could distinguish CC patients from healthy controls.
Sjogren's syndrome in clinical trials of traditional Chinese medicine: protocol for the development of a core outcome set
Authors: Liu Ming , Gao Ya , Yuan Yuan , Shi Shuzhen , Yang Kelu , Shi Jiyuan , Wu Jiarui , Tian Jinhui , Zhang Junhua
Published: August 2020

Background: Sjogren's syndrome (SS) is a chronic autoimmune rheumatic disease, and the incidence of 0.03% to 0.3%. There are an increasing number of randomised controlled trials of traditional Chinese medicine (TCM) for SS. However, there are generally some problems in clinical trials: lack of reporting primary or long term outcomes, and the heterogeneous in different clinical trials’ outcome. Our study aims to determine the priority outcomes and standard TCM syndromes for all stakeholders, and reach agreement on the COS and syndromes to be measured and reported in all future TCM trials in patients with SS.Methods: A phase-wise refinement approach will be used, consisting of three phases, yet complementary, sub-work phases, whereby each phase will inform the next coming phases. The following are the three phases: (Ⅰ-a) Identifying of a long initial list of outcomes through: (1) systematic literature review; (2) semi-structured qualitative interviews. (Ⅰ-b) Identifying an initial list of TCM syndromes through: (1) systematic literature review; (2) referencing ancient Chinese medical books; (3) retrospective studies of medical records. (Ⅱ) Prioritization of outcomes using Delphi survey with different stakeholders, such as health professionals and patients. (Ⅲ) Through consensus meetings with patients and professionals to agree on the final COS and TCM syndromes.Results: We summarized the actions of COS into three points: direct action, indirect action, final action. Our study is very necessary.Conclusion: After the final COSs is completed, we will publish this research in a journal to promote communication.Trial registration number: Core Outcome Measures in Effectiveness Trials Initiative (COMET) number: 1429.
An exploratory study to estimate cost-effectiveness threshold value for life saving treatments in western Iran
Authors: Moradi Najmeh , Woldemichael Abraha , Malekian Parisa , Rotavandi Delnia Moradi , Rezaei Satar
Published: August 2020

Background

Cost-effectiveness analysis provides a crucial means for evidence-informed decision-making on resource allocation. This study aims to elicit individuals' willingness to pay (WTP) for one additional quality-adjusted life-year (QALY) gained from life-saving treatment and associated factors in Kermanshah city, western Iran.

Methods

We conducted a cross-sectional study on a total of 847 adults aged 18 years and above to elicit their WTP for one additional QALY gained by oneself and a family member using a hypothetical life-saving treatment. We used a multistage sampling technique to select the samples, and the Iranian version of EQ-5D-3L, and visual analogue scale (VAS) measures was used to obtain the participants’ health utility value. The Tobit regression model was used to identify the factors affecting WTP per QALY values.

Results

The mean WTP value and standard deviation (SD) was US$ 862 (3224) for the respondents and US$ 1355 (3993) for the family members. The mean utility values using EQ-5D-3L and VAS methods were 0.779 and 0.800, respectively. The WTP for the additional QALY gained by the individual participants using the EQ-5D-3L and VAS methods were respectively US$ 1202 and US$ 1101, while the estimated value of the family members was US$ 1355 (SD= 3993). The Tobit regression models indicated that monthly income, education level, sex, and birthplace were statistically significantly associated (p < 0.05) with both the WTP for the extra QALY values using the EQ-5D-3L and the VAS methods. Besides, education level and monthly income showed statistically significant relationships with the WTP for the additional QALY gained by the family members (p < 0.05).

Conclusion

Our findings indicated that the participants' WTP value of the additional QALY gained from the hypothetical life-saving treatment was in the rage of 0.20 to 0.24 of Iran’s gross domestic product (GDP) per capita, which is far lower than the World Health Organization (WHO) recommended CE threshold value of one. This wide gap reflects the challenges the health system is facing and requires further research for defining the most appropriate CE threshold at the local level.
Acute Flaccid Paralysis: A Registry-based Study of Demographic, Clinical, and Diagnostic Characteristics of Children in a Referral Center in Iran
Authors: Tavasoli Ali Reza , Pazouki Roxana , Hosseinpour Sareh , Ashrafi Mahmoud Reza , Akbari Masood Ghahvechi , Rezaei Sanaz , Parvaneh Nima , Vafaee-Shahi Mohammad , Mohammadi Bahram , Abdi Alireza , Bagheri Sayna
Published: August 2020

Background: Acute Flaccid Paralysis(AFP) is a clinical syndrome characterized by acute progressive weakness in limbs and respiratory and swallowing muscles. Etiologies of AFP mostly include infections in anterior horn cells of the spinal cord, Guillain-Barre syndrome(GBS), transverse myelitis, viral myositis, myasthenia gravis and botulism. An accurate and early diagnosis of AFP is crucial. The aims of this study were to determine the main etiologies and characteristics of AFP in children and also design a diagnostic approach for AFP based on a hospital-based registry system.Method: This retrospective, cross-sectional study is a five-years survey, from 2011 to 2016 in Children’s Medical Center as the main children referral hospital in Iran. Totally 118 patients who had met AFP ICD-10- CM and inclusion criteria were included. All clinical and Paracinical data were collected based on a prepared questionnaire for the study.Result: The mean age of the patients was 6.09 ± 3.60 years old. The most frequent underlying etiologies were GBS, viral myositis and Vaccine-Associated Paralytic Poliomyelitis(VAPP) accounting for 67.8%, 15.3% and 5% of the patients, respectively. In terms of preceding clinical symptoms coryza, fever and gastrointestinal symptoms were more common. The most common neurologic presenting symptom was motor dysfunction. Cerebrospinal fluid analysis mainly indicated increase level of protein in favor of GBS. Elevated Creatine kinase level with the mean of 2184 IU/L has been reported in patients with viral myositis. Brain imaging principally revealed normal results and spinal MRI findings were compatible with the diagnoses of GBS and transvers myelitis. All stool sample results for polio virus detection were negative.Conclusion: In this study, we determined the etiologies of AFP in Iranian children referred to Children’s Medical Center. Guillain-Barre syndrome, viral myositis, transverse myelitis and VAPP were the most common etiologies. We also recommended a diagnostic approach for AFP in pediatric population regards to main etiologies in emergency room of a children referral hospital.
Association of Neuroimaging Markers of Cerebral Small Vessel Disease With Short-Term Outcomes in Patients With Minor Cerebrovascular Events
Authors: Chen Xuemei , Wang Lin , Jiang Junying , Gao Yuanyuan , Zhang Rui , Zhao Xiaoyuan , Shen Tingwen , Dai Qi , Li Junrong
Published: August 2020

Objective: As one of the Magnetic resonance imaging (MRI) makers of cerebral small vessel disease (SVD), increasing evidences have showed that white matter hyperintensity (WMH) can predict the short-term outcome of acute ischemic stroke (AIS). It is unclear that whether neuroimaging markers of SVD are also associated with short-term outcomes of minor cerebrovascular events. In the present study, We investigate neuroimaging markers of SVD in order to explore their roles in prediction of short-term outcome in patients with minor cerebrovascular events. Methods: Consecutive first-ever stroke patients(n=546)from the Affiliated Jiangning Hospital of Nanjing Medical University were enrolled. A total of 388 patients were enrolled according to minor cerebrovascular events definition and exclusion criteria. MRI scans were performed within seven days of stroke onset, and then neuroimaging markers of SVD including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS) , SVD burden scores were assessed. We completed baseline characteristics and evaluated the relationships of short-term outcomes to SVD neuroimaging markers and SVD scores. The 90-day modified Rankin Scale (mRS) was thought as primary outcome and was dichotomized as good functional outcome (mRS 0-1) and poor outcome (mRS 2-6). Secondary outcomes were stroke progression and stroke recurrence. Results: Higher age, National Institutes of Health Stroke Scale (NIHSS) upon admission, lipoprotein-associated phospholipase A2 (LP-PLA2) and lacunes, Fazekas score were correlated with poor functional outcome (P<0.05), But after adjusting for confounding variables, among the neuroimaging markers of cerebral small vessel disease, only Fazekas score (OR, 1.343; 95% confidence interval, 1.020-1.770; P=0.036) was found to be associated with poor outcome at 90 days. Higher Fazekas and SVD scores were not associated with stroke progression or stroke recurrence. Conclusion: WMH can predict the poor functional outcome of minor cerebrovascular events. Adding other neuroimaging markers of SVD and total SVD burden score, however, does not improve the prediction,which indicated WMH can as neuroimaging markers for guiding the treatment of minor cerebrovascular events.
Quality of Life and Associated Factors Among Women With Obstetric Fistula in Ethiopia
Authors: Matiwos Biruktawit , Tesfaw Getachew , Belete Asmare , Abebaw Dessie , shumet shegaye
Published: August 2020

Background: The physical, emotional and social suffering associated with continuous leakage of urine has a profound impact on women quality of life. The aim of this study was to assess quality of life and associated factors among obstetric fistula patients in Ethiopia, has a significant role for further intervention. Objective: To assess quality of life and associated factors among obstetric fistula patients in Ethiopia, 2017. Methods: In this cross-sectional study, 289 women with obstetric fistula were recruited for interviews, using the systematic random sampling technique. The World Health Organization Quality of Life – Brief (WHOQOL-BREF) Version was used to assess quality of life. The Jacob perceived stigma scale and the Oslo-3 social support instruments were used to assess the factors. We computed simple and multiple linear regression analysis to assess factors associated with quality of life. P-value <0.05 was declared statistically significant.Result: Of 289 women studied, only 12.1% felt satisfied with their general state of health and quality of life. In the physical health domain, the mean quality of life score was 40.78±.78. In the psychological domain, the mean quality of life score was 39.96±.82. In the social and environmental domain, the mean quality of life score was 32.9±.95, 36.45±.8 respectively. Duration of incontinence (unstandard β=-3.8,95% CI(-6.95,-.62), patients coming for surgical procedure (β=-4.4, 95% CI(-7.64,-1.2), poor social support(β= -6.14, 95%CI (-8.8,-3.4), Co-morbid anxiety(β= -4, 95% CI (-7,-1.1) and depression(β=-9.2, 95% CI (-12,-6.4) were negatively associated with physical domain of quality of life. Co-morbid anxiety (β= -11,95% CI (-14.8,-7.3), employment(β= 9.1,95%CI(.5, 17.6), number of children(β= 2.1,95%CI(.8, 3.4), and depression(β= -6.3,95%CI(-9.7,-2.9) were associated with a psychological domain. Duration of incontinence (β=-8.1,95%CI(-12.82,-3.4), poor social support(β= -7.8(-12,-3.6), patients coming for surgical procedure (β= -12,95%CI(-17.4,-6.4) and co-morbid anxiety(β= -9.2,95%CI(-13.8, 4.5) were negatively associated with social domain of quality of life. Number of children present (β=2.4,95%CI(.82, 3.6), and poor social support(β= -5.5,95%CI(-9.5,-1.5) were significantly associated with an environmental domain of quality of life. Conclusion and recommendation: Co-morbid depression and anxiety, poor social support, duration of urine incontinence, employment, number of children, and duration of hospital stay were factors significantly associated with domains of QOL. Treating co-morbid depression and anxiety, strong social support and controlling urine incontinence is necessary to increase women’s domain of quality of life.
In vivo optical cellular diagnosis for uterine cervical or vaginal intraepithelial neoplasia using flexible gastrointestinal endocytoscopy - a prospective pilot study-
Authors: Ono Shoko , Nozaki Ayako , Matsuda Kana , Takakuwa Emi , Sakamoto Naoya , Watari Hidemichi
Published: August 2020

BackgrouundFor patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy.MethodsBetween May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient.ResultsA total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08-9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%).ConclusionsOptical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy.Trial registrationThe study was registered with the UMIN database (ID: 000031712).UMIN000031712. Registered 16 March 2017, https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000031712
Cause and incidence of Cancellation of elective surgeries at Gondar University hospital, Ethiopia
Authors: Nigatu Yonas Addisu , Aytolign Habitu Adane
Published: August 2020

Background: High rates of cancellation of surgical procedures are common in hospital settings which may subsequently lead to economic loss to hospital besides burden given to patients, their families and medical teams .It is well recognized that cancellation of patients from elective theatre operating lists increases cost, decreases efficiency, duplicates workload and wastes operating room time.Cancellation of elective surgical procedures also causes significantly emotional trauma to the patients as well as their families and the community in general, and its impact on hospital resources is great due to prolonged hospitalization and high cost of health care.The aim of this study was to find the causes and incidence of surgical patient cancellation at Gondar university hospital, North-west Ethiopia.Methods: prospective observational study was conducted from January 10 to April 10, 2019. Information regarding the cancellation of surgeries were collected from various sources including; the operating room daily surgical schedule, preoperative anaesthesia record sheet, primary physicians, the anaesthetist responsible for the preoperative assessment and conducting the case and by communicating patients if required. Data were checked on daily basis for completeness and were entered to Epi info and analyzed using statistical package for social sciences (SPSS) version 20 software.Result: There were 64 causes of case cancellation. The commonest reasons for cancellation were overbooking of elective surgeries (33.13%).Conclusion: Preventable causes of case cancellation were the most prominent.
Research practices and research misconduct
Authors: Kalichman Michael
Published: August 2020

Background: Research on research integrity has tended to focus on frequency of research misconduct and factors that might induce someone to commit research misconduct. A definitive answer to the first question has been elusive, but it remains clear that research misconduct occurs too often. Answers to the second question are so diverse, it might be productive to ask a different question: What about how research is done allows research misconduct to occur? Methods: With that question in mind, research integrity officers (RIOs) of the 62 members of the American Association of Universities were invited to complete a brief survey about their most recent instance of a finding of research misconduct. Respondents were asked whether one or more good practices of research (e.g., openness and transparency, keeping good research records) were present in their case of research misconduct. Results: Twenty-four (24) of the respondents (39% response rate) indicated they had dealt with at least one finding of research misconduct and answered the survey questions. Over half of these RIOs reported that their case of research misconduct had occurred in an environment in which at least nine of the ten listed good practices of research were deficient. Conclusions: These results are not evidence for a causal effect of poor practices, but it is noteworthy that good research practices such as those listed would make it more difficult if not impossible for someone in such an environment to commit research misconduct.
Gut Microbes and Microbial Metabolites in Colorectal Cancer Complicat Ed With Different Serum Albumin Levels
Authors: Han Shuwen , Wu Wei , Da Miao , Zhou Qing , Xu Jiamin , Zhuang Jing , Liu Jin , Yang Xi
Published: August 2020

Background: Patients with colorectal cancer (CRC) are at risk of malnutrition. Gut microbes and microbial metabolites are involved in the initiation and development of CRC.Aims: To investigate serum protein levels in CRC patients and explore the role of gut microbes and microbial metabolites in CRCs complicated with different serum albumin levels.Methods: Overall, 398 CRC patients and same number of healthy volunteers in Huzhou Central Hospital from January 2016 to December 2018 were recruited to compare serum protein levels. A total of 30 and 56 stool samples from CRC patients were used to detect intestinal microbes and microbial metabolites, respectively. Bacterial 16S V3-V4 and fungal ITS ribosomal DNA genes were sequenced and gas chromatography/mass spectrometry (GC/MS) was performed to detect microbial metabolites. Results: Some serum protein-related indicators in the CRC group were lower than those in the control group (p＜0.05). The total protein and albumin levels in colon cancer patients were lower than those in rectal cancer patients (p＜0.05). The higher abundance of Sutterella is correlated with lower serum albumin level in CRCs. There were statistically significant differences in the abundance of fungi including Agaricomycetes， Simplicillium, Sclerotiniaceae, and Exophiala among patients with different serum albumin levels. Multiple gut bacteria and fungi are closely related to serum albumin levels.We found some characteristic microbial metabolites in CRCs complicated with different serum protein levels.Conclusions: The different serum albumin levels were associated with the gut microbes and microbial metabolites in CRCs.Trial registration: Correlation analysis of intestinal flora and its metabolites with tumor nutritional status in patients with colorectal cancer,ChiCTR1900022460,Registered 12 April 2019,http://www.chictr.org.cn/edit.aspx?pid=37950&htm=4
Correlation Between Psychological Rumination and Symptoms of Traumatic Stress in Patients with Mild Paralysis in Acute Phase of Stroke: A Cross-sectional Study
Authors: Okihara Tetsuya , Koizumi Kohei , Takahashi Hidetoshi , Suzuki Mayumi , Takeda Tomonori , Ishioka Toshiyuki , Hamaguchi Toyohiro , Makita Shigeru
Published: August 2020

Background: Research shows that post-traumatic stress symptoms (PTSS) are common in survivors of acute life-threatening illnesses, and rumination is considered to be associated with PTSS. Additionally, post-stroke symptoms of post-traumatic stress disorder (sPTSD) usually manifest as a type of anxiety disorder after a stroke. This study investigated the prevalence of sPTSD and the relationship between PTSS and rumination.Methods: The participants comprised 29 patients admitted to the Saitama Medical University International Medical Center within one week after experiencing a stroke. The Impact of Event Scale-Revised Japanese version (IES-R-J) and Leuven Adaptation of the Rumination on Sadness Scale Japanese version (LARSS-J) were employed for the evaluation of PTSS, sPTSD, and rumination.Results: The 29 patients (15 males, mean age: 63 ± 11 years) were classified as follows: 17 patients with cerebral infarction, 10 patients with cerebral hemorrhage, and 2 patients with subarachnoid hemorrhage. The ratio of persons with sPTSD (IES-R-J total score > 25) was 34% (10 patients). A significant positive correlation was found between PTSS and rumination (r = 0.460, p < 0.05).Conclusion: The findings indicated that approximately 30% of acute stroke patients experienced sPTSD, and that the severity of PTSS is related to rumination.
A Novel Frameshift Mutation in F9 in a Mixed Breed Dog With Clinical Hemophilia B
Authors: Ryke Erica , Nath Shefali , Chu Erin
Published: August 2020

A male mixed breed dog with clinical Hemophilia B was tested with a direct-to-consumer dog genomics service. After being genotyped as “normal” at three previously published Hemophilia B variants, all coding regions of the dog’s F9 gene were sequenced. A single basepair deletion in exon 5 of F9 led to a frameshift mutation leading to a premature truncation of FIX, including loss of the catalytic domain. The dam for this individual is a Great Pyrenees suggesting this X chromosome variant could segregate within the Great Pyrenees and possibly related breeds. The discovery of this novel variant could be applicable to the Great Pyrenees community should hemophiliac Great Pyrenees be observed at appreciable frequency and emphasizes the utility of genetic testing in mixed breed dogs.
Determinants of Post-Operative Cognitive Decline in Elderly People
Authors: Cartailler Jerome , Loyer Camille , Vanderlynden E. , Nizard Remy , Rabuel Christophe , Baumann Laurence Coblentz , Hourregue Claire , Dumurgier Julien , Paquet Claire
Published: August 2020

Background: Surgery and anesthesia can result in temporary or permanent deterioration of the cognitive functions, for which causes remain unclear. In this pilot study, we analyzed the determinants of cognitive decline following a non-emergency elective prosthesis implantation surgery for hip or knee.Methods: Prospective single-center study investigating psychomotor response time and changes in MoCA scores between the day before (D-1) and 2 days after (D+2) following surgery in Lariboisière Hospital (Paris, France). 60 patients (71.9±7.1-year-old, 72% women) were included. Collected data consisted in sociodemographic data, treatment, comorbidities and type of anesthesia (local, general or both). Furthermore, we evaluated pain and well-being before as well as after the surgery using point scales. Findings: Post-operative (D+2) MoCA scores were significantly lower than pre-operative ones (D-1) with a difference of 2.25+3.0pts (p=0.004), we found no significant difference between locoregional and general anesthesia. Pre-operative benzodiazepine or anticholinergic treatment were also associated to a drop in MoCA scores (p=0.023). Finally, the use of ketamine during anesthesia (p=0.034) and the well-being (p=0.023) evaluated before intervention, were both linked to a reduced cognitive impact.Discussion: In this pilot study, we observed a post-operative short-term cognitive decline following a lower limb surgery. We also identified pre and perioperative independent factors linked to cognitive decline following surgery. In a next stage, a larger cohort should be used to confirm the impact of these factors on cognitive decline.
N2-neutrophils Promote Invasion and Metastasis of Ovarian Cancer by Upregulating MAPK Signaling
Authors: li caixia , Men Chuandi , Yang Weihong , Liu Qi , Liu Shupeng , Cheng zhongping
Published: August 2020

Background: Metastasis is an important factor of high mortality in ovarian cancer. Neutrophils are involved in multiple pathologic mechanisms of cancer,including invasion and metastasis. However, the relationship of neutrophils and invasion and metastasis in ovarian cancer is unclear,as well as the exact mechanism.Methods:To verify the relationship of neutrophils and invasion and metastasis in ovarian cancer,we tested the expression of CD11b in 24 groups of benign and malignant ovarian tumor tissues.And then,we tested the expression of CD11b,CXCL8,and CXCR1 in 16 cases of ovarian cancer,including primary lesions, metastatic lesions and adjacent carcinoma tissues.We successfully build tumor associated neutrophils research model (N1 and N2) and prove that N2-neutrophils can promote the invasion and metastasis of ovarian cancer. Next,we screened the significantly changed MAPK signaling pathway by high-throughput sequencing. And then confirmed this conclusion by molecular biology experiments. Results:The expression of CD11b was significantly higher in malignant tumor than benign tumor tissues tested by western blot and Immunohistochemistry.The expression of CD11b,CXCL8 and CXCR1 is highest in ovarian cancermetastases ,followed by the primary lessions, and then the adjacent carcinoma tissues tested by PCR and WB methods.We proved that N2-neutrophils can promote the invasion and metastasis of ovarian cancer by transwell assay.Forthermore,we detected the related indicators of metastasis including MMP-2,MMP-9,E-Cadherin,N-cadherin and Vimentin by PCR and WB methods.Next,we screened the significantly changed MAPK signaling pathway by High-throughput sequencing through comparing ovarian cancer cells before and after co-cultured with N2-neutrophils. At last,we found the key gene P38 of MAPK signaling pathway by molecular biology experiments. Conclusions: N2-neutrophils promote the invasion and metastasis of ovarian cancer by Upregulating MAPK signaling pathway, find a key gene P38.
Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations
Authors: Liang Xiao , Xu Guobing , Li Zhenbao , Xuan Zihua , Zhao Hongsu , Peng Daiyin , Gui Shuangying
Published: August 2020

Background: Panax notoginseng (PN), the most widely used dietary supplement and herbal in Asian countries. The effect of micronization of PN is not fully clear. The aim of this study was to investigate the effects of the particle size and treatment temperature of Panax notoginseng powder (PNP) and the potential to improve the bioavailability.Methods: Several properties of PNP, including the surface morphology and thermal properties were extensively characterized by scanning electron microscopy (SEM), polarized light microscopy (PLM) and differential scanning calorimetry (DSC). The in vitro release and in vivo bioavailability of Panax notoginseng sapoins (PNS) were investigated by high-performance liquid chromatography (HPLC) and ultra-high-pressure liquid chromatography-MS/MS (UHPLC-MS/MS).Results: The results showed that particle size reduction significantly change the PNS in vitro dissolution and in vivo pharmacokinetic. The PNP with a wide size range (from 60 to 214 μm). Several properties of PNP were extensively characterized, these changes of physicochemical properties of PNP provide a better understanding of the in vitro and in vivo release behaviors of PNS. The in vitro studies demonstrated that the dissolution of PNS and particle size was nonlinear (dose- and size-dependent). The pharmacokinetic parameters of PNP in rats were determined by UHPLC-MS/MS. Powder 4 (90.38 ± 8.28 μm) showed significantly higher AUC0-T values in plasma (P < 0.05). In addition, we also investigated the influence of the hydrothermal treatment of PNP. The results showed that the PNS in vitro release and in vivo bioavailability were highest of PNP pre-treatment at 40°C.Conclusion: The PNP with a particle size around 90 μm and heat pre-treatment at 40°C would be beneficial.
Relatedness of California Mastitis Test Scores and Bacteriological Plate Counts in the Diagnosis of Subclinical Mastitis in White Fulani Cattle From Selected Dairy Herds 
Authors: Suleiman Ahmed Babangida , Hussaini . Ibrahim Mohammeda , Odumosu Bamidele Tolulope
Published: August 2020

BackgroundSubclinical mastitis remains a major challenge in the dairy industries as it affects nutritional content of milk and milk products, volume of milk production and also leads to economic loss. This study was carried out to determine the relationship between California Mastitis Test (CMT) scores and bacteria counts in the diagnosis of subclinical mastitis. A total of 339 white Fulani cattle milk samples were aseptically collected from six geographical regions of Plateau State and screened for mastitis and bacteriological analysis using the California Mastitis Test (CMT), Total Bacterial Count (TBC) and Total Coliform Count (TCC) methods respectively. ResultsThe result of the study reveals that 31.0% of the milk samples were positive for mastitis. Based on the CMT scores, 61.9% of the samples were CMT negative, 7.1% were CMT trace while 6.5%, 11.5% and 13.0% were CMT +, CMT ++ and CMT +++ respectively. Most of the CMT negative samples (55.71%) were culture negative while almost all the CMT +++, were positive (90.91%) culture positive. A positive correlation was observed between CMT scores and plate counts (Total Bacteria count and Total Coliform Count). The Total Bacteria count ranged from 5.7x101 – 5.9x106 CFU/mL while the Total Coliform Count ranged from 0.6x101 – 3.0x105.CMT scores correlates well with bacteriological plate count of the mastitic milk samples. ConclusionThere is a need for the improvement in quality and safety of dairy product because of public health risk associated with it
Infectious Subgenomic Amplicons method to expedite reverse genetics of SARS-CoV-2 and other coronaviruses
Authors: Mélade Julien , Piorkowski Géraldine , Touret Franck , Fourié Toscane , Coutard Bruno , Nougairede antoine , de Lamballerie Xavier
Published: August 2020

There is a need for simple reverse genetics methods to decipher the biological properties of animal and human coronaviruses. Here, we attempted to rescue the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the Feline enteric coronavirus (FeCoV) using the rapid “Infectious-Subgenomic Amplicons” (ISA) method. For each virus, transfection into permissive cells of eight overlapping subgenomic cDNA fragments covering the entire genome allowed reconstruction of the complete virus genome and generated infectious viral particles. Rescued viruses replicated the phenotypic and genotypic characteristics of the original isolates. In conclusion, the ISA method, which had been previously used for RNA viruses with shorter genomes (e.g., flaviviruses, alphaviruses and enteroviruses) can be used to rescue viruses with substantially longer genomes and usefully complements pre-existing methods for reverse genetics of coronaviruses. Its extreme simplicity and versatility makes it a strong option to decipher the biological properties of coronaviruses circulating in human, domestic or wild fauna populations.
Forecast and Guiding role of using Hounsfield unit in retrograde intrarenal surgery for the treatment of renal stone of 2-3 cm: A single center prospective study
Authors: Li Yuzhuo , He Qiqi , wang Fei , Bao Junsheng , Yang Li , Wang Zhiping , Sanjay Gupta
Published: August 2020

Retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) are both important minimally invasive techniques for the treatment of renal stones. With the progress of technology, the application of procedures has been extended. Current surgery choices are made base on stone size, burden and its locations that might limit the predictability and removal of post-operative residual stones. Despite these surgery techniques are maturely used in clinical practice, the patients’ selection have not been standardized in borderline stone. Some patients might suffer several sessions of surgery if intervene decision are not well-designed. In this single-center study, we aimed to determine whether the Hounsfield Unit (HU) value of no-contrast computer computed tomography (NCCT) might offer better guidance in the selection of RIRS or PCNL in renal stones of 2-3 cm, not only in facilitating the stone disintegration, also in providing the potential optimal and less session of setting with great outcomes. A total of 158 patients with kidney stones (2-3 cm) who underwent PCNL/RIRS from March 2016 to January 2019 were enrolled in this study. Gender, stone sizes, locations, average HU value of stone, surgery time, hospital stay time, stone free rate and complications at the time of hospitalization and 3 month follow-up were measured to identify the surgery efficiency. Upon consideration of HU value, the mean surgery time were significantly decreased in RIRS comparing to cRIRS group (47.73 ± 15.52 versus 72.41 ± 27.71 min, p<0.05). Statistically, the surgery time was strong influenced by the HU values both in RIRS (OR: 93.8, p<0.01) and PCNL (OR, 8.21, p<0.05). HU values proved to have a strong positive relation with surgery time in RIRS while a low positive related in PCNL (p<0.05). Overall, for renal stones of 2-3 cm, RIRS proved to be a safe and efficacious treatment option if HU value and other parameters could be comprehensively accounted. Considering HU value before 2-3cm kidney stone lithotripsy seems to be necessary, which might save the surgery time and reduce the potential risk of renal injury, as even if residual stone were detected post-op, ESWL could also be employed and work efficiently. Some patients might not have to perform several sessions of RIRS. Taken together, individual precision surgery might provide ideal treatment and prognosis for patients requiring long-term continuous clinical procedures.
Post nCoV-2 limping Child: Report of two cases and a rapid Review
Authors: Sinaei Reza , Pezeshki Sara , Sinaei Roya , Shiari Reza , Yeganeh Mehrnoush Hassas , Parvaresh Saeedeh , Bazargn Nasrin
Published: August 2020

Background: Identification of the etiology of acute limping in children is challenging. Both benign and life- threatening disorders can present with limp. However, among atraumatic conditions, benign conditions including toxic synovitis and post infectious arthritis are the most common causes of this dilemma. Case Presentation: During the recent COVID-19 pandemic in Kerman, South East of Iran; two pediatric patients referred to the Rheumatology clinic with new onset gait disturbance. One 8 years old boy and the other 6 years old girl who presented with hip joint pain and limping. Both of them had joint effusion jackknife of mild respiratory symptoms and fever. Altogether, precise history taking and accurate physical examination, alongside radiological investigations and positive laboratory results for coronavirus infection emphasized the diagnosis of post Coronavirus arthritis. They treated with rest and Non-Steroidal Anti-Inflammatory Drugs (NSAID) successfully, and fallowed at least for one month later.Conclusions: Here, we described the first report of post n-CoV-2 arthritis in the world in two Iranian pediatric patients, who presented with limp. Contrary to preliminary phantasms, this may indicate that the Corona virus has some rheumatogenic specifications.
Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology
Authors: Jiang Peng , Wang Qian , Wang Yinghong , Li Kai , Sun Yancai
Published: August 2020

Background: Cytochrome P450s (CYPs) are pivotal drug metabolic enzymes and play a crucial part in the development and prognosis of hepatocellular carcinoma (HCC). Among various CYPs, 12 (CYP1A2, 27A1, 2A6, 2A7, 2B6, 2C8, 2C9, 2E1, 2J2, 3A4, 3A5, and 4A11) are recognized as key therapeutic targets for HCC from the perspective of network pharmacology. However, the gene expression and prognosis of these 12 CYPs in HCC remain obscure.Methods: In the current study, the mRNA expression of these 12 CYPs and survival of patients with HCC were investigated by mining data from ONCOMINE, Kaplan–Meier plotter, UALCAN, Human Protein Atlas, cBioPortal, STRING, and DAVID databases. Network pharmacology analysis of sorafenib for HCC treatment was conducted using data from Therapeutic Target Database, Drugbank, Swiss Target Prediction, STITCH, OncoDB.HCC, Liverome, STRING, and DAVID databases.Results: Results showed that the mRNA expression levels of the 12 CYPs were markedly reduced in HCC and negatively correlated with tumor stages and grades (except for CYP3A5). The high expression level of nine CYPs, namely, CYP27A1, 2A6, 2A7, 2C8, 2C9, 2E1, 3A4, 3A5, and 4A11 was significantly correlated with favorable prognosis in patients with HCC, indicating that they may serve as candidate prognostic biomarkers for HCC. Additionally, overexpression of CYP27A1, CYP2A7, CYP2B6, CYP2C9, and CYP3A5 was markedly correlated with favorable overall survival in HCC patients who received sorafenib therapy. Network pharmacology analysis of the administration of sorafenib for HCC treatment suggested that this drug may exert its antihepatocarcinoma effects by regulating the FoxO and ErbB signaling pathways.Conclusion: Characterization of the expression and prognosis of 12 CYPs in HCC, as well as network pharmacology analysis of HCC treatment via sorafenib, may provide novel insights into the discovery of potential prognostic markers of and therapeutic targets in HCC.
Long-Read Metagenomics to Retrieve High-Quality Metagenome-Assembled Genomes from Canine Feces
Authors: Cusco Anna , Perez Daniel , Viñes Joaquim , Francino Olga
Published: August 2020

Background. Metagenomics is a powerful and rapidly developing approach that provides new biological insights into the microbes inhabiting underexplored environments, such as canine fecal microbiome. We investigate long-read metagenomics with Nanopore sequencing to profile the fecal microbiome and to retrieve high-quality metagenome-assembled genomes (HQ MAGs) from a healthy dog.Results. More than 99% of total classified reads corresponded to Bacteria. The most abundant phylum was Bacteroidetes (~80% of total reads), followed by Firmicutes, Proteobacteria, and Fusobacteria. Prevotella (>50%) and Bacteroides (>20%) are the more abundant genera, followed by Fusobacterium, Megamonas, Sutterella, and other fecal-related genera, (each representing <5% of the total bacterial composition). We retrieved eight single-contig HQ MAGs and three medium-quality MAGs, after combining several metagenome dataset assemblies. The HQ MAGs corresponded to Succinivibrio, Sutterella, Prevotellamassilia, Phascolarctobacterium, Enterococcus, Blautia, and Catenibacterium genera. Succinivibrio HQ MAG represents a novel candidate bacterial species. Sutterella HQ MAG is potentially the first reported genome assembly for Sutterella stercoricanis, as assigned by 16S rRNA gene similarity. Prevotellamassilia, Phascolarctobacterium, Catenibacterium, and Blautia sp900541345 HQ MAGs improved the contiguity of previously reported genome assemblies in their respective genera, and the number of rRNA genes and tRNA genes. Finally, Enterococcus hirae and Blautia sp003287895 HQ MAGs represented species that already have a complete reference genome. At the technical level, we demonstrated that a high-molecular weight DNA extraction improved the taxonomic classification of the raw unassembled reads, the metagenomics assembly contiguity, and the retrieval of longer and circular contigs, which are potential HQ MAGs. Conclusions. Long-read metagenomics allowed us to recover HQ MAGs from canine feces of a healthy dog. The high-molecular weight DNA extraction to improve contiguity and the correction of the insertions and deletions to reduce frameshift errors ensure the retrieval of complete single-contig HQ MAGs.
Development and Prospective Validation of a Novel Risk Score for Predicting the Risk of Lower Extremity Deep Vein Thrombosis Among Trauma Patients
Authors: Peng Guoxuan , Wang Qiang , Sun Hong , Gan Lebin , Lu Hongxiang , Deng Zhihong , Sun Jiali , Deng Jin
Published: August 2020

Background: Trauma patients have an increased risk of deep vein thrombosis (DVT). Early identification of patients with a high risk of DVT after trauma is crucial for thromboembolism prophylaxis. We aimed to develop and prospectively validate a novel risk score based on a nomogram to predict lower extremity DVT among trauma patients.Methods: Clinical data were collected from 281 trauma patients who were admitted to our trauma center within 24 h of admission from September 2016 to January 2019 to develop a novel DVT risk score. The DVT risk estimates were then calculated prospectively based on the score in a new study cohort from February 2019 to July 2020. The technique of least absolute shrinkage and selection operator (LASSO) was used to select variables for the early prediction of DVT in trauma patients. The DVT risk assessment score (DRAS) was constructed by incorporating related features based on the LASSO analysis and nomogram prediction model. Further, the trauma patients were divided into various risk groups according to the DRAS. The incidence of lower extremity DVT was compared between groups and the discrimination of the DRAS was assessed using the area under the curve (AUC). Results: Based on the LASSO method, eight variables (age, injury severity score, body mass index, D-dimer level, fibrin degradation products, prothrombin time, prealbumin level, and hemoglobin level) were included in the DRAS. A total of 166 trauma patients were enrolled in this prospective study. Increased risk of DVT after trauma was related to higher DRAS. The area under the receiver operating characteristic (ROC) curve for the DRAS was 0.890(0.840–0.939) in the validation cohort. Moreover, the discriminatory capacity of the DRAS was superior to that of each variable independently and the Modified Wells score (P<0.05). Conclusions: We developed and prospectively validated the DRAS to predict the risk of lower extremity DVT among trauma patients, which may facilitate early identification of high-risk patients.