bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect and Safety of Intraoperative Intraperitoneal Chemotherapy on Patients Suffering From Colorectal Cancer.
Authors: Shang An , Wang Shuang , Yang Yongping , Li Liping , Zhao Zeyun , Li Donglin , Guo Yu , Wang Min
Published: January 2021

BackgroundColorectal cancer (CRC), the third most commonly diagnosed malignant neoplasm and the third most common cause of carcinoma-related mortality, continues to be a major international health problem. And approximately 33% of patients suffer from recurrence after radical surgery. Free malignant cells implanting in the peritoneum is generally accepted for present purposes. We did the study with the aim of evaluating the effects and safety of Intraoperative intraperitoneal chemotherapy (IOC) on patients suffering from colorectal cancer.MethodsIn total, 357 patients who went through colorectal radical surgery were considered eligible between September 23rd, 2017 to December 31st, 2018. 179 patients were treated with surgery alone, and 178 patients received surgery plus IOC. Clinical characteristics, operative findings, postoperative short-term outcomes and Disease- Free survival (DFS) were compared between the 2 groups in the selected population.ResultThe present research involves 357 patients (224 men and 133 women) who underwent surgery alone (n = 179) or surgery plus IOC (n = 178), with a mean (SD) age of 61.9 (10.4) years in the surgery alone group and 61.9 (9.1) in the surgery plus IOC group (P = .52). No significant differences were witnessed between the two groups in surgery-related information and postoperative complications. In patients with stage II colorectal cancer, the Disease- Free 1, 2and 3 years survival rates of surgery alone group were 98%, 91% and 86% respectively; and 96%, 94% and 81% respectively for surgery combined with IOC group (P = .82, Kaplan-Meier log-rank). In stage Ⅲ CRC patients, the survival rate analysis (Kaplan-Meier) showed a 82%, 68% and 61% Disease- Free survival of surgery alone group and a 94%, 85% and 82% of surgery plus IOC group after 1, 2 and 3 years, respectively (P = .002, Kaplan-Meier log rank).ConclusionsIn the present study, we have found that surgery plus IOC generated a favorable prognosis for stage Ⅲ CRC patients but not stage Ⅱ without any side-effects when the dosage of lobaplatin was 0.1 g/L. As a new, safe, and simple procedure, IOC therapy is easily performed anywhere and does not require any special devices or techniques. Thus, IOC is a promising and exciting therapeutic strategy for patients with CRC.
Calcium Sulfate Versus PMMA in One Stage Repair of Critical-sized Femoral Defects: A Vitro Study
Authors: Ma Yunfei , Qin Hanjun , Jiang Nan , Yao Zilong , Lin Qingrong , Zhang Sheng , Chen Yirong , Xu Changpeng , Hu Yanjun , Bin Yu
Published: January 2021

Polymethylmethacrylate (PMMA) cement has been used in Masquelet technique to repair bone defects, but it needs additional surgery like bone grafting. This study was to compare the efficacy between PMMA and calcium sulfate (CS) used as a spacer in one-stage reconstruction of critical-sized segmental bone defects. Sprague Dawley rats (n=30) were used to create models of critical-sized femoral defect (5mm) which were then randomized into CS, PMMA and control groups equally. the bone defects were filled with CS, PMMA or nothing. Gross observation, digital radiography, histological observation and micro-computed tomography were conducted at week 20 after surgery for comparison between the three groups. The expression of Osterix, Nestin and Osteocalcin at the bone defects was also detected by immunofluorescent staining. The results of X-Ray and μCT showed that new bone formation in CS group was superior to that in PMMA group. H&E, Safranin O & fast green and Masson staining showed obvious endochondral ossification and fibrocartilage tissues at the ends of bone defects in CS group. Much more new bone tissue formed near the ends of bone defects in CS group. In addition, osteogenic and angiogenic activities were significantly increased in CS and PMMA groups. Compared with PMMA and control groups, the expression of Osteoblast-associated protein at the bone defects in CS group was higher. In general, due to the degradability of CS and superior osteogenesis ability, CS may replace PMMA as a new filling material in clinical application.
Clinical Course and Risk Factors for Liver Injury of Severe and Critical Patients With COVID-19
Authors: Liu Jingyuan , Du Chunjing , Yang Siyuan , Pu Lin , Xiang Pan , Li Ang
Published: January 2021

Background: Information regarding the clinical course of COVID-19 patients with liver injury is very limited, especially in severe and critical patients. The objective of this study was to describe the characteristics and clinical course of liver function in patients admitted with severe and/or critical SARS-CoV-2 infection, as well as explore the risk factors that affect liver function in the enrolled COVID-19 patients.Methods: Information on clinical characteristics of 63 severe and critical patients with confirmed COVID-19 were collected and analyzed.Results: The incidence of abnormal aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the critical group was significantly higher than in the severe group (respectively 81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, p＜0.05). The time for liver function parameters to reach their extremes was approximately 2-3 weeks after admission. The independent factors associated with liver injury were patients with invasive ventilators, decreased percentages of neutrophils, lymphocytes and monocytes, and sequential organ failure assessment (SOFA) score ≥ 2 (p＜0.05).Conclusions: Abnormal liver tests are commonly observed in severe and critical patients with COVID-19. The patients with severe illness should be closely observed to monitor liver function parameters, particularly when they present with independent risk factors of liver injury.
Prevotella Contributing to the Individual Respons E of e of FOLFOX in Colon Cancer
Authors: Xu Fengguo , Hou Xiaoying , Chu Weihua , Du Hongzhi , Gao Yiqiao , Sun Ruiqi , Qin Siyuan , Tian Yuan , Zhang Pei , Zhang Zunjian
Published: January 2021

While FOLFOX has been the preferred chemotherapeutic strategy in colon cancer treatment, the limited response rate has seriously restricted its application in clinic. The underlying mechanisms of the individual response of FOLFOX remain to be elucidated. In this study, pharmacomicrobiomics integrated with pharmacometabolomics was applied to disentangle the key role of specific gut bacteria and microbiota derived metabolites involved. As a result , significant variation of chemotherapy efficacy was observed in tumor bearing mice after FOLFOX administration. 16S rRNA gene sequencing analysis revealed the relative abundance of Staphylococcus , Jeotgalicoccus , Sphingomonas significantly increased in the FOLFOX sensitive group, whereas Prevotella was higher in the non sensitive individuals . Meanwhile, verification study o n FOLFOX combined with bacteria colonization indicates that Prevotella could attenuate the anti cancer efficacy of FOLFOX in vivo . Furthermore, gut derived metabolite 3-Oxocholic acid (3-Oxo) identified by metabolomics approach was confirmed to associate with Prevotella in fecal samples. In addition, preliminary functional exploration suggested that 3-Oxo could reverse the anti cancer effect of FOLFOX and promote malignant progression Taken together, integrated pharmacomicrobiomics and pharmacometabolomics revealed that Prevotella and related metabolite 3-Oxo may be responsible for individualized FOLFOX efficacy, which provides novel predictive biomarkers for FOLFOX precise medicine as well as targets for colon cancer therapy.
Improvement of Forest Canopy Density Mapping of Spare Forests Using a Novel RS-GIS Based Classification Method
Authors: Naseri Mohammad Hassan , Shataee Shaban
Published: January 2021

The authors have requested that this preprint be removed from Research Square.
Aqueous extract of Parkinsonia aculeata has an anti-urolithiatic effect in rats
Authors: Eghbali Seyed Sajjad , Akbarzadeh Samad , Bargahi Afshar , Mirzaei Kamran , Maleki Nasrollah , Bahtouee Mehrzad , Yazdanpanah Ahmad
Published: January 2021

Introduction: Many antioxidant agents have been studied for prevention and treatment of the kidney stone disease in animals and humans. Parkinsonia aculeate (P. aculeate) has a wide range of pharmacological and biological activities, particularly antioxidant properties. The goal of this research was to investigate the anti-urolithiatic effect of P. aculeate extract on ethylene glycol induced renal calculi.Materials and methods: A total of 42 male Wistar rats were randomly divided into six equal groups with seven rats in each group: Group A served as healthy control group and received distilled water for 30 days. Group B served as ethylene glycol control group and received 1% v/v ethylene glycol in distilled water for 30 days. Group C, D, and E animals (preventive groups) concurrently received 1% v/v ethylene glycol in distilled water along with extract of P. aculeata orally for 30 days in doses of 100 mg/kg (low dose), 200 mg/kg (moderate dose), and 300 mg/kg (high dose), respectively. Group F (treatment groups) received 1% v/v ethylene glycol in distilled water for the first 30 days along with extract of P. aculeata 300 mg/kg orally from 15th to 30th days. At the end of study period, 24-hour urine and serum samples were collected and analyzed. All rats were sacrificed and both kidneys were removed, weighed and histopathologically evaluated for calcium oxalate crystals.Results: Ethylene glycol significantly decreased serum calcium, urinary levels of creatinine, calcium and uric acid. On the contrary, it significantly increased 24-hour urine volume, kidney weight, and calcium oxalate deposits. The highest number of calcium oxalate crystal depositions were in the high dose preventive group (76.6%), which is statistically significant difference with other groups including ethylene glycol control (70%), low dose preventive (72%), treatment (38%), and moderate dose preventive (42%) groups (P value < 0.05). Administration of extract of P. aculeata significantly reduced the production of calcium oxalate stones in moderate dose preventive and treatment group. However, P. Aculeata extract was not effective in reducing the formation of calcium oxalate stones in low dose and high dose preventive groups. Interestingly, the number of calcium oxalate deposits in the renal tubules of high dose preventive group was significantly more than the ethylene glycol control group.Conclusions: Extract of P. aculeata has preventive and therapeutic effects in ethylene glycol induced renal calculi in Wistar rat. Further studies are necessary to clarify the mechanism underlying this effect.
Increased risk of gastro-oesophageal cancers among married couples: Data from the Ardabil Cancer Registry (ACR) in Northwest of Iran, 2002-2016
Authors: Iranparvar-Alamdari Manouchehr , Yazdanbod Abbas , Maleki Nasrollah , Rostami-Mogaddam Majid , Amani Farnaz
Published: January 2021

Background: The study of cancer in spouses may play an important role in the assessment of cancer etiology. This study aims to evaluate the risk of gastro-oesophageal cancers among spouses.Methods: We performed a retrospective cohort study of the Ardabil Cancer Registry (ACR) office for patients with a diagnosis of gastro-oesophageal cancers from 2002 to 2016. Data were collected by trained medical personnel through medical records.Results: A total of 2741 participants diagnosed with gastro-oesophageal cancer were enrolled in this study: 1786 (65.2%) had gastric cancer and 955 (34.8%) had oesophageal cancer. In the 14 years of the study period, twelve couples with gastro-oesophageal cancer were identified. The mean duration at marriage among the couples was 42.5 years of age. A positive history of consanguineous marriage was found in 2 (16.7%) of the cases. Of these 12 couples with gastro-oesophageal cancer, 8 (33.3%) were located in the oesophagus, 15 (62.5%) in the stomach, and one (4.2%) at the gastro-oesophageal junction. Histologically, all gastric cancers were adenocarcinoma and were located mainly in the cardia region (66.7%). However, squamous cell carcinoma was the most common histologic type of oesophageal cancer (87.5%) and were located mainly in the middle thirds and lower thirds of the oesophagus.Conclusions: The presence of shared risk factors among married couples such as lifestyle (smoking and alcohol consumption), nutritional habits, psychological stress, and H. pylori infection, indicating that environmental factors play an important role in the development of gastric cancer.
Unravelling Vitamins as Wonder Molecules for Covid-19 Management via Structure-based Virtual Screening
Authors: Pandya Medha , Shah Sejal , Menamadathil Dhanalakshmi , Gadnayak Ayushman , Juneja Tanzil , Patel Amisha , Das Kajari , Das Jayashankar
Published: January 2021

The emergence situation of coronavirus disease 2019 (COVID-19) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural (NSP3, NSP5, ORF7a, NSP12, ORF3a), structural (Spike & Hemagglutinin esterase) and host protein furin. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin and SARS-COV-2 RNA dependent RNA polymerase. Furin mediated cleavage of the viral spike glycoprotein is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation.
Calcium-dependent serine-threonine phosphatase, calcineurin inactivation mediated by baicalein attenuates prion protein-mediated neuronal cell damage
Authors: Hong Jeong-Min , Moon Ji-Hong , Oh Young Min , Park Sang-Youel
Published: January 2021

Background: Prion diseases are a group of unvaryingly fatal neurodegenerative disorders characterized by neuronal cell death. Calcineurin and autophagy mediate prion-induced neurodegeneration, suggesting that inhibition of calcineurin and autophagy could be a target for therapy. Baicalein has been reported to exert neuroprotective effects against calcium-dependent neuronal cell death. Results: In the present study, we investigated whether baicalein attenuates prion peptide-mediated neurotoxicity and reduces calcineurin. We found that baicalein treatment inhibits prion protein-induced apoptosis. Baicalein inhibited calcium up-regulation and protected the cells against prion peptide‑induced neuron cell death by calcineurin inactivation. Furthermore, baicalein increased p62 protein levels and decrease LC3-II protein levels indicating autophagic flux inhibition and baicalein inhibited prion protein-induced neurotoxicity through autophagy flux inhibition. Conclusions: Taken together, this study demonstrated that baicalein attenuated prion peptide-induced neurotoxicity via calcineurin inactivation and autophagic flux reduction, and also suggest that baicalein may be an effective therapeutic drug against neurodegenerative diseases, including prion diseases.
Menopause Is a Natural Stage of Aging: A Qualitative Study
Authors: Ilankoon IMPS , Samarasinghe Kerstin , Elgán Carina
Published: January 2021

Background Menopause is a biopsychosocial phenomenon encompassing the transition in a woman’s life from being fertile to infertile. Although menopause may result in extremely unpleasant physical symptoms there is evidence of a low rate of reported menopausal symptoms amongst women in Asian cultures. Women’s experiences, views, and responses to menopause which influences women’s daily life and well-being, may vary between different societies and cultures. This study aimed to explore and describe menopausal experiences among women in Sri Lanka. Methods A qualitative exploratory research was conducted among postmenopausal women of 46-55 years of age in the western province of Sri Lanka. Individual interviews with a purposive sample of 20 women were conducted, and data analysis was done using manifest and latent content analysis. Results The results consist of an overall theme, “Menopause is a natural stage of aging” and three categories “Entering a new stage”, “Managing menopause” and “Not the end of life” which emerged from 34 codes. The overall theme highlights that changes in menopause were experienced as a natural change in life, with health problems that are normal for this change and handled with different self-care practices. The category “Entering a new stage” describes the women becoming aware of menopause and its bodily changes. The category “Managing menopause” describes women’s experiences of being able to find their own remedies to ease the menopausal symptoms and by engaging in religious activities and focusing on interaction with people. The category, “Not the end of life” describes women's views of themselves as still valuable because menopause was experienced as a natural part of their lives. Conclusion Women in Sri Lanka managed menopausal problem mainly on their own as they viewed the menopause as a natural stage of aging risking unnecessary suffering and failure to detect preventable complications. Enabling support groups for menopausal women and improving on their health-seeking behaviour by encouraging them to take part in screening for cervical and breast cancer would improve their condition. Further information on additional hormone therapy with a, subsequent follow-up and evaluation by community health nurses and/or midwives, would facilitate Sri Lankan women's transition to menopause.
Comparison of three treatment methods for simple bone cyst in children
Authors: Zhang Ke Xue , Chai Wei , Zhao Jia Jia , Deng Jun Hao , Peng Zhan , Chen Ji Ying
Published: January 2021

Background The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. Methods 83 cases with simple bone cyst were analyzed retrospectively. 28 cases were treated with ABM. 28 cases were treated with ESIN. 27 cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. Results All cases accomplished the follow-up. The effective rate of the ABM+ESIN group was significantly higher than that of the ABM group (P<0.05), and the cure rates of the ESIN group and the ABM+ESIN group were higher than that of the ABM group (P<0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P<0.05, respectively). The times for admission were 2.0±0.0 in the ESIN group, 5.7±1.9 in the ABM group, and 4.7±2.4 in the ABM+ESIN group (P<0.05 when compared with each other). Conclusions The method of ABM combined with ESIN for children’s bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.
The value of Bayesian predictive projection for variable selection: An example selecting lifestyle predictors of young adult well-being
Authors: Bartonicek Adam , Wickham Shay Ruby , Pat Narun , Conner Tamlin S.
Published: January 2021

BackgroundVariable selection is an important issue in many fields such as public health and psychology. Researchers often gather data on many variables of interest and then are faced with two challenging goals: building an accurate model with few predictors, and making probabilistic statements (inference) about this model. Unfortunately, it is currently difficult to attain these goals with the two most popular methods for variable selection methods: stepwise selection and LASSO. The aim of the present study was to demonstrate the use predictive projection feature selection – a novel Bayesian variable selection method that delivers both predictive power and inference. We apply predictive projection to a sample of New Zealand young adults, use it to build a compact model for predicting well-being, and compare it to other variable selection methods. MethodsThe sample consisted of 791 young adults (ages 18 to 25, 71.7% female) from New Zealand who had taken part in the Dunedin Daily Life Study in 2013-2014. Participants completed a 13-day online daily diary assessment of their well-being and a range of lifestyle variables (e.g., sleep, physical activity, diet variables). The participants’ diary data was averaged across days and analyzed cross-sectionally to identify predictors of average flourishing. Predictive projection was used to select as few predictors as necessary to approximate the predictive accuracy of a reference model with all 28 predictors. Predictive projection was also compared to other variable selection methods, including stepwise selection and LASSO.ResultsThree predictors were sufficient to approximate the predictions of the reference model: higher sleep quality, less trouble concentrating, and more servings of fruit. The performance of the projected submodel generalized well. Compared to other variable selection methods, predictive projection lead to models with either matching or slightly worse performance but with much fewer predictors.ConclusionPredictive projection was used to efficiently arrive at a compact model with good predictive accuracy. The predictors selected into the submodel – felt refreshed after waking up, had less trouble concentrating, and ate more servings of fruit – were all theoretically meaningful. Our findings have important implications for applications of variable selection in health research.
Health services utilization and out-of-pocket (OOP) expenditures in public and private facilities in Pakistan: An empirical analysis of the 2013-14 OOP Health Expenditure Survey
Authors: Khalid Faraz , Raza Wajeeha , Hotchkiss David R. , Soelaeman Rieza H.
Published: January 2021

Background As low- and middle-income countries progress toward Universal Health Coverage, there is an increasing focus on measuring out-of-pocket (OOP) expenditure and health services utilization within countries. While there have been several reforms to improve health services coverage and financial protection in Pakistan, there is limited empirical research comparing OOP expenditure and health services utilization between public and private facilities and exploring their determinants, a knowledge gap addressed in this study. Methods We used data from 2013-14 OOP Health Expenditure Survey, a population-based household survey carried out for Pakistan’s National Health Accounts. The analysis included 7,969 encounters from 4,293 households. We conducted bivariate analyses to describe patterns of care utilization, estimated annualized expenditures by type and sector of care, and assessed expenditure composition. We used multivariable logistic regression modeling to identify factors associated with sector of care and generalized linear model (GLM) with log link and gamma distribution to identify determinants of OOP expenditures stratified by type of care (inpatient and outpatient). Results Most encounters (82.5%) were in the private sector and were for outpatient visits (85%). Several public-private differences were observed in annualized expenditures and expenditure components. Logistic regression results indicate males, wealthier individuals, Punjab and Sindh residents, and those in smaller households were more likely to access private outpatient care. In the inpatient model, rural residents were more likely to use a private provider, while Khyber Pakhtunkhwa residents were less likely to use private care. GLM results indicate private sector inpatient expenditures were approximately PKR 6,660 (USD 61.8) higher than public sector expenditures, but no public-private differences were observed for outpatient expenditures. Several demographic factors were significantly associated with outpatient and inpatient expenditures. Of note, expenditures increased with increasing wealth, decreased with increasing household size, and differed by province and region. Conclusions This is the first study comprehensively investigating how healthcare utilization and OOP expenditures vary by sector, type of care, and socio-economic characteristics in Pakistan. The findings are expected to be particularly useful for the next phase of social health protection programs and supply side reforms, as they highlight sub-populations with higher OOP and private sector utilization.
Evaluating the Performance of Diagnostic methods for soil transmitted helminths in the Amhara National Regional State, Northwest Ethiopia
Authors: Niguse Abebe Fenta , Hailu Tadesse , Alemu Megbaru , Nibret Endalkachew , Amor Arancha , Munshea Abaineh
Published: January 2021

Background: Soil-transmitted helminths are more prevalent in tropics and sub-tropics including Ethiopia. Despite their high prevalence, direct saline microscopy with its low sensitivity has been used as a diagnostic method in almost all health facilities in Ethiopia. Alternative diagnostic methods which have higher sensitivity are not yet implemented. Therefore, this study aimed to compare and evaluate the performance of diagnostic methods for soil transmitted helminths. Methods: A cross-sectional study among 520 school children was conducted from October to December, 2019 in Amhara National Regional State. The study participants were selected using systematic random sampling technique. Stool samples were processed via formol ether concentration, Kato-Katz, spontaneous tube sedimentation and agar plate culture techniques. Data was entered into Epi-data version 3.1 and analysis was done using SPSS version 20.0. The sensitivity, specificity, and negative predictive value were calculated against the combined result. Strength of agreement of the diagnostic methods was determined by Kappa value. Results: The Overall prevalence of soil transmitted helminths was 40.8% using combination of methods. The prevalence 24.4%, 22.5%, and 32.4%, respectively was recorded by using formol ether concentration, Kato-Katz and spontaneous tube sedimentation. The highest prevalence of hookworm (29.2%) was detected by the agar plate culture. The sensitivity and negative predictive value of formol ether concentration were 57.9 % and 78.4%, for Kato-Katz thick smear 55.2% and 76.4%, for spontaneous tube sedimentation were 79.2% and 87.5% to soil transmitted helminths detection, respectively. The sensitivity and negative predictive value of agar plate culture to hookworm detection were 86.4% and 93.5%, respectively. Conclusion: Spontaneous tube sedimentation shows higher sensitivity in the detection of soil transmitted helminth infections. Agar plate culture (APC) method also indicated better performance for hookworm detection than other methods. Therefore, the employment of spontaneous tube sedimentation technique for routine laboratory and agar plate culture for research purposes will significantly aid in accurate diagnosis of parasitic infections.
Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial
Authors: Weindelmayer Jacopo , Mengardo Valentina , Veltri Alessandro , Baiocchi Gian Luca , Giacopuzzi Simone , Verlato Giuseppe , de Manzoni Giovanni
Published: January 2021

Background: Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the Authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 four came from Eastern countries. After 2015 only retrospective studies have been published, all with inconsistent results.Methods: ADiGe (Abdominal Drain in GastrEctomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment. The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, readmission rate.Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to patient and caregivers.Discussion: ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure.Trial registration: Prospectively registered (last updated on October 29, 2020) at Clinicaltrials.gov with the identifier NCT04227951, https://clinicaltrials.gov/ct2/show/NCT04227951.
Development of an Engineered Peptide Antagonist against Periostin to Overcome Doxorubicin Resistance in Breast Cancer
Authors: Oo Khine Kyaw , Kamolhan Thanpawee , Soni Anish , Thongchot Suyanee , Mitrpant Chalermchai , O-charoenrat Pornchai , Thuwajit Chanitra , Thuwajit Peti
Published: January 2021

Background: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. Methods: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. Results: The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. Conclusions: This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.
Triple null mutations in starch synthase SSIIa gene homoeologs lead to high amylose and resistant starch in hexaploid wheat
Authors: Schoen Adam , Joshi Anupama , Tiwari Vijay K , Gill Bikram S. , Rawat Nidhi
Published: January 2021

Background: Lack of nutritionally appropriate foods is one of the leading causes of obesity in the US and worldwide. Wheat (Triticum aestivum) provides 20% of the calories consumed daily across the globe. The nutrients in the wheat grain come primarily from the starch composed of amylose and amylopectin. Resistant starch content, which is known to have significant human health benefits, can be increased by modifying starch synthesis pathways. Starch synthase enzyme SSIIa, also known as starch granule protein isoform-1 (SGP-1), is integral to the biosynthesis of the branched and readily digestible glucose polymer amylopectin. The goal of this work was to develop a triple null mutant genotype for SSIIa locus in the elite hard red winter wheat variety ‘Jagger’ and evaluate the effect of the knock-out mutations on resistant starch content in grains with respect to wild type. Results: Knock-out mutations in SSIIa in the three genomes of wheat variety ‘Jagger’ were identified using TILLING. Subsequently, these loss-of function mutations on A, B, and D genomes were combined by crossing to generate a triple knockout mutant genotype Jag-ssiia-∆ABD. The Jag-ssiia-∆ABD had an amylose content of 35.70% compared to 31.15% in Jagger, leading to ~118% increase in resistant starch in the Jag-ssiia-∆ABD genotype of Jagger wheat. The single individual genome mutations also had various effects on starch composition. Conclusions: Our full null Jag-ssiia-∆ABD mutant showed a significant increase in RS without the shriveled grain phenotype seen in other ssiia knockouts in elite wheat cultivars. Moreover, this study shows the potential for developing nutritionally improved foods in a non-GM approach. Since all the mutants have been developed in an elite wheat cultivar, their adoption in production and supply will be feasible in future.
Efficacy and Safety of the Syrup "KalobaTUSS®" as a Treatment for Cough in Children: a randomized, double blind, placebo-controlled clinical trial
Authors: Carnevali Ilaria , Paglia Rita La , Pauletto Laura , Raso Floriana , Testa Marco , Mannucci Carmen , Sorbara Emanuela Elisa , Calapai Gioacchino
Published: January 2021

Background: Acute cough in children often causes discomfort to children and parents, reducing their quality of life. Despite the extensive utilization of over-the-counter remedies for cough, the efficacy of most of these treatments in children has not been confirmed.Methods: We conducted a randomized, double blind, placebo-controlled clinical trial of 106 children with acute cough to evaluate the efficacy and safety of KalobaTUSS®, a paediatric cough syrup based on acacia honey and on Malva sylvestris extract, Inula helenium extract, Plantago major extract, and Helichrysum stoechas extract by using a validated 6 points Likert scale.Results: Children were orally treated with KalobaTUSS® or placebo for eight days. Children receiving KalobaTUSS® showed an early and significant reduction in night-time and day-time cough scores measured using a specific scale and a shorter duration of cough than children treated with the placebo.Conclusions: KalobaTUSS® is well tolerated and produces positive effects by reducing the severity and shortening the duration of cough in children.Trial Registration: Clinicaltrials.gov no. NCT04073251. Retrospectively registered.
The waveform inversion of mainshock and aftershock data of the 2006 M6.3 Yogyakarta earthquake
Authors: Saputra Hijrah , Wahyudi Wahyudi , Suardi Iman , Anggraini Ade , Suryanto Wiwit
Published: January 2021

This study comprehensively investigates the source mechanisms associated with the mainshock and aftershocks of the Yogyakarta earthquake of magnitude Mw = 6.3 on May 27, 2006. Therefore, this study is to provide a more precise answer to the controversial source mechanism. This study uses moment tensor inversion to obtain fault plane parameters and joint inversion to obtain spatial and temporal slip distributions during an earthquake. The coseismic slip distribution is overlaid with the relocated aftershock distribution to see the stress field variations around the tectonic area of the study. Moment tensor inversion uses near-field data, and joint inversion uses near-field and teleseismic body wave data. The data is filtered by trial and error using a bandpass filter with frequency pairs and velocity models from several previous studies. The green's function for moment tensor inversion calculated using the extended reflectivity method and joint inversion computed using the Kikuchi and Kanamori methods. In this study, we apply the Akaike Bayesian Information Criterion (ABIC) method to obtain more stable inversion results. The results of the mainshock and aftershock moment tensor inversion show different fault types. The mainshock fault types are strike-slip and dip-normal types, while the 8th aftershock is of the same type as the mainshock, while the 9th and 16th June are strike slips. The joint inversion results show two asperities. The maximum slip is 0.78 m, with the first asperity 10 km south of the mainshock and the second asperity 10 km north of the mainshock. The obtained source parameters are total seismic moment M0 = 0.4311E + 19 (Nm) or Mw = 6.4, with a source depth of 12 km and a source duration of 28 seconds. Slip distribution overlay with aftershock distribution shows compatibility. The type of focus mechanism that results from this joint inversion is the oblique.
High Aedes spp. larval indices in Kinshasa, Democratic Republic of Congo
Authors: Francis Wat’senga Tezzo , Sylvie Fasine , Zola Manzambi Emile , Carmen Marquetti Maria del , Guillaume Binene Mbuka , Gillon Ilombe , Richard Mundeke Takasongo , Nathalie Smitz , Andre Bisset Juan , Wim Van Bortel , Vanlerberghe Veerle
Published: January 2021

BACKGROUND: Dengue, yellow fever, chikungunya and Zika are among the most important emerging infectious vector-borne diseases worldwide. In the Democratic Republic of Congo (DRC), increases in cases of dengue and outbreaks of yellow fever and chikungunya have been reported since 2010. The main vectors of these arboviruses, Aedes aegypti and Aedes albopictus, have been reported in DRC, but there is a lack of detailed information on their presence and spread to guide disease control efforts.METHODS: In 2018, two cross-sectional surveys were conducted in Kinshasa province (DRC), one in the rainy (January/February) and one in the dry season (July). Four hundred houses were visited in each of the four selected communes (N’Djili, Mont Ngafula, Lingwala and Kalamu). Within the peri-domestic area of each household, searches were conducted for larval habitats which were then surveyed for the presence of Aedes larvae and pupae. A subset of the immature specimens were reared to adults for morphological identification followed by DNA-barcoding of the specimens to validate identifications.RESULTS: The most rural commune (Mont Ngafula) had the highest pupal index of 246 (20) pupae/100 houses and a Breteau Index of 82.2 (19.5)/100 houses, while this latter was 21.5 (4.7), 36.7 (9.8) and 41.7 (7.5) in Kalamu, Lingwala and N’Djili in the rainy (and dry) season, respectively. The House Index was on average across all communes 27.5% (7.6%); and the Container Index 15.0% (10.0%) in rainy (and dry) season, respectively. The vast majority of Aedes positive containers were found outside the houses (adjusted OR 27.4 (95%CI 14.9-50.1)). During the dry season, the most productive containers were the ones used for water storage, whereas in the rainy season rubbish and tires constituted key habitats. Both Ae. aegypti and Ae. albopictus were found. Anopheles larvae were found in different types of Aedes larval habitats, especially during the rainy season. CONCLUSIONS: In both surveys and in all communes, the larval indices (BI) were higher than the arbovirus transmission threshold values established by the World Health Organization. Management strategies for controlling Aedes in Kinshasa need to target the key containers, mainly located in outdoor spaces, for larval habitats destruction or reduction.
The impact of subclinical hypothyroidism on long-term outcomes in older patients undergoing percutaneous coronary intervention
Authors: Liu Yong-Sheng , Wei Mei , Wang Le , Liu Gang , Ma Guo-Ping , Ono Katsushige , Cao Ze-Long , Yang Man , Zheng Ming-Qi
Published: January 2021

Background Subclinical hypothyroidism (SCH) is reportedly associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). The prognostic significance of SCH in the elderly was poorly defined. The purpose of this study was to evaluate the association between SCH and long-term outcomes in older patients undergoing PCI.Methods and Results 3168 patients aged 65 years or older who underwent PCI from January 2012 to October 2013 were included. Patients were divided into SCH group (n=320) and euthyroidism (ET) group (n=2848) based on thyroid function test. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period. There were 227 deaths during the follow-up period including 124 deaths caused by cardiac events. There was no significant difference in mortality rate between the SCH group and the ET group (p>0.05). After adjustment for covariates, compared with patients with ET, the RRs of death from all-cause and cardiac in patients with SCH were 1.261 (95%CI: 0.802-1.982, p=0.315) and 1.231 (95%CI: 0.650-2.334, p=0.524), respectively. When SCH was stratified by age, gender, and degree of thyroid-stimulating hormone elevation, no significant associations were also found in any stratum. Conclusion Our investigation revealed that SCH was negatively associated with the outcome of PCI in older patients.
Graphene Oxide Exacerbates Dextran Sodium Sulfate-Induced Colitis via ROS/AMPK/p53 Signaling to Mediate Apoptosis
Authors: Liu Siliang , Xu Angao , Gao Yanfei , Xie Yue , Liu Zhipeng , Sun Meiling , Mao Hua , Wang Xinying
Published: January 2021

Background: Graphene oxide (GO), a novel carbon-based nanomaterial, has promising applications in biomedicine. However, it induces potential cytotoxic effects on the gastrointestinal (GI) tract cells, and these effects have been largely uncharacterized. The present study aimed to explore the toxic effects of GO on the intestinal tract especially under pre-existing inflammatory conditions, such as inflammatory bowel disease (IBD), and elucidate underlying mechanisms.Results: Our findings indicated that oral gavage of GO worsened acute colitis induced by 2.5% dextran sodium sulfate in mice. In vitro, toxic effects including decreased cell viability, as well as the elevated release of lactic dehydrogenase (LDH) in FHC cell line, an ideal model of intestinal epithelial cells (IECs), were observed. Moreover, GO treatment triggered apoptosis in FHC cells through the activation of reactive oxygen species (ROS)/AMP-activated protein kinase (AMPK)/p53 pathway, as evidenced by the upregulation of cytochrome c (Cytc), Bax, and cleaved caspase-3 (c-cas3) and the downregulation of Bcl-2. Interestingly, pretreatment with an antioxidant, N-acetyl-L-cysteine, and a specific inhibitor of AMPK activation, Compound C (Com.C), effectively inhibited GO-induced apoptosis in FHC cells.Conclusions: Our data demonstrate that GO-induced IECs apoptosis via ROS/AMPK/p53 pathway activation accounts for the exacerbation of colitis in mice. These findings provide a new insight into the pathogenesis of IBD induced by environmental factors. Furthermore, our findings enhance our understanding of GO as a potential environmental toxin, which helps delineate the risk of exposure to patients with disturbed intestinal epithelial barrier/inflammatory disorders such as IBD.
Structural stigma and its impact on healthcare for consumers with Borderline Personality Disorder: protocol for a scoping review
Authors: Klein Pauline , Fairweather A. Kate , Lawn Sharon , Stallman Helen , Cammell Paul
Published: January 2021

BackgroundStructural stigma in health systems experienced by consumers diagnosed with Borderline Personality Disorder (BPD), is a widespread phenomenon that causes major health inequities and harm for this population. Structural stigma in this context relates to institutional policies, cultural norms, and organizational practices that limits consumers’ access to health services, quality of care, and capacity to achieve optimal health and well-being. BPD is a serious mental illness with high morbidity and mortality, characterized by instability in interpersonal relationships, self-image, and emotional and behavioral deregulation, which stem from significant traumatic childhood/life events, and/or biological aetiologies. The objectives of this scoping review are to explore the international literature on structural stigma in healthcare systems specific to BPD, and to provide an overview of the impact of structural stigma on health services for BPD consumers, and their carers/families.MethodsThis scoping review will follow the Joanna Briggs Institute (JBI) scoping review guidelines. We will search the following electronic databases (from inception onwards): MEDLINE, CINAHL, PsycINFO, Scopus, Cochrane Library, and JBI-Evidence databases. Grey literature will be identified through the Google search engine. We will include all types of literature in English, published and unpublished, including any study design, reviews, clinical practice guidelines, policy reports, and other documents. No restrictions on publication date of sources of evidence will be applied. International literature should examine structural stigma associated with BPD in any healthcare setting such as, outpatients, inpatients, primary health care, or community-based facilities. Two reviewers will independently screen all titles, abstracts and full-text citations. Quality appraisal of the included sources of evidence will be assessed using the Mixed Methods Appraisal Tool (MMAT) 2018 version. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., thematic analysis) methods. DiscussionThis review is anticipated to enhance both identification and understanding of those structures in health systems (i.e., institutional policies, cultural norms, and practices), that manifest and perpetuate stigma experienced by consumers with BPD, and their carers/families. The findings can be used to inform future research, policy and practice relating to stigma reduction strategies that can be adopted to improve the provision of BPD-responsive services and care for this population. Systematic review registration: Open Science Framework (https://osf.io/bhpg4).