bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a SNP linkage map and genome-wide association study for resistance to Aeromonas hydrophila in pacu (Piaractus mesopotamicus)
Authors: Mastrochirico-Filho Vito A. , Borges Carolina H. S. , Freitas Milena V. , Ariede Raquel B. , Pilarski Fabiana , Utsunomia Ricardo , Carvalheiro Roberto , Gutierrez Alejandro P. , Peñaloza Carolina , Yáñez José M. , Houston Ross D. , Hashimoto Diogo Teruo
Published: June 2020

Background

Pacu ( Piaractus mesopotamicus ) is one of the most important neotropical aquaculture species in South America. Disease outbreaks triggered by the bacterium Aeromonas hydrophila have resulted in significant losses to pacu production. Selective breeding using genomic information is a powerful strategy to improve disease resistance in fish species. This study aimed to investigate the genetic architecture of resistance to A. hydrophila in pacu via a Genome-Wide Association Study (GWAS) to identify Quantitative Trait Loci (QTLs) and putative genes associated with this trait in 14 pacu full-sib families. An experimental challenge was performed in order to assess the levels of genetic variation for resistance against the bacteria using the following trait definition: binary test survival (TS) and time of death (TD).

Results

The analysis of genetic parameters identified moderate heritability values for both resistance traits: h 2 = 0.20 (± 0.09) for TS and h 2 = 0.35 (± 0.15) for TD. To enable the GWAS, a pacu linkage map was developed using genotype data derived from Restriction Site Associated DNA Sequencing (RAD-Seq), resulting in 27 linkage groups consisting of 17,453 Single Nucleotide Polymorphisms (SNPs). The length of linkage groups varied from 79.95 (LG14) to 137.01 (LG1) cM, with a total integrated map length of 2,755.60 cM. GWAS analysis identified 22 putative QTLs associated to A. hydrophila resistance (defined as genomic regions explaining > 1% of the additive genetic variance for the trait), distributed in 17 linkage groups. Several candidate genes related to immune response were located close to the putative QTLs, such as tbk1 , trim16 , Il12rb2 and lyz2 .

Conclusion

The outputs of this study include the first medium density linkage map for pacu, which can be used as a framework to study different traits relevant to the production of this species. In addition, resistance to A. hydrophila was found to be moderately heritable but with a polygenic architecture suggesting that genomic selection, instead of marker assisted selection, might be tested for efficiently improving resistance to one of the most problematic diseases that affects the South American aquaculture.
Acquisition and maintenance of disgust reactions in an OCD analogue sample: efficiency of extinction strategies through a counter conditioning procedure
Authors: Novara caroline , Lebrun Cindy , MacGregor Alexandra , Vivet Bruno , Therouanne Pierre , Raffard Stephane
Published: June 2020

Background
If obsessive-compulsive disorder (OCD) has long been considered as an anxiety disorder, disgust is the dominant emotion in contamination-based OCD. However, disgust seems resistant to exposure with response prevention partly due to the fact that disgust is acquired through evaluative conditioning. The present research investigates a counter-conditioning intervention in treating disgust-related emotional responses in two groups of individuals with high (HDCC, n = 25) and low (LDCC, n = 23) contamination concerns.
Methods
The two groups completed a differential associative learning task in which neutral images were followed by disgusting images (conditioned stimulus; CS+), or not (CS-). Following this acquisition phase, there was a counterconditioning procedure in which CS + was followed by a very pleasant US, while CS- remained unreinforced.
Results
Following counterconditioning, both groups reported significant reduction in their expectancy of US occurrence and reported less disgust with CS+. For both expectancy and valence, reduction was lower in the HDCC group than in the LDCC group. Disgust sensitivity was highly correlated with both acquisition and maintenance of the response acquired, while US expectation was predicted by anxiety.
Conclusion
Desensitization to disgust handled by counter-conditioning procedure reduces both expectations and conditioned valence.
National Early Warning Score 2 (NEWS2) on admission predicts severe disease and in-hospital mortality from Covid-19 - A prospective cohort study
Authors: Myrstad Marius , Ihle-Hansen Håkon , Tveita Anders Aune , Andersen Elizabeth Lyster , Nygård Ståle , Tveit Arnljot , Berge Trygve
Published: June 2020

Background There is a need for validated clinical risk scores to identify patients at risk of severe disease and to guide decision-making during the covid-19 pandemic. The National Early Warning Score 2 (NEWS2) is widely used in emergency medicine, but so far, no studies have evaluated its use in patients with covid-19. We aimed to study the performance of NEWS2 and compare commonly used clinical risk stratification tools at admission to predict risk of severe disease and in-hospital mortality in patients with covid-19. Methods This was a prospective cohort study in a public non-university general hospital in the Oslo area, Norway, including a cohort of all 66 patients hospitalised with confirmed SARS-CoV-2 infection from the start of the pandemic; 13 who died during hospital stay and 53 who were discharged alive. Data were collected consecutively from March 9th to April 27th 2020. The main outcome was the ability of the NEWS2 score and other clinical risk scores at emergency department admission to predict severe disease and in-hospital mortality in covid-19 patients. We calculated sensitivity and specificity with 95% confidence intervals (CIs) for NEWS2 scores ≥5 and ≥6, quick Sequential Organ Failure Assessment (qSOFA) score ≥2, ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and CRB-65 score ≥2. Areas under the curve (AUCs) for the clinical risk scores were compared using DeLong’s test.Results In total, 66 patients (mean age 67.9 years) were included. Of these, 23% developed severe disease. In-hospital mortality was 20%. Tachypnoea, hypoxemia and confusion at admission were more common in patients developing severe disease. A NEWS2 score ≥6 at admission predicted severe disease with 80.0% sensitivity and 84.3% specificity (Area Under the Curve (AUC) 0.822, 95% confidence interval (CI) 0.690-0.953). NEWS2 was superior to qSOFA score ≥2 (AUC 0.624, 95% CI 0.446-0.810, p<0.05) and other clinical risk scores for this purpose.Conclusion NEWS2 score at hospital admission predicted severe disease and in-hospital mortality, and was superior to other widely used clinical risk scores in patients with covid-19.
Pelvic Organ Prolapse and Uterine Preservation: A survey of female gynaecologists (POP-UP survey)
Authors: Urdzík Peter , Kalis Vladimir , Blaganje Mija , Rusavy Zdenek , Smazinka Martin , Havir Martin , Dudic Rastislav , Ismail Khaled
Published: June 2020

Backround: The aim of this study was to explore the personal views of female gynecologists regarding the management of POP with a particular focus on the issue of uterine sparing surgery. Methods: A questionnaire based survey of practicing female gynaecologists in the Czech Republic, Slovenia and Slovakia. Results : A total of 140 female gynaecologists from 81 units responded to our questionnaire. The majority of respondents stated they would rely on a urogynecologist to aid them with their choice of POP management options. The most preferred options for POP management were sacrocolpopexy and physiotherapy. Almost 2/3 of respondents opted for a hysterectomy together with POP surgery, if they were menopausal, even if the anatomical outcome was similar to uterine sparing POP surgery. Moreover, 81.4% of respondents, who initially opted for a uterine sparing procedure, changed their mind if the anatomical success of POP surgery with concomitant hysterectomy was superior. Discussing uterine cancer risk in relation to other organs had a less significant impact on their choices. Conclusions: The majority of female gynecologists in our study opted for hysterectomy if they were postmenopausal at the time of POP surgery. However, variation in information provision had an impact on their choice.
Decolorization and Detoxification of Triphenylmethane Dyes by isolated endophytic fungus, Bjerkandera adusta SWUSI4 under non-nutritive conditions
Authors: Gao Tiancong , Qin Dan , Zuo Shihao , Peng Yajun , Xu Jieru , Yu Baohong , Song Hongchuan , Dong Jinyan
Published: June 2020

Biodecolorization by microorganisms is a potential treatment technique of triphenylmethane (TPM) dyes as they seem to be environmentally safe. In the present study, the decolourization and detoxification of cotton blue, crystal violet, malachite green and methyl violet by endophytic fungi from metal-contaminated, Sinosenecio oldhamianu, were investigated. Preliminary screening result indicated that SWUSI4, identified as Bjerkandera adusta, demonstrated the best decolorization for the four TPM dyes within 14 days. Furthermore, optimization result demonstrated the decolorization rate could reach above 90% at 24h by live cells of isolate SWUSI4 when 4g biomass was added into 100mL dyes solution with the concentration 50mg L-1 and shaking conditions. Moreover, decolorization mechanism analysis shows that the decolorization was caused by isolate SWUSI4 that mainly including both absorption of biomass and/or degradation of enzymes. Biosorption of dyes was attributed to binding to hydroxyl, amino, phosphoryl alkane, and ester-lipids groups based on fourier transform infrared (FTIR) analyses. The biodegradation potential of SWUSI4 was further suggested by the change of peaks in the Ultraviolet-visible (UV-vis) spectra and detection of manganese peroxidase and lignin peroxidase activities. Finally, the phytotoxicity test confirmed that TPM dyes toxicity of the treatment after by SWUSI4 was significantly lower than that before treatment. These results indicate that an endophytic SWUSI4 could be used as a potential TPM dyes adsorption and degradation agent, thus facilitating the study of the plant-endophyte symbiosis in the bioremediation processes.
Glycopenia-Induced Sympathoadrenal Activation in Diabetes Mellitus And Uncontrolled Arterial Hypertension: An Observational Study.
Authors: Abobarin-Adeagbo Abimbola , Wienke Andreas , Girndt Matthias , Pliquett Rainer U.
Published: June 2020

Background: Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission.Methods: In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous flash glucose monitoring, to 24-hour blood-pressure and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results: 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 hours) than Group-2 patients (0.2 ± 0.3 per 24 hours), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 hours). Plasma norepinephrine and mean arterial blood pressure were not different between Group-1 and Group-3 patients, though higher than in Group-2 patients. At discharge, the daily cumulative insulin dose was reduced in Group-1 (-18.4 ± 24.9 units) and Group-3 patients (-18.6 ± 22.7 units), but remained unchanged in Group-2 patients (-2.9 ± 15.6 units).Conclusions: An association between hypoglycemic events and uncontrolled hypertension was found in this study.
Betaine Inhibits Toll-like Receptor 4 Responses and Restores Intestinal Microbiota in Acute Liver Failure Mice
Authors: Chen Qian , Wang Yao , Jiao Fangzhou , Shi Chunxia , Pei Maohua , Wang Luwen , Gong Zuojiong
Published: June 2020

Background
Previous research has revealed that the gut microbiome has a marked impact on acute liver failure (ALF). Here, we evaluated the impact of betaine on the gut microbiota composition in an ALF animal model. The potential protective effect of betaine by regulating Toll-like receptor 4 (TLR4) responses was explored as well.
Methods
Both mouse and cell experiments included normal, model, and betaine groups. The rat small intestinal cell line IEC-18 was used for in vitro experiments.
Results
Betaine ameliorated the small intestine tissue and IEC-18 cell damage in the model group by reducing the high expression of TLR4, MyD88, TRAF6 and TNF-α. Furthermore, the intestinal permeability in the model group was improved by enhancing the expression of the (ZO)-1 and occludin tight junction proteins. There were 509 operational taxonomic units (OTUs) that were identified in mouse fecal samples, including 156 core microbiome taxa. Betaine significantly improved the microbial communities, depleted the gut microbiota constituents Coriobacteriaceae, Lachnospiraceae, Enterorhabdus and Coriobacteriales and markedly enriched the taxa Bacteroidaceae, Bacteroides, Parabacteroides and Prevotella in the model group.
Conclusion
Betaine effectively improved intestinal injury in ALF by inhibiting the TLR4/MyD88 signaling pathway, improving the intestinal mucosal barrier and maintaining the gut microbiota composition.
Hand grip strength in relation to low back pain and arthralgia in Kurdish men: a cross- sectional study using data from RaNCD cohort study
Authors: Pasdar Yahya , Hamzeh Behrooz , Moradi Shima , Najafi Farid , Moradinazar Mehdi , Shamsi Mohammadbagher , Shakiba Ebrahim
Published: June 2020

Background
Musculoskeletal disorders can reduce quality of life and work capacity. We found better muscle strength can prevent musculoskeletal pain including arthralgia, back, and joint stiffness. This current study was assessed hand grip strength in relation to low back pain and arthralgia in Kurdish men.
Methods
This cross- sectional study was conducted using data from Ravansar non- communicable diseases (RaNCD) cohort study on 2164 men aged 35–65 years. Hand grip strength (HGS) was measured using a hand-held hydraulic hand grip dynamometer. Low back pain, arthralgia, back and joint stiffness were evaluated by the RaNCD cohort study physician using a standard questionnaire.
Results
In current study, 21.39 and 24.58% of studied participants had low back pain and arthralgia. Among the participants with low back pain 14.5% had back stiffness and among the participants with arthralgia 12.8% had joint stiffness. The mean of HGS in participants with arthralgia, back and joint stiffness was significantly less than in participants without these disorders (P < 0.001; P = 0.05; and P = 0.005, respectively). We observed that increasing HGS was associated with lower risk of arthralgia, back and joint stiffness.
Conclusions
Our results highlighted that higher HGS was associated with lower risk of arthralgia, back, and joint stiffness. However, there was not any association between HGS and low back pain. To enhance muscle strength, do exercise and adhere to proper nutrition are suggested to reduce musculoskeletal pain.
Identifying Physician-perceived Barriers to Apragmatictreatment Trial Inrheumatoid Arthritis
Authors: Qu Haiyan , Austin Shamly , Singh Jasvinder
Published: June 2020

Objective: The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a RA pragmatic trial of anti-TNF biologic vs. non-TNF biologic/Janus-Kinase inhibitor initiation after an inadequate response to methotrexate (MTX-IR).Methods: Semi-structured telephone interviews were conducted with 26 rheumatologists in March 2019. An exploratory thematic analysis approach was used to analyze the interview data.Results:Physician perceived patient barriers to the implementation ofa RA pragmatic trial. This theme covers three sub-themes: 1) patients’ personal barriers, 2) patients’ treatment-related factors, and 3) trial-related factors (e.g., patient recruitment, side effects, mode of use, etc.). Physicians perceived clinic barriers interfered with the pragmatic trial enrollment from the clinic or the healthcare system perspective. This theme covered four sub-themes: 1) clinic-related factors, 2) patient-related factors, 3) research personnel, and 4) facilitators (positive factors of the clinic). Conclusions: Our results from the inductive thematic analysis will help researchers understand the key patient and clinic/system factors/barriers that may influence pragmatic RA trial implementation. The themes suggest there are factors that can be modified (e.g., coordinator effort needed, effective patient recruitment during clinic visits, provider engagement) and challenges to overcome (patient insurance status, busy clinic flow, and space issues including limited number of patient rooms). In summary, these themes provide a basis for our and other research teams to develop clinic-centered and patient-centered strategies to implement a pragmatic RA trial.
Prevalence and Measurement of Anxiety and Depression in Nurses During Covid Pandemic in Nepal
Authors: Karki Pramila , Katwal George B. J. , Chandra Ayush , Chandra Avinash
Published: June 2020

BackgroundAnxiety and depression are under reported, underdiagnosed mental illness inhealth worker in Nepal especially during COVID pandemic.The study was carried out as an observational studyon nurses in Nepal. In this study we attempted to assess the incidence and impact of depression and anxietyin nurses who are working upfront in different hospitals during this crisis.ObjectiveThe purpose of the study is to assess the prevalence of anxiety and depression among nurses in Nepal during COVID pandemic who are working in various hospitals.MethodA cross-sectional non-probability purposive sampling with observational analysis was carried out and the sample was collected from nurses working in different hospitals. Prevalence of anxiety and depression was assessed using a structured and validated questionnaire. Anxiety was assessed with theHamilton Anxiety Scale (HAM-A), General Anxiety Disorder Questionnaires (GAD) with a cut-off score for various levels of anxiety while Hamilton Depression Rating Scale (HAM-D)was used to assess depression.ResultThe analysis of these different scales revealed that disabling anxiety prevailed at highest (43.6%) in nursing staff according to HAM-A scale. Moderateanxiety also seemed to be higher (>20%) in GAD questionnaire. ConclusionThis is the first study carried out in Nepal that investigates the mental health of nurses who are working in the frontline in this COVID pandemic situation. The study revealed that our nurses who have given their life in the line are suffering from serious mental health problems.
Associations between bone fractures and post-traumatic stress disorder after the Great East Japan Earthquake in the older adult: a prospective cohort study from the Fukushima Health Management Survey
Authors: Hayashi Fumikazu , Ohira Tetsuya , Nakano Hironori , Nagao Masanori , Okazaki Kanako , Harigane Mayumi , Yasumura Seiji , Maeda Masaharu , Takahashi Atsushi , Yabe Hirooki , Suzuki Yuriko , Kamiya Kenji
Published: June 2020

Background
Bone metabolism is known to be affected by psychological stress, and increased psychological stress could increase fracture risk. The purpose of this study was to clarify the effect of mental health deterioration caused by disaster on fracture risk in the older adult.
Methods
This study analyzed the responses of those who answered the Mental Health and Lifestyle Survey component of the Fukushima Health Management Survey conducted in 2011: a total of 13,768 people aged 65 or more who had no history of fractures at the time of the Great East Japan Earthquake. We were able to track the presence or absence of a fracture until 2016. The analysis included age, sex, physical factors, social factors, psychological factors, and lifestyle factors. A survival analysis was performed on the relationship between each item and the fracture. Then, univariate and multivariate Cox proportional hazard models were constructed to identify fracture risk factors.
Results
A total of 1,687 (12.3%) fractures occurred during the observation period. As a result of univariate and multivariate Cox proportional hazard models, those at high risk of post-traumatic stress disorder (PTSD) (PTSD checklists ≥ 44) (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.01–1.38; P = 0.039), history of cancer (HR: 1.58; 95% CI: 1.28–1.93; P < 0.001), history of stroke (HR: 1.33; 95% CI: 1.08–1.65; P = 0.009), history of heart disease (HR: 1.23; 95% CI: 1.05–1.45; P = 0.012), history of diabetes (HR: 1.21; 95% CI: 1.05–1.39; P = 0.007), and who reported being extremely dissatisfied with sleep or not being able to sleep at all (HR: 1.40; 95% CI: 1.04–1.89; P = 0.025), had a significant increase in fracture risk independent of age and sex.
Conclusions
The results of this study indicate that chronic psychological stress caused by the Great East Japan Earthquake could have contributed to increased fracture risk in the older adult. Therefore, understanding bone mineral density, offering active psychological care to reduce psychosocial stress, and providing sleep guidance are important for preventing fractures in older adult residents, particularly those in evacuation areas.
Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability: A Prospective Study and Updated Meta-Analysis
Authors: Lin Chien-Hen , Chou I-Ching , Hong Syuan-Yu
Published: June 2020

Background
Drug-resistant epilepsy (DRE) affects 7–20% of children with epilepsy. Although some risk factors for DRE have been identified, the results have not been consistent. Moreover, data regarding the risk factors for epilepsy and its seizure outcome in the first 2 years of life are limited.
Methods
We analyzed data for children aged 0–2 years with epilepsy and neurodevelopmental disability (NDD) from January, 2013, through December, 2017. These patients were followed up to compared the risk of DRE in patients with genetic defect (genetic group) with that without genetic defect (nongenetic group). Additionally, we conducted a meta-analysis to identify the pooled prevalence of genetic factors in children with DRE
Results
A total of 96 patients were enrolled. A total of 68 patients were enrolled in the nongenetic group, whereas 28 patients were enrolled in the genetic group. The overall DRE risk in the genetic group was 6.5 times (95% confidence interval [CI], 2.15–19.6; p = 0.03) higher than that in the nongenetic group. Separately, a total of 1308 DRE patients were participated in the meta-analysis. The pooled prevalence of these patients with genetic factors was 22.8% (95% CI 17.4–29.3)
Conclusions
The genetic defect plays a crucial role in the development of DRE in younger children with epilepsy and NDD. The results can serve as a reference for further studies of epilepsy panel design and may also assist in the development of improved treatments and prevention strategies for DRE.
The Prevalence of Frailty in Cancer Patients and Mortality Prediction With a Novel Frailty Index Based Clinical Algorithm-A Multicenter, Prospective, Observational Study
Authors: Jin Xi , Ren Yue , Shao Li , Guo Zengqing , Wang Chang , He Ying , Zhou Lan , Cong Minghua , Ma Hu , Wang Wei , Zhou Chunling , Feng Yongdong , Ba Yi , Gao Jianguo , Lu Miaomiao , Zhang Mengmeng , Gu Xuewei , Song Chunhua , Xu Hongxia , Shi Hanping
Published: June 2020

Purpose To investigate the prediction capacity and status of frailty in Chinese cancer patients in national level, through establishing a novel prediction algorithm. Methods The percentage of frailty in different ages, provinces and tumor type groups of Chinese cancer patients were revealed. The predictioncapacity of frailty on mortality of Chinese cancer patients was analyzed by FI-LAB that is composed of routine laboratory data from accessible blood test and calculated as the ratio of abnormal factors in 22 variables. Establishment of a novel algorithm MCP(mortality of cancer patients)to predict the five-year mortality in Chinese cancer patients was accomplished and its prediction capacity was tested in the training and validation sets using ROC analysis. ResultsWe found that the increased risk of death in cancer patients can be successfully identified through FI-LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5-year follow-up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) were dead while the mean FI-LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0 to 0.73).Frailty (after adjusting for gender, age, and other confounders) could be directly correlated with increased risk of death, with a hazard ratio of 12.67 (95% confidence interval CI: 7.19, 22.31) in comparison with those without frailty. In addition, MCP algorithm presented an area under the ROC (AUC) of 0.691 (95% CI: 0.659-0.684) and 0.648 (95% CI: 0.613-0.684) in the training and validation set, respectively. Conclusion Frailty is common in cancer patients and FI-LAB has high prediction capacity on mortality. The MCP algorithm is a good supplement for frailty evaluation and mortality prediction in cancer patients.
Effects of Traditional Chinese Medicine Combined With Chemotherapy for Extensive-stage Small-cell Lung Cancer Patients on Improving Oncologic Survival: Study Protocol of a Multicenter, Randomized, Single-blind, Placebo-controlled Trial
Authors: Chen Yuyi , Liu Zishen , Yu Mingwei , Zhang Yi , Li Qiwei , Yang Guowang
Published: June 2020

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is characterized by extensive metastases, aggressive progression and poor prognosis. Chemotherapy is applied as a preferred first-line regimen for ES-SCLC, but inadequate for improvingits overall survival. Traditional Chinese medicine (TCM) is widely used in the clinical practice of ES-SCLC for its synergy with chemotherapy. However, there is still no substantial evidence to prove that TCM can effectively improve the long-term efficacy of ES-SCLC patients. The study intends to determine whether theTCM with chemotherapy can improve the overall survival (OS) in treating with ES-SCLC when compared with chemotherapy alone.Method/design:A multicenter, randomized, single-blind, placebo-controlled clinical trial will be conducted to determine whether the TCM granules combined with chemotherapy can improve the OS of ES-SCLC. 270 participants will randomly receive 4-6 cycles (21daysper cycle)of chemotherapy plus TCM granules or placebo. The primary outcome measures is OS. The secondary outcome measures includesprogression-free survival(PFS), objective response rate(ORR), quality of life(QoL) and tumor markers. Visits will be performed at the end of each cycle during the treatment period and then every 3 months in the follow-up period until the patients’ death or study completion.Conclusion:the study’s result will provide a high-level evidence for TCM granules using with chemotherapy on the first-line treatment of ES-SCLC.Trial registration: Chinese Clinical Trial Registry, No. ChiCTR1900022991, registered 6 May 2019 (prospective registration).
Prevalence and Predictors of Diabetes Mellitus Among Persons Living With HIV (PLWH)
Authors: UMAR DAVID MOHAMMED , NAIDOO PANJASARAM
Published: June 2020

Background: Diabetes mellitus is a chronic non-infectious medical condition which is evident by raised levels of glucose in the blood, because the body cannot produce any or enough of the hormone insulin or use insulin effectively. Diabetes, if not well managed leads to complications such as neuropathy, retinopathy, nephropathy which can be fatal. Some of the factors that predisposes to diabetes include older age, higher body mass index, heredity and hypertension. With the availability of HAART for the managing HIV/AIDS infection, life span of persons living with HIV (PLWH) has increased significantly. With increased longevity, the aging population of PLWH also face chronic diseases such as diabetes in addition to HIV. The burden of both HIV and diabetes is high in South Africa, particularly in KwaZulu-Natal. Nevertheless, the prevalence of diabetes among PLWH in KwaZulu-Natal and its predictors is not well understood. Therefore, this study was conducted to determine the prevalence, predictors of diabetes and the outcome of managing diabetes among PLWH.Methods: The study was conducted in four public health care facilities in KwaZulu-Natal after ethical approval and informed consent were obtained. A pretested questionnaire and hospital patient charts were used to collect data. SPSS version was used to analyze the data using descriptive statistics and logistic regression. Results: The prevalence of diabetes among PLWH was 9%. This was higher than the prevalence of diabetes of 5.4% among the general population in South Africa. Just over 47% of those who had diabetes, had uncontrolled blood sugar, with a mean fasting blood sugar (FBS) of 11.7 mmol/L. The predictors of diabetes among PLWH were, male gender and older age. Male PLWH had 65% less chances of having diabetes and those who were between the ages of 18 and 48 years were 88% less probable to have diabetes compared to those who were older than 48 years.Conclusion: Public sector health care facilities in KwaZulu-Natal need to do much more to manage diabetes in PLWH in order to prevent diabetic complications and possible negative impact on the outcome of HIV management.
Heparin-induced thrombocytopenia presenting as splenic hemorrhage following cardiac surgery: a case report
Authors: Ferry Joseph Frank , Youssef Samuel , Wu Pierce , Hegerova Livia
Published: June 2020

Background
Heparin-induced thrombocytopenia with thrombosis (HITT) is a paradoxical prothrombotic complication of anticoagulant therapy. As many as 3% of patients undergoing cardiac surgery develop clinical HIT presenting as thrombocytopenia with or without thrombosis within 5–10 days of heparin exposure. Thrombotic complications associated with HIT carry a mortality rate of 5–10%.
Case presentation:
We report a case of atraumatic splenic hemorrhage due to splenic vein thrombosis as the main indicator of HIT following cardiac surgery in a 62-year-old woman. She presented to the emergency department with acute weakness, dizziness, and malaise. Her evaluation in the emergency department found anemia and thrombocytopenia. A coagulation profile revealed a markedly elevated d-dimer. She underwent a computed tomography scan of the chest, abdomen and pelvis for suspected bleed and was found to have splenic vein thrombosis, right atrial filling defects consistent with atrial thrombus and mild to moderate hemoperitoneum. Surgical consultation was obtained due to splenic hemorrhage. Hematology was consulted on post-operative day 10, however, she unfortunately developed left sided weakness concerning for stroke. A magnetic resonance imaging scan of the brain demonstrated infarct involving distribution of the right anterior cerebral artery. A transesophageal echocardiogram demonstrated a large immobile thrombus within the right atrium with a second, mobile thrombus arising from the left tricuspid valve annulus. Due to a 4Ts score of 7 and markedly positive platelet factor 4 (PF4) IgG antibody a serotonin release assay was not performed given the high probability of HIT. She was cautiously treated with bivalirudin and was transitioned to warfarin anticoagulation. In the following days her platelet count recovered and 3 months later a transthoracic echocardiogram revealed solution of the intracardiac thrombi.
Conclusions
Atraumatic splenic hemorrhage is an unusual presentation of HIT that is reminiscent of the rare bilateral adrenal hemorrhage due to adrenal necrosis that also occurs in HIT. Alternative anticoagulation is the mainstay of therapy for HIT despite hemorrhage, given the underlying acquired hypercoagulability. Despite similarities of the presentation between splenic hemorrhage and bilateral adrenal hemorrhage, splenic hemorrhage is rarely described in the literature. HIT should be considered in patients presenting with thrombocytopenia following cardiac surgery.
Attitude and education needs of emergency doctors in providing palliative and end-of-life care in Hong Kong: A prospective cross-sectional analysis based on self-reported surveys
Authors: Wong Kwun Hang , Yang Marc Li Chuan , Woo Raymond Kam Wing , Wong Oi Fung , Kwong Wing Yan , Tse Choi Fung , Lam Shing Kit , Ma Hin Man , Lit Chau Hung Albert , Shih Yau Ngai
Published: June 2020

Background: With the aging population in Hong Kong, the importance and need of palliative care and end-of-life (EOL) care are brought into the spotlight. The Accident and Emergency Department (AED) is often the first medical contact for the public. The objectives of this study were to evaluate the attitude of emergency doctors in providing palliative and EOL cares in Hong Kong, and to investigate the education needs for emergency doctors in these areas.Methods: A questionnaire study was conducted involving emergency doctors from 6 AEDs in Hong Kong. The questionnaires covered the attitudes of emergency doctors towards the palliative and EOL cares in terms of the role of palliative and EOL care in AED, the specific obstacles in providing such cares, their comfort level with the cares and further education needs The attitudes of emergency doctors from the AEDs with EOL care service were compared with those from the AEDs without such services. Results: One hundred and forty-five emergency doctors completed the questionnaires, in which 60 respondents from the AEDs with EOL care service. Significant proportions from both groups recognized that palliative and EOL cares were an important competence for them, but its role and priority in emergency care were uncertain. Lack of time and access to palliative care specialists/ teams were the major barriers. Participants from AEDs with EOL care service were more comfortable to provide the care and discuss it with patients and relatives. Further education needs identified including management of physical complaints, communication skills and EOL care ethics.Conclusions: The study identified obstacles in promoting palliative and EOL cares in the AEDs in Hong Kong. Education on the communication skills and ethical issues were necessary as well. With the combination of elements of routine AED practice and the basic palliative medicine skill set, it would promote the development of this emerging field in Emergency Medicine in the future.
Risk factors of depression in type 2 diabetes mellitus with lower extremity arterial disease in China
Authors: Chai Sanbao , Zhang Xiaomei , Yuan Ning , Liu Yufang , Xin Sixu , Sun Jianbin , Ji Linong
Published: June 2020

BackgroundWe aimed to evaluate the prevalence and risk factors of depression in type 2 diabetes mellitus with lower extremity arterial disease. Methods: Four hundred and forty-one patients with type 2 diabetes mellitus were recruited from Peking University of International Hospital. All patients completed the Self-rating Depression Scale, which includes 20 items, using a 4-point scale. Univariable and multivariable logistic regression was conducted to investigate risk factors of depression in patients with lower extremity arterial disease. Results: The prevalence of depression in lower extremity arterial disease group was significantly higher than that in non- lower extremity arterial disease group(25% vs 16%, P = 0.018). In lower extremity arterial disease group(n = 215), depression score(46.18 ± 7.38 vs 44.03 ± 6.53, P = 0.003) significantly increased compared with non lower extremity arterial disease group(n = 226). Compared with male depressive patients, the proportion of female depressive patients(38% vs 15%, P = 0.003) was significantly higher in lower extremity arterial disease group. The depression score of female depressive patients(57.83 ± 3.29 vs 55.26 ± 1.59, P = 0.003) was significantly higher than that of male depressive patients. An increased risk of depression in female patients(crude OR: 2.50, 95% CI: 1.38–4.54, P = 0.003; adjusted OR: 2.34, 95% CI: 1.26–4.36, P = 0.008) and in patients with low body mass index(crude OR: 0.88, 95% CI: 0.80–0.96, P = 0.005; adjusted OR: 0.89, 95% CI: 0.81–0.97, P = 0.011) was detected. Conclusion: Both low body mass index and female are risk factors for depression.
Histone Methyltransferase WHSC1 Inhibits Colorectal Cancer Cell Apoptosis via Targeting Anti-apoptotic BCL2
Authors: Wang Yu , Tang Xin , Guo Mei , Sun Gang , Zhou Kun , Pang Wenjing , Hou Yichao , Hou Lidan , Zhu Liming , Cao Dachun , Meng Xiangjun
Published: June 2020

Background: WHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. Colorectal cancer (CRC) is the 4th deadliest and 3rd most frequent cancer globally. However, the role of WHSC1 in CRC progression remains unknown.Methods: qRT-PCR, immunoblotting assays (WB), and immunohistochemistry (IHC) staining was performed to investigate WHSC1 expression levels in CRC tissues and normal tissues. CCK-8 assays, colony formation assays, and flow cytometry were also used to assess the effect of WHSC1 depletion in CRC cell proliferation, apoptosis and oxaliplatin sensitivity in vitro. A cell line-derived xenograft model in nude mice was performed to determine the role of WHSC1 in CRC cell apoptosis in vivo.Results: WHSC1 as well as H3K36me2 were highly expressed in clinical CRC tissues compared with in normal counterparts. High WHSC1 expression was correlated with poorer prognosis in CRC patients. Knockdown of WHSC1 significantly promoted CRC cell apoptosis and inhibited tumour growth in vivo. Further mechanistic investigation revealed that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level, so BCL2 expression is markedly decreased after WHSC1 depletion.Conclusions: Our findings demonstrated that knockdown of WHSC1 promoted colon cancer cell apoptosis and suppressed CRC tumorigenesis through targeting BCL2 transcription, suggesting WHSC1 activity may be a potential therapeutic target for the treatment of CRC.
Gene Expression Patterns Associated With Tumor-Infiltrating CD4+ and CD8+ T Cells In Invasive Breast Carcinomas
Authors: Wang Zhanwei , Xu Jiamin , Yang Xi , Pan Yuefen , Shen Junjun , Liu Jin , Han Shuwen
Published: June 2020

Objective This study investigated the gene expression patterns associated with tumor-infiltrating CD4 + and CD8 + T cells in invasive breast carcinomas.Methods The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4 + and CD8 + T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4 + T cell-related genes and 78 CD8 + T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4 + T cell-related genes, the chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8 + T cell-related genes.Conclusions The chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4 + and CD8 + T cell infiltration, respectively, in BRCA.
Sustained Effects on Lung Function in Community Members Following Exposure to Hazardous PM2.5 Levels from Wildfire Smoke
Authors: Orr Ava , Migliaccio Cristi A.L. , Buford Mary , Dykstra Sarah , Migliaccio Christopher
Published: June 2020

Background: Extreme wildfire events are becoming more common and while the immediate risks to susceptible populations (i.e. elderly, asthmatics) are appreciated, the long-term health effects are not known. Historically, wildfire smoke exposure studies have consisted almost exclusively of retroactive health reports, including emergency department visits, hospital admissions, provider visits with emphasis on specific ICD codes. In 2017, the Seeley Lake, MT area experienced unprecedented levels of wildfire smoke from July 31 to September 18, with a daily average of 220.9 mg/m3. The aim of this study was to provide health assessments in the community as temporally close to the fires as possible and evaluate potential adverse health effects with multiple visits over two years. Additionally, the members of the community of Thompson Falls, MT were evaluated in 2018 as a comparison, due to their Northern Rockies location and 5-fold less smoke exposure during the same time period.Methods: Using the IPHARM (Improving Health Among Rural Montanans) infrastructure and experience to perform mobile health screenings, the Seeley Lake community was visited following the fires. The study resulted in the recruitment of a cohort (n=95, average age: 63 years), for a rapid response screening activity shortly following the wildland fire event, and two follow-up visits in 2018 and 2019. Results: The community experienced 35 of 49 days with >150 mg/m3 of PM2.5 which fell within the range of the Environmental Protection Agency designation of “very unhealthy”. Analysis of spirometry data found a significant decrease in lung function (FEV1/FVC ratio: forced expiratory volume in first second/forced vital capacity) and a more than doubling of participants that fell below the lower limit of normal (13.2% in 2017 to 41.7% in 2018) one year following the wildfire event, and remained decreased two years (35.9%) post exposure. In addition, observed FEV1 was significantly lower than predicted values. Conclusion: These findings suggest that wildfire smoke can have long-lasting effects on human health. As wildfires continue to increase both here and globally, understanding the health implications is vital to understanding the respiratory impacts of these events as well as developing public health strategies to mitigate the effects.
Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients: A Prospective, Multicenter Clinical Trial Protocol
Authors: Chang Xiao , Deng Lei , Ni Wenjie , Li Chen , Han Weiming , Gao Linrui , Wang Shijia , Zhou Zongmei , Chen Dongfu , Feng Qinfu , Liang Jun , Bi Nan , Lv Jima , Gao Shugeng , Mao Yousheng , Xue Qi , Xiao Zefen
Published: June 2020

Background: Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell carcinoma (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety.Methods: Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established.Discussion: This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. Trial registration: ClinicalTrials.gov, NCT03731442, Registered 12 Octomber2018, https://clinicaltrials.gov/NCT03731442
Different Effects of Metabolic Syndrome on Dementia According to Dementia Type: Analysis Based on the National Health Insurance Service Database of Gangwon Province in South Korea
Authors: KIM YEO JIN , Kim Sang Mi , Jeong Dae Hyun , Lee Sang-Kyu , Ahn Moo-Eob , Ryu Ohk-Hyun
Published: June 2020

BackgroundMetabolic syndrome is a cluster of conditions that occur together, increasing the risk of cardiovascular disease. However, the relationshipbetween metabolic syndrome and dementia has remained controversial. Using nationwide population cohort data, we investigated the associationbetween metabolic syndrome and dementia,according to the dementia type.MethodsWe analyzed data of 84,144 individuals,in the aged group of more than 60 years,between January 1, 2009,to December 31, 2009, at Gangwon province by using the information of the(Korean) National Health Insurance Service. After eight years of gap, in 2017, we investigated the relationship between metabolic syndrome and dementia. We classified Dementia either as dementia of the Alzheimer type (AD) or vascular dementia (VD). AD and VD were defined according to criteria in the International Classification of Disease, Tenth Revision, Clinical Modification codes.ResultsMetabolic syndrome was associated with AD, while it was not associated with VD. All five components of metabolic syndrome were associated with AD, independently. However, among components of metabolic syndrome, only the high glucose level was associated with VD. Body Mass Index (BMI), fasting glucose and smoking were also associated with AD. A history of the previous stroke was associated with both AD and VD.ConclusionsMetabolic syndrome was associated with AD, while was not associated with VD. VD was associated only with several risk factors that could affect the vascular state rather than a metabolic syndrome. We suggested that the effect of metabolic syndrome on dementia would be different depending on the type of dementia.