bluuebunny/crossref_metadata_2025 huggingface dataset:
TGFβ1: an Indicator for Tumor Immune Microenvironment (TIME) of Colon Cancer from a Comprehensive Analysis of TCGA
Authors: Wang Jinyan , Wang Jinqiu , Gu Quan , Yang Yan , Ma Yajun , Zhang Quan’an
Published: September 2020

Background: Tumor microenvironment (TME) and tumor-infiltrating immune cells (TIC) greatly participated in the genesis and development of colon cancer (CC). However, there are few researches exploring the dynamic modulation of TME. Methods: In our study, we analyzed the proportion of immune/stromal component and TIC in TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithm. Correlation analysis was carried out to evaluate the association between immune/stromal component in TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, protein–protein interaction (PPI) network construction and COX regression analysis. Transforming growth factor β1 (TGFβ1) was finally overlapping from the above analysis. Furthermore, TGFβ1 was analyzed by paired analysis, Gene Set Enrichment Analysis (GSEA). The intersection between the difference analysis and correlation analysis was also conducted to learn the association between TGFβ1 and TICs.Results: Our result showed that immune component in TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1110 DEGs obtained from difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicted that TGFβ1 was significantly associated with the communication of genes in PPI network and the Hazard Ratio (HR) of CC patients’ survival. In addition, TGFβ1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in TGFβ1 up-regulated group were primarily enriched in immune-related activities and the function of TGFβ1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory (Tregs). Conclusions: The expression of TGFβ1 might be an indicator for tumor immune microenvironment (TIME) of CC and sever as a prognostic factor of CC. Drugs targeting TGFβ1 might be a potential immunotherapy for CC patients in the future.
Establishment and Assessment of a Nomogram for Predicting Blood Transfusion Risk in Posterior Lumbar Spinal Fusion
Authors: Wang Haosheng , Wang Kai , Lv Bin , Xu Haotian , Jiang Weibo , Zhao Jianwu , Dong Rongpeng , Kang Mingyang , Qu Yang
Published: September 2020

Background: The aim of this study was to determine the risk factors and develop a nomogram for blood transfusions after posterior lumbar spinal fusion (PSL).Methods: We conducted a retrospective, single-center study based on 885 patients receiving lumbar PSL, and data was obtained from May 2015 to September 2019. Multivariable logistic regression analysis was conducted to identified risk factors for blood transfusion, and a nomogram was constructed to individually evaluate the risk of blood transfusion. Discrimination, calibration, and clinical usefulness were validated by the receiver operating characteristics (ROC), C-index, calibration plot, and decision curve analysis, respectively. Bootstrapping validation was performed to assess the performance of the model.Results: Of 885 patients, 885 were enrolled in the final study population and 289 receive blood transfusion. Statistical analyses showed the low preoperative hemoglobin (Hb), longer time to surgery, operative time, levels of fusion>1, longer surgery duration, and higher total intraoperative blood loss (IBL) were the risk factors for transfusion. The C-index was 0.898 (95% CI: 0.847–0.949) in this dataset and 0.895 in bootstrapping validation, respectively. Calibration curve showed satisfied discrimination and calibration of the nomogram. Decision curve analysis (DCA) shown that the nomogram was clinical utility.Conclusions: In summary, we investigated the relationship between the blood transfusion requirement and predictors: levels of fusion, operative time, time to surgery, total intraoperative EBL, and preoperative Hb level. Our nomogram with a robust performance in the assessment of risk of transfusion, which can contribute clinicians making clinical decision. However, external validation is still needed in the further.
What Discontinued Trials Teach us About Trial Registration?
Authors: Vellinga Akke , Lambe Kathryn , O'Connor Paul , O'Dea Angela
Published: September 2020

ObjectiveTrial registries were set up to improve transparency, remove duplication, improve awareness and avoid waste. Many trials never reach the point of patient enrolment due to a myriad of reasons. The aim of this study was to investigate the reasons for and characteristics of discontinuation of trials.ResultsA total of 163 discontinued trials were identified and compared to completed trials. A Survey was designed to further explore the nature and conduct of the trial.No differences in registered and categorised information was observed between discontinued and completed trials. Most trials discontinue due to patient or participant recruitment issues, often related to funding. Substantial changes to procedures or the protocol or changes to recruitment strategy were also commonly cited reasons.Survey information was available for 21 discontinued and 28 completed trials and no obvious differences could be identified.Our findings highlight the underlying problem of lack of detail, suboptimal recording, dated information and incomplete reporting of trials within a trial registry which hampers sharing and learning. To date, important progress has been made by the implementation of standards and the requirement of trials to be registered. Our review identifies areas where further improvements can be made.
Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER TBI Study
Authors: Birg Tatiana , Ortolano Fabrizio , Wiegers Eveline J.A. , Smielewski Peter , Savchenko Yan , Ianosi Bogdan Andrei , Helbok Raimund , Rossi Sandra , Carbonara Marco , Zoerle Tommaso , Stocchetti Nino
Published: September 2020

BackgroundAfter Traumatic Brain Injury (TBI) fever is frequent. Brain temperature, which is directly linked to body temperature, may influence brain physiology. Increased body and/or brain temperature may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and outcome. MethodsCENTER-TBI, a prospective, multicenter, longitudinal study on TBI in Europe and Israel, includes a high resolution (HR) cohort of patients with data sampled at high-frequency (from 100 Hz to 500 Hz). In this study, simultaneous BT, ICP and CPP recordings were investigated. A mixed effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes of ICP and CPP during the episodes of BT changes (delta BT ≥0.5 °C, lasting from 15 minutes to 3 hours) up or down-wards. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test. Results Twenty-one patients with 2435 hours of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38° and experienced at least one episode of ICP above 20 mmHg. The linear mixed effects model revealed an association between BT above 37.5°C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n=79) ICP increased while CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n=70). All these changes were of moderate clinical relevance, even if statistically significant (p<0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.ConclusionPatients after TBI usually develop BT> 38° soon after the injury. Brain temperature may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5°C and a higher ICP was identified. The relationship between BT, ICP and CPP become clearer during rapid temperature changes.Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on July 29, 2014
Acceptability of Physician Associate Interns in Primary Care: Results from a Service Evaluation
Authors: Cottrell Elizabeth , Silverwood Victoria , Strivens-Joyce Alex , Minshull Lucy , Edwards John J , Lawton Sarah , Aiello Matt , Turner Sharon
Published: September 2020

Background: Physician associates (PA) form part of the policy-driven response to increased primary care demand and a general practitioner recruitment and retention crisis. However, they are novel to the primary care workforce, have limitations such as being unable to prescribe and order ionising radiation investigations, and there are very limited directly-relevant data to guide the integration of PAs into primary care. To address this, a novel internship scheme was established in Staffordshire to support PAs entering primary care. This evaluation was designed to establish the acceptability of Physician Associate (PA) Interns within primary care.Methods: The Staffordshire PA Internship (SPAI) scheme was introduced in Staffordshire in 2017. PAs were concurrently working in primary and secondary care posts for one year, with protected weekly education sessions to equip them for work in primary care. Within the nine primary care practices hosting 10 PA interns in the first two cohorts, the PA interns, supervising GPs and practice managers, and patients who attended an appointment with a PA intern were invited to participate in the evaluation.Results: By evaluation end, eight of the ten PAs had completed the internship. Overall PA interns were acceptable to practices and patients, however there was ambiguity about the PA role itself, and how best to communicate this, as well as how to operationalise their roles. An expectation-preparedness gap was identified for PAs working in primary care. This resulted in high levels of supervision required for PA interns early within the internship. The internship provided a platform upon which the expectation-preparedness gap could be closed and made the high supervision requirements more acceptable to practices.Conclusions: This test-of-concept SPAI has highlighted that, to ensure successful integration of new PAs into primary care and to support them to reach their full potential, commitments to longer-term, sustainable, cohesive and appropriately funded schemes, including structured and standardised education and supervision, need to be delivered. Without such investment, there is a risk that acceptability of PAs in primary care, and PAs’ views of primary care careers, will be undermined before the profession has attained its full potential.
Comprehensive Home Palliative Care Could Reduce Emergency Department Visits Due to Psychologic Dyspnea Among Cancer Patients: A Retrospective Cohort Study
Authors: Hsu Hua-Shui , Wu Tai-Hsien , Lin Chin-Yu , Lin Ching-Chun , Chen Tsung-Po , Lin Wen-Yuan
Published: September 2020

Objective Dyspnea symptom is a common trigger of emergency department among the terminal illness and cancer patients. The frequent emergency department (ED) visits at the end of life are the indicator of poor-quality care. We examine the emergency department visits rate due to dyspnea symptom among the palliative patients by enhanced home palliative care.MethodsIn our home palliative care team, patients are managed by palliative care specialists, residents, home care nurses, social workers, and chaplains. We enhanced the weekly home palliative care visit time from 5 days a week to 7 days a week, one to two times visit per week based on patient’s need, to devise team-based medical services and formulate standard operating procedures for dyspnea care.ResultsOur team cared for a total of 762 patients with 512 ED visits, and 178 ED visits because of dyspnea (mean ± SD age, 70.4 ± 13.0 years; 49.4% male). Dyspnea (27.8%) was the most common reason recorded for ED visit, followed by pain (19.0%), GI symptoms (15.7%), and fever (15.3%). The analysis of unexposed versus exposed groups revealed that the proportion of non-family workers (42.9% vs.19.4%) and family members (57.1% vs. 80.6%) acting as caregivers significantly changed than basic (P <0.05). Compared with ED visits of unexposed group, the risks evidently decreased 30.7% in exposed group (P <0.05). Conclusion This study proves that comprehensive home palliative care with add two days per week and formulate standard operating procedures for dyspnea could significantly reduce ED visits rate because of controllable dyspnea in the last six months of life.
Analysis of ADAM9 Regulation and Function in Vestibular Schwannoma Primary Cells
Authors: Nattmann Anja , Breun Maria , Monoranu Camelia , Matthies Cordula , Ernestus Ralf-Ingo , Löhr Mario , Hagemann Carsten
Published: September 2020

Objective: Recently, we described a disintegrin and metalloproteinase 9 (ADAM9) overexpression by Schwann cells of vestibular schwannoma (VS) and suggested that it might be a marker for VS tumor growth and invasiveness. This research note provides additional data utilizing a small cohort of VS primary cultures and tissue samples. We examined whether reconstitution of Merlin expression in VS cells regulates ADAM9 protein expression and performed lentiviral ADAM9 knock down to investigate possible effects on VS cells numbers. Moreover, the co-localization of ADAM9 and Integrins α6 and α2β1, respectively, was examined by immunofluorescence double staining.Results: ADAM9 expression was confirmed in VS but not regulated by Merlin. However, ADAM9 knock down led to significant 2.38 fold reduced cell numbers in VS primary cell cultures (p<0.001). While ADAM9 and Integrin α2β1 were co-localized in only 22% (2 of 9) of VS, ADAM9 and Integrin α6 were co-localized in 91% (10 of 11) of VS. Therefore, we provide first observations on possible regulatory functions of ADAM9 expression in VS.
Risk Assessment for Cardiac Arrest : A Deep Learning Approach With Channel Selection
Authors: Yılmaz Atınç
Published: September 2020

Background: Risk of developing cardiovascular diseases, in the world, is increasing day by day. Accordingly, the number of deaths due to heart attacks is quite remarkable. Early risk assessment and diagnosis of heart disease are vital to prevent heart attacks by providing effective treatment planning and evaluation of outcomes. When a patient with high risk of heart attack is not treated correctly, chances of survival may reduce dramatically. For this reason, artificial intelligence-assisted systems can support the decision of doctors and it can anticipate risk without fatal consequences.Methods: In this study, individuals who has heart attack risks are predicted by using a proposed CNNs method. A set of medical data from patients with heart attacks and healthy individuals are provided from the UCI database. Reinforced deep learning and ANFIS architectures are also applied to the same problem in order to compare the results and put forth the efficiency of proposed method. In addition, ROC analysis and measurements of processing times for the applied methods were performed to reveal the performance, accuracy and efficiency of the study.Results: The proposed CNNs method and other methods are tested and evaluated. The accuracy performance of the methods were 94.34% for the proposed CNNs method, 91.58% for the ANFIS, and 92.66% for the deep multilayer neural network. Highest accuracy has been obtained by using the proposed CNNs method, which is 94.34%. The reasons why the proposed CNNs method is better than other methods is the use of channel selection layer, the number of convolution and pooling layers, the filter size used in these layers, and the functions used in the loss and activation layers.Conclusions: In the study, the channel selection formula is introduced in the proposed CNNs model to select the most discriminatory feature filters. Besides, the applicability of proposed CNNs method with images obtained from numerical data has been demonstrated. With the early prediction system proposed, it is now possible to take precautionary measures against possible cardiac arrest. In this study; a new method based on CNNs is proposed for early detection of possible heart attack, which is a great risk for human life. Different from studies in the literature, the channel selection formula is presented in the proposed CNNs method to select the most selective feature filters. Besides differently, it was used in the proposed CNNs method by converting all numerical data from dataset into 2D images. Afterwards, to show whether this the proposed method is applicable or not, the dataset which is numerical form was applied to other methods and compared.
Recreational opium use as a risk factor for coronary artery disease: results from the premature coronary artery disease Milano-Iran (MIran) study
Authors: Maino Alberto , Sadeghian Saeed , Mancini Ilaria , Abbasi Seyed Hesameddin , Poorhosseini Hamidreza , Boroumand Mohammad Ali , Lotfi-Tokaldany Masoumeh , Jalali Arash , Pagliari Maria Teresa , Rosendaal Frits , Peyvandi Flora
Published: September 2020

The spreading of recreational opium use pose new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between opium use and CAD. We set up a case-control analysis, i.e., the premature CAD Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2009 and 2012. Incident cases with CAD were contrasted with controls for recreational opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4–6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9–31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that recreational opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.
Dose All of the Coronary Fistulas been Created by the Reopening Wire After Successful Revascularization of Chronic Total Occlusion?
Authors: Fan Rong , Tan Haipeng , Song Yanan , Yao Wang , Yang Yawei , Wu Feng , Liu Haoqi , Feng Can , Fan Min , Huang Zheyong , Ge Junbo
Published: September 2020

Background: Coronary fistulas may be congenital or acquired generally as consequence of coronary interventions, mainly chronic total occlusion (CTO) reopening. When the reopening wire passes through the occlusion it may microperforate the advential vascular layers, favoring the fistulous communication between coronary vessel and cardiac chambers. But some of acquired coronary fistulas (ACFs) had been already present at the CTO vessels and would been seen after revascularization. This study was designed to investigate the characteristics of ACFs, which albeit mostly benign can cause concern and unnecessary treatment post successful CTO percutaneous coronary intervention (PCI).Methods: Data, including clinical and procedural characteristics, medical history, and findings in electrocardiography, echocardiography and coronary angiography, from 2169 consecutive patients undergoing CTO PCI between January 2018 and December 2019 were analyzed retrospectively. Results: 1844 (85.0%) underwent successful CTO PCI with complete revascularization. Among them, there were 49 cases (mean age, 62.80 ± 11.24 years; 40 men) of ACFs: 24 (49%) involved the right coronary artery, 19 (38.8%) the left anterior descending artery, and 6 (12.2%) the circumflex branch; and 38 (77.6%) were coupled with multiple fistulas (>3), and 29 (59.2%) affected multiple branches of the CTO vessel (>3). The majority of patients with ACFs had a history of MI or Q-wave (n=34, 69.4%), and angina was the most common complaint (n=41, 83.7%). None of them had pericardial effusion, tamponade and Hemodynamic abnormalities before or after PCI.Conclusion: ACFs after successful CTO PCI mostly developed in patients with MI history, originated from the right coronary artery or left anterior descending artery, and involved multiple fistulas and CTO vessel branches.
The Effect of Nanosecond Pulsed Electric Field on Hepatic Veins—A Mid-Term Investigation
Authors: Dong Yeping , Lu Jiahua , Huang Zhiliang , Chen Xinhua , Ren Zhigang , Hong Liangjie , Wang Haiyu , Yang Dezhi , Xie Haiyang , Zhang Wu
Published: September 2020

Background: Nanosecond pulsed electric field (nsPEF) is a novel ablative technique for treating tumours of the liver, kidneys, and other organs. This study investigated the effect of nsPEF on hepatic veins of different diameters and evaluated the feasibility and safety of using nsPEF to ablate tissues in porcine livers.Methods: A total of 15 pigs were included in the study. B-mode ultrasonography was used to guide two-needle nsPEF electrodes inserted adjacent to the left, middle, and right hepatic veins. The animals were followed up at 1 hour and at 1, 3, 7, and 14 days post treatment. Results: During and after the procedure of nsPEF treatment, electrocardiographs (ECGs) detected no cardiovascular events, and B-mode ultrasonography found no hepatic venous thrombosis formation. Follow-up at 1 hour to 7 days post treatment revealed complete ablation of the perivascular tissue within the ablated area. There was no apparent structural damage to the hepatic veins of different diameters, but there appeared to be red blood cells and residual inflammatory cell infiltration in the subendothelial layer from 1 hour to 7 days post treatment. Follow-up blood biochemical tests showed transient damage to the liver and myocardial function, and immediate recovery, which is consistent with the pathological changes.Conclusion: NsPEF achieved complete liver tissue ablation while causing little damage to the hepatic veins. Thus, nsPEF could be used to ablate central tumour lesions that are located nearing the major hepatic veins, thereby avoiding some of the limitations of conventional surgical therapies and thermal ablations.
Renal Replacement Therapy for Burn Patients: A Systematic Review and Meta-Analysis
Authors: Duan ZhiYu , Chen FengKun , Cai GuangYan , Li JiJun , Chen XiangMei
Published: September 2020

Background: To improve the prognosis of burn patients with renal replacement therapy (RRT), we performed this systematic review and meta-analysis.Methods: We searched multiple databases for studies published before February 2020. Studies about adult populations with burn injury, providing epidemiologic data on prevalence or mortality of RRT, were included. Results: A total of selected 58 studies, including 38,787 patients were enrolled in our analysis. The prevalence rates of RRT were 5.14% (95%CI 4.54%-5.74%) in all burn patients and 35.8% (95%CI 29.54%-42.07%) in acute kidney injury (AKI) patients. The prevalence of RRT among burn patients in the intensive care unit (ICU) was 10.92% (95%CI 8.71%-13.14%). The mortality of all burn patients with RRT was 65.52% (95%CI 58.41%-72.64%). The mortality of patients with RRT in ICU was 62.7% (95%CI 53.7%-71.7%). The mortality rate of RRT patients was 30.33% (95%CI 22.06%-38.59%) of the total. There was no significant correlation (r=-0.224, P=0.159) between the year of publication and the mortality of burn patients with RRT. Neither cohort studies nor RCT studies of subgroup analyses show that RRT could reduce the risk of death in burn patients with AKI. Bleeding (10.92%) and secondary infection (9.61%) were the most common RRT-related adverse reactions. Compared with heparin, regional citrate anticoagulation has advantages in superior filter life spans and fewer bleeding episodes. Dialysis-requiring AKI in burn patients could increases the risk of chronic kidney disease progression and end-stage renal disease. About 35% of RRT patients need to maintain hemodialysis temporarily, even if they survive and leave hospital. Conclusions: The prevalence of RRT is not low; approximately, one-third of burn patients with AKI need RRT. The mortality of burn patients with RRT is very high and accounts for 1/3 of the total deaths. There is no evidence that RRT can improve the prognosis of burn patients with AKI. Regional citrate anticoagulation has some advantages in reducing bleeding and extending filter life spans, which may be more suitable for severe burn patients with CRRT.
Risk Factors For COVID-19 Positivity in Hospitalized Patients in A Low Prevalence Setting
Authors: Zohar Iris , Schwartz Orna , David Debby Ben , Mashavi Margarita , Aboulil Mohamad , Yossepowitch Orit , David Shirley Shapiro Ben , Maor‬‏ ‪Yasmin
Published: September 2020

Background: Identifying hospitalized patients with Coronavirus disease 2019 (COVID-19) in a low prevalence setting is challenging. We aimed to identify differences between COVID-19 positive and negative patients. Methods: Hospitalized patients with respiratory illness, or fever, were isolated in the emergency room and tested for COVID-19. Patients with a negative PCR and low probability for COVID-19 were taken out of isolation. Patients with a higher probability for COVID-19 remained in isolation during hospitalization and were retested after 48 hours. Risk factors for COVID-19 were assessed using logistic regression. Results: 254 patients were included, 37 COVID-19-positive (14.6%) and 217 COVID-19-negative (85.4%). Median age was 76 years, 52% were males. In a multivariate regression model, variables significantly associated with COVID-19 positivity were exposure to a confirmed COVID-19 case, length of symptoms before testing, bilateral and peripheral infiltrates in chest X-ray, neutrophil count within the normal range, and elevated LDH. In an analysis including only patients with pneumonia (N=78, 18 positive for COVID-19), only bilateral and peripheral infiltrates, normal neutrophil count and elevated LDH were associated with COVID-19 positivity. Conclusions: The clinical presentation of COVID-19 positive and negative patients is similar, but radiographic and laboratory features may help to identify COVID-19 positive patients and to initiate quick decisions regarding isolation.
Parathyroid Carcinoma with Sarcomatoid Differentiation: A Case Report and Literature review
Authors: Hu Liang , Xie Xiaojun
Published: September 2020

BackgroundParathyroid carcinoma (PC) is a rare thyroid tumor. PC with sarcomatoid differentiation(PCSD) is even rarer and its exact etiology remains unclear. We here report a case of PCSD, and present the clinicopathological features and pathological diagnosis and review the literature. Case presentationA 71-year-old man presented with a mass of 4.5 cm × 3.5 cm in the right neck. The tumor was composed of nest-like transparent cells, and the septum had heterotypic rhabdoid cells with sarcomatoid differentiation. Immunophenotype was as follows: MyoD1, myogenin and desmin were positive; clear cells were positive for CGA, Syn and GATA-3; and Ki-67 proliferation index was 40%. Hematoxylin and eosin staining and immunohistochemistry were performed. The patient was diagnosed with PCSD, and died 6 months after surgery.ConclusionsPCSD is a rare type of primary parathyroid tumor with high malignancy and poor prognosis. Definitive diagnosis should be based on histopathological morphology and immunophenotype, and surgical treatment should be performed as soon as possible.
Chronic Mental Health Impacts of Climate Change Extremes: A Case Study of the Largest Californian Wild Fire
Authors: Silveira Sarita , Kornbluh Mariah , Withers Mathew C. , Grennan Gillian , Ramanathan Veerabhadran , Mishra Jyoti
Published: September 2020

Background. Weather-related disasters such as droughts and fires as accelerated by climate change have led to substantial growth in interest in impacted health outcomes. While physical health outcomes have been studied in this context, our understanding of climate change impacted mental health is at its infancy. This study focuses on the mental health impacts of the largest Californian wildfire to-date, the Camp Fire of 2018.Methods. We investigated a sample of 780 Californian residents with different degrees of disaster exposure, and measured mental health using clinically valid scales for post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD); data were collected six months post-exposure to understand sustained chronic impacts. Data were modeled using multiple-regression analyses. Additionally, we included vulnerability and resilience factors in hierarchical regression analyses.Results. Our primary finding is that direct exposure to large scale fires significantly increased the risk for all three mental health disorders, PTSD, MDD and GAD. Indirect exposure, for those who witnessed but did not personally experience the fires, increased the risk for MDD and GAD. Inclusion of vulnerability and resilience factors led to significantly improved prediction of all mental health outcomes. Low socio-economic status, childhood trauma and sleep disturbances were identified as vulnerability factors, while self-reported resilience had a positive effect on mental health. Mindfulness was associated with lower MDD and GAD symptom scores.Conclusion. Overall, our study demonstrates that climate-related extremes such as fires severely impact long-term mental wellbeing. Additionally, pre-existing adverse life events, resilient personality traits and lifestyle factors play an important role in the development of psychopathology after such disasters. Unchecked climate changes of magnitude projected for the latter half of this century risk severely impacting the mental wellbeing of the global population.
Relationship Among Atrial Fibrillation, CHADS2 Score and Ischaemic Stroke in Patients With Coronary Artery Disease: A Propensity Score Matching Study
Authors: Shi Boqun , Liu Demin , Wang Qian , Geng Xue , Hou Qian , Gu Guoqiang , Xie Ruiqin , Cui Wei
Published: September 2020

Objective: The purpose of this study was to investigate the relationship among atrial fibrillation (AF), CHADS2 score and ischaemic stroke in patients with coronary artery disease.Methods: A total of 2335 patients with coronary artery disease were included. They were divided into a nonischaemic stroke group (n=1997) and an ischaemic stroke group (n=388). Propensity score matching (PSM) was used to match ischaemic stroke patients with nonischaemic stroke patients in a 1:4 ratio. The relationship between AF, CHADS2 score and ischaemic stroke was evaluated using a univariate generalized linear model in different age, body mass index, and coronary artery disease subgroups. Univariate and multivariate generalized linear models were used to evaluate the relationship between AF and ischaemic stroke in different models.Results: Compared with the nonischaemic stroke group, the rate of AF (8.81% vs. 14.20%, P=0.002) in the ischaemic stroke group was higher. The proportion of patients with ischaemic stroke was significantly different between the AF group and the non-AF group (19.04% vs. 28.74%, P=0.003). With increasing CHADS2 score, the incidence of AF gradually increased (P for trend <0.001). With increasing AF burden, the rate of ischaemic stroke increased continuously (P for trend <0.001). Subgroup analysis showed that the trend towards increased stroke risk in the AF group was consistent across the various subgroups. Multivariate analysis demonstrated that paroxysmal and nonparoxysmal AF were not associated with ischaemic stroke compared with the absence of AF.Conclusion: After adjusting for confounding factors, the correlation between AF and ischaemic stroke decreased. Atherosclerotic factors may play an important role in ischaemic stroke in patients with coronary heart disease.
Enhanced Cell Survival and Therapeutic Benefits of IL-10-expressing Multipotent Mesenchymal Stromal Cells for Muscular Dystrophy
Authors: Kasahara Yuko Nitahara , Kuraoka Mutsuki , Oda Yuki , Kinoh Hiromi Hayashita , Takeda Shin’ichi , Okada Takashi
Published: September 2020

Background: Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and are immunosuppressive. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the IL-10 based on anti-inflammatory properties and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.Methods: We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of using AAV/IL-10 vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. The systemic treatment of IL-10-MSCs derived from dental pulp (DPSCs) was comprehensive analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ ), which has a severe phenotype similar to DMD patient. Results: In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hind-limb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into CXMDJ model resulted in long-term engraftment of cells, slightly increased serum levels of IL-10.IL-10-hDPSCs showed remarkably reduced the expression of pro-inflammatory MCP-1 and IL-6, and upregulated stromal-derived factor-1 (SDF-1). In fact, MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability, and recovery in tetanic force with concomitantincrease in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in the IL-10-hDPSC-treated CXMDJ . Conclusions: In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscleand also protected muscles with physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy, through the beneficialIL-10 paracrine effects and may exert SDF-1.
CircNFIX promotes progression of pituitary adenoma via CCNB1 by sponging miR-34a -5p
Authors: Cheng Jianhua , Nie Ding , Li Bin , Gui SongBai , Li ChuZhong , Zhang YaZhuo , Zhao Peng
Published: September 2020

Background: Previous studies have shown that CCNB1 affects the invasiveness of pituitary adenomas, and it is of great significance to find the upstream mechanism of regulating CCNB1.Methods: RT-qPCR was used to measure the expression of circNFIX and miR-34a-5p in pituitary adenoma tissues. Western blotting was used to detect the expression of CCNB1 in pituitary adenomas. The relationship between circNFIX and miR-34a-5p was determined using dual-luciferase reporter assays. Pituitary adenoma cell invasion, migration and proliferation were analyzed using transwell, colony formation and CCK-8 assays, respectively. Additionally, xenograft experiments were performed to determine the effect of circNFIX silencing on tumor growth. Results: In pituitary adenoma tissues, the expression of circNFIX (has-circ_0005660) and CCNB1 were upregulated, while miR-34a-5p expression was downregulated. The silencing of circNFIX or overexpression of miR-34a-5p inhibited cell invasion, migration and proliferation. Inhibition of miR-34a-5p expression reversed the inhibitory effect of circNFIX silencing on the progression of pituitary adenoma. Conclusions: CircNFIX affects cell invasion, migration, and proliferation in pituitary adenomas by sponging miR-34a-5p through CCNB1. Therefore, circNFIX is expected to serve as a potential target for the treatment of pituitary adenomas.
Determinants of Unintended Pregnancies Among Currently Married Women in Uganda
Authors: Wasswa Ronald , Kabagenyi Allen , Atuhaire Leonard
Published: September 2020

Background: Unintended pregnancies are no longer bound to teenagers or school going children, married women in Uganda as well experience such pregnancies though little has been investigated on them. This study therefore examines the determinants of unintended pregnancies among currently married women in Uganda.Methods: In this study, we used data from the 2016 Uganda Demographic and Health Survey (UDHS) which comprised of 11,223 married women aged 15-49 years. Analysis was done using descriptive analysis, logistic regression, Poisson regression, log-rank test for survival functions, cox proportional hazards model, and the generalized structural equation model.Results: The study revealed that 45% of the pregnancies were unintended while 3 in 10 married women were not using contraceptives. At the bivariate level; unintended pregnancy was associated with the highest wealth quintile (OR=0.45, 95%CI=0.40-0.49) while contraceptive use was associated with higher education level (OR=4.90, 95% CI=4.10-5.86). Similarly, children ever born were associated with married women from rural areas (IRR=4.34, 95% CI=4.30-4.39). At the multivariate level, married women from northern region (AOR=0.55, 95% CI=0.45-0.64) had lower odds and Muslim married women with more children (AOR=1.04, 95% CI=1.01-1.07) had higher odds of unintended pregnancy.Conclusion: Unintended pregnancies are directly and indirectly influenced by higher fertility and improver use of contraceptive. Married women who had more children and were: from poor households, with lowest education, in Central region, in rural areas, with low age at first birth, with older partners and were Muslim were more likely to have unintended pregnancies. Also, married women who were using contraceptives and were: older age, Anglican, from wealthiest households, in agricultural or domestic sector and higher parity were associated with higher risk of unintended pregnancies. The government should make efforts in reducing the fertility among married women by investing in programs and policies like: sensitization of women on the effectiveness in use of contraceptives, making contraceptives affordable and easily accessible to all people in different regions of the country with emphasis on who already have four or more children. Extension of higher education to all people will lead to reduced risks of unintended pregnancies.
Multiregion sequencing reveals the genetic correlation of esophageal squamous cell carcinoma and matched cell-free DNA
Authors: Yuan Zuyang , Wang Xinfeng , Geng Xiao , Li Yin , Mu Juwei , Tan Fengwei , Xue Qi , Gao Shugeng , He Jie
Published: September 2020

Background: The aim of this study was to assess whether both ubiquitous and heterogeneous somatic mutations could be detected in circulating cell-free DNA (cfDNA) from patients with esophageal squamous cell carcinoma (ESCC). Methods: Paired multi-regional tumor tissues, cfDNA and white blood cells (WBCs) collected from five ESCC patients before treatment from a prospective study (NCT02395705). Of them, samples from Cohort 1 (E102 and E110) were sequenced by whole-exome sequencing (WES) and those from Cohort 2 (E104, E111 and E121) were sequenced by targeted captured sequencing with a panel of 560 cancer-related genes respectively. To call somatic single nucleotide variations (SNVs) by comparing the solid tumor or cfDNA with matched WBCs, the minimal variant allele frequency (VAFmin) as 0.1% and P value <0.05 were allowed. Results: Genomic DNA (gDNA) and plasma-derived cfDNA from 26 samples were successfully sequenced. In Cohort 1, 596 (596/712, 83%) and 562 (562/796, 71%) were heterogeneous SNVs in E102 and E110 respectively. There was a statistically significant linear relationship between the VAFs for tumor and cfDNA (R2 = 0.78, P <0.0001). In Cohort 2, 296 (296/323, 92%), 384 (384/423, 91%) and 331 (331/357, 93%) were heterogeneous SNVs in E104, E111 and E121respectively. cfDNA could recover an average of 60.7% (31/51; range, 35.7%-76.2%) of somatic mutations present in matched solid tumors. The correlation of VAFs between cfDNA and matched solid tumor was significantly positive (r2 =0.92, P <0.0001).Conclusions: Both sequencing approaches revealed the highly intratumoral heterogeneity in ESCC and enabled the detection of both ubiquitous and heterogeneous mutations in cfDNA. Further validation in cfDNA is required to define its potential utility for ESCC in clinical practice. Trial registrationAll patients selected in this study were from the registered clinical trial from ClinicalTrials.gov (NCT02395705). Date of registration: March 24, 2015.
Greyscale 2D nanograting fabrication by multistep nanoimprint lithography and ion beam etching
Authors: Buhl Janek , Yoo Danbi , Köpke Markus , Gerken Martina
Published: September 2020

The application of nanopatterned electrode materials is a promising method to improve the performance of thin-film optoelectronic devices such as organic light-emitting diodes and organic photovoltaics. Light coupling to active layers can be enhanced by employing individual nanopatterns specifically tailored to the device structure. During the development process typically a range of different nanopatterns need to be evaluated. Fabrication of each of these nanopatterns using electron-beam lithography is time and cost intensive, particularly for larger scale devices, due to the serial nature of electron beam writing. Here, we present a meth-od to generate nanopatterns of varying depth with different nanostructure designs from a single one-dimensional grating template structure with fixed grating depth. We employ multiple subsequent steps of UV nanoimprint lithography and ion beam etching to fabricate greyscale two-dimensional nanopatterns. After each imprint step, the imprint resist is cured and etched to maintain the structural conformity. In this work we present variable greyscale nanopatterning of the widely used electrode material indium tin oxide. We demonstrate the fabrication of periodic pillar-like nanostructures with different period lengths and heights in the two grating directions. The patterned films can be used either for immediate device fabrication or pattern reproduction by convention-al nanoimprint lithography. This parallel processing approach promises cost-efficient large-scale nanopattern variation for the device development process.
Diagnosis of Coronavirus disease by measuring serum concentrations of IL-6 and blood Ferritin
Authors: Yazdanpanah Parviz , Vafaei Farzad , Javdansirat Saeed , pouranfard Jalal , Afrouz Sajad
Published: September 2020

Objectives: Coronavirus disease 2019 (COVID-19) associated by infection and high death rate. The unresolved questions about the fatality rate of COVID-19 is most probably related to cytokine storm syndrome. There is currently no specific medication. Understanding the pathogenic pathway of this disease will lead to production of treatment and decreases of death rate. The aim of this study is to investigate changes of peripheral blood parameters (Interleukin-6 and Ferritin) in COVID-19 patients, which may be beneficial in the management of patients.Methods: In this case-control study, we collected data of 270 subjects in two groups including 133 patients with severe type COVID-19 (case) and 137 patients with nonsevere (control) between March 20 and May 21, 2020, and the clinical symptoms and inflammatory indications of patients diagnosed by laboratory test in Shahid Jalil hospital of Yasuj University of medical Sciences were collected to explore potential markers for disease monitoring. The data were analyzed by SPSS software version 20. Descriptive statistics, T-test and bivariate correlation tests were used to analyze. Results: The enrolled COVID-19 patients consisted of 53.4% males and 46.6% females with the medium age of 45.56±18.55 years and there were 50.04% males and 49.6% females with the medium age of 45.59±17.0 years for non COVID-19 patients. There was no significant difference in the age and sex ratio between two population under study. The proportion interstitial abnormalities evidenced by CT imaging in COVID-19 patients was 91.0%, while, 4.4% abnormalities was found in non COVID-19 patients. The frequency of positive RT-PCR test for case and control groups were 88.0% and 3.6%, respectively. The mean IL-6 and Ferritin levels and hematological parameters in two groups of patients with COVID-19 and non- COVID-19, were significantly different across all comparisons.There was a direct positively correlated between serum level of IL-6, Ferritin levels and hematological parameters including WBC, Lymphocytes, Neutrophils and Hb, except for platelets (negatively correlate), with COVID-19. Conclusions: In conclusion, inflammatory markers specifically IL-6 and Ferritin and hematological parameters (WBC, Lymphocytes, Neutrophils, Platelet and Hb) were correlated with the severity of COVID-19. Measurement of IL-6, Ferritin and hematological indices might be workable tests to diagnosis and prognosis of patients with COVID-19.
Analysis of Risk Factors for Non-Union After Surgery for Limb Fractures: A Case-Control Study of 669 Subjects
Authors: Xu Qiang , Zhang Bin , Dai Min , Liu Xuqiang
Published: September 2020

Objective: Although a large number of clinical and animal experimental studies have explored factors affecting fracture healing, there are only a few examples of systematic research on these factors for limb fractures. The purpose of this study was to analyse the risk factors for limb fracture non-union in order to improve non-union prevention and early detection.Methods: A total of 223 patients with non-union after surgery for limb fractures performed at our institution from January 2005 to June 2017 were included as the case group, while a computer-generated random list was created to select 446 patients with successful bone healing who were treated during the same period as the control group, thus achieving a ratio of 1:2. The medical records of these patients were reviewed retrospectively. Age, sex, body mass index, obesity, smoking, alcohol, diabetes, hypertension, osteoporosis, fracture type, multiple fractures, non-steroidal anti-inflammatory drugs (NSAIDs) use, delayed weight bearing, internal fixation failure, and infection data were analysed and compared between the two groups. A multivariate logistic regression model was constructed to determine relevant factors associated with non-union.Results: The multivariate logistic regression analysis revealed that osteoporosis, open fractures, NSAIDs use, delayed weight bearing, failed internal fixation, and infection were independent risk factors for non-union after surgery for limb fractures.Conclusions: Osteoporosis, open fracture type, NSAIDs use, delayed weight bearing, failed internal fixation, and infection were found to be the main causes of bone non-union; clinicians should, therefore, take targeted measures to intervene in high-risk groups early.