bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultimate Molecular Theory of Sweet Taste
Authors: He Huazhong
Published: January 2021

More than thirty years ago, I proposed a theory about sweet and bitter molecules’ recognition by protein helical structures. Unfortunately the papers could not go to public platform until now. The sweet and bitter taste theory is updated and presented in separated papers1,2. The sweet taste theory conveys that sweet molecules are recognized by receptor protein helical structures and the recognition process is a dynamic action, in which the sweet receptor protein helix has a torsion-spring-like oscillation between helical structures of 3.6 and 3 amino acids per turn. To help this kind of oscillation, there are two kinds of hydrogen donor and hydrogen acceptor DH-B entities for both receptor and sweet molecules: H-bond or non-H-bond. The distances between DH and B could be up to ~ 8.5 Å. The receptor H-bond type DH-B entities are the NH-O pairs forming H-bonds in protein helices; the receptor non-H-bond type DH-B entities are the ones from two pairs of NH-Os forming H-bonds which are about one turn away. To facilitate this kind of movement, the interaction of DH-Bs of a sweet molecule with those of sweet receptor, through a pair of complementary hydrogen bonds, must have hydrogen bond complementarities, which means Hbond type of ligands’ DH-Bs reacts on non-H-bond type of receptor’s O-NHs, and vice versa. As the oscillation may have different extent, it translates to sweet intensity. As recognition sites are only associated with a small fraction – helix structure of whole sweet receptor, multiple binding sites or multiple receptors are well expected.
Reversing the Irreversible: Thermodynamic Stabilization of Lithium Aluminum Hydride Nanoconfined Within a Nitrogen-Doped Carbon Host
Authors: Cho YongJun , Li Sichi , Snider Jonathan , Marple Maxwell , Strange Nicholas , Sugar Joshua , Gabaly Farid El , Schneemann Andreas , Kang Sungsu , Kang Min-ho , Park Hayoung , Park Jungwon , Wan Liwen , Mason Harris , Allendorf Mark , Wood Brandon , Cho Eun Seon , Stavila Vitalie
Published: January 2021

A general problem when designing functional nanomaterials for energy storage is the lack of control over the stability and reactivity of metastable phases. Using the high-capacity hydrogen storage candidate LiAlH4 as an exemplar, we demonstrate a new approach to thermodynamic stabilization of metastable metal hydrides by coordination to nitrogen binding sites within the nanopores of N-doped CMK-3 carbon (NCMK-3). The resulting LiAlH4@NCMK-3 material releases H2 at temperatures as low as 126 °C with full decomposition below 240 °C, bypassing the usual Li3AlH6 intermediate. Moreover, >80% of LiAlH4 can be regenerated under 100 MPa H2, a feat previously thought to be impossible. The nitrogen sites lower the energy barrier for regenerating the hydride by changing the density of states in the vicinity of the Fermi level, effectively acting as solvation sites for lithium ions. Theoretical calculations provide a rationale for the unprecedented solid-state reversibility, which derives from the combined effects of nanoconfinement, Li adatom formation, and charge redistribution between the metal hydride and the host.
The Roles of Emotional Intelligence, Neuroticism, and Academic Stress on the Relationship Between Psychological Distress and Burnout in Medical Students
Authors: Yusoff Muhamad Saiful Bahri , Hadie Siti Nurma Hanim , Yasin Mohd Azhar Mohd
Published: January 2021

Background: Stress and burnout commonly threaten the mental health of medical students in Malaysia and elsewhere. This study aimed to explore the interrelations of psychological distress, emotional intelligence, personality traits, academic stress, and burnout among medical students. A cross-sectional study was conducted with 241 medical students. Validated questionnaires were administered to measure burnout, psychological distress, emotional intelligence, personality traits, and academic stress, respectively. A structural equation modelling analysis was performed by AMOS. Results: The results suggested a structural model with good fit indices, in which psychological distress and academic stress were noted to have direct and indirect effects on burnout. The burnout levels significantly increased with the rise of psychological distress (p-value < 0.01) and academic stress (p-value < 0.01). Neuroticism was only found to have significant indirect effects on burnout, whereby burnout increased when neuroticism increased (p-value < 0.010). Emotional intelligence had a significant direct effect on lowering burnout with the incremental increase of emotional intelligence (p-value < 0.05), but it was significantly reduced by psychological distress and neuroticism (p-value < 0.001). Conclusion: This study showed significant effects that psychological distress, emotional intelligence, academic stress, and neuroticism have on burnout. Academic stress and neuroticism significantly increased psychological distress, leading to an increased burnout level, while emotional intelligence had a significant direct effect on reducing burnout; however, this relationship was compromised by psychological distress and neuroticism, leading to increased burnout. Several practical recommendations for medical educators, medical students, and medical schools are discussed.
Expression and Function of C1orf132 Long-Noncoding RNA, in Breast Cancer Cell Lines and Tissues
Authors: Shafaroudi Afsaneh Malekzadeh , Sharifi-Zarchi Ali , Rahmani Saeid , Nafisi Nahid , Mowla Seyed Javad , Lauria Andrea , Oliviero Salvatore , Matin Maryam Moghadam
Published: January 2021

MIR29B2CHG/C1orf132 is the host gene for generating miR-29b2 and miR-29c. Here, we employed bioinformatics and experimental approaches to decipher expression of C1orf132 in breast cancer cells and tissues. Our data demonstrated a significant downregulation of C1orf132 in triple-negative breast cancer. We also predicted a putative promoter for the longer transcripts of C1orf132. The functionality of the distal promoter was confirmed by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 approach revealed no expression alteration of neighboring genes, CD46 and CD34. However, the expression of miR-29c was reduced by half, suggesting an enhancer effect of the distal promoter on miR-29c generation. Furthermore, the promoter knock-out an elevation of migration ability in MCF12A edited cells. Moreover, the expressions of cell mobility genes e.g., CDH2, FGF2, FGFR1 and the stem cell and EMT-associated transcription factor ZEB1 were significantly elevated in edited cells. RNA sequencing data on the edited and unedited cells revealed many up- and down-regulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.
Impact of Antiviral Treatment on Long-Term Prognosis in Non-Immunocompromised Patients With CMV Reactivation
Authors: Park Ga Eun , Ki Hyun Kyun , Ko Jae-Hoon
Published: January 2021

Background. Reactivation of human cytomegalovirus (CMV) occurs in non-immunocompromised patients with or without specific organ involvement, but it is still unknown whether it has a clinical implication on long-term prognosis or not.Methods. A retrospective cohort study evaluating non-immunocompromised adult patients with CMV reactivation was conducted during the period between January 2010 and February 2018. Patients were divided into ganciclovir-treated and non-treated groups. Patients who died within 30 days from CMV reactivation were excluded as they died from complex causes of conditions. Survivors were followed for 30-months to evaluate long-term prognosis.Results. A total of 136 patients with CMV reactivation was included, consisting of 66 ganciclovir-treated (48.5%) and 70 non-treated (51.5%) patients. Overall, patients were old-aged (median 70 years old) and most were treated with pneumonia of any cause (91.2%). More patients in ganciclovir-treated group were treated at intensive care unit (43.9% vs 24.3%, respectively) and had higher viral load over 5,000 copies/ml (48.5% vs 22.9%) than non-treated group (all P < 0.05). Primary and secondary endpoints including 30-months survival (28.0 vs 38.9%, respectively) and 12-months survival (40.3% vs 49.2%) were not statistically different between the ganciclovir-treated and non-treated groups. In the multivariate analyses, ganciclovir treatment was not associated with 30-months survival (HR 1.307 95% CI 0.759-2.251) and 12-months survival (HR 1.533 95% CI 0.895-2.624).Conclusion. In a retrospective cohort study evaluating non-immunocompromised patients with CMV reactivation, ganciclovir treatment was not associated with long-term prognosis. Antiviral treatment in this condition would not be necessary unless organ involvement is suspected.
Perspectives of Residency Training Amid The COVID-19 Pandemic: Impact on Mental Health and Training  
Authors: Moini Ashraf , Maajani Khadijeh , Omranipour Ramesh , Zafarghandi Mohammad Reza , Aleyasin Ashraf , Oskoie Roya , Alipour Sadaf
Published: January 2021

Background

COVID-19 has affected the training programs and the clinical schedules of surgical wards in many countries, including Iran. Also, the continuous involvement with COVID-19 patients has caused stress in health care workers; among them residents are on the frontlines of care delivery. Therefore, we designed a study to assess mental effects of these circumstances, and the effects on General Surgery and Obstetrics & Gynecology residency training.
Methods

We used a questionnaire consisting of 47 questions about personal, familial and demographic characteristics; training activities, and mental effects of COVID-19.
Results

The answer rate was 63.5%. (127 filled questionnaires). Around 96% of the residents had emotional problems, 85.9% were highly stressed about contracting COVID-19, 81.3% were worried about transferring it to their family; and 78% believed that their residency training had been impaired.
Conclusion

Overall, our study shows the negative impact of COVID-19 on the mental health and on the training of residents. We propose that appropriate emotional support and suitable planning for compensation of training deficits is provided for residents.
Association of vasopressor use with mortality in severe traumatic brain injury: a nationwide retrospective cohort study in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Hirayama Atsushi , Ogura Hiroshi , Shimazu Takeshi
Published: January 2021

Background: Maintaining of cerebral perfusion pressure (CPP) is frequently incorporated in severe traumatic brain injury management algorithms. However, there is limited evidence on prevalent clinical practices regarding a preferred method for achieving such CPP aims. We conducted a nationwide retrospective cohort study to determine the association between the use of vasopressors and mortality following hospital discharge in patients with severe traumatic brain injury, and to determine whether the use of vasopressors affects emergency department mortality or the occurrence of cognitive dysfunction.Methods: Data were collected between January 2004 and December 2018 from the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged ≥16 years with severe traumatic brain injury, without other major injuries, were examined. A severe traumatic brain injury was defined based on the Abbreviated Injury Scale code and a Glasgow Coma Scale score of 3–8 on admission. Multivariable analysis and propensity score matching were performed. Statistical significance was assessed using 95% confidence intervals (CIs).Results: In total, 10 284 patients were eligible for analysis, with 650 patients (6.32%) included in the vasopressor group and 9634 patients (93.68%) included in the non-vasopressor group. The proportion of deaths on hospital discharge was higher in the vasopressor group than in the non-vasopressor group (81.69% [531/650] vs. 40.21% [3,874/9,634]). This finding was confirmed by multivariable logistic regression analysis (adjusted odds ratio [OR], 5.71; 95% CI: 4.56–7.16). Regarding propensity score-matched patients, the proportion of deaths on hospital discharge remained higher in the vasopressor group than in the non-vasopressor group (81.66% [530/649] vs. 50.69% [329/649]) (OR, 4.33; 95% CI: 3.37–5.57). The vasopressor group had a higher emergency department mortality rate than the non-vasopressor group (8.01% [52/649] vs. 2.77% [18/649]) (OR, 3.05; 95% CI: 1.77–5.28). There was no reduction in complications of cognitive disorders in the vasopressor group (5.39% [35/649] vs. 5.55% [36/649]) (OR, 0.97; 95% CI: 0.60–1.57).Conclusions: In this population, the use of vasopressors for severe traumatic brain injury was associated with higher mortality on hospital discharge. Our results could not reach the conclusion that vasopressor therapy is beneficial in improving clinical outcomes in patients with severe TBI.
Integrated Lianhua-Qingwen and Western Medicine Versus Western Medicine-Only Therapies Against COVID-19: A Systematic Review and Meta-Analysis
Authors: Wang Zhen , Liu Haomiao , Wu Min , Zhou Yanzhang , Che Jiaxing , Zhang Shuangxi , Meng Deyu , Liu Jiankang , Ma Le , Peng Yunhua , Long Jiangang
Published: January 2021

Background

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome, has resulted in a global outbreak.
Objective

To systematically review the therapeutic reports on COVID-19 treated with integrated herbal medicine “Lianhua-Qingwen”and Western medicine to evaluate the efficacy and safety of the treatment.
Methods

PubMed, Embase, Web of Science, CNKI, CBM and other databases were searched to locate the clinical trials of integrated Lianhua-Qingwen and Western medicine treatment for COVID-19. The herbal medicine Lianhua-Qingwen reported in the treatments is in the form of capsules or granules. Two researchers of our team independently carried out data extraction and quality assessment of the collected literature according to the Cochrane systematic review methodology, calculated combined relative risk (RR) or weighted mean difference (MD)/standardized mean difference (SMD) .
Results

This meta-analysis included 13 studies collected, a total of 1182 cases of patients with common type COVID-19. Comparison of integrated Lianhua-Qingwen and Western medicine treatment with conventional Western medicine treatment found that the effective combined RR value was 1.18 (95% CI: 1.09, 1.27; I2 = 37%), and the RR value of CT image improvement rate was 1.12 (95% CI: 1.03, 1.23; I2 = 38%). The rate of progressing to critical cases decreased by 50% (RR: 0.50; 95% CI: 0.35, 0.73; I2 = 0%); the RR value of the fever disappearance rate was 1.43 (95% CI: 1.24, 1.65; I2 = 0%); the RR value of the cough disappearance rate was 1.97 (95% CI: 1.45, 2.68; I2 = 0%); the RR value of the rate of recovery from fatigue was 1.51 (95% CI: 1.15, 2.03; I2 = 0%). Compared with conventional Western medicine treatment, the integrated therapy shortened the duration of fever by 1.33 days (95% CI: -1.92, -0.73; I2 = 5%). The number of adverse reactions decreased by 49% (RR = 0.51; 95% CI: 0.14, 1.82; I2 = 76%).
Conclusion

Therapy of integrated Lianhua-Qingwen and Western medicine treatment is more effective for the treatment of patients with common type COVID-19, more effective in CT improvement rate, and more effective in reducing the rate of progressing to critical cases significantly and with fewer adverse reactions.
Neuroimaging Features of COVID-19: Retrospective Northern Italy Multicenter Study and a Scoping Review of the Prevalence of COVID-19 Associated Acute Cerebrovascular Diseases
Authors: Giorgianni Andrea , D'Amore Francesco , Vinacci Gabriele , Agosti Edoardo , Politi Letterio , Vito Andrea De , Polistena Alessandra , Valvassori Luca , Trentadue Mirko , Nicoli Lisa , Sozzi Carlo , Balbi Sergio , Mercuri Anna , Terrana Alberto , Triulzi Fabio , Silvia Casale , Nuzzi Nunzio , Asteggiano Francesco , Genovese Valentina , Lafe Elvis , Bianchini Elena , Bernasconi Pietro , Colli-Tibaldi Enrico , Longhi Laura , Bandiera Francesca , Baruzzi Fabio
Published: January 2021

Background The primary aim of this study was to provide additional data of neuroimaging features of coronavirus disease 2019 (COVID-19) in a large-scale population admitted in several northern Italy institutions. The secondary aim was to analyze acute cerebrovascular disease (CVD) prevalence in COVID-19. Methods A database of confirmed COVID-19 hospitalized patients who developed acute neurological symptoms and underwent any neuroimaging was retrospectively gathered from twelve institutions based in Lombardy from February 21st to July 10th. To assess the prevalence of CVD we conducted a scoping review following the PRISMA extension guidelines for scoping reviews. We searched PubMed/Medline, SCOPUS and EMBASE databases for peer-reviewed in-press or published studies from December to January 2021 reporting CVD in COVID-19 patients. Results Out of 90 COVID-19 patients who were referred to neuroimaging, 78 (87%) showed CVD, in particular 65 had acute ischemic strokes (AIS), 8 had intracerebral hemorrhages, 2 subarachnoid hemorrhages (SAH) and 3 showed clinical and imaging findings in keeping with posterior reversible encephalopathy syndrome (PRES); 6 patients (7%) showed clinical and imaging findings highly suggestive of encephalitis; 3 patients (3%) showed demyelinating diseases: 1 case of MS progression, 1 case of newly diagnosed MS and 1 case of acute disseminated encephalomyelitis (ADEM); 2 cases (2%) acuity of chronic subdural hematoma (cSDH); 1 patient (1%) with Guillain Barré syndrome. In addiction two patients with CVD developed cauda polyradiculitis and tetraparesis. In our scoping review out of 3275 studies, 24 satisfied the inclusion criteria: in a pooled total population of 136198 patients, the pooled prevalence of CVD was 0.9%. In particular 0.8% of AIS and 0.1% of ICH and 0.003% of PRES. Conclusions Our study shows a high prevalence of CVD among patients who developed acute neurological symptoms, which is in line with papers reporting data comparable to ours. The heterogeneity of clinical reports, however, constitutes a limitation when comparing our findings with those of the clinical papers. Nonetheless, CVD could be a frightening association with COVID-19, particularly in critically ill patients. Healthcare policymakers and clinicians should be prepared to a likely increase in workload and to rearrange the strategy of healthcare delivery.
Construction and Validation of an Immune-related Gene Pairs Prognostic Model for Breast Cancer
Authors: Zhong Ying , Wang Zhe , Zhou Yidong , Mao Feng , Lin Yan , Guan Jinghong , Shen Songjie , Xu Yali , Huang Xin , Wang Xuefei , Sun Qiang
Published: January 2021

Background: Immunotherapy plays an increasingly important role in the treatment of advanced female breast cancer, which has the highest mortality rate among malignant tumors. The purpose of this study was to identify immune-related genes associated with breast cancer prognosis as possible targets of immunotherapy, and their related biological processes and signaling pathways.Methods: Clinical data and gene expression profiles of patients with breast cancer were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and divided into training (n = 1053) and verification (n = 508) groups. CIBERSORT was used to predict differences in immune cell infiltration in patient subsets stratified according to risk. Gene Ontology (GO) enrichment analysis was used to identify pathways associated with immune-related genes in patient subsets stratified according to risk.Results: The prognostic model composed of 27 immune-related gene pairs significantly distinguished between high- and low-risk patients. Univariate and multivariate analyses indicated that the model was an independent prognostic factor for breast cancer. Among the identified genes, APOBEC3G, PLXNB1, and C3AR1 had not been previously studied in breast cancer and warrant further exploration. CCR chemokine receptor binding, regulation of leukocyte-mediated cytotoxicity, T cell migration, T cell receptor complex, and other pathways were significantly enriched in low-risk patients. M2 and M0 macrophages were more highly expressed in high-risk than in low-risk patients. CD8+ T cells and naïve B cells were more abundant in low-risk than in high-risk patients.Conclusion: The immune-related gene pairs prognostic model developed in the current study can help assess breast cancer prognosis and provides a potential target and research direction for breast cancer immunotherapy in the future.
Behavioural Support and Nicotine Replacement Therapy for Smokeless Tobacco Cessation: Protocol for a Pilot Randomised-controlled Multi-country Trial
Authors: Siddiqui Faraz , Bauld Linda , Croucher Ray , Jackson Cath , Kellar Ian , Kanaan Mona , Pokhrel Subhash , Huque Rumana , Iqbal Romaina , Khan Javaid Ahmed , Mehrotra Ravi , Siddiqi Kamran
Published: January 2021

Background: Smokeless Tobacco (ST) is consumed globally by more than 350 million people, with approximately 85% of all users based in South and Southeast Asia. In this region, ST products are cheap and easily accessible. Evidence-based interventions to people quit ST use are lacking. This study aims to test the feasibility of conducting a future definitive trial of ST cessation, using a culturally adapted behavioural intervention, and/or nicotine replacement therapy (NRT) in three South Asian countries. Methods: We will conduct a randomised, factorial design pilot trial in Bangladesh, India and Pakistan. Daily ST users will be recruited from primary health care settings in Dhaka, Noida and Karachi. Participants will be individually randomised to receive Intervention A (4 or 6 mg NRT chewing gum for 8-weeks), Intervention B (BISCA: face-to-face behavioural support for ST cessation), combination of Interventions A and B, or Usual Care (Very Brief Advice - VBA). Participants will provide demographic and ST use related data at baseline, and at 6, 12 and 26 weeks follow-up. The primary trial outcome will be validated abstinence to all forms of tobacco at 26 weeks, using a carbon monoxide breath test and salivary cotinine level. Secondary outcomes will be self-reported point prevalence of tobacco use at 6, 12 and 26 weeks. An embedded process evaluation (at 6 weeks) and data collection on health resource use and quality of life (at baseline and 26 weeks) will also be conducted. We will report on the feasibility of intervention delivery, recruitment, randomisation and retention. Discussion: The widespread and continued use of ST products in South Asia is consistent with a high rate of associated diseases and negative impact on the quality of life. The identification of feasible, effective and cost-effective interventions for ST is necessary to inform national and regional efforts to reduce ST use at the population level. Findings of this pilot trial will inform the development of larger trials for ST cessation among South Asian users, with relevance to wider regions and populations having high rates of ST use. Trial registration: ISRCTN identifier 65109397Trial funding: NIHR (programme reference 17/63/76/ Global Health Research Groups)
Overexpression of a novel oncogene Cadherin 6 correlates with tumor progression and poor prognosis in gastric cancer
Authors: Zhao Zongxian , Li Shuliang , Li Shilong , Wang Jun , Lin Hai , Fu Weihua
Published: January 2021

BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.
Matrix stiffness mediates glioma cells stemness through an integrin/JAK/STAT3 signaling pathway
Authors: Yao Wu , Bei Tao , Tangming Peng , Xiaobo Yang , Lilei Peng , Xiangguo Xia , Ligang Chen , Zhong Chuanhong
Published: January 2021

Background：Matrix stiffness in tumor microenvironment is tightly correlated with the tumor progression in solid cancer. However, the potential role of matrix stiffness in glioma progression remains controversial. Our study aimed to explore the underlying mechanism of glioma progression induced by matrix stiffness. Methods: Atomic force microscopy analysis was performed to examine the stiffness of tumor tissues. tunable polyacrylamide (PA) hydrogels were used for cells culture with different matrix stiffness. CCK-8 analysis was used to examine the cells proliferation. Colony formation analysis and subcutaneous tumor-bearing mice model were used to detect the capability of tumorigenesis. Western blotting and immunofluorescent staining were performed to examine the signals activation in glioma cells. Results: In our study, we observed a higher matrix stiffness in high degree glioma tissues from patients. We demonstrated that a higher stiffness culture system could mediate the upregulation of stemness in glioma cells, resulting in the strengthen capability of tumor growth and relapse in glioma. In mechanism, we observed activation of integrin α5β1/JAK1/STAT3/c-Myc signaling pathway in glioma cells under the simulation of a higher matrix stiffness. Combination of STAT3 inhibitor STAT3-IN-1 and chemotherapeutic temozolomide (TMZ) obviously suppressed the xenogenous glioma mice model, which revealed strengthen anticancer effects and improved outcome.Conclusion: We demonstrated that a higher matrix stiffness could promote glioma progression through an integrin α5β1/JAK1/STAT3/c-Myc signaling pathway. Blockade of STAT3 signals improved the anticancer effects of chemotherapy, providing new insights for glioma therapy in clinic.
Protection of Coenzyme Q-10 Against Contrast-induced Acute Kidney Injury in Diabetic Rats
Authors: Couto Sheila Marques Fernandes , Fonseca Cassiane Dezoti da , Watanabe Mirian , Vattimo Maria de Fátima Fernandes
Published: January 2021

Background: Diabetes Mellitus (DM) is a important risk factor for Contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI share oxidative damage and inflammation mechanisms that induction of protective and cellular adaptation enzymes as coenzyme Q-10 (COQ-10). The aim of this study was to investigate the therapeutic potential of COQ-10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats submitted to the CI-AKI model. Methods: Wistar rats, male, randomized into four groups: Citrate- control animals, received citrate buffer (streptozotocin vehicle, 0.4 ml); DM- animals that received streptozotocin (60 mg/kg); DM+IC: DM animals, treated with iodinated contrast (IC, 6 ml/kg); DM+IC+COQ-10: DM animals treated with COQ-10 (10 mg/kg) and that received with IC (6 ml/kg). The protocols lasted 4 weeks. Were evaluated the renal function by inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis.Results: DM animals showed reduced renal function which was reflected with an increase of serum creatinine and significant reduced of inulin clearance, as well as a reduction on RBF, increased RVR and redox imbalance with a higher urinary peroxides, nitrate lipid peroxidation levels and depletion of thiols in renal tissue. IC treatment exacerbated theses changes in DM + IC. COQ-10 administration ameliorates renal function, prevented hemodynamic changes, neutralize oxidative damage and progression of the histologic damage in the DM+IC+COQ-10 group. Conclusion: This study is the first that demonstrated a renoprotection of COQ-10 in experimental model of risk factor of DM for CI-AKI. COQ-10 presented an antioxidant effect on the CI-AKI in diabetic rats, by improving function and renal hemodynamics, preserving morphology and reducing oxidative stress.
Molecular Mechanisms of TanshinoneIIA in Hepatocellular carcinomatherapy via WGCNA-based Network Pharmacology Analysis
Authors: Zhao Han , Guo Jing , Chi Qingjia , Fang Meng
Published: January 2021

Background: Hepatocellular carcinoma (HCC) is a worldwide malignant tumor that caused irreversible consequences. The studies of Tanshinone IIA showed that Tanshinone IIA has played a notable role in HCC treatment. However, it is still to be investigated to discover the potential targets and associating mechanism of Tanshinone IIA against HCC. Methods: To analyze the correlation between genes and specific clinical features, we applied weighted gene co-expression network analysis (WGCNA), which can help us identify the targets of Tanshinone IIA related to the clinical features of Hepatocellular carcinoma. Results: We screened out 105 overlapping genes by integrating the predicted targets of Tanshinone IIA and the gene expression profile of HCC from the Cancer Genome Atlas (TCGA) database. For WGCNA, we used the RNA-seq profile of the overlapping genes and the related clinical information of HCC from TCGA. And 23 genes related to clinical tumor grade in the important module (R2 = 0.37) were imported for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) analysis. Compared to the key genes in the significant module from WGCNA with the high connectivity nodes from the PPI network, we can analyze three hub genes, AURKB, KIF11, and PLK1, for further verification. We tested the binding of Tanshinone IIA to the targets of Hepatocellular carcinoma using Autodock Vina. The survival curve validated that the three hub genes represented a poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that the three hub genes were effective in diagnosis. The mRNA expression of the three hub genes was upregulated in the HCC than the normal. AURKB, KIF11 and PLK1 were further upregulated in advanced tumor stage and grade. Moreover, AURKB, KIF11 and PLK1 also had higher protein expression in HCC tissues. Conclusions: In the study, WGCNA revealed grade-specific gene modules, indicating that Tanshinone IIA probably plays its therapeutical effect in the differentiation process of HCC. And the study partly interpreted the pharmacological mechanism of Tanshinone IIA against HCC.
T-cell Non-Hodgkin Lymphoma of the Ileum Presenting as Perforation and Peritonitis: A Case Report
Authors: Yong Tian , Xiang Zhang Zheng , Li Chuan Fang , Ming Tian Qing , Gang Ye , Song Qiao
Published: January 2021

Background Non-Hodgkin Lymphoma (NHL) of the ileum presenting as perforation and peritonitis is a rare disease, derived from intestinal intraepithelial T lymphocytes.The degree of malignancy is extremely high. The pathogenic factors of ileal perforation caused by NHL are not clear yet, Chromosome and immune system abnormalities, which may be related to the NHL, are indistinguishable from other benign and malignant conditions and clinically nonspecific. Case presentation Here,We described an 84 year old male with abdominal pain for four days and aggravating for three hours. The pain was initially considered as gastrointestinal perforation, and was initially located at the upper abdomen area.The persistent insidious pain,and was accompanied by nausea, vomiting and fever. According to the abdominal physical examination, the patient had pain all over his abdomen, rebound pain and muscle tension, and bowel sounds were reduced on auscultation. The abdominal CT scan showed abdominal cavity free gas.We diagnosed the patient with peritonitis due to the perforation of the hollow viscus. We promptly performed exploratory laparotomy.Intraoperative findings,showed perforations in the ileum that were approximately 40 cm from the ileocecal region and had a size of 3～8 mm. Segmental distribution was observed, and the intestinal contents overflowed with purulent moss around the perforation surface. Resection and ileostomy were performed as intervention, and the clinical histopathological examination showed the T-cell lymphoma. Conclusion:Timely emergency surgery is the key to the treatment of the ileal perforation caused by T-cell lymphoma.Resection and ileostomy were performed as intervention, and the subsequent histopathological examination showed T-cell lymphoma. Clinical follow-up was performed, and the patient was advised to go to the oncology department for further chemotherapy.
Conditions and Barriers for Quality Improvement Work. A Qualitative Study of How Professionals and Health Centre Managers Experience Audit and Feedback Practices in Swedish Primary Care
Authors: Arvidsson Eva , Dahlin Sofia , Anell Anders
Published: January 2021

BackgroundHigh quality primary care is expected to be the basis of many health care systems. Expectations on primary care are rising as societies age and the burden of chronic disease grows. To stimulate adherence to guidelines and quality improvement, audit and feedback to professionals is often used, but the effects vary. Even with carefully designed audit and feedback practices, barriers related to contextual conditions may prevent quality improvement efforts. The purpose of this study was to explore how professionals and health centre managers in Swedish primary care experience existing forms of audit and feedback, and conditions and barriers for quality improvement, and to explore views on the future use of clinical performance data for quality improvement. MethodsWe used an explorative qualitative design. Focus groups were conducted with health centre managers, physicians and other health professionals at seven health centres. The interviews were audio recorded, transcribed and analysed using qualitative content analysis.ResultsFour different types of audit and feedback that regularly occurred at the health centres were identified. The main part of the audit and feedback was “external”, from the regional purchasers and funders, and from the owners of the health centres. This audit and feedback focused on non-clinical measures such as revenues, utilisation of resources, and the volume of production. The participants in our study did not perceive that existing audit and feedback practices contributed to improved quality in general. This, along with lack of time for quality improvement, lack of autonomy and lack of quality improvement initiatives at the system (macro) level, were considered barriers to quality improvement at the health centres.ConclusionsProfessionals and health centre managers did not experience audit and feedback practices and existing conditions in Swedish primary care as supportive of quality improvement work. From a professional perspective, audit and feedback with a focus on clinical measures, as well as autonomy for professionals, are necessary to create motivation and space for quality improvement work. Such initiatives also need to be supported by quality improvement efforts at the system (macro) level, which would favour transformation to a primary care based system.
Triage Category and Factors Influencing Priority of Acute Myocardial Infarction Patients at Tikur Anbessa Specialized Hospital
Authors: Tola Firaol Birhanu
Published: January 2021

Background: - Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. AMI should be treated within a “golden time”, which is < 90 minutes from the onset of the symptom to balloon insertion. Late recognition of diagnosis has increase mortality and long term outcome of the patients in AMI patients. Patients in high priority triage categories were under triage which leads to long waiting time. Determine the associated factors for high priority triage category scale of AMI patients.Result: Among the total of 131 study participants, 91(69.5%) of them were males. The mean age of the study participants were 54 year with the standard deviation of 12.75. Patients who were categorized under high priority triage category accounts 47.3% of the total study participants with 95% CI (38.9-56.5). Among the total study participants 78(59.5%) of them were ST elevation myocardial infarction. Having more than 5 years of triage experience (OR: 13.63, 95% CI (2.32-79.86)) and having Triage early warning score of 5-10 during admission (OR: 65.28, 95% CI (5.39-790.52)) has a significant association on categorizing AMI patients in High priority triage category.Conclusion & Recommendation: Nearly half of the patients at emergency room were categorized under high priority. Triage early warning score and triage nurse experience were the factors which had a significant effect on categorizing AMI patients as high priority triage. Assigning of senior nurses at emergency triage room could improve triage category and early diagnosis and treatment for AMI patients at Tikur Anbessa Specialized Hospital.
Multiplex Immunoassay of Cytokines for The Short-Term Prognosis Predictive Value of Patients With Acute-on-Chronic Liver Failure
Authors: Zheng Yongyuan , Zhang Genglin , Wu Lina , Xiong Jing , Wang Lu , Li Xuejun , Li Jianguo , Xie Chan , Peng Liang
Published: January 2021

Background: Since the systemic inflammation has been found to be associated with disease progression and mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF), the objective of this study was to detect inflammatory factors in ACLF patients by a Luminex-based multiplex immunoassay system for high throughput screening of the cytokine with the most prognostic value.Methods: Luminex-based multiplex immunoassay technology was used to determine the concentrations of 48 cytokines in total at once in serum samples from 40 patients with HBV-ACLF, 30 patients with chronic hepatitis B (CHB) and 25 healthy volunteers as normal controls (NC). Then, the receiver operating characteristic (ROC) curve analysis was applied to evaluate the prognostic prediction accuracy. Besides, Kaplan–Meier curves was used to analyze survival, while the Cox regression analysis to determine the mortality predictors.Results: The level of IL-6, IL-10, IL-15, IL-18, M-CSF, IP-10 and CXCL9 were significantly higher in patients with HBV-ACLF than in either patients with CHB or NC subjects, while the level of EGF, PDGF-AA, PDGF-AB/BB, MDC and sCD40L were significantly lower. The concentrations of IL-6, CXCL9, and IL-15 was higher in non-surviving patients with HBV-ACLF than in surviving patients while MDC was lower. Increased serum IL-6 was positively correlated with disease severity. The ROC curve analysis showed that IL-6 and CXCL-9 accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na. Kaplan–Meier analysis showed an association between the increase in serum concentration of IL-6 as well as CXCL9 and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that only serum IL-6 was an independent predictor of overall survival in patients with HBV-ACLF.Conclusion: Although HBV-related ACLF patients have significantly increased serum levels of multiple cytokines, only serum IL-6 levels could be an independent prognostic biomarker in patients with HBV-ACLF.
Identification of Novel Potential Biomarkers in Hepatocarcinoma Cancer; A Transcriptome Analysis
Authors: kakar Mohib , Mehboob Muhammad , Akram Muhammad , Iqbal Imran , Ijaz Hafza , Aziz Ubair , Lodhi Adil , Rasheed Madiha , Deng Yulin , Dai Rongji
Published: January 2021

The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Gene Expression Omnibus (GEO) contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server GEO. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and functional enrichment analysis was performed to extract rational information from a set of DEGs. The protein-protein relationship networking search method was used for extracting interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. We identified the top 10 hub genes through Cytohubba plugin. These genes include cell cycle regulatory cyclins and cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarker studies that could promote selective molecular therapy for HCC.
Comorbidities of COVID-19 Patients with Low Cycle Threshold (Ct) Value of Nucleocapsid (N) Gene: An Application to Cluster-Based Logistic Model.
Authors: Rudra Sujan , Das Shuva , Hoque Md. Ehsanul , Kalam Abul , Rahman Mohammad Arifur , Shizuka Swagata Nandy , Rahman Tazrina
Published: January 2021

Background: Coronavirus disease 2019 (COVID-19) is a health crisis throughout the world. The widely used Real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) method is most capable of describing the patient’s condition. Comorbidities can make patients more critical.Methods: In this study, we shed light on the low cycle threshold (Ct) value of the N gene in the rRT-PCR test of the COVID-19 patients who had comorbidities, cure rate, and the needfulness of ICU (Intensive Care Unit) management. We had conducted the research in the Molecular Biology Laboratory of Chittagong Medical College between May and August 2020, then took the telephone interview with 300 positive patients who fulfilled the study criteria. We applied cluster-based logistic regression to analyze the data.Results: Low Ct value of the N gene found 1.324 times more in Type 2 DM patients and 1.871 times higher in hypertensive patients, and hospitalized patients are 2.480 times more vulnerable to shift in ICU.Conclusions: While infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) frequently causes severe diseases, suspected cases with comorbid conditions should go through the rRT-PCR as early as possible.
Physical Fitness in Spanish Naval Cadets. A 4-year Study
Authors: Oliveira Iris de , Vila Helena , Burgos-Martos Franciso , Carral Jose M Cancela
Published: January 2021

Background: Military physical readiness largely depends on Soldiers maintaining the level of general health and physical fitness to perform their requisite occupational duties in garrison and deployment environments. To know the physical fitness of naval cadets throughout its formative stage, will help us define a training program tailored to your needs. The objective of this study was to analyse the physical fitness of the cadets enrolled in the Military training in the academic year 2018-2019 in the XXXX.Methods. A longitudinal correlational-descriptive design was developed. 167 of the 292 students who participated in the global analysis participated in the pre and post (first and second semester) physical fitness tests (153 males and 14 females, mean age 21.86±3.5) and were stratified by age groups. Anthropometric and data from the Spanish army physical fitness assessment system (2 min Push-Ups, 1000 and 50m races, Vertical Jump and 50m swimming) was used. A descriptive, inferential and correlational analysis was carried out and the level of significance set for the study was p≤0.05.Results. Inferential analysis between marks by age group and for the total sample shows statistical differences for the total sample in the 1000m and 50m race (p<0.001) and in Vertical Jump test (p<0.01). There was significant statistical correlation between all the five tests developed.Conclusion. The level of physical fitness of cadets at the XXXX appears to be acceptable when compared to other countries military naval corps. A coherence between training and evaluation is of extremely importance and probably a rethinking on resistance and power strength should be necessary.
Body Composition in Female Patients with Adhesion Capsulitis of the Shoulder: A Case-Control Study
Authors: Fujiwara Motoi , Ito Masaaki , Yi Shuang-Qin
Published: January 2021

Background: Many studies have attempted to clarify factors associated with the development of shoulder periarthritis. In its early stage, omalgia impairs normal, everyday life. Due to this pain, muscle force decreases in the affected side of the upper limb, and a change occurs in body composition distribution, especially in the upper limb. Currently, body composition distribution can be measured using dual energy X-ray absorptiometry (DEXA). Methods: 102 patients with unilateral shoulder pain over 3 months (5 males and 97 females, mean age: 62.5 ± 10.5 years) were assigned to the shoulder pain group (painful group). The control group consisted of 237 patients without shoulder pain (20 males and 197 females, mean age: 59.8 ±14.2 years). These factors were measured using a QDR-4500 DEXA scanner (Hologic Co., Ltd.). Results: Mean values of bone mineral density were 0.57 ±0.09 g/cm2 on the affected side and 0.59 ± 0.08 g/cm2 on the non-affected side in the painful group. Mean values in the control group were 0.57 ± 0.14 g/cm2 on the left side and 0.58 ±0.09 g/cm2 on the right side. There was no significant difference between the shoulder with and without pain, affected and non-affected side. Mean proportions of the upper limb that was fat were 40.1 ± 9.5% on the affected side and 35.7 ±9.8% on the non-affected side in the painful group. In the control group, the means were 39.2 ±11.1% on the left side and 37.5 ± 10.9% on the right side. The mean muscle masses of the upper limb were 1548.5 ±304.2 g on the affected side and 1723.5 ±321.5 g on the non-affected side in the painful group. There was a significant difference between the affected and non-affected side. Conclusions: We measured the body composition of the upper limb. Muscle mass of upper limb was significantly different between the affected and non-affected sides.