bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic line Cell Differentiation of bone marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds
Authors: Li Zhao , Du Yue , Wang Xin
Published: June 2020

Background: To evaluate the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) to pancreatic line Cells on rat acellular pancreatic bioscaffold (APB). Methods: Fresh pancreata from 20 Adult Sprague Dawley rats (between 6 and 7 weeks old) were soaked and perfused using Easy-Load Digital Drive peristaltic pumps. After BMSCs were isolated and identified, they were dynamic cultured on the APB and static cultured in tissue culture flask(TCF). Based on whether the differentiation was induced by the growth factors (GF) in the culture system, our study was divided into 4 groups: BMSCs cultured in TCF without any GF(TCF-GF(-)), BMSCs cultured in TCF with GF(TCF-GF(+)), BMSCs cultured on APB without GF(APB-GF(-)), BMSCs cultured on APB with GF (APB-GF(+)).The cytological behavior such as the proliferation and differentiation of BMSCs in all the above kinds of culture system with or without GF were assessed by morphological observation, flow cytometry, ELASA analysis, qRT-PCR assay and western blot analysis. Results: 4ml/min was the most appropriate flow rate for the dynamic culture of BMSCs. Under culture conditions, BMSCs populations could attach to and proliferate within the APB. APB could promote the proliferation and viability of BMSCs significantly better in dynamic culture with optimal flow rate 4ml/min, when compared to the static culture system. Also, the proliferation rate of BMSCs in the APB groups were significantly increased compared to TCF system. During the pancreatic line cell differentiation process, APB could induce BMSCs into pancreatic-like cells which expressed markers such as pancreatic duodenal homeodomain containing transcription factor (PDX-1) and pancreatic exocrine transcription factor (PTF-1) higher at mRNA levels compared to TCF system. In contrast, the marker Oct4 (octamer-binding transcription factor 4) was expressed at a lower level in APB group. For the pancreatic functional cytoketatins including α-Amylase(α-Amy), cytokeratin 7(CK7), fetal liver kinase-1 (Flk-1),and C-peptide, they were all expressed at higher level in APB group than in the TCF group. And metabolic enzymes secretion such as amylase and insulin were promoted significantly in APB system. By scanning electron microscope(SEM) and transmission electron microscopy(TEM), the ultrastructure of BMSCs in the APB group could further demonstrated the morphological characteristics of pancreatic-like cells. In addition, in both the dynamic and static system, GF could significantly facilitate the function of proliferation, differentiation and cell engraftment . Conclusion: Together our data show the capacity of APB , 3D pancreatic biomatrix, promoting BMSCs differentiate toward pancreatic line phenotypes, and the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.
Unmet Mental Health Needs in the General Population: Perspectives of Belgian Health and Social Care Professionals
Authors: Rens Eva , Dom Geert , Remmen Roy , Michielsen Joris , Broeck Kris Van den
Published: June 2020

Background: Many people with mental health problems do not receive appropriate mental health care, resulting in a considerable level of unmet mental health needs. Epidemiological research has shown that some people are at increased risk for unmet mental health needs and has identified both structural and attitudinal barriers to mental health care. However, epidemiological studies may not provide the complete picture and qualitative research about unmet mental health needs is scarce. This study aimed to explore unmet mental health needs in the general population from the perspectives of professionals working with vulnerable groups.Methods: Four focus group discussions and two interviews were held with a total of 34 social work, mental health and primary care professionals in one rural and one urban primary care zone in the province of Antwerp, Belgium. All transcripts were thematically analyzed.Results: Five themes emerged: (1) socio-demographic determinants and mental disorder characteristics associated with unmet mental health needs; (2) attitudinal barriers; (3) structural barriers; (4) consequences of unmet mental health needs; and (5) recommendations for meeting unmet mental health needs.Conclusions: Finding suggest that unmet mental needs are associated with socio-demographic and mental disorder characteristics, and attitudinal and structural barriers. For example, professionals mentioned care-avoiders and difficult access for complex cases due to strict criteria. The high level of unmet need results in feelings of burden and powerlessness among professionals. Professionals discussed good practices and recommendations for optimal and more equitable mental health care provision, which should ideally be targeted at those in the greatest need.
Probiotic camel milk powder improves glycemic control, dyslipidemia, adipose tissue and skeletal muscle function in T2DM patients: a randomized trial
Authors: Fang Bing , Zhang Ming , Dong Lijie , Zhou Xiaojuan , Ren Fazheng , Ge Shaoyang
Published: June 2020

Background: Due to the close association between gut microbiota and diabetes, probiotic dairy products draw a lot of attention in the development of functional foods with anti-diabetic activity. Methods: 28 type II diabetic patients twice a day received 10 grams of camel milk powder supplemented with BBA6 and camel milk powder (control) over a total of 4 weeks. Results: After the intervention, there was a significant decrease in fasting blood glucose, serum content of total cholesterol, the cardiovascular risk index (TC/HDL-C), the pro-inflammatory cytokines (IL-6, MCP-1) and adipokines (adiponectin, resistin, lipocalin-2, adipsin). Myokines (irisin, osteocrin) increased significantly, indicating possible improvement in skeletal muscle function. Gut microbiota analysis suggested a significant enrichment in unclassified_f__Sphingomonadaceae and depletion in Eggerthella after the 4-week intervention with the probiotic camel milk powder, there were also elevated fecal concentrations of elevated fecal concentrations of proline, uracil and galactinol accompanied with a decreased norleucine, glycerol, sedoheptulose, palmitic acid, 5-aminovaleric acid, inositol and γ-aminobutyric acid. Conclusion: Dietary supplement with 10 grams of probiotic camel milk powder twice a day for a consecutive 4 weeks can significantly decrease fasting blood glucose of type 2 diabetic patients. This functional food also improves dyslipidemia, inflammation and functions of adipocytes and skeletal muscle, indicating the possibility of probiotic camel milk powder as a dietary treatment that target metabolic syndrome such as diabetes. Trial registration: ClinicalTrials, NCT04296825, Registered 5th March 20206 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04296825.
Identification of Potential Target Genes in HER-2 Positive Breast Cancer by Bioinformatics Analysis.
Authors: Wang Song , Quan Yi , Lyu Hongying , Deng Jian
Published: June 2020

Background: HER-2 positive breast cancer has a high risk of for relapse, metastasis and drug resistance, and is correlated with a poor prognosis. Thus, the study objective was to reveal target genes and key pathways in HER-2 subtype breast cancer. Methods: The gene expression dataset (GSE29431) was downloaded from the Gene Expression Omnibus database(GEO), and the differentially expressed genes (DEGs) were determined using LIMMA package in R software. Subsequently, Functional enrichment analysis were performed in ClusterProfiler package of R platform. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction (PPI) network of DEGs. Module analysis and target genes were identified by Cytoscape software. Further more, The influence of target genes on overall survival (OS) was assessed using the Kaplan-Meier plotter database.Results: The differential expression analysis revealed 96 genes were up-regulated while 407 genes were down-regulated in HER-2 positive breast cancer tissue compared to normal breast tissue. Functional enrichment analysis showed that the DEGs were mainly involved in regulation of lipid metabolic process, PPAR signaling pathway and PI3K-Akt signaling pathway. PPI network construction revealed a total of 199 nodes and 560 edges, and 12 target genes were identified by the highest value of degree. In addition, target genes were associated with worse overall prognosis, including NUSAP1, PTTG1, CEP55, TOP2A, CCNB1, CENPF, MELK, AURKA, UBE2C, BUB1B, KIF20A and RRM2.Conclusion: The present study identified 12 target genes associated with the development of HER-2 subtype breast cancer, which may help to provide new biomarkers and therapeutic targets.
Synergistic Effect of Depression and Cerebrovascular Disease in Mid- to Late-life on the Risk for Dementia: A Nationwide Population-based Cohort Study
Authors: Jang Yoo Jin , Kang Cinoo , Myung Woojae , Lim Shinn-Won , Kim Ho , Kim Doh Kwan
Published: June 2020

Background: Dementia is a progressive neurocognitive disease with a substantial social burden. No apparent breakthroughs in treatment options have evolved so far, suggesting that disease prevention for at-risk populations is essential. Depression and cerebrovascular disease (CVD) are known independent risk factors for dementia, but no studies have examined whether the risk for dementia among people with both illnesses is higher than the sum from each effect individually. This study aims to evaluate the dementia risk among people with depression, CVD, or both, compared to those with neither.Methods: A population-based cohort study analyzing the Korean National Health Insurance Service-National Sample Cohort database was conducted for all individuals aged over 50 years. This population had not been diagnosed with dementia at baseline, and was followed up from January 1, 2005, to December 31, 2013. The analyses used a time-varying Cox proportional hazard regression model that was adjusted for potential confounding factors. The synergistic effect of depression and CVD was estimated by calculating the attributable proportion (AP) due to interaction.Results: A total of 242,237 participants were included in the analytical sample, and 12,735 (5.3%) participants developed dementia. Compared with participants without depression or CVD, the adjusted hazard ratio for the incidence of dementia for those with depression alone was 2.35 (95% CI 2.21-2.49); CVD alone, 3.25 (95% CI 3.11-3.39); and comorbid depression and CVD, 5.02 (95% CI 4.66-5.42). The synergistic effect between depression and CVD was statistically significant (AP due to interaction = 0.08, P-value = 0.037), whereby 8% of incident dementia among those with comorbid depression and CVD was attributed to the concomitance of the two illnesses.Conclusions: In this population-based nationwide cohort with a long-term follow-up, depression and CVD were associated with an increased risk of dementia, and their coexistence had a synergistic association.
In Vivo Antidepressant Efficacy of 3-substituted Thietane-1, 1-dioxide Derivative - A Preliminary Study for Novel Anti-depression Therapy in Neurological Disorders
Authors: Nikitina Irina L. , Beeraka Narasimha M. , Gaisina Gulnara G. , Bulygin Kirill V. , Galimova Elmira F. , Galimov Shamil N. , Nikolenko Vladimir N. , Mikhaleva Liudmila M. , Somasundaram Siva G. , Kirkland Cecil E. , Avila-Rodriguez Marco , Aliev Gjumrakch
Published: June 2020

Background: Psychosocial stress-induced depressive behavior is linked to etiology of several neurological diseases viz., PTSD, and neurodegenerative disease like Alzheimer’s disease (AD). The repeated bouts of social stress defeat can be induced using Resident-Intruder-Paradigm (RIP) and chronic mild social stress (CMSS) animal models to assess the stress-induced depressive behavioral patterns. The aim of this study to examine the anti-depressive efficacy of 3-methoxythietane-1,1-dioxide (N-14) in RIP models of behavioral alterations.Methods: In this study, we have used Sprague-Dawley rats in Resident-Intruder-Paradigm (RIP), where intruders interacted with residents Day 0 to Day +5 for 10 minutes to invoke CMSS in intruders and became defeated/submissive rats due to the depressive-like behavioral alterations in social activity, explorations, grooming, defense, aggressive behavior, and social interaction, freeze, and rearing etc., with residents. Group I is control intact animals, group II received N-14 alone; group III received CMSS, and group IV received cotreatment of N14 with CMSS. N-14 (2 mg/kg) was administered intraperitoneally from Day 0 to Day +5 to intact animals and intruder animals under conditions of CMSS. Several behavioral tests viz., forced swim test, open field test, and elevated-plus maze test were used to examine the above behavioral dynamic parameters.Results: the dynamic interaction between Residents and Intruders during the study showed substantial alterations in exploratory activity, aggressiveness, and defensive behavior, body weight, and thymus mass in stressed animals. N-14 cotreatment has mitigated sociability, exploratory activity, and aggressiveness and increased social adaptability and defensive behavior. Extensive rise in active forms of defense and submission latency indicate that N-14 has induced antidepressant activity with a psycho-sedative component of action.Conclusion: Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate depressive-behavioral symptoms in intruders. Since it is a preliminary study, we have not examined any pathophysiological and molecular signaling to delineate the efficacy of N-14 in retarding depressive-behavioral symptoms. Our future studies will address these aspects to fully consider N-14 as a novel therapy against stress-induced depression in neuropsychiatric and neurodegenerative disorders (ex. AD) using in vivo and clinical models.
Plasma calprotectin was associated with platelet activation and no-reflow phenomenon in acute coronary syndrome
Authors: Song Nian-Peng , Zhen Xiao-Wen , Li Liu-dong , Zhong Lin , Wang Hua , AN YI
Published: June 2020

Background No-reflow occurs in 3–4% of all percutaneous coronary interventions and has a strong negative impact on clinical outcomes of acute coronary syndrome. Therefore, the discovery of a biomarker that can early predict the occurrence of no-reflow has great clinical significance. Calprotectin is found to be a biomarker of plaque instability and is identified to be a novel diagnostic and prognostic biomarker of cardiovascular diseases. But the association of plasma calprotectin with platelet activation and no-reflow phenomenon in acute coronary syndrome is not clear. Methods In this study performed at Yantai Yuhuangding Hospital from 2017 to 2018, a total of 176 Chinese patients with acute coronary syndrome who had undergone percutaneous coronary interventions were recruited consecutively, aged from 30 to 88 years. The coronary angiography and percutaneous coronary intervention procedures were performed and angiographic no-reﬂow was defined as a thrombolysis in myocardial infarction scores grade less than 3. Blood samples were collected immediately at admission for detection of plasma calprotectin and platelet–monocyte aggregates formation. Statistical analysis was performed for the variable’s comparisons between groups and for the prediction value of plasma calprotectin for no-reflow.Results In this study, we have demonstrated that acute coronary syndrome patients with higher plasma calprotectin had an elevated level of platelet activation and a higher incidence of no-reflow. Plasma calprotectin level was independently associated with platelet activation and no-reflow in patients with acute coronary syndrome. Despite that platelet activation biomarker platelet–monocyte aggregate was associated with no-flow, only plasma calprotectin and serum low density lipoprotein cholesterol acted as independent predictors of no-reflow in patients with acute coronary syndrome.Conclusion Plasma calprotectin was associated with platelet activation and may act as an early prediction biomarker of no-reflow in patients with acute coronary syndrome.
Operating bedside cardiac ultrasound program in emergency medicine residency: a retrospective observation study from the perspective of performance improvement
Authors: Kim Kihong , Jung Jae Yun , Park JoongWan , Lee Minsung , Lee Yonghee
Published: June 2020

Background
Point-of-care Ultrasound is one of useful diagnostic tools in emergency medicine practice and considerably depends on physician’s performance. This study was performed to evaluate performance improvements and favorable attitudes through structured cardiac ultrasound program for emergency medicine residents.
Methods
Retrospective observational study using the Point-of-care ultrasound (PoCUS) database in one tertiary academic-teaching hospital emergency department has been conducted. Cardiac ultrasound education and rotation program has been implemented in emergency medicine residency program. Structured evaluation sheet for cardiac ultrasound and questionnaire toward PoCUS have been developed. An early-phase and a late-phase case were selected randomly for each participant. Two emergency medicine specialists with expertise in PoCUS evaluated saved images independently. We used a paired t-test to compare the performance score of each phase and the results of the questionnaire. Multivariable linear regression analysis was conducted to evaluate the association between the characteristics of participants and performance improvements.
Results
During the study period, a total of 1,652 bedside cardiac ultrasounds were administered. Forty-six examinations conducted by 23 emergency medicine residents were randomly selected for analysis. The performance score increased from 39.5 to 56.1 according to expert A and 45.3 to 62.9 according to expert B (p-value < 0.01 for both). The average questionnaire score, which was analyzed for 17 participants, showed improvement from 18.9 to 20.7 (p-value < 0.01). In multivariable linear regression analysis, younger age, higher early-phase score and higher confidence had a negative association with a greater improvement of performance, while the number of examinations had a positive association.
Conclusions
Bedside cardiac ultrasound performance and attitudes toward PoCUS have been improved through structured residency program.
Prognostic Value of Quantitative 18F-FDG PET/CT Parameters Measured in Primary Tumors and Suspicious Lymph Nodes in Patients with Esophageal Carcinoma.
Authors: Tustumi Francisco , Takeda Flávio Roberto , Duarte Paulo Schiavom , Albenda David Gutiérrez , Sallum Rubens Antonio Aissar , Junior Ulysses Ribeiro , Buchpiguel Carlos Alberto , Cecconello Ivan
Published: June 2020

Background: Quantitative 18F-FDG PET/CT parameters have been described as prognostic indicators in esophageal cancer. The aim of this study was to evaluate the prognostic value of the maximum standardized uptake value (SUVmax), metabolic tumor value (MTV) and total lesion glycolysis (TLG) measured in the primary tumor and suspicious lymph nodes. A cohort study was performed to assess the association of SUVmax, MTV and TLG measured prior to and post neoadjuvant therapy with overall survival (OS) of patients with esophageal cancer who received trimodal therapy. The quantitative techniques were applied in the primary tumor and suspicious lymph nodes. The OS rates were analyzed. Results: Before neoadjuvant therapy, 106 patients underwent PET/CT, and 39 patients underwent post-neoadjuvant therapy PET/CT exams. Before neoadjuvant therapy, PET/CT showed that all the variables of the evaluated lymph nodes were statistically significant in predicting OS. Post neoadjuvant therapy, none of the PET/CT variables of lymph nodes were related to prognosis. On the other hand, all primary tumor volumetric variables were related to overall survival. The MTV (HR: 4.66; 95% CI: 1.54-14.08) and TLG (HR: 4.86; 95% CI: 1.66-14.26) of the primary tumor post neoadjuvant therapy and the variations in MTV (HR: 2.95; 95% CI: 1.01-3.52) and TLG (HR: 3.49; 95% CI: 1.01-3.52) of the primary tumor pre-to-post-neoadjuvant therapy were prognostic variables. Conclusion: In patients with esophageal cancer, the burden of disease in suspicious lymph nodes and the primary tumor prior to therapy and the residual burden of disease in the primary tumor post therapy assessed by PET/CT were associated with prognosis.
The Effects of Everyday-Life Exposure to Polycyclic Aromatic Hydrocarbons on Biological Age Indicators
Authors: Pavanello Sofia , Campisi Manuela , Mastrangelo Giuseppe , Hoxha Mirjam , Bollati Valentina
Published: June 2020

BackgroundFurther knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti- benzo[a]pyrene diolepoxide (B[a]PDE–DNA) adducts.MethodsThe study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and through measures of target dose [B[a]PDE–DNA]. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction methods. Structural equation modelling analysis evaluated these complex relationships.ResultsIn two models investigating LTL and LmtDNAcn, we found an ordered relationship between these measurements and PAH exposure (diet, indoor, outdoor, traffic, residential). Acting through anti-B[a]PDE–DNA adduct formation, we detected reduced LTL (p=0.028) and LmtDNAcn (p=0.018) levels, particularly in males (LTL p=0.006; LmtDNAcn p=0.0001). Active smoking only increased LTL (p=0.0001). Besides this, the most significant determinants of PAH exposure causing an increase in anti-B[a]PDE–DNA were indoor and diet (p=0.0001 for each). while the least significant was outdoor. Lastly, the presence of detoxifying GSTM1 decreased adduct levels.Conclusion New findings stemming from our study suggest that LTL and LmtDNAcn erosion depends on certain preventable everyday life exposure to PAHs. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases, including lung cancer.Capsule:Everyday life exposure to polycyclic aromatic hydrocarbons shortens leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.
Control of COVID-19 in Australia through quarantine: the role of Special Health Accommodation (SHA) in New South Wales, Australia
Authors: Fotheringham Penelope , Anderson Teresa , Shaw Ms Miranda , Jewitt Joseph , Storey Ms Hannah , Hutchings Owen , Cartwright Jason , Gupta Leena
Published: June 2020

Background The first COVID-19 cases were diagnosed in Australia on 25 January 2020. Initial epidiemiology showed that the majority of cases were in returned travellers from overseas. One aspect of Public Health response was to introduce compulsory 14 day quarantine for all travellers returning to NSW by air or sea in Special Health Accommodation (SHA).MethodsThe SHA was established with a comprehensive governance structure, clinical management through rpavirtual hospital remote management and site management with health care workers, NSW Police and accommodation staff.Findings From 29 March to 29 April 2020, 373 returned travellers were admitted to the SHA from Sydney Airport. 88 (26.1%) of those swabbed were positive for SARS-CoV 2, 0.91% of all returning air travellers. The day of diagnosis of COVID-19 varied from Day 1 to Day 13, with 63.6% (n=56) of these in the first week of quarantine. 50% of the people in the SHA were referred to rpavirtual for ongoing clinical management. 7 patients required admission to hospital for ongoing clinical care.InterpretationThe Public Health response to COVID-19 in Australia included early and increased case detection through testing, tracing of contacts of confirmed cases, social distancing and prohibition of gatherings. In addition to these measures, the introduction of mandated self-quarantine for travellers to Australia was integral to the successful containment of COVID-19 in NSW and in Australia through the prevention of transmission locally and interstate from returning travellers.
Effects of Age, Gender, and Menopausal Status on Small Dense Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Fractions; JMS-II Cohort Study
Authors: Izumida Toshihide , Nakamura Yosikazu , Sato Yukihiro , Ishikawa Shizukiyo
Published: June 2020

Background:Small dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the effect of age, gender, and menopausal status on sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.Methods:We examined the baseline cross-sectional data from the Jichi Medical School-II Cohort Study, including 5,208 participants (2,397 men and 2,811 women). To assess age-related trends, the sdLDL-C and sdLDL-C/LDL-C ratios were plotted against gender. We evaluated the effect of age and menopausal status using multiple linear regression analysis.Results:We observed that in men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked at 50–54 years, and then decreased. In women, we observed relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years, followed by a downward or pleated trend. The crossover of sdLDL-C levels for the genders occurred at 70–74 years, but we could not observe any sdLDL-C/LDL-C ratio crossover. Standardized sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year old men, premenopausal women, and postmenopausal women were 26.6, 22.7, and 27.4 mg/dL and 0.24, 0.15, and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (P<0.001).Conclusions:sdLDL-C and sdLDL-C/LDL-C ratios show different distributions by age, gender, and menopausal status with trends different from other lipids. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences, and menopausal status.
Monitoring the spatiotemporal epidemiology of Covid-19 incidence and mortality: a small-area analysis in Germany
Authors: Rohleder Sven , Bozorgmehr Kayvan
Published: June 2020

Background: As response to the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), countries worldwide have implemented mitigation and control measures at national and subnational level. Timely monitoring of risks of SARS-CoV-2 incidence and associated deaths at small-area level is essential to inform local response strategies. However, the potentials of spatial epidemiology to contribute to this aim are yet untapped in most countries. Using the example of Germany, we analysed the spatiotemporal epidemiology of SARS-CoV-2 incidence and associated deaths at district level to develop a tool for monitoring incidence and mortality rates and to estimate district-specific risks of disease incidence.

Methods: We conducted a longitudinal small-area analysis for 401 districts to assess the district-specific risks of SARS-CoV-2 incidence by using nationally representative data from the national surveillance system in Germany on a daily basis (January 28 th to May 4 th 2020). We used a Bayesian spatiotemporal model to estimate the district-specific risk ratios (RR) of SARS-CoV-2 incidence and the posterior exceedance probability for RR thresholds greater than 1, 2 or 3, respectively. We further calculated standardised incidence (SIR) and mortality ratios (SMR) stratified by sex and age groups to assess the spatial distribution of SARS-CoV-2 incidence and deaths.

Results: A total of 85 districts (21 % of all districts) showed a RR greater than 3, and 63 districts (16 % of all districts) exceed the RR threshold with a probability of greater than 80 %. Median RR was 1.19 (range 0-523.08), and the median SIR and SMR were 0.34 (range 0-423.94) and 0 (range 0-343.39), respectively. Elevated RR, and correspondingly high SIR and SMR, were observed in at-risk districts (identified by the spatiotemporal model) in southern and western districts of Germany. Daily updates of district-specific risk, SIR and SMR are implemented in a web-based platform.
Conclusions: Our approach provides an informative and timely tool to monitor the district-specific risks of SARS-CoV-2 incidence and associated deaths. This approach can be used to inform local authorities for decision-making and strategy planning on containing the SARS-CoV-2 pandemic.
Integrative pharmacogenomic profiling identifies novel cancer drugs and gene networks modulating ferroptosis sensitivity in pan-cancer
Authors: Yang Haitang , Zhao Liang , Yao Feng , Gao Yanyun , Marti Thomas M. , Schmid Ralph A. , Peng Ren-Wang
Published: June 2020

Background: Ferroptosis is an apoptosis-independent cell death program implicated in various diseases including cancer. Emerging evidence has demonstrated the promise of pharmacological induction of ferroptosis as a novel anti-cancer approach, but the molecular underpinnings of ferroptosis regulation and biomarkers associated with sensitivity to ferroptosis indcuers has been poorly defined.

Methods: By implementing integrated pharmacogenomic analysis, we correlated the sensitivity of small-molecule compounds (n=481) against the transcriptomes of solid cancer cell lines (n=659). The potential of a drug compound to modulate ferroptosis was determined by significant (empirical p-value < 0.01) association of drug effectiveness with SLC7A11 expression. To establish generalized gene signatures for ferroptosis sensitivity and resistance, we interrogated drug effects of multiple ferroptosis inducers (n=7) with transcriptomic data of pan-solid cancer cells. Finally, the ferroptosis gene signature was applied to The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) project to identify cancer patients and cells that likely benefit from ferroptosis-based therapeutics.

Results: We report, for the first time, the comprehensive identification of cancer drugs with the potential to induce ferroptosis and a generalized gene expression signature predicting ferroptosis response in pan-cancer. Informed by the findings, we reveal an unanticipated role for class I histone deacetylase (HDAC) in regulating ferroptosis and show that targeting HDAC significantly enhances the ferroptosis-promoting effect of Erastin in lung cancer cells. Moreover, our data indicate that small cell lung cancer (SCLC) and isocitrate dehydrogenase ( IDH )-mutant brain tumors are highly primed for ferroptosis, suggesting that relaunching ferroptosis might be an innovative strategy to target these malignancies.

Conclusions: Expanding arsenal targeting aberrant ferroptosis and deciphering gene networks dictating ferroptosis sensitivity shed light on ferroptosis regulatory networks and may facilitate biomarker-guided stratification for ferroptosis-based therapy.
Nrf2 protects against drowning-induced acute lung injury via inhibiting ferroptosis
Authors: Qiu Yu-bao , Wan Bin-bin , Liu Gang , Wu Ya-xian , Chen Dan , Lu Mu-dan , Chen Jun-liang , Yu Ren-qiang , Chen Dao-zhen , Pang Qing-feng
Published: June 2020

Background

Drowning-induced acute lung injury (ALI) has been a major cause of accidental death worldwide. Severe oxidative stress injury is the key factor in drowning-induced ALI. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress Ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 attenuates drowning-induced ALI via inhibiting ferroptosis.

Methods

In this study, we employed Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the beneficial roles of Nrf2 on drowning-induced ALI and the underlying mechanisms.

Results

In this study, we firstly showed that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential. However, ML385 promoted cell death and lipid ROS production. Furthermore, Nrf2 knockout aggravated seawater drowning-induced ALI in mice.

Conclusions

In summary, these results suggest that Nrf2 alleviate drowning-induced ALI in MLE-12 cells and mice through inhibiting ferroptosis.
A Case of Vestibular Schwannoma with Oral Burning Sensation: Surgical Complication or Burning Mouth Syndrome?
Authors: Suga Takayuki , Takenoshita Miho , Tu Trang T.H , Hong Chaoli , Takao Chihiro , Watanabe Motoko , Akira Toyofuku
Published: June 2020

Background: Vestibular schwannoma (VS) or acoustic neuroma is a benign brain tumor. Despite improvements in surgical technique, the removal of VS is related to some complications of which the recovery is difficult and sometimes lead to permanent deficits. About 10.7% of complication of vestibular schwannoma surgery is reported to affect facial or tongue area, including numbness of pain, which is similar to a typical symptom of burning mouth syndrome (BMS). However, up to our knowledge, there is no documented case of BMS either comorbid with vestibular schwannoma or occur due to surgery complications. Clinical Presentation: A 46-year-old woman complained about left-sided facial pain, a burning sensation on the left side of her tongue and maxilla, and a spontaneous bitter taste. Four years before her first visit to our clinic, left-sided facial pain and burning sensation on the left side of the tongue suddenly became severe. She visited a neurosurgeon and VS was found in the left cerebellopontine angle. After the tumor was removed, facial pain, burning sensation of the tongue, and bitter taste improved simultaneously but quickly recurred after a while. The patient had a panic attack because of severe pain and started visiting a psychiatrist. The psychiatrist diagnosed her as having somatic symptom disorder and depression, prescribing sertraline 100 mg, zolpidem 5 mg, and lorazepam 1.0 mg and referred her to our clinic. At the first visit, no abnormal intraoral nor extraoral findings were detected. Based on the characteristics of the pain, we made a diagnose of BMS. Amitriptyline was initiated at 10 mg/day and increased to 30 m. Within 1.5 months, the pain and burning sensation of the tongue and maxilla almost remitted completely, whereas bitter taste showed moderate improvement. Conclusions: Our case suggests there might be an exceptional case in which BMS and VS can occur simultaneously. Specifically, an oral burning sensation and dysgeusia after VS surgery are not always a case of surgical complication or untreatable.
Can a penalized-likelihood estimation algorithm be used to reduce the injected dose or the acquisition time in 68Ga-DOTATATE PET/CT studies?
Authors: Chicheportiche Alexandre , Goshen Elinor , Godefroy Jeremy , Grozinsky-Glasberg Simona , Oleinikov Kira , Meirovitz Amichay , Gross David J. , Ben-Haim Simona
Published: June 2020

Background: Both image quality and quantitative accuracy of PET depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered today the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In the present study, we aim to compare the performance of a PL algorithm (Q.Clear, GE Healthcare) and 3D OSEM for 68Ga-DOTATATE (68Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68Ga-DOTA studies were included. The data were acquired in list mode and reconstructed using 3D OSEM and Q.Clear with various values of the regularization parameter β, and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β=300-1100; 1.0 min/bp: β=600-1300 and 0.5 min/bp: β=800-2200). Evaluation was performed using a phantom and clinical data. Finally, two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. Results: Clinical images reconstructed with Q.Clear , set at 1.5 and 1.0 min/bp using β = 1100 and 1300 respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUVmax of 14 % and 11%, in SNR of 18% and 10%, and in SBR of 14% and 12%, respectively. Reconstruction using 0.5 min/bp and β = 2200 resulted in SUVmax, SNR and SBR with a relative difference < 1%. Visual assessment yielded similar results with mean scores for Q.Clear (1.5, 1.0 and 0.5 min/bp) vs 3D OSEM (1.5 min/bp) of 3.58 vs 3.38, 3.64 vs 3.47 and 3.60 vs 3.61, respectively. Conclusion: 68Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp resulted in increased tumor SUVmax and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β =1300 enabled a one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.
Credit ratings and firm value
Authors: M. Hull Robert
Published: June 2020

A topic of relevance to financial managers is the relation between a credit rating and firm value (VL). The general aim of this paper is to elucidate this relation with a specific objective of helping C corp managers choose an optimal target rating (OTR). To achieve these goals, we use the Capital Structure Model (CSM) to compute a series of firm value (VL) outcomes matched to credit ratings. The maximum VL (max VL), among all VL outcomes, identifies OTR. This identification begins with the matching of credit spreads and ratings by Damodaran (2019) for three firm categories: small, large, and financial service (FS). Given these spreads, we can compute costs of borrowing with these costs needed to compute VL and other numerical outcomes. Besides costs of borrowing, our numerical outcomes are based on other key inputs including US $1,000,000 in before-tax cash flows, C corp tax rates, and a sustainable growth rate. Major findings that guide managers include the following. First, Moody’s A3 is the most common OTR. Second, growth firms generally require higher ranked OTRs. Third, compared to small and large firms, FS firms attain greater max VL values, higher optimal debt-to-firm value ratios (ODVs), and generally lower ranked OTRs. Fourth, relative to small firms, large firms gain less from growth even though they attain greater max VL outcomes. Fifth, only for FS firms can we find outcomes where operational cash flows are better spent on interest payments than retained internally for growth.
Detecting change in precipitation indices using observed (1977–2016) and modeled future climate data in Portland, Oregon, USA
Authors: Cooley Alexis Kirsten , Chang Heejun
Published: June 2020

This study addresses how regional changes to precipitation may be identified by exploring the effect of temporal resolution on trend detection. Climate indices that summarize precipitation characteristics are used with Mann–Kendall monotonic testing to investigate precipitation trends in Portland, Oregon (OR) from 1977 to 2016. Observational records from rain gages are compared with downscaled global climate models to determine trends for the historic (1977–2005) and future (2006–2100) periods. Standard indices created by the Expert Team on Climate Change Detection and Indices (ETCCDI) are deployed. ETCCDI indices that summarize conditions at the annual level are generated alongside a limited number of ETCCDI indices summarized at the monthly level. For the future climate, the indices summarized at the annual level demonstrate trends indicative of an intensifying hydrologic cycle. The historical record depicted by annual indices does not show trends. The historical record is viewed differently by changing the indices to monthly summaries, which causes trend detection to increase and hallmark indicators of an intensifying hydrologic cycle to become apparent.
Protective Effects of Polydatin Against Dementia-Related Disorders
Authors: Tang Kim San
Published: June 2020

:

Dementia is a collection of symptoms affecting a person’s cognition. Dementia is
debilitating, and therefore, finding an effective treatment is of utmost importance. Resveratrol,
which exhibits neuroprotective effects, has low bioavailability. However, its glucoside polydatin is
more bioavailable. Here, the evidence that supports the protective role of polydatin against dementia-
related diseases such as Alzheimer’s disease, vascular dementia, alcohol-related dementia, and
Lewy body dementias is presented. The beneficial effects of polydatin from a mechanistic perspective
are specifically emphasized in this review. Future directions in this area of research are also
discussed.
When Sick Brain and Hopelessness Meet: Some Aspects of Suicidality in the Neurological Patient
Authors: Costanza Alessandra , Amerio Andrea , Aguglia Andrea , Escelsior Andrea , Serafini Gianluca , Berardelli Isabella , Pompili Maurizio , Amore Mario
Published: June 2020

:

Neurological diseases expose individuals to a higher risk of suicidal ideation and suicidal
behavior, including completed suicides and suicide attempts. They also represent a paradigmatic arena
to study the etiopathogenic mechanisms underlying suicidality because they are emblematic of the heterogeneity
and complexity of mutual interrelationships characterizing this issue. On the one hand, neurological
diseases imply strictly biological impairments that are postulated to be the basis of vulnerability
to suicide or result in the need for treatments for which a suicidal risk has been hypothesized. On
the other hand, they question some subjective experiences of neurological patients, up to near existential
positions. Often, in fact, they are accompanied by severe hopelessness. The latter may originate in,
particularly for the most severe neurological diseases, the absence of curative treatments, unpredictable
disease progression that leads to acute relapses or chronicity, a decrease in autonomy or selfidentity,
progressive social isolation, a sense of becoming useless, and perception of feeling stigmatized.
This may ultimately cause a slip into experiencing an absurd condition. At the confluence of
neurobiology and hopelessness, frequent psychiatric comorbidities may play a primary role. To conclude,
neurological patients require special attention from clinicians in form of openly verbalizing and
exploring the suicidal thematic, inquiring about protective and risk factors, and promptly initiating
both a psychopharmacological treatment and, where possible, psychological support.
Research Progress on Thermal Conductivity of Graphdiyne Nanoribbons and its Defects: A Review
Authors: Tian Wenchao , Cheng Chunmin , Wang Chuqiao , Li Wenhua
Published: June 2020

Background:

Graphdiyne has a unique pi-conjugated structure, perfect pore distribution and
adjustable electronic properties of sp2, sp hybrid planar framework. Due to the presence of acetylenic
bonds, it has more excellent properties compared to grapheme, such as a unique structure-dependent
Dirac cone, abundant carbon bonds and a large bandgap. As one of the important raw materials for
nanodevices, it is extremely important to study the thermal properties of graphdiyne nanoribbon.

Objective:

This paper mainly introduces and discusses recent academic research and patents on the
preparation methods and thermal conductivity of graphdiyne nanoribbons. Besides, the applications in
engineering and vacancy defects in the preparation process of graphdiyne are described.

Methods:

Firstly, taking thermal conductivity as an index, the thermal conductivity of graphdiyne with
various vacancy defects is discussed from the aspects of length, defect location and defect type. In addition,
the graphdiyne nanoribbons were laterally compared with the thermal conductivity of the graphene
nanoribbons.

Results:

The thermal conductivity of graphdiyne with defects increases with the length and width,
which is lower than the intrinsic graphdiyne. The thermal conductivity of the acetylene chain lacking
one carbon atom is higher than the one lacking the benzene ring. Typically, the thermal conductivity is
larger in armchair than that of zigzag in the same size. Moreover

Conclusion:

Due to the unique structure and electronic characteristics, graphdiyne has provoked an extensive
research interest in the field of nanoscience. Graphdiyne is considered as one of the most promising
materials of next-generation electronic devices.
Pain Perception and Management: Where do We Stand?
Authors: Afridi Bilal , Khan Haroon , Akkol Esra K. , Aschner Michael
Published: June 2020

Background:

Pain is often flammable, sharp and sometimes described as an electrical
shock. It can be categorized in three different ways as nociceptive, neuropathic and inflammatory.
Nociceptive pain always originates in specific situations such as in trauma. Neuropathic pain results
in nerve damage. In inflammatory pain, inflammatory mediators are involved in the sensitization
of nociceptors. It is important to control the pain as it affects the individual physically, mentally,
and socially.

Objective:

Recognizing pain physiopathology and pain pathways, defining the relationship between
receptor and transmitter is critical in developing new treatment strategies. In this review, current
information on the definitions, classifications, and physiological and chemical mechanisms involved
in pain are reviewed.

Methods:

Various search engines were used to gather related articles/information. Only peer-reviewed
journals were considered. Additional, books/chapters of standard publishers were also included
in the article.

Results:

With a better understanding of the physiological and chemical mechanisms that play a
role in pain, significant improvements have been made in pain treatment. Various oral or intravenous
drugs, local injection treatments, physical and occupational therapy, electrical stimulation, alternative
medicine applications, psychological support, and surgical applications are routinely performed
in the treatment, dependent upon the type, severity and cause of the pain.

Conclusions:

Improved understanding of pain physiopathology will serve as the basis for future improvements
in the delivery of efficacious and reliable treatments, and is likely to rely on novel technological
innovations.