bluuebunny/crossref_metadata_2025 huggingface dataset:
Shifting clinical relevance from ‘what is the matter to what matters’ utilising Legitimation Code Theory. A comparative investigation of medical students’ social accountability perceptions.
Authors: Whittenbury Kingsley James
Published: February 2022

Pedagogy for socially accountable medical professionalism lacks systematic integration of relevant social and biomedical facts. A sociological gaze and change in medical discourse may be transformative. A mixed methods study compared perceptions of social justice in healthcare of forty medical student participants from diverse social positions enrolled in two Australian medical schools. The ‘capability to aspire’ to prosocial professionalism links Sen’s capability theory and Bourdieu’s theory of practice to compare outsiders and insiders in a traditional and a socially accountable program. Comparison of First and Final Year cohorts aimed to identify the regulative discourses of each program. Demographic, short answer and multi-choice questions, and semi-structured audio-recorded interview tested participants’ aspirations, knowledges and reasoning related to social accountability. All cohorts supported social justice learning and agreed Indigenous, refugee and migrant groups were most disadvantaged in Australian health care. Final Year participants had greater awareness of health system shortfalls in social accountability, citing professional discourses lacking equity awareness, unfair patient responsibilisation, system overload and mismatch to Indigenous health needs. Less intention to practice in areas of health need was shown by participants with zero and multiple devalorised social identities than those with single equity identities. A common finding was inability to modify clinical reasoning to recognise what matters for equity needs, making ‘health equity’ a threshold concept. Critical reflexivity on human contexts of illness production was best realised by outsiders, unrelated to program. International participants held stronger perceptions of mismatch between the Australian health system and Indigenous health needs. Results inform a socio-science approach to learning health equity that builds on students’ prosocial values, social identities, and meaning-making of social contexts. A re-contextualising principle to validate health equity perspectives in medical pedagogy, and knowledge management system to integrate social and medical discourses, are proposed. The potential benefits of biosemiotic, edusemiotic and semioethic approaches to the humanising turn in medical education are discussed. Legitimation Code Theory provides a means to systematise diverse discourses in medical education. Biosemiotic concepts of lifeworld and dialogical communication may further cultivate students’ sociological and moral imagination of health production, and creativity for socially accountable solutions to emergent illness.
Lithospheric Based Eco-decontamination and Fate Elucidation of Fungicide Fluopyram Containing Benzamides Background
Authors: Naeem Hamna , Ahmad Khuram Shahzad
Published: February 2022

Fungicide Fluopyram (FLP) containing benzamides class has been scrutinized for the first time for its ecotoxicity and environmental lithosphere stationed fate from various climatic zones. Fate-decisive research inclusive of examining FLP's response in perspective of alteration via adsorption/desorption and disintegration in hydrolytic, photolytic, and bio-degradative procedures. Sorptive interactions determination was done by the batch equilibration approach and indicated its dependency on the chemico-physical properties of the soils. Fragile adsorptive interactions between soils and FLP molecules were established, as indicated by physio-sorption and a fragile exothermic response indicated by negative Gibbs free energy values (-8 to -15.3 kJ mol-1). The soil with the maximal adsorption, Kd(ads) =8.6 µg mL−1, was procured to have a significant organic matter content (1.30 %), resulting in a C-type isotherm that was scrutinized using a linear and Freundlich model. The analytical techniques, inclusive of ultraviolet-visible spectrophotometric and high-performance liquid chromatography procedures have been endeavored to examine FLP fate elucidation. Hydrolysis, photolysis, and biodegradation tests procured minimum halflives of 7.45, 1.29, and 5.77 days while the most remarkable were 10.6, 7.96, and 10.6 days, respectively. The results demonstrated that FLP displayed medium binding and thus low persistence in the tested soils while being extremely susceptible to transformative mechanisms. Current research can be embraced to include further augmentation of these degradative ways and to develop realistic methods for environmental cleanup through natural routes.
Financial Access of Adult People with Disability to Health Services: Rural Population Study from Iran
Authors: Hosseini-Shokouh Sayyed-Morteza , Shams Lida , nasiri Taha , Darvish Tahere
Published: February 2022

Background People with disabilities (PWDs) account for a significant percentage of the world's population, with a higher prevalence in less developed countries. Access to healthcare services is the main component of health systems performance, with lower access for PWDs living in rural areas. The current study aimed to investigate PWD's access to healthcare services in rural areas of Iran and, secondly, factors that contribute to this issue.Methods Following a cross-sectional design, the current descriptive-analytical study is performed in the north of Iran. Using the quota sampling technique, 471 PWDs were recruited. Data were collected using a valid and reliable questionnaire, covering three dimensions of access, by face-to-face interview. Data analysis was administered using central tendency indicators and multiply regression by SPSS version 17. Statistical significance was considered when p-value<0.05.Results The mean score of PWD's access to healthcare services for dimensions of utilization, availability, and affordability was 8.91(±6.86), 14.54(±2.3), and 51.91(±8.78), indicating very low, low, and moderate levels of access. All three regression models were significant (P<0.05), and variables of gender, age, marital status, education level, residence status, the income of the household head, receiving financial aid, and house area showed a significant effect (P<0.05).Conclusion This study demonstrated the seriousness of paying attention to PWD's financial access to healthcare services, particularly in rural areas of Iran. Hence, policymakers should better focus on this problem, mainly regarding accessibility and utilization and factors that result in inequalities.
Neutrophil Infiltration Induces Myocardial Injury In COVID-19 Post-Mortem Cases
Authors: Han Yaling , Zhang Quanyu , Zhang Huarong , Yan Xiaowei , Ma Sicong , Yao Xiaohong , Shi Yu , Ping Yifang , Cao Mianfu , Peng Chengfei , Wang Shuai , Luo Min , Yan Chenghui , Zhang Shuyang , Han Yaling , Bian Xiuwu
Published: February 2022

Objectives: The pathological features of severe cardiac injury induced by COVID-19 and relevant clinical features is unknown.Methods: This autopsy cohort study, including hearts from 26 deceased patients hospitalized in intensive care unit due to COVID-19, was conducted at four sites in Wuhan, China. Cases were divided into neutrophil-infiltration group and no-neutrophil group according to histopathological identification of neutrophilic infiltrates or not.Results: Among 26 cases, four cases had active myocarditis with histopathological examination. All cases with myocarditis accompanied with extensive neutrophil infiltration, while cases without myocarditis did not. Detection rates of interleukin-6 (100% vs 4.6%) and tumor necrosis factor-a (100% vs 31.8%) in neutrophil-infiltration group were significantly higher compared to no-neutrophil group (p<0.05 for both). At admission, patients with neutrophil infiltration in myocardium had significantly higher baseline values of aspartate aminotransferase, D dimer and high-sensitivity C reactive protein compared to other 22 patients (p<0.05 for all). During hospitalization, patients with neutrophil infiltration had a significantly higher maximum of creatine kinase (CK)-MB (median 280.0 vs 38.7IU/L, p=0.04), and a quantitatively higher top Troponin I (median 1.112 vs 0.220ng/ml, p=0.56) than patients without neutrophil infiltration. Conclusions: In hearts from deceased patients with severe COVID-19, active myocarditis was commonly infiltrated with neutrophils. Cases with neutrophil-infiltrated myocarditis had a series of severe abnormal laboratory tests at admission, and a high maximum of CK-MB during hospitalization. Role of neutrophil on severe heart injury and even systemic condition in COVID-19 should be emphasized.
BMI1 Promotes Cholangiocarcinoma Progression and Correlates with Antitumor Immunity in An Exosome-Dependent Manner
Authors: Liu Zengli , Hu Chunxiao , Zheng Lijie , Liu Jialiang , Li Kangshuai , Li Xingyong , Wang Yue , Mu Wentao , Chen Tianli , Shi Anda , Qiu Bo , Zhang Xin , Zhang Zongli
Published: February 2022

Background: Cholangiocarcinoma (CCA) is a class of malignant tumors originating from bile duct epithelial cells. Due to difficult early diagnosis and limited treatment, the prognosis of CCA is extremely poor. BMI1 is dysregulated in many human malignancies. However, the prognostic significance and oncogenic role of BMI1 in cholangiocarcinoma (CCA) are not well elucidated. Methods: In the present study, we investigated its clinical importance and the potential mechanisms in the progression of CCA. We detected BMI1 expression in a large CCA cohort. We demonstrated BMI1 was substantially upregulated in CCA tissues and was identified as an independent prognostic biomarker of CCA. Moreover, overexpression of BMI1 promoted CCA proliferation, migration, and invasion. And, BMI1 knockdown could inhibit proliferation and metastases of CCA in vitro and in vitro/vivo validation. Interestingly, we found that CCA-derived exosomes contain BMI1 proteins, which can transfer BMI1 between CCA cells. The unique BMI1-containing exosomes promote CCA proliferation and metastasis through autocrine/paracrine mechanisms. In addition, we demonstrated that BMI1 inhibits CD8+T cell-recruiting chemokines by promoting repressive H2A ubiquitination in CCA cells. Conclusions: BMI1 is an unfavorable prognostic biomarker of CCA. Our data demonstrate a novel function of BMI1 in CCA tumorigenesis and metastasis mediated by exosomes. Besides, BMI1 inhibition may augment immune checkpoint blockade to inhibit tumor progression by activating cell-intrinsic immunity of CCA
Adult and Pediatric All-Terrain Vehicle (ATV) Injury Patterns and Outcomes in a Community Trauma Center
Authors: Foote Christopher , Doan Xuan-Lan , Vanier Cheryl , Palacio Carlos
Published: February 2022

Background
All-terrain vehicle (ATV) crashes result in severe morbidity in trauma. Limited data on these injury patterns come from large urban academic centers, but studies show increased use of ATVs in small rural communities with fewer resources, where these injuries are more likely to be treated. This study uses injury patterns to determine impact on community trauma systems based on length of stay.
Methods
The trauma registry of a level II trauma center was reviewed for ATV crash patients from January 2015 to December 2020. Injury type and frequency were grouped by proportion and 95% confidence interval based on ‘score’ method, and co-incidences were first screened with Fisher’s exact test, with significant p-value<0.01. Factors influencing length of stay in hospital/ICU were analyzed in a linear model and log-transformed dependent variable with significance based on sequential nested likelihood ratio analysis. Descriptive statistics were back transformed.
Results
Out of 7,787 trauma patients admitted during the study, 127 were involved in ATV crashes with 62 adults (age>18) and 65 pediatric patients. Injuries to skin/soft tissue and extremities were most common in both adult (68% and 42%, p<0.001) and pediatric (56% and 38%, p<0.001). Paired injuries included head bleeds with skull fractures (p<0.001) in both adults and pediatrics, pediatrics alone with spine and rib fractures (p=0.01). Length of stay in hospital increased for extremity injuries in both groups (mean (SD); adults 5.8 (2.4) vs 3.0 (2.2) days and pediatrics 4.0 (2.2) vs 2.6 (2.0) days, P=0.048). Pediatric patients had shorter overall hospital length of stay compared to adults (mean (SD); 3.1 (2.1) vs 3.9 (2.4) days respectively, P=0.009). Mortality was low with only a single adult death.
Conclusions
The findings from our retrospective study among ATV-related injuries on a community level II trauma center demonstrates skin/soft tissue injuries and extremity injuries were most common. We can also predict prolonged hospital length of stay in those with extremity injuries and those older than 18 years of age, requiring greater resources with longer hospital stay. No factors were predictive of longer ICU stays and mortality was very low with a single adult death in our population.
Antibacterial Activity of Essential Oils Extracted From the Unique Chinese Spices Cassia Bark, Bay Fruits, and Cloves
Authors: Jiang Chunling , Meng Jing , Ou Jie , Xie Qingchao , Pan Yingjie , Zhao Yong , Liu Haiquan
Published: February 2022

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three species with Chinese characteristics unique and widely used by the public were selected: cassia bark (bark of Cinnamomum camphoraPresl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%), and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Vibrio parahaemolyticus, Listeria monocytogenes and 4 kinds of Listeria. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices, and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.
An Assessment of Current Concussion Identification and Diagnosis Methods in Sports Settings. A Systematic Review
Authors: Daly Ed , Pearce Alan J , Finnegan Emma , Cooney Ciara , McDonagh Maria , Scully Grainne , McCann Michael , Doherty Ronan , White Adam , Phelan Simon , Howarth Nathan , Ryan Lisa
Published: February 2022

BackgroundConcussion in sport is an ongoing global concern. The head injury assessment (HIA) by the field of play is acknowledged as the first step in recognising and identifying concussion. While previous systematic literature reviews have evaluated the sensitivity of sideline screening tools and assessment protocols, no systematic review has evaluated the research designs and assessments used in a field setting. This systematic review investigated existing screening and diagnostic tools used in research as part of the HIA protocol to identify concussion that are currently used in professional, semi-professional and amateur (club) sports settings. MethodsA systematic searching of relevant databases was undertaken for peer-reviewed literature between 2015 and 2020. ResultsTwenty-five studies met the inclusion criteria. Studies were of moderate to good quality, reporting a variety of designs. The majority of studies were undertaken in professional/elite environments with medical doctors and allied health practitioners (e.g., physical therapists) involved in 88% of concussion assessments. While gender was reported in 24 of the 25 studies, the majority of participants were male (77%). There was also a variety of concussion assessments (n=20) with the sports concussion assessment tool (SCAT) used in less than half of the included studies. ConclusionThe majority of studies investigating concussion HIAs are focused on professional/elite sport. With concussion an issue at all levels of sport, future research should be directed at non-elite sport. Further, for research purposes, the SCAT assessment should also be used more widely to allow for consistency across studies.
Machine Learning-Based Classifiers To Predict Metastasis In Colorectal Cancer Patients
Authors: Borumandnia Nasrin , Akbari Abolfazl , Gramifar Mohammad , Talebi Atefeh , Pourhoseingholi Mohamad Amin , Azizpour Mazaher , Tabaeian Seidamir Pasha , Sedaghat Meghdad
Published: February 2022

Background: The increasing prevalence of colorectal cancer (CRC) in the past three decades in Iran has made it as a key public health burden. The goal of the study was to predict the metastasis in CRC patients using machine learning approach. Methods: This study is focused on 1127 CRC patients, who underwent proper treatments in tertiary Taleghani Hospital. The machine learning approach including Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), Regression Tree (RT) and Logistic Regression (LR) were used for the prediction of metastasis in CRC. Receiver operating characteristic (ROC) curve, sensitivity, specificity and AUC were carried out to evaluate the performance of the approaches Results: Out of 1127 patients, 183(16%) experienced metastasis. In prediction of metastasis, the NN and RF had the most sensitivity. Also the specificity of NN and DT were greater in comparison to other methods. The NN had the highest AUC (0.99%), topmost sensitivity (98.5%) and accuracy (99.6%).Conclusion: Both tumor stage and size of tumor were regarded as indispensable variables in RF model, whereas the NN generally outperformed other ML-based approaches.
SARS-CoV-2 Suppression and Early Closure of Bars and Restaurants: A Longitudinal Natural Experiment
Authors: Takaku Reo , Yokoyama Izumi , Tabuchi Takahiro , Oguni Masaki , Fujiwara Takeo
Published: February 2022

Despite severe economic damage, full-service restaurants and bars have been closed in hopes of suppressing the spread of SARS-CoV-2 worldwide. This paper explores whether the early closure of restaurants and bars in February 2021 reduced symptoms of SARS-CoV-2 in Japan. Using a large-scale nationally representative longitudinal survey, we found that the early closure of restaurants and bars decreased the utilization rate among young persons (OR 0.688; CI95 0.515-0.918) and those who visited these places before the pandemic (OR 0.754; CI95 0.594-0.957). However, symptoms of SARS-CoV-2 did not decrease in these active and high-risk subpopulations. Among the more inactive and low-risk subpopulations, such as elderly persons, no discernible impacts are observed in both the utilization of restaurants and bars and the symptoms of SARS-CoV-2. These results suggest that the early closure of restaurants and bars without any other concurrent measures does not contribute to the suppression of SARS-CoV-2.
Transforming China's Power Systems To Facilitate Carbon Reductions
Authors: Pan Mingjie , Xie Da , Gu Chenghong , Liu Gaowei , Wang Xitian , Zhao Chenghan
Published: February 2022

In order to fulfill China's commitment to reaching the carbon peak by 2030 and carbon neutrality by 2060, it is crucial to reduce carbon emissions from its power systems, especially from coal-fired power generation. Here we examine how China's electricity generation mix, i.e., the share of electricity generated by different types of power sources, can be reformed to maximize carbon reductions. We use China's national development in the SSP5 scenario (a specific scenario of Shared Socio-Economic Pathways) from the Global Change Analysis Model (GCAM) as the base scenario and recalculate SSP5's electricity sector. We calculate the generation mix of six regional power grids, under the constraint of frequency stability, to find out the national minimum share of coal-fired power and corresponding carbon emissions, and then develop a carbon reduction pathway. We observe that under the base scenario, China could achieve carbon neutrality by 2060 with the contribution of adjusting the generation mix and significantly reducing the share of coal-fired generation. If other appropriate strategies are adopted, such as optimizing the structure of transmission networks and promoting energy storage, China's power systems are well positioned to completely drop coal by 2100 and China can achieve carbon peak and neutrality more quickly.
Epiregulin, Epigen and Betacellulin Antibodies and Axial Elongation in Young Guinea Pigs with Lens-Induced Myopization
Authors: Dong Li , Zhang Rui-Heng , Li Yi-Fan , Wu Hao-Tian , Li He-Yan , Shi Xu-Han , Zhou Wen-Da , Jonas Jost. B. , Wei Wen-Bin
Published: February 2022

Background: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation.Methods: The experimental study included 30 guinea pigs (age:3-4 weeks) which underwent bilateral lens-induced myopization and received three intraocular injections of 20µg of epiregulin antibody, epigen antibody and betacellulin antibody in weekly intervals into their right eyes, and of phosphate-buffered saline into their left eyes. Seven days after the last injection, the animals were sacrificed. Axial length was measured by sonographic biometry. Results: At baseline, right eyes and left eyes did not differ (all P>0.10) in axial length in neither group, nor did the interocular difference in axial length vary between the groups (P=0.19). During the study period, right and left eyes elongated (P<0.001) from 8.08±0.07mm to 8.59±0.06mm and from 8.08±0.07mm to 8.66±0.07mm, respectively. The interocular difference (left eye minus right eye) in axial elongation increased significantly in all three groups (epiregulin-antibody:from 0.03±0.06mm at one week after baseline to 0.16±0.08mm at three weeks after baseline;P=0.001); epigen-antibody group:from -0.01±0.06mm to 0.06±0.08mm;P=0.02; betacellulin antibody group:from -0.05±0.05mm to 0.02±0.04mm;P=0.004). Correspondingly, interocular difference in axial length increased from -0.02±0.04mm to 0.13±0.06mm in the epiregulin-antibody group (P<0.001), and from 0.01±0.05mm to 0.07±0.05mm in the epigen-antibody group (P=0.045). In the betacellulin-antibody group the increase (0.01±0.04mm to 0.03±0.03mm) was not significant (P=0.24). Conclusions: The EGF family members epiregulin, epigen and betacellulin may be associated with axial elongation in young guinea pigs, with the effect decreasing from epiregulin to epigen and to betacellulin.
Highly Time-Resolved 4d Mr Angiography Using Golden-Angle Radial Sparse Parallel (Grasp) Mri
Authors: Goldman-Yassen Adam E. , Raz Eytan , Borja Maria J. , Chen Duan , Derman Anna , Dogra Siddhant , Block Kai Tobias , Dehkharghani Seena
Published: February 2022

Current dynamic MRA techniques are limited by temporal resolution and signal-to-noise penalties. GRASP, a fast and flexible MRI technique combining compressed-sensing, parallel imaging, and golden-angle radial sampling, acquires volumetric data continuously and can be reconstructed post hoc for user-defined applications. We describe a custom pipeline to retrospectively reconstruct ultrahigh temporal resolution, dynamic MRA from GRASP imaging obtained in the course of routine practice. GRASP scans were reconstructed using a custom implementation of the GRASP algorithm and post-processed with MeVisLab (MeVis Medical Solutions AG, Germany). Twenty consecutive examinations were scored by three neuroradiologists for angiographic quality of specific vascular segments and imaging artifacts using a 4-point scale. Unsubtracted images, baseline-subtracted images, and a time-domain intensity gradient dataset were available in 2D and 3D reconstructions. Distinct arterial and capillary phases were identified in all reconstructions, median of 2 frames (IQR1-3 and 2-3, respectively). Median rating for vascular segments was 3 (excellent) in all reconstructions and for nearly all segments, with excellent intraclass correlation (range 0.91-1.00). No cases were degraded by artifacts. GRASP-MRI obtained in routine practice can be seamlessly repurposed to produce high quality 4D-MRA with sub-second resolved, isotropic cerebrovascular angiography. Further exploration into diagnostic accuracy in disease-specific applications is warranted.
Epidemic Analysis of Peste Des Petits Ruminants in India
Authors: Zhang Shuwen , Liang Ruirui , Yang Qiaoling , Yang Yunfeng , Qiu Songyin , Zhang Hui , Qu Xiaosheng , Chen Qin , Niu Bing
Published: February 2022

BackgroundPeste des petits ruminants (PPR) is a serious disease that damages goats, sheep and other small ruminants. As one of the earliest and most serious countries, PPR has seriously threatened India's animal husbandry economy. ResultsIn this study, the spatial and temporal characteristics of the PPR outbreak were analyzed. Between 2010 and 2018, the epidemic in India broke out all over the country in a cluster distribution. Herd concentration in southern India is an area with high mortality of PPR, and the outbreak time of PPR has significant seasonality. Then, the analysis of the development and transmission of the disease showed that under the natural infection conditions without control measures, India reached the outbreak peak within 15 days. Finally, scenario tree quantitative risk analysis showed that the average probability of infecting PPRV in live sheep exported from India was 1.45×10-4. ConclusionsThis study analyzed the prevalence of PPR in India. The analysis of transmission dynamics on the development of the epidemic provides a reference for the prevention and control of the epidemic. At the same time, it provides risk analysis and suggestions on trade measures for the trading countries of India.
Experimental study on dynamics of the multi-individual clapping interacting system
Authors: Su Shilan , Xiao Jinghua , Gao Jian , Wu Ye
Published: February 2022

Clapping synchronization in the concert hall is one of the paradigmatic phenomena in daily life. Though the multi-individual clapping system has been widely investigated for its rich dynamics, little is known about the interaction - a foundation of synchronization. The goal of this study is to uncover the dynamics underlying interaction by observing individuals synchronizing clapping rhythms. We find three coupling states in the multi-individual clapping process: local synchronization, complete synchronization, and complete desynchronization. The statistical analysis shows that the clapping rhythms of arbitrary two individuals in the system exhibit long-range cross-correlations, i.e., the next clapping beat to be played by one individual is dependent on the entire history of the system. Surprisingly, we find that the mean-field for the system with a small number of individuals (N<5) is not necessary for the emergence of the synchronization process. To understand these findings, we propose a theoretical model for mutually interacting individuals, which can well reproduce the statistical characteristics of the multi-individual clapping process and suggest a physiologically motivated explanation for the occurrence of the multi-individual clapping synchronization. Though this study provides an understanding about the fundamental characteristics of the multi-individual clapping interacting system, the statistical framework and theoretical model may also be applied to study the dynamics of other complex systems with multiple coupled oscillators.
Ponatinib for RAS-Driven Multiple Myeloma: Efficacy in the High-Risk VQ Myeloma Model
Authors: Flietner Evan , Wen Zhi , Rajagopalan Adhithi , Jung Oisun , Wiesner Joshua , You Xiaona , Zhou Yun , Kingstad-Bakke Brock , Callander Natalie , Rapraeger Alan , Suresh M. , Asimakopoulos Fotis , Zhang Jing
Published: February 2022

Multiple myeloma (MM) is a malignant plasma cell cancer. Mutations in RAS pathway genes are prevalent in advanced and proteasome inhibitor (PI) refractory MM. As such, we recently developed a VQ MM mouse model recapitulating human advanced/high-risk MM. Using VQ MM cell lines we conducted a re-purpose screen of 147 FDA-approved anti-cancer drugs with or without trametinib (Tra), a MEK inhibitor. Consistent with its high-risk molecular feature, VQ MM displayed reduced responses to PIs and de novo resistance to the Bcl2 inhibitor, venetoclax. Ponatinib (Pon) is the only tyrosine kinase inhibitor that showed moderate MM killing activity as single agent and strong synergism with Tra in vitro. Combined Tra and Pon treatment significantly prolonged the survival of VQ MM mice regardless of treatment schemes. However, this survival benefit was moderate compared to that of Tra alone. Further testing of Tra and Pon on cytotoxic CD8 T cells showed that Pon, but not Tra, blocked T cell function in vitro, suggesting that the negative impact of Pon on T cells may partially counteract its MM-killing synergism with Tra in vivo. Our study provides strong rational to comprehensively evaluate agents on both MM cells and anti-MM immune cells during therapy development.
Role Of VEGFB In Electrical Pulse Stimulation Inhibits Apoptosis In C2C12 Myotubes
Authors: Guo LanLan , Li YanJun , Xing Zheng , Zhang JingBo , Zhang Jing
Published: February 2022

Skeletal muscle is the major effector organ for exercise. It has been proposed that the expression of VEGFB in skeletal muscle is significantly related to apoptosis. However, whether the decrease in VEGFB in skeletal muscle participates in the occurrence of skeletal muscle apoptosis and whether exercise inhibits apoptosis by promoting the expression of VEGFB in skeletal muscle cells have not been reported thus far. Here, we developed in vitro experiments to mimic the effect of exercise through electrical pulse stimulation (EPS) to observe the effect of EPS on apoptosis and the change in VEGFB expression in differentiated myotubes. In addition, we employed RNA interference experiments to explore whether VEGFB is directly involved in the regulation of myotube apoptosis during EPS. Our results showed that exogenous VEGFB167 significantly inhibited C2C12 myotube apoptosis induced by TNF-α treatment and that endogenous VEGFB in differentiated C2C12 myotubes was upregulated significantly by EPS. In addition, EPS decreased the expression of the apoptotic indicators Bax and Bcl-2 at the mRNA level and downregulated the protein expression of cleaved caspase-3. The antiapoptotic effect of EPS weakened substantially as VEGFB in C2C12 myotubes was inhibited. Taken together, exercise-like EPS inhibits apoptosis by promoting the expression of C2C12 myotube-derived VEGFB.
Screening of miRNA prognostic biomarkers of gastric adenocarcinoma and biological function analysis of their target genes
Authors: Zheng Guoliang , Yang Dong , Zhao Yan , Zheng Zhichao
Published: February 2022

Objective To identify microRNA (miRNA) prognostic biomarkers of stomach adenocarcinoma (STAD).Methods Bioinformatics analysis were performed by screening of miRNA sequencing and clinical data in TCGA-STAD database and identification of differentially expressed miRNAs (DEMs) using the R software package. The data were randomly divided (1:1) into a training set and a test set to construct a linear prognostic risk model of miRNAs for Cox regression analysis. To evaluate the predictive power of the prognostic model, Kaplan–Meier survival analysis and generation of receiver operating characteristic (ROC) curves were performed in the test group and all patients with gastric cancer, respectively. The miRNA-target genes were predicted using the prognostic model, and then their biological functions were analyzed. Results A total of 267 DEMs were identified (185 upregulated, 82 downregulated). The reliability of DEMs in the model was verified by qPCR. Five miRNAs (miR-135b-3p, miR-196b-3p, miR-942-3p, miR-143-5p, and miR-9-3p) were identified as independent prognostic factors by univariate and multivariate COX analyses. According to Kaplan–Meier survival analysis, the overall survival rate in the high-risk group was lower than that in the low-risk group. A total of 2,498 miRNA target genes were predicted, mainly enriched in Notch, MAPK, and TGF-beta signaling pathways. qPCR analysis confirmed that the five DEMs in the model were consistent with bioinformatics analysis results of the DEMs in the TCGA-STAD database. Conclusion The prognostic risk model with the five differentially expressed miRNAs can be used to predict the prognosis of STAD, which will help to further guide clinical treatment.
South Korean Validation of the COVID-related-PTSD Scale in a Non-clinical Sample Exposed to the COVID-19 Pandemic
Authors: Lee Hwa Jung , Kim Ye Jin , Lee Dong Hun
Published: February 2022

The threat of COVID-19 outbreak in South Korea and around the globe challenges on not only physical health but also on mental health, it can be referred to traumatic events to citizens. The aim of the present study is to examine the psychometric properties of Posttraumatic Stress Disorder Checklist (PCL-5), named as K-COVID-related-PTSD, which investigate PTSD symptomology in the context of COVID-19 pandemic in South Korea. Total of 1434 South Korean population were included in this study. The results of confirmatory factor analysis demonstrated a superior fit for the seven-factor hybrid model consisting of reexperiencing, negative affect, anxious arousal, dysphoric arousal, avoidance, anhedonia, and externalizing behaviors. Also K-COVID-related-PTSD showed high internal consistency and the validity (concurrent validity) was confirmed by that the scale was significantly associated with negative mental health outcomes (somatization, depression, anxiety, anger, stress, negative affect, job burnout, and suicidal ideation). Overall, the current results demonstrate the South Korean COVID-related-PTSD is a valid scale therefore can be considered for future pandemic related studies.
Fluoroscopy-only Based Interventional Closure of the Left Atrial Appendage in Patients With Atrial Fibrillation
Authors: Ebelt Henning , Linss Luisa , Roehl Peter , Pertschy Uta , Schwenzky Andreas
Published: February 2022

Objectives: The aim of this study was to determine whether echocardiography is dispensible during interventional LAA closure when preplanning is done by cardiac CT.Background: Interventional closure of the LAA is an established treatment alternative for patients with atrial fibrillation who are at risk for bleeding events under oral anticoagulation. Today, most LAAC procedures are guided by TEE which, however, leads to the need for patient sedation and might even cause direct harm to the patient. Technical improvements in device design and interventional experience might allow to abstain from TEE.Methods: Fluoro-FLX is a prospective single center study to evaluate how often TEE leads to a procedural change during interventional LAAC if a dedicated CT planning algorithm is applied and the newest generation of the WATCHMAN device (WATCHMAN FLX) is used. The study hypothesis is that under these circumstances fluoroscopy-only guided LAAC is non-inferior to a TEE-guided approach, the primary endpoint is defined as the percentage of LAAC procedures without interruption by TEE. All procedures are pre-planned by cardiac CT and finally guided by fluoroscopy only while TEE is carried out in the background during the intervention for safety reasons. Results: In none of 31 consecutive patients, TEE led to a change of the fluoroscopy-guided LAAC (success ratio: 1.00; CI: 0.94 – 1.00) thereby meeting the primary endpoint of non-inferiority. There were no procedure-related adverse cerebrovascular events (no pericardial effusion, TIA, stroke, systemic embolism, device embolism, death).Conclusions: Our data suggest that it is feasible to perform LAAC under sole fluoroscopic guidance if pre-planning is performed by cardiac CT and WATCHMAN FLX is used.
Short Periods of Bipolar Anodal TDCS Induce No Instantaneous Dose-Dependent Increase in Cerebral Blood Flow in the Targeted Human Motor Cortex
Authors: Liu Marie Louise , Karabanov Anke Ninija , Piek Marjolein , Petersen Esben Thade , Thielscher Axel , Siebner Hartwig Roman
Published: February 2022

Background
Anodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability. Yet, it is still unknown which current intensity produces the strongest effect on regional neural activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pc-ASL MRI) can map regional cortical blood flow (rCBF) and may thus be useful to probe the relationship between current intensity and neural response at the individual level.
Objective
Here we employed pc-ASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing.
Methods
Nine healthy right-handed participants received 30 seconds of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pc-ASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed.
Results
Apart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS.
Conclusion
Short-duration bipolar aTDCS does not produce instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity.
Clinical factors predicting the severity of obstructive sleep apnea in interstitial lung disease
Authors: Iijima Yuki , Tamaoka Meiyo , Shimada Sho , Yamana Takashi , Shibata Sho , Sakakibara Rie , Ejima Masaru , Honda Takayuki , Mitsumura Takahiro , Shirai Tsuyoshi , Okamoto Tsukasa , Furusawa Haruhiko , Tateishi Tomoya , Miyazaki Yasunari
Published: February 2022

Background and Objectives: Obstructive sleep apnea (OSA) is known to be one of the common complications of interstitial lung disease (ILD). Although it is suspected that the incidence of OSA and the progression of ILD are closely related to each other, the clinical features of ILD with such complications are not fully understood. The aim of this study is to clarify specific clinical factors in ILD patients that predict the complication and the severity of OSA.Study Design and Method: ILD patients in our institute were prospectively investigated for the incidence of OSA by polysomnography (PSG).Results: All 33 patients were diagnosed with OSA. Univariate regression analysis showed a lower Diffusing capacity of the lung for carbon monoxide (DLco) and a lower respiratory rate (RR) predicted a higher HI and a higher AI, respectively. Multivariate regression analysis showed a lower DLco and a lower RR also predicted a higher apnea hypopnea index (AHI).Conclusions: A high prevalence of OSA was exhibited in our study of ILD patients. Lacking rapid breathing pattern and impaired diffusing capacity were predictive factors for the severity of OSA. The examination of sleep disorders should be actively considered for these patients.Short title: The relationship between ILD and OSA
Towards defining muscular regions of interest from axial magnetic resonance imaging with anatomical cross-reference: A scoping review of lateral hip musculature
Authors: Perraton Zuzana , Lawrenson Peter , Mosler Andrea B. , Elliott James M. , II Kenneth A. Weber , Flack Natasha N. , Cornwall Jon , Crawford Rebecca J. , Stewart Christopher , Semciw Adam I.
Published: February 2022

Background
Measures of hip muscle morphology and composition (e.g., muscle size and fatty infiltration) are possible with magnetic resonance imaging (MRI). Standardised protocols or guidelines do not exist for evaluation of hip muscle characteristics, hindering reliable and valid inter-study analysis. This scoping review aimed to collate and synthesise MRI methods for measuring lateral hip muscle size and fatty infiltration to inform the future development of standardised protocols.
Methods
Five electronic databases (Medline, CINAHL, Embase, SportsDISCUS and AMED) were searched. Healthy or musculoskeletal pain populations that used MRI to assess lateral hip muscle size and fatty infiltration were included. Lateral hip muscles of interest included tensor fascia late (TFL), gluteus maximus, gluteus medius, and gluteus minimus. Data on MRI parameters, axial slice location, muscle size and fatty infiltrate measures were collected and analysed. Cross referencing for anatomical locations were made between MRI axial slice and E-12 anatomical plastinate sections.
Results
From 2692 identified publications, 79 studies contributed data on volume (n = 31), cross sectional area (CSA) (n = 24), and fatty infiltration (n = 40). Heterogeneity was observed for MRI parameters and anatomical boundaries scrutinizing hip muscle size and fatty infiltration. Seven single level axial slices were identified that provided consistent CSA measurement, including three for both gluteus maximus and TFL, and four for both gluteus medius and minimus. For assessment of fatty infiltration, six axial slice locations were identified including two for TFL, and four for each of the gluteal muscles.
Conclusions
Several consistent anatomical levels were identified for single axial MR slice to facilitate muscle size and fatty infiltration muscle measures at the hip, providing the basis for reliable and accurate data synthesis and improvements in the validity of future between studies analyses. This work establishes the platform for standardised methods for the MRI assessment of lateral hip musculature and will aid in the examination of musculoskeletal conditions around the hip joint. Further studies into whole muscle measures are required to further optimise methodological parameters for hip muscle assessment.
Moderate hyperuricemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency
Authors: Kurra Venla , Eräranta Arttu , Paavonen Timo , Honkanen Teemu , Myllymäki Juhani , Riutta Asko , Tikkanen Ilkka , Lakkisto Päivi , Mustonen Jukka , Pörsti Ilkka
Published: February 2022

Background: Hyperuricemia may predispose to renal damage, but in end-stage renal disease lower uric acid concentrations have been associated with higher mortality. In experimental studies, uric acid has promoted renal fibrosis and inflammation, but some studies have shown nephroprotective effects probably due to alleviated oxidative stress. We studied the influence of moderate hyperuricemia on kidney morphology in 5/6 nephrectomized rats.Methods: Three weeks after subtotal nephrectomy or sham-operation, rats were put on 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Blood pressure was monitored using tail-cuff. At close of the study, blood, urine, and kidney samples were taken, and renal histology, mast cell count, and oxidative stress markers were determined. Kidney tissue inflammation and fibrosis were evaluated using RT‑PCR and immunohistochemistry.Results: Oxonic acid diet increased plasma uric acid levels by >80 µmol/l without influencing blood pressure. Creatinine clearance was reduced by ~60% in both remnant kidney groups, and by ~30% in hyperuricemic sham-operated rats. In remnant kidney rats with suppressed plasma renin activity, moderate hyperuricemia decreased glomerulosclerosis, tubulointerstitial damage, and kidney mast cell count, but did not influence the fibrosis marker collagen I mRNA content. In both hyperuricemic groups, the mast-cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue COX‑2 levels were decreased.Conclusions: Hyperuricemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately increased plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental chronic renal insufficiency.
A mathematical model reveals the influence of NPIs and vaccination on SARS-CoV-2 Omicron Variant
Authors: Wang Bin-Guo , Wang Zhi-Cheng , Wu Yan , Xiong Yongping , Zhang Jiangqian , Ma Zhihui
Published: February 2022

A SVEIR SARS-CoV-2 Omicron variant model is proposed to provide some insight to coordinate non-pharmaceutical interventions(NPIs) and vaccination. Mathematically, we define the basic reproduction number R0 and the effective reproduction number Re to measure the infection potential of Omicron variant and formulate a optimal disease control strategy. Our inversion results imply that the sick period of Omicron variant in the United States is longer than that of Delta variant in Indian; The decreasing of the infectious period of the infection with infectiousness implies that the risk of hospitalization is reduced; but the increasing period of the infection with non-infectiousness signifies that Omicron variant lengthens the period of nucleic acid test being negative; Optimistically, Omicron's death rate is only a quarter of Delta's. Moreover, we forecast that the cumulative cases will exceed 100 million in the United States on 28 February, 2022 and the daily confirmed cases will reach a peak on 2 February, 2022. The results of parameters sensitivity analysis imply that NPIs is helpful to reduce the number of confirmed cases. Especially, NPIs are indispensable even if all the people were vaccinated when the efficiency of vaccine is relatively low. By simulating the relation ships of the effective reproduction number Re , the vaccination rate and the efficacy of vaccine, we find that it is impossible to achieve the herd immunity without NPIs while the efficiency of vaccine is lower than 88.7%. Therefore, the herd immunity area is defined by the evolution of relationships between the vaccination rate and the efficacy of vaccine. Finally, we present that the disease-induced mortality rate demonstrates the periodic oscillation and an almost periodic function is deduced to match the curve. A discussion completes the paper.AMS Subject Classification (2020): 34A34; 34D20; 92D30