bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable representation of a naturalistic movie emerges from episodic activity with gain variability
Authors: Xia Ji , Marks Tyler , Goard Michael , Wessel Ralf
Published: January 2021

Visual cortical responses are known to be highly variable across trials within an experimental session. However, the long-term stability of visual cortical responses is poorly understood. Chronic imaging experiments in V1 showed that neural responses to repeated natural movie clips were unstable across weeks. Single neuronal responses consisted of sparse episodic activity which were stable in time but unstable in spike rates across weeks. Further, we found that the individual episode, instead of neuron, served as the basic unit of the week-to-week fluctuation. To investigate how population activity encodes the stimulus, we extracted a stable one-dimensional representation of the time in the natural movie, using an unsupervised method. Moreover, most week-to-week fluctuation was perpendicular to the stimulus encoding direction, thus leaving the stimulus representation largely unaffected. We propose that precise episodic activity with coordinated gain changes are keys to maintain a stable stimulus representation in V1.
Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing
Authors: Wang Zhoufeng , Li Zhe , Zhou Kun , Zhang Li , Yang Ying , Luo Wenxin , Qiao Wenliang , Wang Chengdi , Wang Gang , Ni Yinyun , Dai Shuiping , Guo Tingting , Ji Guiyi , Xu Minjie , Liu Yiying , Su Zhixi , Che Guowei , Li Weimin
Published: January 2021

Lung adenocarcinomas (LUAD) start as precancerous lesions such as atypical adenomatous hyperplasia (AAH), develop stepwise into adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), then eventually progress toward invasive adenocarcinoma (IA). To date the cellular heterogeneity across these distinct clinical stages and the underlying molecular events driving tumor progression remain largely unclear. In this study, we performed single-cell RNA sequencing on 52 specimens from 25 patients spanning the four clinical stages. By assessing the expression pattern of marker genes among 268,471 cells, we identified 16 major cell types. We demonstrated that AT2 feature cell types (AT2-like cells) were associated with malignant composition. AT2-like subcluster emerged first in AAH and partially lost AT2 cell transcriptional identity, accompanied with a gain of stemness during cell transition. In addition, genes related to energy metabolism, ribosome synthesis were upregulated in the early stage of LUAD, leading us to identify new markers including miRNA10 and β-hydroxybutyric acid to diagnose early-stage LUAD noninvasively in the blood. We also identified MDK and TIMP1 as potential biomarkers to facilitate our understanding of LUAD pathogenesis. Taken together, our data identified a new mechanism in LUAD evolution, and provided a robust basis for diagnosis and treatment of LUAD.
Demand-side solutions to climate change mitigation consistent with high levels of wellbeing
Authors: Creutzig Felix , Niamir Leila , Bai Xuemei , Cullen Jonathan , Díaz-José Julio , Figueroa Maria , Grübler Arnulf , Lamb William , Leip Adrian , Masanet Eric , Mata Erika , Mattauch Linus , Minx Jan , Mirasgedis Sebastian , Mulugetta Yacob , Nugroho Sudarmanto , Pathak Minal , Perkins Patricia , Roy Joyashree , du Can Stephane de la Rue , Saheb Yamina , Steg Linda , Steinberger Julia , Ürge-Vorsatz Diana
Published: January 2021

Climate mitigation solutions are often evaluated in terms of their costs and potentials. This accounting, however, shortcuts a comprehensive evaluation of how climate solutions affect human well-being, which, at best, may only be crudely related to cost considerations. Here, we systematically list key sectoral mitigation options on the demand side, and categorize them into avoid, shift and improve categories. We show that these options, bridging socio-behavioral, infrastructural and technological domains, can reduce counterfactual sectoral emissions by 50-80% in end use sectors. Based on expert judgement and literature survey, we then evaluate 324 combinations of wellbeing outcomes and demand side options. We find that these are largely beneficial in improving wellbeing across all measures combined (76% have positive, 22% neutral, and 2.4% have negative effects), even though confidence level is low in the social dimensions of wellbeing. Implementing demand-side solution requires i) an understanding of malleable not fixed preferences, ii) consistently measuring and evaluating constituents of wellbeing, and iii) addressing concerns of incumbents in supply-side industries. Our results shift the emphasis in the climate mitigation solution space from supply-side technologies to demand-side service provision.
All-in-one rheology of multicellular aggregates
Authors: Mary Gaëtan , Mazuel François , Nier Vincent , Fage Florian , Nagle Irène , Devaud Louisiane , Bacri Jean-Claude , Asnacios Sophie , Asnacios Atef , Gay Cyprien , Marcq Philippe , Wilhelm Claire , Reffay Myriam
Published: January 2021

Tissues are generally subjected to external stresses, a potential stimulus for their differentiation or remodelling.
While single-cell rheology has been extensively studied, mechanical tissue behavior under external stress
is still poorly known because of a lack of adapted set-ups. Herein we introduce magnetic techniques designed both to form aggregates of controlled size, shape and content
(magnetic molding) and to deform them under controlled applied stresses over a wide range of timescales and amplitudes (magnetic rheometer).
We explore the rheology of multicellular aggregates (F9 cells) using both standard assays (creep and oscillatory response) and an innovative broad spectrum solicitation coupled with inference analysis.
We find that multicellular aggregates exhibit a power-law response with non-linearities leading to tissue stiffening at high stress. Comparing magnetic measurements on aggregates to isolated F9 cells characterization by parallel-plates rheometry, we reveal the role of cell-cell adhesions in tissue mechanics. Thanks to its versatility, the magnetic rheometer thus stands as an essential tool
to investigate model tissue rheology.
Tailoring P-N Conversion in All-solid-state Polymer Composites with A Record Ionic Thermopower
Authors: Chi Cheng , An Meng , Qi Xin , Li Yang , Zhang Ruihan , Liu Gongze , Huang He , Dang Hao , Wang Yan , Ma Weigang , Huang Baoling , Zhang Xing
Published: January 2021

All-solid-state organic polymer composites are promising ionic thermoelectric (i-TE) materials, however, the transition from aqueous to organic gelation always sacrifices their thermoelectric performance, especially the n-type thermopowers are severely unexplored, leaving the unrealized large-scale application of p-n integrated i-TE devices. Herein, we successfully developed all-solid-state PVDF-HFP/NaTFSI/PC (PhNP) with ultrahigh thermopower (Si) of +20 mV K-1. The experimental and molecular simulation results detailly specified the relationship between the interactions among ions and polymers and the highly enhanced thermopower. Meanwhile, a major scientific breakthrough in p-n conversion from +20 to -6 mV K-1 was achieved by incorporating tris(pentafluorophenyl)borane (TPFPB) to capture Na+ and TFSI- anions dominating the thermodiffusion process. As a result, an all-solid-state i-TE generator generated a high voltage over 2.6 V at ΔT=10 K and exhibited excellent cyclic stability under ambient air condition employing only 13 pairs of p-n couples, showing great potential for developing high-performance i-TE systems.
Propensity Score Analysis Comparing Survival Between Definitive Chemoradiotherapy and Esophagectomy with Adjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma
Authors: Chang Yi Lin , Cheng Ya Fu , Chen Hui Shan , Wu Siao Chi , Hung Wei Heng , Chen Heng Chung , Huang Chang Lun , Cheng Ching Yuan , Wang Bing Yen
Published: January 2021

Background: The purpose of the current study is to compare definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with cT1-3/N0-3 esophageal squamous cell carcinoma in survival.Methods: Records from 2008 to 2014 of 4931 patients with clinical T1-3/N0-3 esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or esophagectomy with adjuvant chemoradiotherapy were obtained from the Taiwan Cancer Registry. Univariable and multivariable analyses were performed and propensity score matching was used to minimize the bias. Overall survival was compared between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy, and also in the three different clinical stages.Results: Definitive chemoradiotherapy was performed on 4381 patients, and 550 patients received esophagectomy adjuvant chemoradiotherapy. Each group produced 456 patients for comparison after propensity score matching. The 1-year, 2-year, and 3-year overall survival rates for matched patients in with definitive chemoradiotherapy group were 57.18%, 31.92%, and 23.8%. The 1-year, 2-year, and 3-year overall survival rates for matched patients treated in the esophagectomy with adjuvant chemoradiotherapy group were 72.35%, 45.74%, and 34.04%(p<0.0001). In multivariable analysis, treatment modality was an independent prognostic factor. Esophagectomy with adjuvant chemoradiotherapy provided better survival outcome than definitive chemoradiotherapy for patients with clinical stage II/III disease. As for patients with clinical stage I disease, there was no significant survival difference between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy.Conclusions: Esophagectomy with adjuvant chemoradiotherapy provided better survival than definitive chemoradiotherapy in clinical II/III esophageal squamous cell carcinoma. However, more data are needed to conduct a convincing conclusion in clinical stage I patients.
The RNA-binding protein RGGA is a sugar-responsive cofactor of the 5'-3' exonuclease XRN4 that post-transcriptionally meditates plant growth
Authors: Liu Hongmei , Yu Ru , Zhang Hong , Gao Xinlei , Zhu Changxiang , Wu Changai , Geng Liwei , Du Jinwen , Ma Haoran , Song Yunzhi , Zhou Shumei
Published: January 2021

Sugar-regulated gene expression is a ubiquitous mechanism for carbohydrate allocation and utilization by keeping a balance among source and sink organs in plants. Previous studies have shown that excess sugar represses the expression of the genes implicated in photosynthesis and sugar metabolism. However, the mechanism is still largely unknown. Here, we found that the mutant of Arabidopsis RGGA, RGG repeats RNA-binding protein A coding gene, grew faster than wild type (Col-0) in MS medium. In rgga, mRNA half-live of the genes related to sucrose transport and metabolism, chlorophyll synthesis, root development as well as certain transcription factors was obviously longer than those of Col-0. Further study revealed that AtRGGA could interact with 5'-3' exonuclease AtXRN4, and guide it to the target mRNAs for their degradation. When AtRGGA is absent or its interaction domain is deleted, AtXRN4 self can't recognize the target mRNAs, which leads to a dramatically increase in transcript levels of the above gene subsets, and thus promotes the growth of Arabidopsis with exogenous sucrose supply. And only 5-day sucrose supply could trigger the vigorous growth of rgga. These findings suggest that the regulation of mRNA stability mediated by RGGA plays a critical role in sugar suppression, and implicates a possibility to unlock the growth potential by modulating sugar utilization at post-transcriptional level in plants.
Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer
Authors: Patwa Aalok , Yamashita Rikiya , Long Jin , Keren Leeat , Angelo Michael R. , Rubin Daniel
Published: January 2021

Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.
The Effect of Kuchala (Arum Korolkowii Regel, 1873) Tuber Tincture to Increase of the Serum Testosterone in the Adult Male Guinea Pigs (Cavia Porcellus Linnaeus, 1758)
Authors: Aldayarov Nurbek , Jumabekova Jarkinay , Kurmanbekova Gulbubu , Omurzakova Nurjamal , Kydyralieva Bermet , Sharshenalieva Gulnara , Borkoev Bakyt , Salieva Kalipa , Tulobaev Askarbek , Salykov Ruslan , Chekirov Kadyrbay
Published: January 2021

Background: Kuchala (Arum korolkowii Regel) is a medicinal plant often used in folk medicine in the Kyrgyz Republic. As a medicinal raw material, the tuber’s tincture is used in small doses to increase human sexual potency. However, there is no scientific evidence in support of the medicinal effects of kuchala. For these reasons, we decided to study the pharmacological effect of kuchala tuber tincture on the sexual potency of adult male guinea pigs. We analyzed the effect of kuchala at the age of ±48-months, in 12 male guinea pigs. A preparation of 10% tuber tincture of kuchala in 70% ethanol was administered perorally to the male guinea pigs in the form of a once-daily dose of 150 µl for 30 days. The study data were obtained by ethological, hematological and serum biochemistry, gross anatomical, histological and statistical methods.Results: The hematological and serum biochemistry parameters were significantly different between the control and the experimental group. The neutrophils’ percentage in the experimental group was significantly lower (dР < 0.001) than in the control group. On the other hand, the lymphocyte counts were significantly higher in the experimental group (dР < 0.001). The RBC counts, Hgb, Hct, MCH and MCHC were significantly higher in the experimental group (dР < 0.001; dР < 0.001; cР < 0.01; dР < 0.001; dР < 0.001 respectively) than in the control group. In contrast, the color indicator and the mean platelet volume were higher (bР < 0.05) and significantly higher (dР < 0.001) respectively in the control group than in the experimental group. The ALT and AST levels were lower in the experimental than in the control group (both dР < 0,001). The testosterone concentration in serum was much higher (dР < 0,001) in the experimental group. Microscopically, some structural damages were found in the liver of the experimental animals indicating a metabolic disorder. However, the testes showed an improvement in spermatogenesis in the experimental compared with the control group.Conclusions: The 10% kuchala tuber tincture in 70% ethanol has a positive effect in terms of improving the sexual potency of adult guinea pigs by increasing the production of testosterone and increasing spermatogenesis.
LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8
Authors: Allen Ryan , Michell Danielle , Cavnar Ashley , Zhu Wanying , Makhijani Neil , Contreras Danielle , Raby Chase , Semler Elizabeth , DeJulius Carlisle , Castleberry Mark , Zhang Youmin , Ramirez Marisol , Zhao Shilin , Duvall Craig , Doran Amanda , Sheng Quanhu , Linton MacRae , Vickers Kasey
Published: January 2021

Macrophages present a spectrum of phenotypes that mediate both the pathogenesis and resolution of atherosclerotic lesions. Inflammatory macrophage phenotypes are pro-atherogenic, but the natural factors that instigate this polarization are largely unknown. Here, we demonstrate that microbial small RNAs (msRNA) are enriched on LDL and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of the ribonucleic acid sensor toll-like receptor 8 (TLR8). Removal of msRNA cargo during LDL re-constitution yields particles that readily promote sterol loading but fail to stimulate inflammatory activation. Competitive antagonism of TLR8 with non-targeting locked nucleic acids (nt-LNA) was found to prevent nLDL-induced macrophage polarization in vitro, and re-organize lesion macrophage phenotypes in vivo, as determined by single-cell RNA sequencing. Critically, this was associated with reduced disease burden in distinct mouse models of atherosclerosis. These results identify LDL-msRNA as instigators of atherosclerosis-associated inflammation and support alternative functions of LDL beyond cholesterol transport.
Estimating genetic variability among diverse lentil collections through novel multivariate techniques
Authors: Iqbal Muhammad Sajjad , Hussain Syed Atiq , Akbar Muhammad , Ilyas Kashif , Ghafoor Abdul , Arshad Noshia , Munir Saba , Ali Muhammad Azhar , Masood Hajra , Zafar Samina , Ahmad Tahira , Shaheen Nazra , Mashooq Rizwana , Sajjad Hifsa , Zahoor Munaza , Bashir Faiza , Shahbaz Khizra , Arshad Hamna , Fatima Noor , Nasir Faiza , Hashmi Aysha Javed , Chaudhary Sofia , Islam Muhammad
Published: January 2021

Lentil is a significant legume crop throughout the world where Pakistan stands at 18th position with 8610 tons from 17457 hectares. It is nutritionally rich in protein, carbohydrates, mineral, fat and fiber that can potentially meet food security resolving malnutrition issues. Lentil 220 collections representing Pakistan 184, Syria 14, USA 22 and 04 of unknown origin were studied for high yield, yield contributing traits and early cooking time. Results revealed high variability, 6122 (Pakistan) was considered as best during both years due to its performance as seed yield (68 ± 1.7), biological yield (264 ± 2.8), pod size (0.61 ± 0.01), seed per pod (2), cooking time (11 minutes) and hard seed (0). Comparatively 6122 (Pakistan) and 6042 (Syria) produced the highest biological yield which could also be an efficient source for fodder. 5698 (Pak) and 6015 (USA) took 161–172 days in 2018 while 24783 (unknown) and 5561 (Pak) were matured early in 2019. Lowest cooking time 10 minutes was observed in 6074 and 5745 of Pakistani origin. Lentil with the lowest cooking time saves energy and resources, develops adequate flavor, texture and improves protein digestibility. Pearson correlation matrix, Principal component analysis, structural equational model, cluster analysis, heritability showed promising results. In conclusion 12 genotypes were selected on high yield potential and recommended for lentils breeding including 5664, 5687, 6084, 6062, 6122, 6058, 6087, 5689, 6042, 6074, Markaz 2009 & Punjab 2009.
A Novel Survival Model Based on Ferroptosis-related Gene Signature for Overall Survival Prediction in Bladder Cancer
Authors: Liang Yingchun , Ye Fangdie , Xu Chenyang , Zou Lujia , Hu Yun , Jiang Haowen
Published: January 2021

Background: The effective treatment and prognosis prediction of bladder cancer(BLCA) remains a medical problem. Ferroptosis is an iron-dependent form of programmed cell death. Ferroptosis are closely related to tumor occurrence and progression, but the prognostic value of ferroptosis-related genes (FRGs) in BLCA remains to be further clarified. In this study, we identified a FRGs signature with potential prognostic value for patients with BLCA. Methods: The corresponding clinical data and the mRNA expression profile of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to extract FRGs related to survival time, Cox regression model was applied to construct a multigene signature. Both principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were performed for functional annotation. Results: Clinical traits were combined with FRGs, so that 15 prognostic-related FRGs were identified by Cox regression. High expression of CISD1, GCLM, CRYAB, SLC7A11, TFRC, ACACA, ZEB1, SQLE, FADS2, ABCC1, G6PD and PGD are related to poor survival rates of BLCA patients. Multivariate Cox regression constructed a prognostic model with 7 FRGs and divided patients into two risk groups. Compared with the low-risk group, the overall survival(OS) of patients in the high-risk group was significantly lower (P <0.001). In multivariate regression analysis, the risk score was shown to be an independent predictor of OS (HR> 1, P <0.01). ROC curve analysis verified the predictive ability of the model. In addition, the two risk groups displayed different immune statuses in the ssGSEA and different distributed patterns in PCA. Conclusion: Our research suggests that a new gene model related to ferroptosis can be applied for the prognosis prediction of BLCA. Targeting FRGs may be a treatment option for BLCA.
The Effects of Working Hours on Health Based on China’s Observations
Authors: Chu Liming
Published: January 2021

Background: At a time of rapid economic development, the quality of the labor force is an issue worthy of attention, and health is an important factor in the quality of the labor force. In recent years, the working hours of the workers have been continuously extended, and excessive labor has gradually become a common phenomenon, directly affect the health level of workers, but also not conducive to social stability and economic development.To understand the relationship between labor market performance and health is of great significance to expand the factors influencing the health level of labor force.Method: From the perspective of working hours, this study uses China Family Panel Studies(CFPS) data and order probit model to explore the impact of working hours on labor health, further analyze the heterogeneity of whether to participate in medical insurance, and explore the difference of education level.Result: First, the depreciation rate of healthy capital increases, and the increment of healthy capital decreases, thus lowering the health level of the labor force. Second, working hours have a more significant impact on the self-rated health of the labor force who does not participate in medical insurance. Thirdly, the work time of junior high school and below has more significant impact on self-rated health, and the work time of labor who is not in the 41-50 age stage has more significant impact on health.Conclusion: This paper focuses on the relationship between working hours on workforce health using the oprobit model. Based on the literature on the impact of workforce health levels, the variables are tightly controlled to address estimation bias caused by omitted variables and to ensure the credibility of the results.
Microarray Profiling in Fibrogenesis Imperfecta Ossium
Authors: Dhiman Vandana , Saini Samarth , Bhadada Sanjay , Bhasin Manoj , Rao Sudhaker
Published: January 2021

Fibrogenesis imperfecta ossium (FIO) is a rare, metabolic bone disease clinically characterized by generalized bone pain and fragility fractures in both the axial and appendicular skeleton. The etiology of the disease is unknown and the pathogenesis is poorly understood. In this disorder, collagen arrangement in the bone is disorganized , and causes abnormalities in the organic bone matrix. Genetic cues causing this defect in collagen arrangement are largely undetermined. Microarray analysis showed remarkable changes in gene expression , when we compared gene expression of FIO with the control. Differential gene expression analysis revealed 50 gene signatures, which can be used to organize novel ways to diagnose and treat FIO patients.
A study of the Relationship between Human Capital Accumulation and Economic Growth: A case of Liberia
Authors: Dukuly Faliku S. , Huang Kun
Published: January 2021

The neutral of this study is to examine the human capital effect on Liberia’s economic growth and empirically estimates the contribution of human capital accumulation within the Liberian economy from 2000 to 2019. We used a time-series data of linear regression (OLS) model where data is taken from the World Bank Development Indicators to test our observed variables using the Eviews7 statistical tool. The final linear regression model displayed Population (POP) growth rate as a positive and significant factor for GNI accumulation, while the model predicates government HEALTH expenditure, LIFE expectancy at birth, and foreign AID to be negative and not significant statistically. The result raises a concern that low expenditure on health could cause limited life expectancy and also hinder the attainment of human capital while placing the overall labor force at risk in the Liberian economy.
Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia Via Nrf2 Antioxidation Pathway Dependent Cerebral Microvascular Protection
Authors: Fan Xiao-Di , Yao Ming-Jiang , Yang Bin , Han Xiao , Wang Guang-Rui , Li Peng , Xu Li
Published: January 2021

Background: Stroke is one of the most devastating diseases worldwide. Chinese herbal preparation SaiLuoTong capsule (SLT) showed outstanding therapeutic effects over stroke and its sequelae. This study is to elucidate the mechanism. Methods: We duplicated cerebral ischemia model in rats by permanent MCAO, and simulated ischemia injury in cultured hCMEC/D3 cells with oxygen and glucose deprivation/reoxia (OGD/R); we treated them with SLT. Brain infarction volumes and micromorphology were examined with TTC and HE stainings, respectively; neurological function injuries were valued with deficits scoring; brain water contents were measured with the wet-dry method; and expressions of claudin-1, occludin, Nrf2 and HO-1 were examined with western blot assay and immunohistochemstry or immunocytofluorescnce stainings; activities of SOD and contents of GSH were measured by colorimetric method; cell viabilities were measured by CCK8 method; cell monolayer permeabilities were assessed by FITC-dextran diffusion method. Results: SLT (33 mg/kg) significantly decreased infarction volumes, relieved neuron degenerations and neuron loss, and ameliorated neurological functions; SLT also significantly inhibited elevations in brain water content and decreases of claudin-1 and occludin expressions; additionally SLT significantly increased the nucleus translocation of Nrf2, elevated expression of HO-1, and raised activity of SOD and content of GSH (p<0.05 or 0.01, compared with the model group, in quantitative data). These testified SLT’s anti-stroke effect, and hint the possible key role of cerebral blood vascular endothelial cells (CBVEC) protection and Nrf2 pathway in SLT’s therapy. In hCMEC/D3 cells, SLT significantly inhibited the drop in cell viabilities; SLT also significantly facilitated the nucleus translocation of Nrf2, and increased the expression of HO-1, the activity of SOD, and the content of GSH (in comparison to the model group, p<0.05 or 0.01). Lastly, the anti-OGD/R effects of SLT in hCMEC/D3 cells, including raising cell viabilities, inhibiting the elevation in cell monolayer permeabilities, and preserving the expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. These undoubtedly confirmed SLT’s protective effect on CBVEC and the obligatory role of Nrf2 pathway in it. Conclusion: SLT’s therapeutic effect on brain ischemia is related to its protection on CBVEC, which is dependent on the activation of Nrf2 pathway.
Use of Vasopressors Increases the Risk of Mortality in Severe Traumatic Brain Injury: A Nationwide Retrospective Cohort Study in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Hirayama Atsushi , Ogura Hiroshi , Shimazu Takeshi
Published: January 2021

Background: Pharmacological elevation of blood pressure is frequently incorporated in severe traumatic brain injury (TBI) management algorithms. However, there is limited evidence on prevalent clinical practices regarding resuscitation for severe TBI using vasopressors. We conducted a nationwide retrospective cohort study to determine the association between the use of vasopressors and mortality following discharge from hospital in patients with severe TBI, and to determine whether the use of vasopressors affects emergency department mortality or the occurrence of cognitive dysfunction.Methods: Data were collected between January 2004 and December 2018 by the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged ≥ 16 years with severe TBI, without other major injuries, were examined. A severe TBI was defined based on the Abbreviated Injury Scale code and a Glasgow Coma Scale score of 3–8 on admission. Multivariable and propensity score matching analyses were performed. Statistical significance was assessed using a 95% CI.Results: In total, 10,284 patients were eligible for analysis, with 650 patients (6.32%) included in the vasopressor group and 9,634 patients (93.68%) included in the non-vasopressor group. The proportion of deaths on hospital discharge was higher in the vasopressor group than in the non-vasopressor group (81.69% [531/650] vs. 40.21% [3,874/9,634]). This finding was confirmed by multivariable logistic regression analysis (adjusted odds ratio [OR], 5.71; 95% confidence interval [CI]: 4.56–7.16). Regarding propensity score-matched patients, the proportion of deaths on hospital discharge remained higher in the vasopressor group than in the non-vasopressor group (81.66% [530/649] vs. 50.69% [329/649]) (OR, 4.33; 95% CI: 3.37–5.57). The vasopressor group had a higher emergency department mortality rate than the non-vasopressor group (8.01% [52/649] vs. 2.77% [18/649]) (OR, 3.05; 95% CI: 1.77–5.28). There was no reduction in complications of cognitive disorders in the vasopressor group (5.39% [35/649] vs. 5.55% [36/649]) (OR, 0.97; 95% CI: 0.60–1.57).Conclusions: In this population, the use of vasopressors for severe TBI was associated with higher mortality on hospital discharge. Our results suggest that vasopressors should be avoided in most cases of severe TBI.
Negative Drift of Sedation Depth In Critically Ill Patients Receiving Constant Minimum Alveolar Concentration of Isoflurane, Sevoflurane, or Desflurane: A Randomized Controlled Trial
Authors: Georgevici Adrian Iustin , Kyprianou Theodoros , Herzog-Niescery Jennifer , Procopiuc Livia , Loganathan Sivakkanan , Weber Thomas Peter , Bellgardt Martin
Published: January 2021

Background: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC’s reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0 – awake N_Index 100), might drift downward over time despite constant MAC values.Methods: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. Results: Thirty patients were recruited (female/male: 10/20, age 64±11, Simplified Acute Physiology Score II 30±10). In the first 24 hours, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58±0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index=43−0.7·hours (R2=0.76), showing a strong negative correlation between sedation’s duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43–0.9, 45–0.8, and 43–0.4·hours for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group.Conclusions: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration.Trial registration: NCT03860129.
Recombinant Adenovirus Expressing Vesicular Stomatitis Virus G Proteins Induce both Humoral and Cell-mediated Immune Responses in Mice and Goats
Authors: Xue Xiaojuan , Yu Zhaorong , Jin Hongyan , Liang Lin , Li Jiayang , Li Xiaolu , Wang Yong , Cui Shangjin , Li Gang
Published: January 2021

Background: Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines.Results: Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions: The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.
Effects of Unweighting on Gait Kinematics During Walking on a Lower-Body Positive-Pressure Treadmill in Patients with Hip Osteoarthritis
Authors: Kataoka Yoshiaki , Shimizu Tomohiro , Takeda Ryo , Tadano Shigeru , Saito Yuki , Osuka Satoshi , Ishida Tomoya , Samukawa Mina , Irie Tohru , Takahashi Daisuke , Iwasaki Norimasa , Tohyama Harukazu
Published: January 2021

Background: Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activities. Treadmills that support the body weight (BW) reduce the load on the lower limbs, and those equipped with a lower-body positive-pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device. Methods: A total of 15 women with hip OA and 15 age-matched female controls wore a three-dimensional (3-D) motion analysis system and walked at a self-selected speed on the LBPP treadmill. Data regarding self-reported hip pain using a numeric rating scale (NRS) in which the scores 0 and 10 represented no pain and the worst pain, respectively, under three different BW conditions (100%, 75%, and 50%) were collected. Moreover, 3-D peak joint angles during gait under each condition were calculated and compared. Results: In the hip OA group, the NRS pain scores at 50% and 75% BW conditions significantly decreased compared with that at 100% BW condition (50%, P=0.002; 75%, P=0.026), and the peak hip extension angle decreased compared with that in the healthy controls (P=0.044). In both groups, unweighting significantly decreased the peak hip (P<0.001) and knee (P<0.001) flexion angles and increased the peak ankle plantar flexion angle (P<0.001) during walking. Conclusions: Unweighting by the LBPP treadmill decreased pain in the hip OA group but did not drastically alter the gait kinematics compared with that in the control group. Therefore, regarding the use of the LBPP treadmill for patients with hip OA, clinicians should consider the benefits of pain reduction rather than the kinematic changes.
Frailty Indexed Classification of Bangladeshi Older Adults’ Physio-psychosocial Health and Associated Risk Factors- A Cross-sectional Survey Study
Authors: Rahman Mohammad Meshbahur , Hamiduzzaman Mohammad , Akter Saleha , Farhana Zaki , Hossain Mohammad Kamal , Hasan Mohammad Nayeem , Islam Md. Nazrul
Published: January 2021

Background: Frailty is associated with healthy ageing, and it has been identified as a means of measuring older adults’ physio-psychosocial health. We know about the ageing trends and common diseases of older adults living in South Asia, but literature to date does not widely feature their health status based on frailty, especially in Bangladesh. This study aims to understand the prevalence of frailty in Bangladeshi older adults; classify their health status; and investigate associated risk factors. Methods: A cross-sectional study was conducted in the north-eastern region (i.e. Sylhet City Corporation) of Bangladesh. Four hundred participants aged 55 years and above were randomly selected, attended a health assessment session and completed a multi-indicator survey questionnaire. We developed a 30-indicator Frailty Index (FI30) to assess the participant’s health status and categorized: good health (no-frailty/Fit); slightly poor health (mild frailty); poor health (moderate frailty); and very poor health (severe frailty). Pearson chi-square test and binary logistic regression analysis were conducted.Results: The participants’ mean age was 63.6 years, and 61.6% of them were assessed in poor to very poor health (moderate frailty/36.3% - severe frailty/25.3%). The eldest, female and participants from lower family income were found more frailty than their counterparts. Participants aged 70 years and above were more likely (adjusted OR: 4.23, 95 % CI: 2.26–7.92, p < 0.0001) to experience frailty (medical conditions) than the pre-elderly age group (55-59 years). Female participants were more vulnerable (adjusted OR=1.487, 95% CI: 0.84-2.64, p < 0.0174) to frailty (medical conditions) than male. Also, older adults who had higher family income (Income>$473.3) found a lower risk (adjusted OR: 0.294, 95% CI: 0.11-0.76, p<0.011) of frailty (poor health).Conclusion: Our study results confirm the prevalence of frailty-related disorders in Bangladeshi older adults and highlight the importance of targeted clinical and community-led preventive care programs.
Use of community-based interventions to promote Family Planning use among Pastoralist women in Ethiopia: Cluster randomized controlled trial
Authors: Alemayehu Mussie , Medhanyie Araya Abrha , Reed Elizabeth , Bezabih Afework Mulugeta
Published: January 2021

Background: - Afar region is one of the pastoralists dominated regions in Ethiopia. The region is characterized by a low contraceptive prevalence rate (CPR) with 5.4%. Lack of awareness, husband objection, and religious influence was the reasons attributed to low CPR in the region. As objective we assessed the effect of a community-based interventions for promoting FP use among pastoralist communities of Afar region state, Ethiopia.Methods: The design was parallel, cluster randomized controlled trial (CRT) recruiting married women. It had three arms: 1) women’s education on FP, 2) male involvement in FP education and 3) control with one to one ratio. A total of 33 kebeles (lowest administrative structure) were randomized and allocated. Women’s FP education and male involvement in FP education were the interventions. It was implemented using 1) health education on FP to married women and men by faema leaders (a traditional community-based structure that serves as a social support group) 2) Video-assisted message on FP, and 3) Assisting the faema leader using health workers. The intervention was given for a total of 9 months. FP use and intentions were measured as outcome variables based on woman’s perspectives. Cluster level summaries considering a cluster effect analysis was performed. The result was presented with adjusted risks and 95% CI. A p-value <0.05 was used to declare statistically significant.Results: There was a positive change in the proportion of married women who use FP in the women’s FP education arm, absolute risk (AR) of 0.13(95% CI,0.08,0.17) and male involvement arm with AR of 0.29 (95% CI, 0.23,0.34) as compared to the control arm. In the control arm, the proportion of FP use was 4.3%, whereas it was 17.5% with women who receive FP education and 34% in the male involvement arm. Furthermore, the proportion of married women who had high intention to use FP was high in arms of women’s FP education and male involvement with AR=3.4(95% CI: 2.48,4.91) and AR=2.1 (95% CI: 1.5,2.95), respectively as compared with the control arm. Conclusion: The present study highlighted the effctienesswomen’s education on FP and male involvement in FP education brings a significant change in increasing the number of women who use FP and intention. Using the community-led support groups in the pastoralist community appears to be effective in increasing the number of women FP users and intention to use.Trial registration: NCT03450564
Self-reported Morbidities, Nutritional Characteristics, and associated factors in Institutionalized and Non-Institutionalized Elderly
Authors: Abdelhafid Benksim , Rachid Ait Addi , Elhassania Khalloufi , Aziz Habibi , Mohammed Cherkaoui
Published: January 2021

AbstractBackground: As the world's population ages and people live longer, it seems important to ensure that older people have a good quality of life and positive subjective well-being. The objective of this study is to determine socio-economic, health and nutritional characteristics of institutionalized and non-institutionalized elders in the province of Marrakech.Methods: This study was conducted among 368 elderly people in the province of Marrakech between March 2017 and June 2019. Of all participants, 180 elderly people reside in a public establishment and 188 of them live at home. Data on health conditions, nutritional status, functional and socio-economic characteristics were collected. Statistical analysis used SPSS software.Results: Institutionalized elders were illiterate (80.0%), had low incomes (95.5%), and unmarried (73.3%).They reported no children (56.1%) and no health insurance (98.9%). Institutional residents suffered from malnutrition (22.2%), hearing impairments (35.6%) and severe edentulism (43.3%). There was no significant difference between both groups on daily activities and depression. A multivariate analysis identified a model with three significant variables associated with non-institutionalized elders: health insurance (P=0.001; OR=107.49), number of children (P=0.001; OR=1.74) and nutritional status (p=0.001; OR=3.853). The data were analyzed by using SPSS version 16.0. Statistical significance was set at p<0.05.Conclusions: This study shows that the institutionalization of the elderly is considerably induced by various factors such as nutritional problems, lack of health insurance and family structure. To mitigate the effects of this phenomenon, home care strategies and preventive actions should be carried out to delay the referral of the elderly to institutions and to keep them socially active.
GLUT5 (SLC2A5) enables fructose-mediated proliferation independent of ketohexokinase
Authors: Liang Roger Jie , Taylor Samuel , Nahiyaan Navid , Song Junho , Murphy Charles J , Dantas Ezequiel , Cheng Shuyuan , Hsu Ting-Wei , Ramsamooj Shakti , Grover Rahul , Hwang Seo-Kyoung , Ngo Bryan , Cantley Lewis C , Rhee Kyu Y , Goncalves Marcus DaSilva
Published: January 2021

Background: Fructose is an abundant source of carbon and energy for cells to use for metabolism, but only certain cell types use fructose to proliferate. Tumor cells that acquire the ability to metabolize fructose have a fitness advantage over their neighboring cells, but the proteins that mediate fructose metabolism in this context are unknown. Here, we investigated the determinants of fructose-mediated cell proliferation. Methods: Live cell imaging and crystal violet assays were used to characterize the ability of several cell lines (RKO, H508, HepG2, Huh7, HEK293T (293T), A172, U118-MG, U87, MCF-7, MDA-MB-468, PC3, DLD1 HCT116, and 22RV1) to proliferate in fructose (i.e. the fructolytic ability). Fructose metabolism gene expression was determined by RT-qPCR and western blot for each cell line. A positive selection approach was used to “train” non-fructolytic PC3 cells to utilize fructose for proliferation. RNA-seq was performed on parental and trained PC3 cells to find key transcripts associated with fructolytic ability. A CRISPR-cas9 plasmid containing KHK-specific sgRNA was transfected in 293T cells to generate KHK -/- cells. Lentiviral transduction was used to overexpress empty vector, KHK, or GLUT5 in cells. Metabolic profiling was done with Seahorse metabolic flux analysis as well as LC/MS metabolomics. Cell Titer Glo was used to determine cell sensitivity to 2-deoxyglucose in media containing either fructose or glucose. Results: We found that neither the tissue of origin nor expression level of any single gene related to fructose catabolism determine the fructolytic ability. However, cells cultured chronically in fructose can develop fructolytic ability. SLC2A5, encoding the fructose transporter, GLUT5, was specifically upregulated in these cells. Overexpression of GLUT5 in non-fructolytic cells enabled growth in fructose-containing media across cells of different origins. GLUT5 permitted fructose to flux through glycolysis using hexokinase (HK) and not ketohexokinase (KHK). Conclusions: We show that GLUT5 is a robust and generalizable driver of fructose-dependent cell proliferation. This indicates that fructose uptake is the limiting factor for fructose-mediated cell proliferation. We further demonstrate that cellular proliferation with fructose is independent of KHK.