bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homogenous Multifunctional Microspheres Induce Ferroptosis to Promote the Anti-hepatocarcinoma Effect of Chemoembolization
Authors: Chen Minjiang , Li Jie , Shu Gaofeng , Shen Lin , Qiao Enqi , Zhang Nannan , Fang Shiji , Chen Xiaoxiao , Zhao Zhongwei , Tu Jianfei , Song Jingjing , Du Yong-zhong , Ji Jiansong 
Published: December 2021

Abstract
Transcatheter arterial chemoembolization (TACE) is one of the main palliative therapies for advanced hepatocellular carcinoma (HCC), which is also regarded as a promising therapeutic strategy for cancer treatment. However, drug-loaded microspheres (DLMs), as commonly used clinical chemoembolization drugs, still have the problems of uneven particle size and unstable therapeutic efficacy. Herein, gelatin was used as the wall material of the microspheres, and homogenous gelatin microspheres co-loaded with adriamycin and Fe3O4 nanoparticles (ADM/Fe3O4-MS) were further prepared by a high-voltage electrospray technology. The introduction of Fe3O4 nanoparticles into DLMs not only provided excellent T2-weighted magnetic resonance imaging (MRI) properties, but also improved the anti-tumor effectiveness under microwave-induced hyperthermia. The results showed that ADM/Fe3O4-MS plus microwave irradiation had significantly better antitumor efficacy than the other types of microspheres at both cell and animal levels. Our study further confirmed that ferroptosis was involved in the anti-tumor process of ADM/Fe3O4-MS plus microwave irradiation, and ferroptosis marker GPX4 was significantly decreased and ACSL4 was significantly increased, and ferroptosis inhibitors could reverse the tumor cell killing effect caused by ADM/Fe3O4-MS to a certain extent. Our results confirmed that microwave mediated hyperthermia could amplify the antitumor efficacy of ADM/Fe3O4-MS by activating ferroptosis and the introduction of Fe3O4 nanoparticles can significantly improve TACE for HCC. This study confirmed that it was feasible to use uniform-sized gelatin microspheres co-loaded with Fe3O4 nanoparticles and adriamycin to enhance the efficacy of TACE for HCC.
Inflammatory Cytokine Levels in Pulmonary Embolism Severity: A Retrospective Study
Authors: Li Xiaoming , Li Yukun , Ye Wenjing , Chen Xi , Guo Xuejun , Gu Wen 
Published: December 2021

Abstract
Background: Inflammatory cytokines are involved in the development of venous thromboembolism (VTE) and may influence the mortality. But the association between their levels and severity of pulmonary embolism (PE) is unclear. This study aimed to investigate the association of inflammatory cytokines and PE severity. Methods: We retrospectively analyzed patients who were admitted to Xinhua Hospital with a confirmed diagnosis of PE between Jan 2019 and Apr 2021. Inflammatory cytokines were compared among different severities of PE groups. Spearman rank-order correlation analysis and multivariate Logistic regression analysis were used to analyze the relationship between cytokine level and PE severity. In addition, we estimated the association between comorbidities and PE severity by using multivariate Logistic regression analysis. Results: A negative correlation between IL-8 level and PE severity was found (r=-0.466, P=0.018). Comorbidities of coronary heart disease [3.76 (1.99-7.10) (P=0.000)], deep venous thrombosis [2.40 (1.15-5.01) (P=0.019)], respiratory failure [2.92 (1.33-6.4) (P=0.007)] were correlated with the severity of PE. Conclusions: IL-8 level is negative correlated with PE severity. Patients with comorbidities regarding coronary heart disease, deep venous thrombosis, and respiratory failure may have higher risk to surfer a more sever PE.
Motor Point Heatmap of the Calf
Authors: Schriwer Elias , Juthberg Robin , Flodin Johanna , Ackermann Paul W. 
Published: December 2021

Abstract
Background: Contractions of muscles in the calf induced by neuromuscular electrical stimulation (NMES) may prevent venous thromboembolism. However, compliance to NMES-treatment is limited by the use of suboptimal stimulation points which may cause discomfort. Knowledge of where one is most likely to find muscle motor points (MP) could improve NMES comfort and compliance.Aims: To anatomically map the MPs of the calf as well as to calculate the probability of finding a MP in different areas of the calf. Material and Methods: On 30 healthy participants (mean age 37 years) anatomical landmarks on the lower limbs were defined. The location of the four most responsive MPs on respectively the medial and lateral calf muscle bellies were determined in relation to these anatomical landmarks using a MP search pen and a pre-set MP search program with 3 Hz continuous stimulation. The anatomy of the calves was normalized and subdivided into a matrix of 48 (6x8) smaller areas (3x3cm), from upper medial to lower lateral, in order to calculate the probability of finding a MP in one of these areas. The probability of finding a MP was then calculated for each area and presented with a 95% confidence interval.Results: The MP heat map displayed a higher concentration of MPs proximally and centrally on the calf. However, there were wide inter-individual differences in the location of the MPs. The highest probability of finding a MP was in area 4, located proximally and medially, and in area 29, located centrally and around the maximum circumference, both with 50% probability (95% CI: 0.31-0.69). The second highest probability of finding MPs was in areas 9, 10, 16, proximally and medially, all with 47% probability (95% CI: 0.28-0.66). These areas 4, 9, 10, 16 and 29 exhibited significantly higher probability of finding motor points than all areas with a mean probability of 27% and lower (p<0.05) The lateral and distal outskirts exhibited almost zero probability of finding MPs. Conclusions: This MP heat map of the calf could be used to expedite electrode placement and to improve compliance in order to receive consistent and enhanced results of NMES treatments.
Same People, Different Results: Categorizing Cancer Registry Cases across the Rural-Urban Continuum
Authors: Schiefelbein Andrea M. , Taylor Amy K. , Krebsbach John K. , Zhang Jienian , Haimson Chloe E. , Varley Patrick R. , Skala Melissa C. , Eason John M. , LoConte Noelle K. 
Published: December 2021

Abstract
Background: Many rural-urban indexes are utilized in United States cancer research. This variation introduces inconsistencies between studies with a rural-urban component. Recommendations to date on which index to utilize have prioritized index geographical unit over feasibility of index inclusion in analysis. We evaluated rural-urban indexes and recommend one index for use to increase comparability across studies.
Methods: We assessed nine U.S. rural-urban indexes regarding their respective rural and urban code ranges; geographical unit, land area, and population distributions; percent agreement; suitability as continuous variables in analysis; and feasibility of integration into national, state, and local cancer research. We referenced 1,569 Wisconsin Pancreatic Cancer Registry patients to demonstrate how rural-urban index choice impacts patient categorization.
Results: Six indexes categorized rural and urban areas. Indexes agreed on binary rural-urban designation for 88.8% of the U.S. population. As ternary variables, they agreed for 83.4%. For cancer registry patients, this decreased to 73.4% and 60.4% agreement, respectively. Rural-Urban Continuum Codes (RUCC) performed the best with ability to differentiate metropolitan, micropolitan, and rural counties, are available for retrospective and prospective studies, and can be coded continuously for analysis.
Conclusions: Whether a patient was categorized as urban or rural changed depending on which index was used when applied to a cancer registry data set. We conclude that RUCC is an appropriate and feasible rural-urban index to include in cancer research, as it is standardly available in national cancer registries in its 9-code format and can be matched to patient’s county of residence for local research and it had the least amount of fluctuation of the indices analyzed. Utilizing RUCC as a continuous variable across studies with a rural-urban component will increase reproducibility and comparability of results and eliminate the choice of rural-urban index as a potential source of discrepancy between studies. Trial registration: Not applicable
Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron
Authors: Yuen Kwok-Yung , Shuai Huiping , Chan Jasper Fuk-Woo , Hu Bingjie , Chai Yue , Yuen Terrence Tsz-Tai , Huang Xiner , Yoon Chaemin , Hu Jingchu , Liu Huan , Shu Jialu , Liu Yuanchen , Zhu Tianrenzheng , Zhang Jinjin , Hou Yuxin , Cai Jian-Piao , Zhang Jinxia , Zhou Jie , Yin Feifei , Yuan Shuofeng , Zhang Bao-Zhong , Huang Jiandong , Chu Hin 
Published: December 2021

Abstract
SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human populations. The variant contains 34 changes in its spike protein including 15 substitutions at the receptor-binding domain (RBD). While recent reports reveal that the Omicron variant can robustly escape from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown. Here, we investigate the virological features and pathogenesis of the Omicron variant using in vitro and in vivo models. Our results demonstrate that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 but not in VeroE6 cells. Further mechanistic investigations reveal that the Omicron variant is deficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT, Alpha, Beta, and Delta variant, which explained its inefficient replication in Calu3 and Caco2 cells. Importantly, the replication of the Omicron variant is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is significantly attenuated in virus replication and pathogenicity in comparison with WT and previous variants. Our data suggest the current global vaccination strategy has forced SARS-CoV-2 into a new evolutionary trajectory towards reduced replication fitness in exchange of better immune escape. These findings are critical for setting policy in the pandemic control and disease management of COVID-19.
WITHDRAWN: Skin Cells State and its Effect on Visual Perception
Authors: Khalifa Samar 
Published: December 2021

Abstract
Skin is the indicator of the human's state of health and whether he or she is fresh or not. The paper investigates the role of skin on visual perception mechanisms to see or detect the freshness degree in other humans through a review of some ideas about this concept. The paper includes the role of skin cells on perception through inhibition and excitation, beauty, and face symmetry
Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models
Authors: Miyagi Yasuyo , Fujiwara Kyoko , Hikishima Keigo , Utsumi Daisuke , Katagiri Chiaki , NIshimura Masahiko , Takagi Hiroshi , Ishiuchi Shogo 
Published: December 2021

Abstract
Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.
CRISPR/Cas9-Mediated Gene Editing of Vacuolar ATPase Subunit D Mediates Phytohormone Biosynthesis and Virus Resistance in Rice
Authors: Lu Qinghua , Luo Xiangwen , Yang Xiao , Zhou Tong , Zhang Yu , Lan Ying , Zhang Deyong , Zheng Limin , Li Yixing , Li Li , Zhang Songbai , Liu Yong 
Published: December 2021

Abstract
Background: Vacuolar ATPases (v-ATPases) are proton pumps for proton translocation across membranes that utilize energy derived from ATP hydrolysis; Previous research revealed Osv-ATPases mediates phytohormes levels and resistance in rice. Osv-ATPase subunit d (Osv-ATPase d) is part of an integral, membrane-embedded V0 complex of V-ATPases complex, whether Osv-ATPase d involves in phytohormes biosynthesis and resistance in rice remains unknown.Finding: The knockout mutant line (line 5) of Osv-ATPase d was generated using the CRISPR/Cas9 system, mutation of Osv-ATPase d did not show any detrimental effect on plant growth or yield productivity. Transcriptomic results showed Osv-ATPase d probably involved in mediating the biosynthesis of plant hormones and resistance in rice. Mutation of Osv-ATPase d significantly increased JA and ABA biosynthesis than wild type. Compared to wild type, mutation of Osv-ATPase d increased the resistance against Southern rice black-streaked dwarf virus (SRBSDV), however, decreased the resistance against Rice stripe virus (RSV) in rice. Conclusion: Taken together, our data reveal the Osv-ATPase d mediates phytohormone biosynthesis and virus resistance in rice, which can be selected as a potential target for resistance breeding in rice.
Humoral Response among Patients with Interstitial Lung Disease Vaccinated with the BNT162b2 SARS-Cov-2 vaccine - A Prospective Cohort Study
Authors: Pertzov Barak , Shmueli Einat , Zvi Haim Ben , Massarweh Amir , Barkan Tamar , Ness Assaf , Shostak Yael , Freidkin Lev , Shtraichman Osnat , Kramer Mordechai R 
Published: December 2021

Abstract
Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. We aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.Methods: We conducted an observational prospective cohort study to evaluate the rate of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement one serology test was drawn from all patients 4-6 months after the second vaccine dose. Two age and sex matched control groups were created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June to August 2021.Results: All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P=1.0). The antifibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [ IQR, 207-811] AU/ml vs 820.75 [IQR, 459-1313] AU/ml; P<0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P<0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [ IQR, 4.25-165] AU/ml vs 970.1 [IQR, 505-1926] AU/ml; P<0.001). Conclusion: IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, maintain a 100% seropositivity rate, 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD, treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose, moreover treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.
Neuromodulatory Mechanisms оf a Memory Loss Preventive Effect of Alpha-Lipoic Acid in an Experimental Rat Model of Dementia
Authors: Staykov Hristian , Lazarova Maria , Hassanova Yozljam , Stefanova Miroslava , Tancheva Lyubka , Nikolov Rumen 
Published: December 2021

Abstract
This study evaluates some of the neuromodulatory mechanisms of the memory loss preventive effect of alpha-lipoic acid (ALA) in a scopolamine (Sco)-induced rat model of an Alzheimer’s disease (AD) type dementia. Our results confirmed that Sco administration induces significant memory impairment, worsens exploratory behaviour and habituation; it increases acetylcholinesterase (AChE) activity and induces pathological monoamine content changes in the brain prefrontal cortex and hippocampus. ALA administration prevented to a large extent Sco-induced memory impairment; it also improved exploratory behaviour and preserved habituation; it decreased AChE activity, reversing it to Control group levels and corrected aberrant monoamine levels in the brain prefrontal cortex and hippocampus. According to the data available, this is the first time that ALA-induced changes in AChE and monoamine levels in the brain prefrontal cortex and hippocampus (brain structures related to learning and memory) have been demonstrated in a Sco-induced rat model of AD type dementia.
Evaluating an e-Learning Program to Strengthen the Capacity of Humanitarian Workers in the MENA Region: The Humanitarian Leadership Diploma
Authors: Saleh Shadi , Brome Dayana , Mansour Rania , Daou Tracy , Chamas Amar , Naal Hady 
Published: December 2021

Abstract
Background: The Middle East and North Africa (MENA) region is consistently plagued with humanitarian crises while having little response capacity. Despite their obvious growing need, there exist limited educational opportunities for humanitarian workers to develop their capacity in humanitarian topics. The present study evaluates an online training program, the Humanitarian Leadership Diploma (HLD), which targeted humanitarian workers across the MENA region.Methods: A mixed-methods design was used, comprising short and long-term quantitative and qualitative data, targeting individual and organizational-level outcomes. A total of 28 humanitarian workers across the MENA region enrolled in the program starting September 2019 until October 2020, 18 of which completed the full diploma. Short-term quantitative data such as knowledge assessments, course evaluations, and reflective commentaries were collected from all learners, whereas long-term qualitative data was collected only from those who completed the full diploma and from peers at their organizations, 6 months after completion. Data was triangulated, analyzed using qualitative content analysis, and reported as themes.Results: The program was overall successful given multiple factors reported by participants such as enhanced knowledge, high satisfaction, and improved practice, with some important challenges being identified. Themes under the strengths category related to (1) online learning, (2) significance of diploma, (3) course content, (4) instructors, (5) transfer of learning into practice, and (6) personal development. Themes under the challenges category related to (1) barriers to applying changes in behavior and performance, (2) engagement and interaction, and (3) pedagogical approach.Conclusion: This is one of very few evaluations of locally developed and delivered online learning programs for humanitarian actors in the MENA region. The findings are especially important as they may inform researchers and humanitarian actors looking to design and deliver similar programs in the MENA region or other fragile settings. Key recommendations are discussed in the manuscript, and include to combine synchronous and asynchronous approaches, design concise course materials, limit theoretical pedagogical approaches, ensure topics are contextualized to the region, and consider continuous engagement strategies for learners.
Robust Estimation Method Based on Function Model of Successive Approximation
Authors: Xiaoming Ye 
Published: December 2021

Abstract
In measurement practice, the residuals in least squares adjustment usually show various abnormal discrete distributions, including outliers, which is not conducive to the optimization of final measured values. Starting with the physical mechanism of dispersion and outlier of repeated observation errors, this paper puts forward the error correction idea of using the approximate function model of error to approach the actual function model of error step by step, gives a new theoretical method to optimize the final measured values, and proves the effectiveness of the algorithm by the ability of responding to the true values. This new idea is expected to be the ultimate answer of robust estimation theory.
Evidence of gender equity in pupils’ achievement in phonics, when exposed to adult and children-generated illustrations
Authors: Ibenegbu Christopher Ifeanyi 
Published: December 2021

Abstract
The study examined evidence of gender equity in pupils achievement in phonics, when exposed to adult and children-generated illustrations in Njikoka Local Government Area of Nigeria. The study employed a non-equivalent quasi‐experimental 2 x 2 factorial research design. Some 158 primary two pupils from 4 schools were used for the study. The English Achievement Test (EAT) was used to collect data. Three hypotheses were tested. The data were analysed using descriptive statistics and Analysis of Covariance (ANCOVA). The results showed that there was a significant main effect for the mode of illustration on pupils’ achievement in phonics F(1,153) = 21.315, p=.000; there was no significant main effect of gender F(1,153) = 1.082, p =.300, and there was no significant interaction effect of mode of illustration and gender F(1,153) = .701, p =.404. The study recommended that since the children-generated illustrations were more effective in teaching phonics and enhancing pupils achievement in phonics, the Ministries of Education should ensure that textbook authors incorporate children-generated illustrations in the instructional materials for pupils in primary schools. Mode of illustration had no differential effects on male and female pupils achievement in phonics. As such the present system of teaching both males and females in the same class should be encouraged. Authors and publishers of children’s books should engage pupils’ in illustrating their books.