bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting The xCT Antiporter Sensitizes High Risk DLBCL to Doxorubicin-Containing Therapy
Authors: Wei Xiaolei , Wei Yongqiang , Song Jialin , Mai Yun , Yuan Fei , Zhang Jinghang , Feng Ru , Ye Bihui Hilda 
Published: August 2021

Abstract
Background. Although outcomes in diffuse large B-cell lymphoma (DLBCL) have dramatically improved following the introduction of R-CHOP two decades ago, one-third of the patients fail to attain durable remission and require salvage and additional therapies. Many attempts to improve upon R-CHOP efficacy by incorporating targeted agents have failed, suggesting a need to better understand the mechanisms underlying R-CHOP resistance/responsiveness. We have previously reported that Doxorubicin (Dox), the main cytotoxic ingredient in CHOP, has subtype-specific mechanisms of cytotoxicity in DLBCLs due to differences in its subcellular distribution pattern. Specifically, Dox-induced cytotoxicity in the therapy refractory ABC-DLBCLs is largely dependent on oxidative stress rather than the DNA damage response. These findings suggest that R-CHOP outcome could be modulated by manipulating oxidative stress response in DLBCL cells. This study focuses on xCT, the light chain of the cystine/glutamate antiporter xc` that controls the rate-limiting step for glutathione (GSH) biosynthesis. We demonstrate novel roles of the xCT-GSH-ROS axis in maintenance and therapeutic response of high risk DLBCLs. Methods. Prognostic significance of xCT protein expression in a cohort of 87 DLBCL patients treated with R-CHOP were evaluated. Dynamic changes of the cellular GSH pool to Dox treatment were examined. xCT inhibition was achieved using a small molecular inhibitor sulfasalazine (SASP) and through shRNA-mediated knock-down. The ability of SASP to sensitize ABC-DLBCL/double-hit lymphomas to Dox-containing therapy was investigated in cell line and NSG-based xenograft models. Results. Dox elicits a rapid antioxidant response characterized by a GSH spike that can be eliminated by suppressing the xCT antiporter function. Mechanistically, xCT inhibition depleted the total GSH pool and markedly enhanced the p38-dependent apoptosis response following Dox treatment. Furthermore, supporting a role of the xCT-GSH axis in clinical response to Dox-containing therapies, xCT expression predicts poor prognosis among ABC-DLBCL but not GCB-DLBCL patients treated with R-CHOP. Finally, we demonstrate that combinatorial treatment with Dox and SASP produced marked synergy in xenograft models for ABC-DLBCL/double-hit lymphomas. Conclusions. In ABC-DLBCL, the xCT-GSH-p38 axis plays a critical role in survival response to Dox-containing therapies. xCT inhibition may hold significant promise to improve the first-line treatment outcome of patients with high risk DLBCL.
Menstrual Abnormalities and Their Association With Stress and Quality of Life Among Females Studying Health Sciences
Authors: Alaskar Batool , Alhunaif Sara , Shaheen Mise Alreem , Alkadri Hanan 
Published: August 2021

Abstract
BackgroundMenstrual abnormalities seem to occur more frequently in students studying medicine and health sciences. Menstrual abnormalities have the potential to impact women’s health, their physical and emotional wellbeing as well as social and school functioning, there is a clear need for better understanding of these disease processes, their associations, and impact on quality of life. The present study aims to explore the association between menstrual abnormalities, psychological disturbances and eating disorders among female students studying health sciences subjectsMethodsThis was a cross-sectional study, in which students from all health science colleges at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Saudi Arabia, were asked to partake by answering questions pertaining to their demographic data, menstrual patterns, perceived stress, and quality of life using Perceived Stress Scale (PSS ) and the 20-Item Short Form Health Survey (SF-20) respectively. All statistical analyses were done using IBM SPSS Statistics software.ResultsMost respondents had a normal length cycle, duration and flow. Many of our respondents reported some type of premenstrual symptoms with mixed symptoms being the most prevalent 44%. Those who had mixed premenstrual symptoms also had high levels of perceived stress (p<0.001). However, there was no correlation between menstrual cycle length and duration and levels of perceived stress. Regarding the SF-20 quality of life components who had premenstrual symptoms including pain, psychological symptoms , and mixed symptoms did poorly on the physical, social, and mental health aspects of quality of life.DiscussionOur findings are in line with those identified by other authors who demonstrate a strong positive correlation with premenstrual symptoms and perceived stress and also an association between menstrual abnormalities and quality of life and activities of daily living. Due to the cross-sectional nature of the study, causality cannot be determined and prospective studies are recommended in the futureConclusionsWe found that those who had menorrhagia, premenstrual symptoms, or eating disorders reported high levels of stress. We have also demonstrated a link between premenstrual symptoms, menstrual abnormalities, PCOS , and worse quality of life. We hope that this unique study will shed some light on the struggles faced by health science female students and help policy makers enhance mental and reproductive/endocrinological health care access for them
Thermally Induced Reduction of Hot Cracking Susceptibility in Electron Beam Welding of CuCr1Zr: A Numerical Approach
Authors: Chin R. , Effertz P. S. , Pires I. , Enzinger N. 
Published: August 2021

Abstract
Electron Beam Welding (EBW) is a highly effective and accurate welding process that is being increasingly used in industrial work and is of growing importance in manufacturing. In the current study, solidification cracking in EBW of a CuCr1Zr cylindrical geometry was explored. To investigate and prevent occurrence of hot cracking, a thermomechanically coupled numerical model was developed using Finite Element Method (FEM). An additional heat source was considered, in order to influence the resulting residual stress state, namely to minimize tensile stresses in the fusion zone during solidification. Hence, a methodical assessment of relevant parameters, such as the power, the diameter of the additional heat source and the distances between both heat sources was employed using Design of Experiments (DoE). It was found that for a particular parameter configuration, solidification cracking most likely could be averted.
Extracellular Vesicles Derived from Cytokine-Activated CD8+ T Cell Exhibit Broad Anticancer Activity
Authors: Zhang Lin , An Yang , Yang Xuena , Yu Wenwen , Li Baihui , Ji Zhenyu , Meng Shuai , Yang Quanyong , Wang Limei , Wei Feng , Yang Lili , ren xiubao 
Published: August 2021

Abstract
Background: Extracellular vesicles (EVs) are the nano-sized membrane particles secreted by various cell types, which are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells (CAR-T) and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we reported another EV released by cytokine-activated CD8+ T cells (caCD8-EVs) and its phenotype and function. Methods: CaCD8-EVs were purified by ultracentrifugation and phenotypically characterized by flow cytometry. The cytotoxicity induced by caCD8-EVs was assessed using the CellTiter-Glo Viability assay in vitro and xenograft tumor established in vivo. The uptake of caCD8-EVs was detected by a Live Cell Imaging System and flow cytometry. Mass spectrometry and protein bioinformatics analysis, together with western blotting and real-time PCR, were used to investigate the effect of caCD8-EVs on the cancer cells.Results: CaCD8 cells released EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokines cocktail ex vivo. Phenotype analysis showed that caCD8-EVs carried cytotoxic T cell membrane molecules (CD3, CD8 and TCRs) and partially inherited NKG2D molecule which was inductively expressed on the caCD8 T cells. In contrast, the nano-particles were devoid of checkpoint proteins on their surface. Notably, caCD8-EVs displayed extensive cytotoxicity against cancer cells, but limited effects on non-cancerous cell lines. Uptake assessment showed that actively dividing tumor cells were more likely to capture caCD8-EVs compared with resting cells. Mechanism analysis demonstrated for the first time that caCD8-EVs contained not only typical cytotoxic proteins (i.e., granzyme B and perforin) but also IFNg that participated in EVs-induced cytotoxicity.Conclusion: Our data reveal the characteristics of caCD8-derived EVs and support the use of these EVs as a novel potential approach for cancer therapy.
Capturing a Tetratomic Nitrogen Ring cyclo-N4 inside an Aza[ 82 ]fullerene
Authors: Wang Yuanyuan , Hu Ziqi , Shen Wangqiang , Zhou Tonghui , Aoyagi Shinobu , Yang Yihao , Wang Zhiyong , Yu Pengwei , Su Jie , Coronado Eugenio , Lu Xing , Shi Zujin 
Published: August 2021

Abstract
Synthesis of polymeric nitrogen compounds is a formidable task due to the proneness of nitrogen to the formation of N ≡ N triple bond, one of the strongest chemical bonds known. Here, we report an arc-discharge approach to successfully stabilize the elusive four-membered nitrogen ring (cyclo-N4) in an unprecedented endohedral metallofullerene Dy2N4@C81N (Dy-I). Its molecular structure has been unambiguously determined by X-ray crystallography to show a covalently bonded cyclo-N4 plane bridging two dysprosium ions inside an aza[82]fullerene cage, highlighting the stabilization of cyclo-N4 as a concurrent result of fullerene encapsulation and metal coordination. Our computational results further reveal a six-center-one-electron (6c-1e) bond delocalized over the inverse-sandwich Dy-N4-Dy cluster. This chemical peculiarity stems from the diffuse radical character of the highly anionic cyclo-N43− ligand, which is confirmed by electron paramagnetic resonance (EPR) spectrum of Y2N4@C81N (Y-I).
Asparaginase Like 1 Predicts Unfavourable Prognosis and Facilitates Gastric Cancer Progression Through Inhibits GSK3-β
Authors: Yang Hao , Li Yiming , Zhang Yu , Zeng Zhijun , Fang Zhenhao , Yin Junda , Li Xi , Yang Zhiyou , Xiong Ying , Liu Guodong , Wu Wei 
Published: August 2021

Abstract
Background:ASRGL1 plays critical roles in various biological processes and pathologic conditions,including cancer. However, the prognostic importance and biologic functions of ASRGL1 in gastric cancer (GC) are still unclear.Methods:qRT-PCR, western blot and immunohistochemistry analyses were used to determine ASRGL1 expression in GC samples and cell lines. The clinical significance of ASRGL1 was assessed in 100 patients with GC. A series of functional experiments were performed to explore the role and molecular mechanism of ASRGL1 on GC progression. Results:ASRGL1 was upregulated in GC tissues and cell lines. High ASRGL1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes and recurrence of GC patients. Moreover, silencing ASRGL1 in AGS cells significantly inhibited cell proliferation, migration, invasion, whereas overexpression of ASRGL1 significantly enhanced the above abilities of BGC-823 cells. Further mechanism study indicated that these phenotypic changes were mediated by PI3K/AKT and WNT signaling. Finally, we proved that ASRGL1 exerted its tumor-promoting effect by interacting with GSK3-β.Conclusions:ASRGL1 is up regulated in gastric cancer, while it promotes the GC cell proliferation, migration and invasion via interacting with GSK3-β . At the same time it also serves as a potential prognostic factor in patients with GC. ASRGL1 can be used as a new target for diagnosis and treatment of gastric cancer.
Evaluation of Women’s Empowerment in a Community-Based Human Papillomavirus Self-Sampling Social Entrepreneurship Program (Hope Project) in Peru: Mixed-Method Study
Authors: Shin Michelle B. , Garcia Patricia J. , Dotson Mary Elizabeth , Valderrama María , Chiappe Marina , Ramanujam Nimmi , Krieger Marlee , Ásbjörnsdóttir Kristjana , Barnabas Ruanne V. , Iribarren Sarah J. , Gimbel Sarah 
Published: August 2021

Abstract
Background: Understanding the community women’s sense of relational and financial empowerment in the social entrepreneurship context could be the key to developing a sustainable pathway to scale-up community-based human papillomavirus (HPV) self-sampling programs in low-resource settings. The Hope Project, social entrepreneurship from Peru, trains women (Hope Ladies) to promote HPV self-sampling among other women in their communities. This study aims to evaluate the Hope Ladies’ relational/financial empowerment after participating in the program. Methods: We used a parallel mixed-method design. The Hope Ladies participated in semi-structured in-depth interviews (n= 20) and an eight-questions five-point Likert scale survey that evaluated their relational (n=19)/financial (n=17) empowerment after participating in the social entrepreneurship. The interview and the survey questions were developed using validated empowerment frameworks, indicators, and theory: 1) Kabeer’s conceptual framework, 2) International Center for Research on Women (ICRW)’s economic empowerment indicators, and 3) the Relational Leadership Theory (RLT), respectively. Deductive content analysis was used to evaluate the interviews with pre-determined codes and categories of empowerment. Descriptive statistics were used to analyze the survey results. Results: All Hope Ladies reported experiencing empowerment in the social entrepreneurship. Interviews: The women reported challenges and improvement in three categories of empowerment: 1) resources (balancing the roles between the household and working as a Hope Lady, camaraderie with other Hope Ladies, recognition from the community as a resource); 2) agency (improved ability to express themselves, increased knowledge about reproductive health, ability to speak out against male-dominant culture and fear of cervical cancer-related stigma); and 3) achievement (increased economic assets, improved ability to make financial decisions from increased supplemental income, widened social network and capital, and technology skills development). Survey: All (100%) agreed/totally agreed an increase in social contacts, increased unaccompanied visits to a healthcare provider (86%), improved confidence in discussing reproductive topics (100%), improved ability to make household decisions about money (57% pre-intervention vs. 92% post-intervention). Conclusions: The Hope Ladies’ reported improved relational/financial empowerment through participating in community-based social entrepreneurship. More studies are needed to elucidate the relationship between empowerment and worker retention/performance to inform the scale-up of HPV self-sampling social entrepreneurship.
Give and Take: Salmonella Enterica Alters Macrosteles Quadrilineatus Feeding Behaviors Resulting in Altered S. Enterica Populations and Distribution on Leaves
Authors: Harrod Victoria L. , Groves Russell , Guillemette Ellie , Barak Jeri 
Published: August 2021

Abstract
Hemipteran insects are ubiquitous inhabitants of the phyllosphere. Changes in microbial phyllosphere communities have recently been demonstrated following infestation by Macrosteles quadrilineatus (Aster Leafhopper). Although epiphytic Salmonella enterica populations naturally decline in the phyllosphere of plants, M. quadrilineatus infestation facilitated the growth of the bacterial pathogen populations. Here, we demonstrate that cellular damage by insect stylet penetration results in a localized beneficial niche on the leaf surface, leading to enhanced S. enterica populations. We measured S. enterica populations and colonization patterns on plants infested with Hemipterans with distinct feeding behaviors. M. quadrilineatus infestation resulted in higher solute leakage and significantly greater bacterial populations than plants absent of insects. Following immigration via contaminated irrigation water, the highest populations of S. enterica are naturally found on the tips of tomato leaflets. We discovered M. quadrilineatus feeding preference altered the natural distribution of S. enterica populations, and that the presence of S. enterica altered the distribution of probing attempts. These findings elucidate how cellular damage resulting from insect feeding drives changes in bacterial colonization of the phyllosphere.
Genomics of FOXP3 Enhance Treg and Maintain Immune-homeostasis
Authors: Choudhury Shouhartha 
Published: August 2021

Abstract
The immunologic theorem is a subject of self also non-self differentiation directly combat infections and maintains the energy of self-antigens. Immune privilege of T-cells is prevailing via crucial and superficial prospect. The T-cell promotes the function of immune replication and implant antigens. The regulatory T-cells (Treg) impart the progress of diseases also prevent immunity. X chromosome encoded FOXP3 is a regulator of segregation and immunosuppressive function. Nuclear factor FOXP3 regulated lineage-specific polarity of Treg crucially maintains immune-homeostasis. The functional inhibitions of helper T cells by FOXP3-inhibitory peptide constitute an imprint to enhance immunotherapy. The enlightenment of FOXP3 contributed to a novel concern in the experiment of suppressor T lymphocytes and mechanisms of immune homeostasis. In this exploration, I aimed to view FOXP3 functions from the FOX family in Homo sapiens and compare them with Mus musculus. Therefore, I performed a bioinformatics pipeline for the experimentation of the forkhead box P3 and their family. My finding data supported the FOX family of TF’s play a preventive strategy during the development. A ray of FOXP3 enhances Treg and maintains immunity against infections. The specific bioinformatics analysis epitomized FOXP3 as a T-cell dependent gene that can help to interpret the outcome in infection biology.
Factors associated with mothers’ health care-seeking behaviours for childhood fever in Burkina Faso: Findings from repeated cross-sectional household surveys
Authors: Badolo Hermann , Bado Aristide Romaric , Hien Hervé , Méda Nicolas , Susuman Appunni Sathiya 
Published: August 2021

Abstract
IntroductionFever is one of the most frequent reasons for paediatric consultations in Burkina Faso, but health care-seeking behaviours and the factors associated with health care-seeking in the event of childhood fever are poorly documented. This study aims to help fill this gap.MethodsThis study used the data from the baseline and endline surveys conducted to evaluate the impact of the Performance-Based Financing (PBF) program in Burkina Faso. Univariate and multivariate binary logistic regression analyses were used to identify the factors associated with appropriate healthcare-seeking for childhood fever. Odds ratios (ORs) were estimated to assess the strength of associations and used 95% confidence intervals for significance tests. Data were cleaned, coded and analysed using Stata software version 16.1.ResultsAmong the children under five who had a fever, 75.19% and 79.76 sought appropriate health care in 2013 and 2017, respectively. Being 24–59 months old (AOR: 0.344, 95% CI: 0.182–0.649 in 2013) and 79,2% (AOR: 0. 208, 95% CI: 0.115–0.376 in 2017), living in a very wealthy household households (AOR: 2.014, 95% CI: 1.149–3.531 in 2013 and AOR: 2.165, 95% CI: 1.223–3.834 in 2017), having a mother with a secondary or higher level of education or having made at least four antenatal care visits were significantly associated with seeking appropriate health care for childhood fever. Living in an area where the health facility is safe was also significantly associated with seeking appropriate care for childhood fevers.ConclusionThe findings underscore the need for interventions that would improve appropriate health care-seeking among mothers for their children. These interventions could include mothers’ sensitization to the benefits of modern health care use, increasing women’s education, improving household wealth status, improving the level of prenatal and postnatal care use and improving health care quality and safety in health facilities.
A Population-Based Threshold of Protection for COVID-19 Vaccines
Authors: Goldblatt David , Fioré-Gartland Andrew , Johnson Marina , Hunt Adam , Bengt Christopher , Zavadska Dace , BROWN JEREMY , Workman Lesley , Zar Heather , Montefiori David , Shen Xiaoying Shen , Dull Peter , Plotkin Stanley , Siber George , Ambrosino Donna 
Published: August 2021

Abstract
Correlates of protection for COVID-19 vaccines are urgently needed to license and deploy additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform calibrated to the international standard. IgG anti-Spike antibodies correlated significantly with efficacies for original virus and alpha variant and were highly correlated with ID50 neutralization in a validated pseudoviral assay. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies was 154 BAU/ml (95%CI 42-559), and for the vaccine studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA studies) was 60 BAU/ml (95%CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.