bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalase-deficient mice induce aging faster through lysosomal dysfunction
Authors: Dutta Raghbendra Kumar , Lee Joon No , Maharjan Yunash , Park Channy , Choe Seong-Kyu , Ho Ye-Shih , Kwon Hyug Moo , Park Raekil 
Published: December 2022

Abstract
Background
Lysosomes are a central hub for cellular metabolism and are involved in the regulation of cell homeostasis through the degradation or recycling of unwanted or dysfunctional organelles through the autophagy pathway. Catalase, a peroxisomal enzyme, plays an important role in cellular antioxidant defense by decomposing hydrogen peroxide into water and oxygen. In accordance with pleiotropic significance, both impaired lysosomes and catalase have been linked to many age-related pathologies with a decline in lifespan. Aging is characterized by progressive accumulation of macromolecular damage and the production of high levels of reactive oxygen species. Although lysosomes degrade the most long-lived proteins and organelles via the autophagic pathway, the role of lysosomes and their effect on catalase during aging is not known. The present study investigated the role of catalase and lysosomal function in catalase-knockout (KO) mice.

Methods
We performed experiments on WT and catalase KO younger (9 weeks) and mature adult (53 weeks) male mice and Mouse embryonic fibroblasts isolated from WT and KO mice from E13.5 embryos as in vivo and in ex-vivo respectively. Mouse phenotyping studies were performed with controls, and a minimum of two independent experiments were performed with more than five mice in each group.

Results
We found that at the age of 53 weeks (mature adult), catalase-KO mice exhibited an aging phenotype faster than wild-type (WT) mice. We also found that mature adult catalase-KO mice induced leaky lysosome by progressive accumulation of lysosomal content, such as cathespin D, into the cytosol. Leaky lysosomes inhibited autophagosome formation and triggered impaired autophagy. The dysregulation of autophagy triggered mTORC1 (mechanistic target of rapamycin complex 1) activation. However, the antioxidant N-acetyl-L-cysteine and mTORC1 inhibitor rapamycin rescued leaky lysosomes and aging phenotypes in catalase-deficient mature adult mice.

Conclusions
This study unveils the new role of catalase and its role in lysosomal function during aging.
Dyslipidemia induced large-scale network connectivity abnormality facilitates cognitive decline in the Alzheimer’s disease
Authors: Wang Qing , Zang Feifei , He Cancan , Zhang Zhijun , Xie Chunming ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

Abstract
Background
Although lipid metabolite dysfunction contributes substantially to clinical signs and pathophysiology of Alzheimer’s disease (AD), how dyslipidemia promoting neuropathological processes and brain functional impairment subsequently facilitates the progression of AD remains unclear.

Methods
We combined large-scale brain resting-state networks (RSNs) approaches with canonical correlation analysis to explore the accumulating effects of lipid gene- and protein-centric levels on cerebrospinal fluid (CSF) biomarkers, dynamic trajectory of large-scale RSNs, and cognitive performance across entire AD spectrum. Support vector machine model was used to distinguish AD spectrum and pathway analysis was used to test the influences among these variables.

Results
We found that the effects of accumulation of lipid-pathway genetic variants and lipoproteins were significantly correlated with CSF biomarkers levels and cognitive performance across the AD spectrum. Dynamic trajectory of large-scale RSNs represented a rebounding mode, which is characterized by a weakened network cohesive connector role and enhanced network incohesive provincial role following disease progression. Importantly, the fluctuating large-scale RSNs connectivity was significantly correlated with the summative effects of lipid-pathway genetic variants and lipoproteins, CSF biomarkers, and cognitive performance. Moreover, SVM model revealed that the lipid-associated twenty-two brain network connections represented higher capacity to classify AD spectrum. Pathway analysis further identified dyslipidemia directly influenced brain network reorganization or indirectly affected the CSF biomarkers and subsequently caused cognitive decline.

Conclusions
Dyslipidemia exacerbated cognitive decline and increased the risk of AD via mediating large-scale brain networks integrity and promoting neuropathological processes.
These findings reveal a role for lipid metabolism in AD pathogenesis and suggest lipid management as a potential therapeutic target for AD.
Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
Authors: Chen Yingtai , Yin Jianhua , Zhao Lulu , Zhou Guangyu , Dong Shichen , Zhang Yueming , Niu Penghui , Ren Hu , Zheng Tianjiao , Yan Juan , Li Wenbin , Ma Peiqin , Zhang Cuijuan , Wei Chen , Church George , Li Guibo , Zhao Dongbing 
Published: December 2022

Abstract
Background
Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level.

Methods
Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT.

Results
Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells.

Conclusions
In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.
Knowledge-based DVH estimation and optimization for breast VMAT plans with and without avoidance sectors
Authors: Fogliata Antonella , Parabicoli Sara , Paganini Lucia , Reggiori Giacomo , Lobefalo Francesca , Cozzi Luca , Franzese Ciro , Franceschini Davide , Spoto Ruggero , Scorsetti Marta 
Published: December 2022

Abstract
Background
To analyze RapidPlan knowledge-based models for DVH estimation of organs at risk from breast cancer VMAT plans presenting arc sectors en-face to the breast with zero dose rate, feature imposed during the optimization phase (avoidance sectors AS).

Methods
CT datasets of twenty left breast patients in deep-inspiration breath-hold were selected. Two VMAT plans, PartArc and AvoidArc, were manually generated with double arcs from ~ 300 to ~ 160°, with the second having an AS en-face to the breast to avoid contralateral breast and lung direct irradiation. Two RapidPlan models were generated from the two plan sets. The two models were evaluated in a closed loop to assess the model performance on plans where the AS were selected or not in the optimization.

Results
The PartArc plans model estimated DVHs comparable with the original plans. The AvoidArc plans model estimated a DVH pattern with two steps for the contralateral structures when the plan does not contain the AS selected in the optimization phase. This feature produced mean doses of the contralateral breast, averaged over all patients, of 0.4 ± 0.1 Gy, 0.6 ± 0.2 Gy, and 1.1 ± 0.2 Gy for the AvoidArc plan, AvoidArc model estimation, RapidPlan generated plan, respectively. The same figures for the contralateral lung were 0.3 ± 0.1 Gy, 1.6 ± 0.6 Gy, and 1.2 ± 0.5 Gy. The reason was found in the possible incorrect information extracted from the model training plans due to the lack of knowledge about the AS. Conversely, in the case of plans with AS set in the optimization generated with the same AvoidArc model, the estimated and resulting DVHs were comparable. Whenever the AvoidArc model was used to generate DVH estimation for a plan with AS, while the optimization was made on the plan without the AS, the optimizer evidentiated the limitation of a minimum dose rate of 0.2 MU/°, resulting in an increased dose to the contralateral structures respect to the estimation.

Conclusions
The RapidPlan models for breast planning with VMAT can properly estimate organ at risk DVH. Attention has to be paid to the plan selection and usage for model training in the presence of avoidance sectors.
LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC
Authors: Cai Yunshi , Lyu Tao , Li Hui , Liu Chang , Xie Kunlin , Xu Lin , Li Wei , Liu Hu , Zhu Jiang , Lyu Yinghao , Feng Xuping , Lan Tian , Yang Jiayin , Wu Hong 
Published: December 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is the world’s third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet.

Methods
CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of β-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2).

Results
CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of β-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and β-catenin, thus promoting the nuclear translocation of β-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis.

Conclusions
Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/β-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/β-catenin axis may be used as a potential therapeutic target for HCC treatment.
Self-adaptive forward–backward splitting algorithm for the sum of two monotone operators in Banach spaces
Authors: Bello Abdulmalik U. , Chidume Charles E. , Alka Maryam 
Published: December 2022

AbstractIn this work, we prove the weak convergence of a one-step self-adaptive algorithm to a solution of the sum of two monotone operators in 2-uniformly convex and uniformly smooth real Banach spaces. We give numerical examples in infinite-dimensional spaces to compare our result with some existing algorithms. Finally, our results extend and complement several existing results in the literature.
Effectiveness of enhanced check during acute phase to reduce central venous catheters-associated bloodstream infections: a before-after, real-world study
Authors: Lv Yu , Huang Xiaobo , Xiang Qian , Yang Qin , Chen Jin , Cai Minhong , Wang Pingping , Jia Ping , Wang Hui , Xie Caixia , Li Luting , Zhang Dingding , Wei Daoqiong , Wu Jiayu 
Published: December 2022

Abstract
Background
To evaluate the effectiveness of enhanced check to the duration of the central venous catheters associated bloodstream infections (CABSIs), and the impact on infection rates.

Methods
A before-after, real-world study in six adult intensive care units was conducted. All adult patients who had only one central venous catheter were included during two consecutive periods. The intervention period, added cross-check that all patients with central venous catheter (CVC) need to be performed, and included nurses' checks for insertion practices and doctors' checks for maintenance practices. Propensity scores matching were used to account for potential confounding, and restricted cubic spline was served as visualizing the CABSI risk.

Results
A total of 2906 patients with 26,157 CVC-days were analyzed. After intervention, the density incidence of CABSI decreased from 10.24 to 6.33/1,000 CVC-days (P < 0.001), and the acute period of rapid increase in CABSI risk was shortened, 6.5 to 5 days for femoral-vein catheterization and 7 to 5.5 days for subclavian-vein catheterization. For jugular-vein catheterization, the acute onset period disappeared.

Conclusion
Enhanced check during the first 7 calendar days after CVC insertion shortens the duration of the CABSI acute phase and tends to decrease CABSI rate.
Food insecurity and outcomes during COVID-19 pandemic in sub-Saharan Africa (SSA)
Authors: Onyeaka Helen , Tamasiga Phemelo , Nkoutchou Hugue , Guta Ashenafi Teshome 
Published: December 2022

AbstractThe outbreak of COVID-19 led to the implementation of lockdowns and social distancing regulations to curb the spread of infections. Consequently, the lockdowns impeded the movement of smallholder farmers, agricultural inputs, and food products thereby disrupting the food supply chains in SSA. Therefore, this paper examines the relationship between food security indicators (accessibility, availability, utilization, stability) and COVID-19. This study uses ordinary least square regression (OLS) models to study the relationship between the food security indicators and COVID-19. The study considers 9 out of 48 sub-Saharan African countries (Benin, Burkina Faso, Cameroon, Chad, Madagascar, Mali, Mauritania, Nigeria, Senegal) due to data availability restrictions. The result of the analysis indicated that a rise in COVID-19 levels negatively impacts all the 4 indicators of food security without exception. This paper underscores the need to consider the disruptions of food security indicators such as diet, nutritional content, access and availability, affordability, and food supply chains. Moreover, the paper discusses mitigating strategies that may alleviate SSA’s food security amidst the COVID-19 pandemic. We recommend that SSA countries invest in quality agricultural and food production infrastructure and supporting industries that contribute directly to the food supply chain, such as agro-processing, fertilizer production and transport. Another important dimension of the COVID-19 and food insecurity syndemic is the income shocks that occurred as a consequence of the COVID-19 outbreak. Like many factories, companies, and service providers closed shop (especially the informal sector), people lost their incomes as a result of loss of employment and, in many instances, no social protection. Therefore, we recommend that SSA governments develop affordable, sustainable, and targeted social protection/insurance systems that extend to the informal sector of the economy.
The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production
Authors: Wu Di , Fu Linglong , Wen Weizhang , Dong Na 
Published: December 2022

AbstractHost defense peptides (HDPs) are small molecules with broad-spectrum antimicrobial activities against infectious bacteria, viruses, and fungi. Increasing evidence suggests that HDPs can also indirectly protect hosts by modulating their immune responses. Due to these dual roles, HDPs have been considered one of the most promising antibiotic substitutes to improve growth performance, intestinal health, and immunity in farm animals. This review describes the antimicrobial and immunomodulatory roles of host defense peptides and their recent applications in animal production.
Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer
Authors: Cousin Sophie , Toulmonde Maud , Kind Michèle , Guegan Jean-Philippe , Bessede Alban , Cantarel Coralie , Bellera Carine , Italiano Antoine 
Published: December 2022

AbstractBreast cancer is one the most common cause of cancer death in women worldwide. We report here the first phase II study investigating a virus genetically engineered for tumor-selective replication in patients with breast cancer. Ten patients were treated with a combination of low-dose oral cyclophosphamide and intra-venous JX-594, a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF) and β-galactosidase. Best response as per RECIST criteria was stable disease for 2 patients and progressive disease for 8 patients. Median progression-free and overall survival were 1.6 months (95% CI: [1.1–1.9]) and 14.4 months (95% CI: [2.0 – NA]) respectively. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as IFN gamma. Whether the combination of JX-594 with an immune checkpoint inhibitor is associated with meaningful clinical activity is therefore worth to investigate.
Commending rather than condemning: Moral elevation and stigma for male veterans with military sexual trauma
Authors: Staley Gracie , Zaidan Ana Clara Vieira , Henley Katrina , Childers Lucas G. , Daniel Ray , Lauderdale Sean A. , McGuire Adam P. 
Published: December 2022

Abstract
Background
Using an experimental study, we examined the link between state moral elevation and stigmatic beliefs surrounding male veterans with military sexual trauma (MST).

Methods
Undergraduate students were presented with a video or written narrative of a male veteran self-disclosing how they struggled with and overcame MST (n = 292). Participants completed measures regarding trait and demographic characteristics at baseline, then measures immediately after the disclosure stimulus to assess immediate elevation and stigma-related reactions.

Results
Results suggest state-level elevation in response to a veteran self-disclosing their experience with MST was negatively correlated with harmful stigmatic beliefs about MST. A greater predisposition to experience elevation and PTSD symptoms were linked with stronger elevation responses to the stimulus.

Conclusion
Findings support the need for further exploration of elevation and its potential to impact public stigma for male veterans with MST.
Development and evaluation of a novel dietary bisphenol A (BPA) exposure risk tool
Authors: Hartle Jennifer C. , Zawadzki Roy S. , Rigdon Joseph , Lam Juleen , Gardner Christopher D. 
Published: December 2022

Abstract
Background
Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) is primarily from the diet through canned foods. Characterizing dietary exposures can be conducted through biomonitoring and dietary surveys; however, these methods can be time-consuming and challenging to implement.

Methods
We developed a novel dietary exposure risk questionnaire to evaluate BPA exposure and compared these results to 24-hr dietary recall data from participants (n = 404) of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study, a dietary clinical trial, to validate questionnaire responses. High BPA exposure foods were identified from the dietary recalls and used to estimate BPA exposure. Linear regression models estimated the association between exposure to BPA and questionnaire responses. A composite risk score was developed to summarize questionnaire responses.

Results
In questionnaire data, 65% of participants ate canned food every week. A composite exposure score validated that the dietary exposure risk questionnaire captured increasing BPA exposure. In the linear regression models, utilizing questionnaire responses vs. 24-hr dietary recall data, participants eating canned foods 1–2 times/week (vs. never) consumed 0.78 more servings (p < 0.001) of high BPA exposure foods, and those eating canned foods 3+ times/week (vs. never) consumed 0.89 more servings (p = 0.013) of high BPA exposure foods. Participants eating 3+ packaged items/day (vs. never) consumed 62.65 more total grams of high BPA exposure food (p = 0.036).

Conclusions
Dietary exposure risk questionnaires may provide an efficient alternative approach to 24-hour dietary recalls to quantify dietary BPA exposure with low participant burden.

Trial registration
The trial was prospectively registered at clinicaltrials.gov as NCT01826591 on April 8, 2013.
Postoperative prosthetic mitral valve occlusion due to left atrial thrombus during veno-arterial extracorporeal membrane oxygenation: a case report
Authors: Kiuchi Naoto , Seino Yusuke , Yamamoto Mai , Katagiri Seidai , Takagi Shunichi , Nomura Takeshi , Suzuki Takahiro 
Published: December 2022

AbstractBackgroundAnticoagulation using heparin is generally used to prevent thrombus formation during mechanical circulatory support, such as veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, during the early period following cardiac surgery, anticoagulation becomes more difficult due to the greater risk of critical bleeding complications.Case presentationA 71-year-old man presented with acute prosthetic valve occlusion caused by left atrial thrombus formation and bioprosthetic valve thrombosis during peripheral VA-ECMO following mitral valve replacement (MVR) despite continuous heparin administration and loading of antiplatelet agents. The VA-ECMO flow rate decreased 10 h after the intensive care unit (ICU) admission after MVR. Exploratory transesophageal echocardiography (TEE) examination revealed a left atrial thrombus, prosthetic valve obstruction by the thrombus, and an intrapericardial hematoma.ConclusionsIntracardiac thrombus formation might occur during VA-ECMO despite appropriate anticoagulation and loading of antiplatelet agents. Exploratory TEE examination was helpful in the detection of intra-atrial thrombus formation after cardiac surgery and surgical decision-making.