bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescent cells develop PDK4-dependent hypercatabolism and produce lactate to promote cancer resistance and aging
Authors: Dou Xuefeng , Fu Qiang , Long Qilai , Liu Shuning , Zou Yejun , Fu Da , Xu Qixia , Jiang Zhirui , Ren Xiaohui , Zhang Guilong , Wei Xiaoling , Li Qingfeng , Campisi Judith , Zhao Yuzheng , Sun Yu 
Published: January 2023

Abstract
Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here we highlight upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon cellular senescence, a tendency adversely correlated with cancer patient survival after chemotherapy. Senescent cells exhibit increased aerobic glycolysis and enhanced lactate production, but subject to reversal upon PDK4 inhibition. Distinct from the cancer cell-featured Warburg effect, however, senescent cells sustain mitochondrial respiration and redox activity, adopting a special form of metabolic reprogramming. Media from PDK4+ stromal cells change global expression and promote malignancy of recipient cancer cells in vitro, while targeting PDK4 causes tumor regression in vivo. The metabolite lactate causes NOX1 upregulation and ROS production in mitochondrion-disabled cells, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype (SASP). In preclinical trials, PDK4 intervention alleviates physical dysfunction and prevents age-associated frailty, conditions frequently observed in advanced life. Together, our study substantiates the hypercatabolic nature of senescent cells, and reveals a metabolic link between cellular senescence, lactate production, chronological aging and age-related pathologies including but not limited to cancer.
Cervical cancer screening for PLWHIV; experiences from an innovative cervical screening and treatment program in Nigeria
Authors: Ogunsola Olabanjo Okunlola , Ajayi Oluseye Ayodele , Ojo Temitope Olumuyiwa , Osayi Emmanuel , Wudiri Kucheli , Amoo Babatunde , Ayoka-Ikechukwu Rita , Olumeyan Olufemi , Ifechelobi Chukwuemeka , Okonkwo Prosper , Yewande Akinro 
Published: January 2023

Abstract
We evaluated cervical cancer program for women living with HIV (WLHIV) to determine program screening rate, primary case finder screening accuracy and treatment and post-treatment screening rate among screen-positive patients.
Methods
A one-year review of cervical cancer program data among WLHIV aged 15-49 years on HIV care across forty-one comprehensive ART sites supported by APIN (a PEPFAR implementing partner) in Nigeria was conducted from October 2020 to July 2021. Initial screening was done using visual inspection with acetic acid (VIA) followed by a gynaecologist expert review through a program-designed software named AVIVA, as a confirmatory test. Associations were measured between the primary case finder screening accuracy and study covariates at p-value of 0.05.
Results
About 10,289 asymptomatic women aged 15-49 years living with HIV were screened for cervical cancer by primary case finders using VIA-based screening test. 732 (7.1%) had a positive screening test suggestive of precancerous lesions or cervical cancer. 315 (43.0%) of VIA positive women had treatment using thermal ablation and less than one-third (21.6%) of those treated came back for post-treatment screening test. Primary case finder screening sensitivity, specificity, positive predictive and negative predictive accuracy using gynaecologist review as confirmatory test were 60.8%, 71.5%, 41.7% and 84.5% respectively. Overall screening accuracy was 68.8%.
Conclusion and Recommendation
This innovative approach to cervical cancer screening among WLHIV yielded modest results in preventing program error and wastages. Wider deployment of expert-based reviews of VIA though AVIVA software might be a veritable approach to improve screening accuracy in low resource settings.
Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
Authors: Mitsi Elena , Diniz Mariana , Reine Jesus , Collins Andrea , Robinson Ryan , Hyder-Wright Angela , Farrar Madlen , Liatsikos Konstantinos , Hamilton Josh , Onyema Onyia , Urban Britta , Solorzano Carla , Lambe Teresa , Draper Simon , Weiskopf Daniela , Sette Alessandro , Maini Mala , Ferreira Daniela 
Published: January 2023

Abstract
Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.
Cascaded hard X-ray self-seeded free-electron laser at MHz-repetition-rate
Authors: Liu Shan , Grech Christian , Guetg Marc , Karabekyan Suren , Kocharyan Vitali , Kujala Naresh , Lechner Christoph , Long Tianyun , Mirian Najmeh , Qin Weilun , Serkez Svitozar , Tomin Sergey , Yan Jiawei , Abeghyan Suren , Anton Jayson , Blank Vladimir , Boesenberg Ukrike , Brinker Frank , Chen Ye , Decking Winfried , Dong Xiaohao , Kearney Steve , Civita Daniele La , Madsen Anders , Maltezopoulos Theophilos , Rodriguez-Fernandez Angel , Saldin Evgueni , Samoylova Liubov , Scholz Matthias , Sinn Harald , Sleziona Vivien , Shu Deming , Tanikawa Takanori , Terentyev Sergey , Trebushinin Andrei , Tschentscher Thomas , Vannoni Maurizio , Wohlenberg Torsten , Yakopov Mikhail , Geloni Gianluca 
Published: January 2023

Abstract
The European XFEL is currently the only high-repetition rate hard X-ray free electron laser (FEL) facility in operation worldwide. We significantly improved its capabilities by installing a cascaded Hard X-ray Self-Seeding (HXRSS) system, composed of two single-crystal monochromators. With this system, mJ-level pulses in the photon energy range of 6 -14keV with a bandwidth around 1eV (corresponding to about 1mJ/eV spectral density) were generated. Combined with the burst-mode, multi-MHz repetition rate of the European XFEL accelerator, the cascaded HXRSS setup provides two orders of magnitude higher average spectral brightness than any other FEL facility. At 2.25 MHz repetition rate and photon energies in the 6-7 keV range, we observed for the first time heat-load effects on the HXRSS crystals, substantially altering the spectra of subsequent X-ray pulses. Using the cascaded self-seeding scheme, we successfully reduced this effect to below detection level. These results open up exciting possibilities in a wide range of scientific fields, exploiting the extreme brightness and the narrow bandwidth of HXRSS pulses.
Evolutionary dynamics in spatial public goods games with environmental feedbacks
Authors: Ding Rui , Wang Xianjia , Zhao Jinhua , Gu Cuiling , Chen Wenman , Huang Xingjun 
Published: January 2023

Abstract
Conflicting interests between individuals and groups are always emphasized in collective actions towards goals such as resource sustainability and environmental protection. These social dilemmas can be modeled by public goods games and collective risk dilemmas. However, the reality is that multiple generations share a common pool of resources, which leads to a high cost of today’s overexploitation to the welfare on future generations. Therefore, such delayed effects generate a multigenerational conflict. By establishing the relationship between individual payoffs and regional environmental quality, we build a coupled social-ecological coevolutionary model. To study how cooperative behaviors spread in a public goods game with environmental feedbacks and which factors influence it, we explore the mechanisms behind certain phases and phase transitions by monitoring the spatial distribution of strategies and the environmental quality of all regions. Some counterintuitive results can be obtained. For example, sometimes the stronger the ability of cooperators to improve the environment, the lower the overall level of cooperation in the system, which is related to the invasion of cooperative clusters by defectors in the crack of clusters. Moreover, the destructive power of defection and the cost of cooperation have a more complex effect on the system.
Extension of the Projected Gradient and Armijo’s Rule Concepts for Solving Convex Nonlinear Multiobjective Optimization Problems
Authors: Appolinaire TOUGMA , SOMÉ Kounhinir , COMPAORÉ Abdoulaye 
Published: January 2023

Abstract
In this work, we propose a method for solving a boundary constraints multiobjective optimization problems. The algorithm combines the projected gradient with a modified version of the Armijo Rule and the weighted sum to find the best solutions. Under the assumption that the objective functions are differentiable and convex, the convergence to an optimal Pareto point is established. Furthermore, we have successfully solved test problems with which we have calculated some performance indicators related to the convergence and diversity of obtained solutions. All these results have allowed us to highlight effectiveness and efficiency of our method.
Time-Based Dynamic Changes Of Gene Expression In The Hypoxic T47D Cell Line Duration Of Hypoxia: RNA Sequencing Approach
Authors: Annisa Annisa , Purnomosari Dewajani 
Published: January 2023

Abstract
Background : Uncontrolled proliferation of tumor cells leads to hypoxia. Hypoxia can cause changes in hypoxia responsive genes transcriptions as an adaptation to limited oxygen. RNA sequencing in breast cancer cells is still varied and is known to change with the duration of treatment. The aim of this project was to compare the mRNA profiles between normoxia and hypoxia of T47D breast cancer cells using RNA-seq.
Methods : T47D breast cancer cell cultured under hypoxic conditions (0.5% oxygen) for 6, 24 and 48 h. RNA was extracted using the Qiagen allprep DNA/RNA/Protein Mini kit. Total RNA with RNA Integrity Number >7 will be sequenced to reveal gene expression profiles.
Results: 143,875,430 out of 169,314,448 reads (85%) were passed filtering. Of those, 26.684,288 reads (18.45%) are from 6 hours hypoxia, 29,178,225 reads (20.28%) from hypoxia 24 hours, 27,615,450 reads (19.19%) from hypoxia 48 hours. While 24,514,359 reads (17.94%) are from the normoxia group. During treatment, 23 genes were differentially expressed between groups; three genes are downregulated, and the rest are upregulated. Three genes (TAF1C, CD63, TM7SF2) were upregulated in the normoxia group, two genes (CYP1A1 and VCP) were upregulated in 6 hours of hypoxia. Two genes (NEBL and KDM3A) were upregulated in 24 hours hypoxia, while six genes (ERBB3, PIKP1, Ro60, ESRP1, KLF6, MKRN2) were upregulated in 48 hours hypoxia group.
Conclusion: Gene expression profiles between treatment and control group are different. Modulation of gene expression during hypoxia plays a role in glycolysis, proliferation, growth, and migration.
TNFR2 mediates pancreatic cancer proliferation, migration, and invasion via the NF‑κB signaling pathway
Authors: Gao Zetian , Zhang Qiubo , Chen Hang , Li Hong , Chen Jiayi , Kang Jingyu , Gao Hui , Yu Hang , Song Yufei , Zhang Xie 
Published: January 2023

Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2) contributes to the development and progression of several tumors. In this study, we investigated the clinicopathologic data and outcomes of pancreatic cancer patients and elucidated the molecular mechanisms of TNFR2.
Method: We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal (n = 171) and malignant (n = 179) pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting.
Results: TNFR2 was more highly expressed in PDAC cells and tissues than in controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion in vitro. Mechanistically, TNFR2 binds to TNF-ɑ and activates the NF-κB signaling pathway.
Conclusion: TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF‑κB signaling pathway. TNFR2 may become a therapeutic target.
Identifying high snakebite risk area under climate change: Implications for community education and antivenom distribution
Authors: Yousefi Masoud , Yousefkhani Saeed Hosseinian , Grünig Marc , Kafash Anooshe , Rajabizadeh Mahdi , Pouyani Eskandar Rastegar 
Published: January 2023

Abstract
Snakebite is a global health problem and yearly snakebites have been estimated up to 5 million leading to about 100,000 deaths each year. While those numbers are showing that snakebite is one of the largest risks from wildlife, little is known about venomous snake distribution, spatial variation in snakebite risk, potential changes in snakebite risk pattern due to climate change, and vulnerable human population. As a consequence, management and prevention of snakebite is hampered by this lack of information. Previous studies suggest that habitat suitability models are effective tools in predicting snakebite risk areas under current and future climate and identifying vulnerable human population. Here we used an ensemble approach of five different habitat suitability modeling algorithms for 10 medically important venomous snakes to quantify snakebite risk pattern, map snakebite hotspots, calculate community composition changes and changes in vulnerability to snakebite in Iran under current and future climate (years 2041–2070 and 2071–2100). We identified areas with high snakebite risk in Iran and showed that snakebite risk will increase in some parts of the country. We also found mountainous areas (Zagros, Alborz, Kopet-Dagh mountains) will experience highest changes in species composition. We underline that in order to improve snakebite management, areas which were identified with high snakebite risk in Iran need to be prioritized for the distribution of antivenom medication and awareness rising programs among vulnerable human population.
Residual Stress Analysis of TC4/Inconel718 Functionally Graded Material Produced by Laser Additive Manufacturing Based on Progressive Activation Element Method
Authors: Zhao Hongjian , Gao Chi , Wang Zihao , Wang Quanyi , Liu Changsheng , zhan yu 
Published: January 2023

Abstract
With the continuous development of preparation technology, laser additive manufacturing (LAM) has become one of the effective ways to manufacture functionally graded materials due to its unique layer-by-layer stacking technology. However, the repeated and repeated rapid heating and cooling processes in the manufacturing process will generate large residual stress inside the structure, resulting in the destruction of the structure. In this paper, based on a new finite element method called progressive activation element method (PAE), a thermomechanical coupling model for simulating the process of LAM is established, and the influence of laser power and composition ratio of transition layers on the residual stress of the overall structure is discussed. The results show that there is a positive correlation between the laser power and the residual stress. The PAE method is compared with the traditional “Model Change” method, and it is found that the PAE method has advantages in computational efficiency, especially when calculating the residual stress of functionally graded materials, the efficiency can be improved by about 1650%. When the TC4/Inconel718 functionally graded material is prepared experimentally, the optimal composition ratio of the transition layers is 8:2. This paper provides reference for the understanding and reasonable suppression of residual stress of functionally graded materials in LAM.
Development of a Quality of Work Life scale for community pharmacists in Japan: A questionnaire survey
Authors: Kato Yuta , Sekiya Takashi , Ishii Ryo , Hirako Yoji , Satoh Hiroki , Kimura Hiromichi 
Published: January 2023

Abstract
Background: Human resource management may be difficult for community pharmacists because of recent drastic changes in work volume and content. In Japan, few studies have been conducted on job satisfaction, well-being, and quality of work life (QWL) among community pharmacists. Focusing on QWL, a more comprehensive concept than job satisfaction, this study aimed to develop a multi-trait-based QWL scale for Japanese community pharmacists (QWLS for JCP) and test its reliability and validity.
Methods:A questionnaire survey was conducted among 2027 pharmacists working in pharmacies, with the cooperation of 20 corporations running pharmacies. The collected data were subjected to principal component factor analysis with Promax rotation using SPSS28.
Results: The following five significant components were identified based on factor analysis using data from 1966 pharmacists. These form the basis of the QWLS for JCP: “Influence of work on mind and body,” “Relationships with colleagues,” “Relationship with the boss,” “Meaning of existence in the workplace,” and “Pride in work.” Cronbach’s alpha, which expresses reliability, was between 0.585 and 0.854 for these subscales.
Conclusions: The QWLS for JCP significantly explained the concept of QWL, which means that its validity was sufficient.
Rejection Sensitivity and Psychological Well-being: Moderating Role of Self-esteem and Socio-demographics
Authors: Zulfiqar Najia , Khan Muhammad Ahmer , Saleem Nadia 
Published: January 2023

Abstract
The present study aimed to examine the moderating effects of self-esteem and socio-demographics of gender, age, family system, and the number of friends on the relationship between rejection sensitivity and psychological well-being. Participants were adolescents (n = 112; M = 16 years) and emerging adults (n = 189; M = 23 years) who belonged to nuclear (n = 181) or combined family system (n = 120) and had limited friends (n = 185) or numerous friends (n = 116). Almost an equal number of boys (n = 150) and girls (n = 151) responded to the Rejection Sensitivity Questionnaire, Rosenberg Self-esteem Scale, and Ryff’s Psychological Well-being Scale. The hypothesis stated that rejection sensitivity will predict poor psychological well-being, and high self-esteem will decrease the negative effects of rejection sensitivity on psychological well-being. Findings indicated that rejection sensitivity was a significant negative predictor of psychological well-being and accounted for 14% of the variance in the outcome measure. Rejection sensitivity and high self-esteem had a significant negative correlation and buffered its negative effects on psychological well-being. Participants, i.e., boys, emerging adults, belonging to the nuclear family system, and with more friends, reported having more psychological well-being than their counterparts. The study has intrapersonal and interpersonal behavioral implications at individual, social, and community levels to safeguard behavior from rejection sensitivity, low self-esteem, and poor psychological health. Parents, teachers, policy-makers, psychologists, sociologists, and mental health practitioners can practically benefit from the findings to foster positive behavior and implement prevention-intervention support.
Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.
Authors: Oliviero Barbara , Cas Michele Dei , Zulueta Aida , Maiello Roberta , Villa Alessandro , Martinelli Carla , Favero Elena Del , Falleni Monica , Montavoci Linda , Varchetta Stefania , Mele Dalila , Donadon Matteo , Soldani Cristiana , Franceschini Barbara , Maestri Marcello , Piccolo Gaetano , Barabino Matteo , Bianchi Paolo , Banales Jesus M , Mantovani Stefania , Mondelli Mario , Caretti Anna 
Published: January 2023

Abstract
Cholangiocarcinoma (CCA) is a rare cancer with global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Higher ceramide and dihydroceramide content was associated with vascular invasion, larger tumor size and relevant expression of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory capacity of iCCA-derived EVs, demonstrating the role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may facilitate iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.