bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation
Authors: Chu Gerard J. , Bailey Charles G. , Nagarajah Rajini , Sagnella Sharon M. , Adelstein Stephen , Rasko John E. J. 
Published: December 2023

Abstract
Background
Chimeric antigen receptor (CAR) T-cells have revolutionized the treatment of CD19- and B-cell maturation antigen-positive haematological malignancies. However, the effect of a CAR construct on the function of T-cells stimulated via their endogenous T-cell receptors (TCRs) has yet to be comprehensively investigated.

Methods
Experiments were performed to systematically assess TCR signalling and function in CAR T-cells using anti-mesothelin human CAR T-cells as a model system. CAR T-cells expressing the CD28 or 4-1BB costimulatory endodomains were manufactured and compared to both untransduced T-cells and CAR T-cells with a non-functional endodomain. These cell products were treated with staphylococcal enterotoxin B to stimulate the TCR, and in vitro functional assays were performed by flow cytometry.

Results
Increased proliferation, CD69 expression and IFNγ production were identified in CD8+ 4-1BBζ CAR T-cells compared to control untransduced CD8+ T-cells. These functional differences were associated with higher levels of phosphorylated ZAP70 after stimulation. In addition, these functional differences were associated with a differing immunophenotype, with a more than two-fold increase in central memory cells in CD8+ 4-1BBζ CAR T-cell products.

Conclusion
Our data indicate that the 4-1BBζ CAR enhances CD8+ TCR-mediated function. This could be beneficial if the TCR targets epitopes on malignant tissues or infectious agents, but detrimental if the TCR targets autoantigens.
Role of epithelial splicing regulatory protein 1 in cancer progression
Authors: Kwon Mi Jeong 
Published: December 2023

AbstractAs aberrant alternative splicing by either dysregulation or mutations of splicing factors contributes to cancer initiation and progression, splicing factors are emerging as potential therapeutic targets for cancer therapy. Therefore, pharmacological modulators targeting splicing factors have been under development. Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific splicing factor, whose downregulation is associated with epithelial–mesenchymal transition (EMT) by regulating alternative splicing of multiple genes, such as CD44, CTNND1, ENAH, and FGFR2. Consistent with the downregulation of ESRP1 during EMT, it has been initially revealed that high ESRP1 expression is associated with favorable prognosis and ESRP1 plays a tumor-suppressive role in cancer progression. However, ESRP1 has been found to promote cancer progression in some cancers, such as breast and ovarian cancers, indicating that it plays a dual role in cancer progression depending on the type of cancer. Furthermore, recent studies have reported that ESRP1 affects tumor growth by regulating the metabolism of tumor cells or immune cell infiltration in the tumor microenvironment, suggesting the novel roles of ESRP1 in addition to EMT. ESRP1 expression was also associated with response to anticancer drugs. This review describes current understanding of the roles and mechanisms of ESRP1 in cancer progression, and further discusses the emerging novel roles of ESRP1 in cancer and recent attempts to target splicing factors for cancer therapy.
Anopheles gambiae s.s. resistance to pyrethroids and DDT in semi-urban and rural areas of the Moyen-Ogooué Province, Gabon
Authors: Boussougou-Sambe Stravensky Térence , Ngossanga Barclaye , Doumba-Ndalembouly Ange Gatien , Boussougou Lynda Nouage , Woldearegai Tamirat Gebru , Mougeni Fabrice , Mba Thierry Ndong , Edoa Jean Ronald , Dejon-Agobé Jean Claude , Awono-Ambene Parfait , Kremsner Peter G. , Kenguele Hilaire M. , Borrmann Steffen , Mordmüller Benjamin , Adegnika Ayôla Akim 
Published: December 2023

Abstract
Background
Pyrethroids are the main insecticides used in vector control for malaria. However, their extensive use in the impregnation of long-lasting insecticidal nets (LLINs) and indoor residual spraying has led to the development of resistance, threatening its success as a tool for malaria control. Baseline data prior to large scale distribution of LLINs are important for the implementation of efficient strategies. However, no data on the susceptibility of malaria vectors is available in the Moyen-Ogooué Province in Gabon. The aim of this study was to assess the susceptibility to pyrethroids and organochlorides of malaria vectors from a semi-urban and rural areas of the province and to determine the frequency of insecticide resistance genes.

Methods
Larvae were collected from breeding sites in Lambaréné and Zilé and reared to adults. Three to five-day old female Anopheles gambiae sensu lato mosquitoes were used in cone tube assays following the WHO susceptibility tests protocol for adult mosquitoes. A subsample was molecularly identified using the SINE200 protocol and the frequency of Vgsc-1014 F and − 1014 S mutations were determined.

Results
Anopheles gambiae sensu stricto (s.s.) was the sole species present in both Lambaréné and Zilé. Mosquito populations from the two areas were resistant to pyrethroids and organochlorides. Resistance was more pronounced for permethrin and DDT with mortality lower than 7% for both insecticides in the two study areas. Mosquitoes were statistically more resistant (P < 0.0001) to deltamethrin in Lambaréné (51%) compared to Zilé (76%). All the mosquitoes tested were heterozygous or homozygous for the knockdown resistance (Kdr) mutations Vgsc-L1014F and Vgsc-L1014S with a higher proportion of Vgsc-L1014F homozygous in Lambaréné (76.7%) compared to Zilé (57.1%).

Conclusion
This study provides evidence of widespread resistance to pyrethroids in An. gambiae s.s., the main malaria vector in the Moyen-Ogooué Province. Further investigation of the mechanisms underlining the resistance of An. gambiae s.s. to pyrethroids is needed to implement appropriate insecticide resistance management strategies.
Exploring the varied manifestations of structural violence in the lives of children on the autism spectrum and their families: a qualitative longitudinal study in Kurdistan, Iran
Authors: Khougar Ansar , Baba Ahmadi Paria , Ranjbar Hadi , Ahadi Mahsa , Ahadi Parisa 
Published: December 2023

Abstract
Background
There are many dimensions regarding autism that are closely connected to social structures, policies, and power dynamics, silently impacting the well-being of individuals within the autism spectrum. This research aims to explore these overlooked aspects using a theoretical framework called "structural violence."

Methods
The study was conducted in Kurdistan, Iran, and a qualitative longitudinal approach was chosen. A purposive sampling method was employed to select the participants, with 11 parents taking part. The study data comprised 29 interviews using a topic guide conducted over a span of 2 years. Thematic analysis and a matrix-based approach were utilized for data analysis. To enhance the scientific rigor of this research, four criteria, including Guba and Lincoln’s principles, were implemented to ensure methodological accuracy.

Results
The research findings highlight four primary forms through which structural violence impacts children on the autism spectrum and their families: access to healthcare, geographic disparities, awareness and stigma, and poverty and financial burden. Additionally, the study identified 11 subthemes related to structural violence in the context of autism and families.

Conclusions
We illustrated how structural forces create barriers to accessing adequate healthcare services, exacerbate discrimination based on ethnicity and geography, perpetuate stigma, and contribute to poverty and the inability to meet basic needs. These factors not only worsen health issues but also deepen existing disparities in healthcare access and outcomes for children on the autism spectrum and families. We emphasize the urgent need for systemic changes to address these issues. It is essential to promote public awareness, provide better access to health and support services, and address economic and political factors that contribute to these inequalities.
Targeting CRAF kinase in anti-cancer therapy: progress and opportunities
Authors: Wang Penglei , Laster Kyle , Jia Xuechao , Dong Zigang , Liu Kangdong 
Published: December 2023

AbstractThe RAS/mitogen-activated protein kinase (MAPK) signaling cascade is commonly dysregulated in human malignancies by processes driven byRASorRAFoncogenes. Among the members of the RAF kinase family, CRAF plays an important role in the RAS-MAPK signaling pathway, as well as in the progression of cancer. Recent research has provided evidence implicating the role of CRAF in the physiological regulation and the resistance to BRAF inhibitors through MAPK-dependent and MAPK-independent mechanisms. Nevertheless, the effectiveness of solely targeting CRAF kinase activity remains controversial. Moreover, the kinase-independent function of CRAF may be essential for lung cancers withKRASmutations. It is imperative to develop strategies to enhance efficacy and minimize toxicity in tumors driven byRASorRAFoncogenes. The review investigates CRAF alterations observed in cancers and unravels the distinct roles of CRAF in cancers propelled by diverse oncogenes. This review also seeks to summarize CRAF-interacting proteins and delineate CRAF's regulation across various cancer hallmarks. Additionally, we discuss recent advances in pan-RAF inhibitors and their combination with other therapeutic approaches to improve treatment outcomes and minimize adverse effects in patients withRAF/RAS-mutant tumors. By providing a comprehensive understanding of the multifaceted role of CRAF in cancers and highlighting the latest developments in RAF inhibitor therapies, we endeavor to identify synergistic targets and elucidate resistance pathways, setting the stage for more robust and safer combination strategies for cancer treatment.
Rictor mediates p53 deactivation to facilitate the malignant transformation of hepatocytes and promote hepatocarcinogenesis
Authors: Wang Chun , Kang Hui , Yi Yun , Ding Yang , Wang Fan , Luo Jie , Ye Mingliang , Hong Yinghui , Xia Chao , Yan Junwei , Liu Lan , Liu Jing , Zhong Zibiao , Zhang Zhonglin , Zhao Qiu , Chang Ying 
Published: December 2023

Abstract
Background
Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear.

Methods
Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo.

Results
Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P < 0.05). In mice, xenograft tumors overexpressing miR-192 exhibited lower Rictor expression levels, leading to higher p53 activity, and these tumors displayed slower growth compared to untreated HCC cells.

Conclusions
Rictor dynamically shuttles between the nucleus and cytoplasm during HCC development. Its pivotal oncogenic role involves binding and inhibiting p53wt activity within the nucleus in early hepatocarcinogenesis. Targeting Rictor presents a promising strategy for HCC based on p53 status.
Lumbar spine bone mineral density in women breastfeeding for a period of 4 to 6 months: systematic review and meta-analysis
Authors: Ferreira Larissa Brazolotto , Tirapeli Keny Gonçalves , Silva Carla Cristiane , Goldberg Tamara Beres Lederer 
Published: December 2023

Abstract
Background
During the breastfeeding period, important transient changes in calcium homeostasis are verified in the maternal skeleton, to meet the demand for calcium for breastmilk production. The literature is inconclusive regarding the causes and percentages of involvement of bone densitometry resulting from exclusive breastfeeding (4 to 6 months).

Methods
This article aims to systematically review the literature, to determine the occurrence, intensity, and factors involved in alterations in maternal bone mineral density (BMD), during a period of 4 to 6 months of exclusive breastfeeding. The search descriptors “woman”, “breastfeeding”, “human milk”, and “bone mineral density” were used in the electronic databases of the Virtual Health Library, Scielo (Scientific Electronic Library Online), CAPES Periodicals Portal, LILACS, Embase, PubMed/Medline, Cochrane, Scopus, and Web of Science in June 2023. Inclusion criteria for breastfeedingmothers were; aged to 40 years, primigravida, exclusively breastfeeding, with BMD assessments using dual-energy X-ray absorptiometry (DXA), with values expressed at baseline and from 4 to 6 months postpartum. The Jadad scale, Newcastle–Ottawa Scale, and Oxford Centre for Evidence-based Medicine – levels of evidence were adopted to assess the quality of the studies. For the meta-analytical study, statistical calculations were performed.

Results
Initially, 381 articles were found using the search strategy and 26 were read in full. After risk of bias analysis, 16 articles remained in the systematic review and four were included in the meta-analysis. The studies showed a reduction in bone mass in the lumbar spine in the first months postpartum (4 – 6 months), when compared with a longer period of breastfeeding (12–18 months). The breastfeeding group presented a greater impact in the meta-analysis than the control group (non-breastfeeding, pregnant, or immediate postpartum), with a reduction in BMD in the lumbar spine of -0.18 g/cm2 (-0.36, -0.01 g/cm2); 95% Confidence Interval, on a scale from 0 to 10.

Conclusions
Our results demonstrated a transitory reduction in bone densitometry of the lumbar spine during exclusive breastfeeding for 4 to 6 months, which was gradually restored later in the postpartum period. More prospective studies are needed to better understand the topic.

Trial registration
PROSPERO platform (nº CRD42021279199), November 12th, 2021.
Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer
Authors: Zheng Le-Wei , Liu Cui-Cui , Yu Ke-Da 
Published: December 2023

AbstractLiquid–liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecular condensate (BMC) formation via dynamic aggregation. LLPS changes individual molecules into membrane-free, droplet-like BMCs with specific functions, which coordinate various cellular activities. The formation and regulation of LLPS are closely associated with oncogenesis, tumor progressions and metastasis, the specific roles and mechanisms of LLPS in tumors still need to be further investigated at present. In this review, we comprehensively summarize the conditions of LLPS and identify mechanisms involved in abnormal LLPS in cancer processes, including tumor growth, metastasis, and angiogenesis from the perspective of cancer hallmarks. We have also reviewed the clinical applications of LLPS in oncologic areas. This systematic summary of dysregulated LLPS from the different dimensions of cancer hallmarks will build a bridge for determining its specific functions to further guide basic research, finding strategies to intervene in LLPS, and developing relevant therapeutic approaches.
The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls
Authors: Bemmouna Doha , Lagzouli Amine , Weiner Luisa 
Published: December 2023

AbstractBackgroundEmotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC).MethodsA total of 724 participants (ASC = 154; BPD = 111; NC = 459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group.ResultsED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD.LimitationsASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions.ConclusionsED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults.
Ilm-NMR-P31: an open-access 31P nuclear magnetic resonance database and data-driven prediction of 31P NMR shifts
Authors: Hack Jasmin , Jordan Moritz , Schmitt Alina , Raru Melissa , Zorn Hannes Sönke , Seyfarth Alex , Eulenberger Isabel , Geitner Robert 
Published: December 2023

AbstractThis publication introduces a novel open-access 31P Nuclear Magnetic Resonance (NMR) shift database. With 14,250 entries encompassing 13,730 distinct molecules from 3,648 references, this database offers a comprehensive repository of organic and inorganic compounds. Emphasizing single-phosphorus atom compounds, the database facilitates data mining and machine learning endeavors, particularly in signal prediction and Computer-Assisted Structure Elucidation (CASE) systems. Additionally, the article compares different models for 31P NMR shift prediction, showcasing the database’s potential utility. Hierarchically Ordered Spherical Environment (HOSE) code-based models and Graph Neural Networks (GNNs) perform exceptionally well with a mean squared error of 11.9 and 11.4 ppm respectively, achieving accuracy comparable to quantum chemical calculations.
Existence and convergence of best proximity points for generalized pseudo-contractive and Lipschitzian mappings via an Ishikawa-type iterative scheme
Authors: Pragadeeswarar V. , Gopi R. 
Published: December 2023

AbstractIn this article, we prove the existence of the best proximity point for the class of nonself generalized pseudo-contractive and Lipschitzian mappings. Also, we approximate the best proximity point through the proposed Ishikawa’s iteration process for the case of nonself-mappings. Finally, we provide an example to illustrate our main result.
Intelligent urbanism with artificial intelligence in shaping tomorrow’s smart cities: current developments, trends, and future directions
Authors: Yan Zhenjun , Jiang Ling , Huang Xiaoli , Zhang Lifang , Zhou Xinxin 
Published: December 2023

Abstract21st century has witnessed a profound metamorphosis in human civilization, primarily driven by the confluence of advanced network technologies and industrial modernization. This transformative period has expanded our understanding of the world, paving the way for innovative concepts such as the “smart city”. At its essence, a smart city harnesses the power of artificial intelligence (AI) to revolutionize urban living, presenting a paradigm shift towards more efficient service models and an elevated standard of living for its inhabitants. Integrating AI into the fabric of urban infrastructure marks a monumental leap in societal evolution, underscoring the imperative to cultivate and advance AI technologies. This paper endeavors to elucidate the multifaceted applications of AI within the domains of smart cities, illuminating its pivotal role in shaping and advancing our contemporary era. From intelligent transportation systems and energy management to public safety and healthcare, AI permeates various aspects of urban life, ushering in unprecedented efficiencies and novel solutions to age-old challenges. The symbiotic relationship between AI and smart cities is explored in detail, showcasing how AI technologies are instrumental in optimizing resource allocation, improving decision-making processes, and ultimately enhancing the overall quality of life. Furthermore, this paper delves into the imperative of fostering the development and advancement of AI technologies within the context of smart cities. It underscores the interconnectedness of technological progress and urban development, emphasizing how a concerted effort to cultivate AI capabilities can propel cities into a future marked by sustainable growth, resilience, and innovation. The exploration of challenges and opportunities in deploying AI within urban environments adds a critical dimension to the discourse, encouraging a balanced consideration of ethical, regulatory, and societal implications. In conclusion, this paper seeks to contribute to the ongoing dialogue surrounding smart cities and the transformative impact of AI. By shedding light on the diverse applications of AI within urban landscapes and emphasizing its pivotal role in shaping the trajectory of our era, it underscores the critical importance of advancing AI technology development for the continued progress of smart cities and, by extension, the broader global community.