bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease
Authors: Li Chenfei , Liu Qi , Chang Qing , Xie Meiqin , Weng Jiali , Wang Xiaohui , Li Mengnan , Chen Jiani , Huang Yan , Yang Xiaohua , Wang Kai , Zhang Na , Chung Kian Fan , Adcock Ian M. , Zhang Hai , Li Feng
Published: December 2023

Background

Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence.

Methods

Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1β, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively.

Results

There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1.

Conclusions

Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.

Graphical Abstract
Robinin inhibits pancreatic cancer cell proliferation, EMT and inflammation via regulating TLR2-PI3k-AKT signaling pathway
Authors: Zhang Wenwen , Liu Wenting , Hu Xingchen
Published: December 2023

Purpose

To investigate the anti-tumor effect of Robinin (Toll-like receptor 2 inhibitor) in pancreatic cancer cells via regulating tumor microenvironment.

Methods

The effects of Robinin on cell proliferation or migration in Mia-PACA2 and PANC-1 were determined, using CCK8 or wound healing assay, respectively. The typical markers of EMT (αSMA and snail) and the inflammation markers (IL-6 and TNF-α) were all detected by western blot. CU-T12-9 (TLR2 agonist) was used to rescue Robinin’s effect. PI3k-p85α and Phosphorylated-AKT (p-AKT) were evaluated, compared to the β-actin and AKT, using western blot.

Results

Robinin significantly inhibited cell proliferation and migration in Mia-PACA2 and PANC-1, compared to HPNE (**P < 0.01). Robinin also attenuated the expression of α-SMA and snail in Mia-PACA2, and PANC-1 (**P < 0.01). Besides, it was found that expression of IL-6 and TNF-α were diminished in presence of Robinin in Mia-PACA2, and PANC-1 (**P < 0.01). Western blot confirmed that Robinin could target on TLR2, and further downregulated PI3k-AKT signaling pathway to exert biological function.

Conclusions

Robinin exerts anti-tumor effect perhaps via downregulating inflammation and EMT in pancreatic cancer cell through inhibiting TLR2-PI3k-AKT signaling pathway. Robinin may be a novel agent in adjuvant therapy of pancreatic cancer.
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

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

As 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

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

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

The 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

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

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

Liquid–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

Background

Emotion 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).

Methods

A 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.

Results

ED 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.

Limitations

ASC 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.

Conclusions

ED 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

This 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

In 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

21st 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.
Risk factors analysis and survival prediction model establishment of patients with lung adenocarcinoma based on different pyroptosis-related gene subtypes
Authors: Wen Ziang , Pei Bei , Dai Longfei , Lu Peng , Li Xiangyu , Zhang Chengxin , Ge Shenglin
Published: December 2023

Background

Lung adenocarcinoma (LUAD) is a common cancer with a poor prognosis. Pyroptosis is an important process in the development and progression of LUAD. We analyzed the risk factors affecting the prognosis of patients and constructed a nomogram to predict the overall survival of patients based on different pyroptosis-related genes (PRGs) subtypes.

Methods

The genomic data of LUAD were downloaded from the TCGA and GEO databases, and all data were filtered and divided into TCGA and GEO cohorts. The process of data analysis and visualization was performed via R software. The data were classified based on different PRGs subtypes using the K-means clustering method. Then, the differentially expressed genes were identified between two different subtypes, and risk factors analysis, survival analysis, functional enrichment analysis, and immune cells infiltration landscape analysis were conducted. The COX regression analysis was used to construct the prediction model.

Results

Based on the PRGs of LUAD, the patients were divided into two subtypes. We found the survival probability of patients in subtype 1 is higher than that in subtype 2. The results of the logistics analysis showed that gene risk score was closely associated with the prognosis of LUAD patients. The results of GO analysis and KEGG analysis revealed important biological processes and signaling pathways involved in the differentially expressed proteins between the two subtypes. Then we constructed a prediction model of patients’ prognosis based on 13 genes, including IL-1A, P2RX1, GSTM2, ESYT3, ZNF682, KCNF1, STK32A, HHIPL2, GDF10, NDC80, GSTA1, BCL2L10, and CCR2. This model was strongly related to the overall survival (OS) and also reflects the immune status in patients with LUAD.

Conclusion

In our study, we examined LUAD heterogeneity with reference to pyroptosis and found different prognoses between the two subtypes. And a novel prediction model was constructed to predict the OS of LUAD patients based on different PRGs signatures. The model has shown excellent predictive efficiency through validation.
The Human Genome Organisation (HUGO) and a vision for Ecogenomics: the Ecological Genome Project
Authors: Capps Benjamin , Chadwick Ruth , Lederman Zohar , Lysaght Tamra , Mills Catherine , Mulvihill John J. , Oetting William S. , Winship Ingrid ,   HUGO Committee on Ethics, Law and Society,   HUGO Executive Board
Published: December 2023

Background

The following outlines ethical reasons for widening the Human Genome Organisation’s (HUGO) mandate to include ecological genomics.

Main

The environment influences an organism’s genome through ambient factors in the biosphere (e.g. climate and UV radiation), as well as the agents it comes into contact with, i.e. the epigenetic and mutagenic effects of inanimate chemicals and pollution, and pathogenic organisms. Emerging scientific consensus is that social determinants of health, environmental conditions and genetic factors work together to influence the risk of many complex illnesses. That paradigm can also explain the environmental and ecological determinants of health as factors that underlie the (un)healthy ecosystems on which communities rely. We suggest that The Ecological Genome Project is an aspirational opportunity to explore connections between the human genome and nature. We propose consolidating a view of Ecogenomics to provide a blueprint to respond to the environmental challenges that societies face. This can only be achieved by interdisciplinary engagement between genomics and the broad field of ecology and related practice of conservation. In this respect, the One Health approach is a model for environmental orientated work. The idea of Ecogenomics—a term that has been used to relate to a scientific field of ecological genomics—becomes the conceptual study of genomes within the social and natural environment.

Conclusion

The HUGO Committee on Ethics, Law and Society (CELS) recommends that an interdisciplinary One Health approach should be adopted in genomic sciences to promote ethical environmentalism. This perspective has been reviewed and endorsed by the HUGO CELS and the HUGO Executive Board.
Pharmacotherapy for attention deficit/hyperactivity disorder in youth with avoidant restrictive food intake disorder: a case series of patients prescribed stimulant medication in a partial hospitalization program for eating disorders
Authors: Finn Daphna M. , Menzel Jessie E. , Gray Emily , Schwartz Terry
Published: December 2023

Background

Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects may be especially problematic when using stimulants to treat ADHD in the context of a restrictive eating disorder, such as avoidant restrictive food intake disorder (ARFID), although these diagnoses are often comorbid in children. This paper presents a combined approach to treating ADHD comorbid with ARFID using stimulant medication and behavior management within a partial hospitalization program (PHP) and intensive outpatient program (IOP)for eating disorders. The aim of this paper is to determine if the continued or new use of stimulant medication allows for adequate weight restoration by reviewing a series of cases receiving the combined treatment.

Case presentations

Consecutive patients with a historical or new diagnosis of ADHD when presenting for treatment for ARFID were included in this case series. This series included 10 patients (8 male, 2 female) who received pharmacotherapy using stimulants and behavior management interventions involving structured mealtimes and contingency management. All treatment occurred within the context of a PHP/IOP for childhood eating disorders. All youth were able to effectively continue on stimulant medication, show clinical benefit in core ADHD symptoms, and able to gradually restore weight. In all cases, stimulant medications were not discontinued, but in some cases, doses were optimized (increased or decreased), switched to a different stimulant, or augmented with non-ADHD medication, such as mirtazapine, to support the management of ADHD while concurrently assisting in weight gain as necessary for the treatment of ARFID. Only one patient was newly started on a stimulant medication; as this was near the end of her treatment stay, limited conclusions can be drawn from this case.

Conclusions

These findings support the use of pharmacotherapy, including continuing stimulant medication, when combined with behavior management strategies as a potentially effective treatment approach for ADHD in youth with ARFID in the PHP/IOP setting. Future studies using more rigorous methodology, longer follow-up times, and within other treatment settings are needed.
Challenges and opportunities of AI in inclusive education: a case study of data-enhanced active reading in Japan
Authors: Toyokawa Yuko , Horikoshi Izumi , Majumdar Rwitajit , Ogata Hiroaki
Published: December 2023

In inclusive education, students with different needs learn in the same context. With the advancement of artificial intelligence (AI) technologies, it is expected that they will contribute further to an inclusive learning environment that meets the individual needs of diverse learners. However, in Japan, we did not find any studies exploring current needs in an actual special needs context. In this study, we used the learning and evidence analysis framework (LEAF) as a learning analytics-enhanced learning environment and employed Active Reading as an example learning task to investigate the challenges and possibilities of applying AI to inclusive education in the future. Two students who attended a resource room formed the context. We investigated learning logs in the LEAF system while each student executed a given learning task. We detected specific learning behaviors from the logs and explored the challenges and future potential of learning with AI technology, considering human involvement in orchestrating inclusive educational practices.
Seismic wave attenuation (1/Qp) in the crust underneath the Eastern and eastern Southern Alps (Europe): imaging effects of faults, fractures, and fluids
Authors: Jozi Najafabadi Azam , Haberland Christian , Handy Mark R. , Le Breton Eline , Weber Michael
Published: December 2023

We present a novel three-dimensional model of compressional wave attenuation (1/QP) for the Eastern and eastern Southern Alps in Europe that includes the eastern part of the Adriatic indenter, termed here the Dolomites Sub-Indenter. Our approach employed waveform data from the SWATH-D network, a dense temporary network operational between 2017 and 2019, as well as selected stations of the larger AlpArray Seismic Network. A spectral inversion method using frequency-independent quality factor QP, was applied to derive 3578 path-averaged attenuation values (t*) from 126 local earthquakes. These were then inverted using the damped least square inversion (local earthquake tomography) for the attenuation structure. The resulting QP model, which builds on and complements a previously calculated 3-D velocity model (VP and VP/VS), exhibits good resolution down to ~ 20 km depth. Several anomalies can be correlated with the distribution of other physical parameters (VP and VP/VS) and regional tectonic features. Notably, the Friuli-Venetian region exhibits the highest attenuation (lowest QP) anomaly, coinciding with low VP values and increased VP/VS. This anomaly is likely associated with a high density of faults and fractures, as well as the presence of fluid-filled sediments along the active thrust front in the eastern segment of the Southern Alps. Another intriguing observation is the low attenuation (high QP) anomaly along the northwestern edge of the Dolomites Sub-Indenter (NWDI), located south of the Periadriatic fault and east of the Giudicarie fault, where seismicity is notably absent. This anomaly coincides with Permian magmatic rocks at the surface and may be a measure of their strength at depth.

Graphical Abstract
Redefining precision and efficiency in orthognathic surgery through virtual surgical planning and 3D printing: a narrative review
Authors: Lee Yong-Chan , Kim Seong-Gon
Published: December 2023

Orthognathic surgery, essential for addressing jaw and facial skeletal irregularities, has historically relied on traditional surgical planning (TSP) involving a series of time-consuming steps including two-dimensional radiographs. The advent of virtual surgical planning (VSP) and 3D printing technologies has revolutionized this field, bringing unprecedented precision and customization to surgical processes. VSP facilitates 3D visualization of the surgical site, allowing for real-time adjustments and improving preoperative stress for patients by reducing planning time. 3D printing dovetails with VSP, offering the creation of anatomical models and surgical guides, enhancing the predictability of surgical outcomes despite higher initial setup and material costs. The integration of VSP and 3D printing promises innovative and effective solutions in orthognathic surgery, surpassing the limitations of traditional methods. Patient-reported outcomes show a positive post-surgery impact on the quality of life, underlining the significant role of these technologies in enhancing self-esteem and reducing anxiety. Economic analyses depict a promising long-term fiscal advantage with these modern technologies, notwithstanding the higher initial costs. The review emphasizes the need for large-scale randomized controlled trials to address existing research gaps and calls for a deeper exploration into the long-term impacts and ethical considerations of these technologies. In conclusion, while standing on the cusp of a technological renaissance in orthognathic surgery, it is incumbent upon the medical fraternity to foster a collaborative approach, balancing innovation with scrutiny to enhance patient care. The narrative review encourages the leveraging of VSP and 3D printing technologies for more efficient and patient-centric orthognathic surgery, urging the community to navigate uncharted territories in pursuit of precision and efficiency in the surgical landscape.
The study of serum muscarinic acetylcholine receptor subtype 3 (m3AChR)-Specific autoantibodies level in rheumatoid arthritis patients with secondary sjogren syndrome
Authors: Fakher Hagar Elsayed , El Gazzar Nagat Mohammed , Mabrouk Maaly Mohamed , Nada Doaa Waseem
Published: December 2023

Background

Dry eyes and mouth are symptoms of Sjogren syndrome, which can occur on its own and be referred to as primary Sjogren syndrome or in conjunction with other rheumatic diseases like rheumatoid arthritis and be referred to as secondary Sjogren syndrome. Anti-muscarinic type 3 receptors have been linked to neurological issues as well as secretory dysfunction in Sjogren patients. Consequently, the purpose of this study is to determine the serum level of muscarinic acetylcholine receptor subtype 3 (m3AChR)-specific autoantibodies in rheumatoid arthritis (RA) patients and evaluate its relationship to disease activity, functional disability, and to study its role in the development of secondary Sjogren syndrome manifestations in those patients.

Methods

In this cross-sectional study, 30 RA patients with secondary Sjogren syndrome signs and 30 RA patients without secondary Sjogren syndrome manifestations were included, along with 30 healthy volunteers who were aged, and sex matched as controls. All participants underwent thorough clinical examination, evaluation of disease activity using the DAS28 score, assessment of functional status using the modified health assessment questionnaire (MHAQ), and evaluation of the serum level of (m3AChR) by (ELISA).

Results

When compared to RA patients without secondary Sjogren syndrome and healthy controls (20.09 ± 4.24, 18.36 ± 3.59 ng/ml respectively), the serum level of m3AChR antibodies among 30 RA patients with secondary Sjogren syndrome considerably increased (mean 25.98 ± 4.81 ng/ml).Analysis of the m3AChR’s (ROC)-curve revealed that the three groups under study differed significantly (P < 0.001), with the AUC (0.806), cutoff (> 22.63ng/ml), sensitivity (73.33%), and specificity (86.67%) all exceeding the threshold. Additionally, there was a significant positive connection between the serum level of m3AChR and the following variables (P < 0.05): DAS scores, MHAQ score, number of tender & swollen joints, and acute phase reactants.

Conclusion

Autoantibodies against m3AChR may be one of the serum components involved in the pathophysiology of secondary Sjogren syndrome in RA patients, and because of their high sensitivity and specificity, they can be utilized as a diagnostic marker in these individuals.
The effect of an adapted digital mental health intervention for sickle cell disease on engagement: a pilot randomized controlled trial
Authors: Nardo Emily V. , Parchuri Ektha , O’Brien Julia A. , Crosby Lori , Porter Jerlym , Palermo Tonya , Nikolajski Cara , Treadwell Marsha , Hillery Cheryl A. , Szigethy Eva , Jonassaint Charles R.
Published: December 2023

Introduction

Despite promising outcomes, lack of engagement and poor adherence are barriers to treating mental health using digital CBT, particularly in minority groups. After conducting guided focus groups, a current mental health app was adapted to be more inclusive for minorities living with SCD.

Methods

Patients between the ages of 16–35 with SCD who reported experiencing anxiety or depression symptoms were eligible for this study. Once enrolled, participants were randomly assigned to receive one of two versions of a mental health app: 1) the current version designed for the general population or 2) the adapted version. Baseline measures for depression, anxiety, pain, and self-efficacy were completed at the start of the study and again at post-intervention (minimum 4 weeks).

Results

Compared to baseline, mean scores for pain decreased an average of 3.29 (p = 0.03) on a 10-point scale, self-efficacy improved 3.86 points (p = 0.007) and depression symptoms decreased 5.75 points (p = 0.016) for the group that received the adapted app. On average, control participants engaged with the app 5.64 times while the participants in the experimental group engaged 8.50 times (p = 0.40). Regardless of group assignment, a positive relationship (r = 0.47) was shown between app engagement and a change in depression symptoms (p = 0.042).

Discussion

Target enrollment for this study sought to enroll 40 participants. However, after difficulties locating qualified participants, enrollment criteria were adjusted to expand the population pool. Regardless of these efforts, the sample size for this study was still smaller than anticipated (n = 21). Additionally, irrespective of group approximately 40% of participants did not engage with the app. However, despite a small sample size and poor engagement, this study 1) demonstrated the feasibility of implementing socially relevant changes into a mental health app and 2) indicated that participants in the intervention group displayed better outcomes and showed trends for greater app interaction.

Conclusion

These promising results should encourage future researchers to continue exploring ideal adaptations for implementing digital CBT in minority populations. Future studies should also consider implementing post-intervention surveys to help identify common factors relating to a lack of engagement.

Trial registration

This trial (NCT04587661) was registered on August 12th, 2020.
Impasse and Genre in American Politics and Literature
Authors: Shulman George
Published: December 2023

This chapter analyzes Richard Hofstadter’s critique of “the paranoid style” and its influential impact on the terms and tone of liberal and left engagement with the event of Donald Trump. The chapter’s claim is that Hofstadter’s argument engages a genre of criticism, originating in the Federalist Papers, that attacked democratic critics of the constitution by pitting political realism and maturity against the irrational exuberance of populism. The chapter shows that this genre of criticism, invoked now to defend a civic nationalism in crisis, cannot offer a compelling counterfiction to the right by imaginatively engaging pervasive alienation and drawing citizens at a loss toward a sustainable future and a reimagined democracy. Inspired by the example of American novelists, the chapter asks what kind of genre or “style” might offer an effective response to the paranoid style gripping almost half the US population?
Resonant Apophenia
Authors: Lepselter Susan
Published: December 2023

This chapter describes the affects and poetics of uncanny conspiracy theory, especially UFO abduction. Drawing on ethnographic research, the chapter explores the interplay of ordinary life and consiuracy theory in the 1990s US Southwest through the trope of abduction. It explores how apophenia—the desire to make connections—functions in the poetics of everyday discourse to reveal unstated traumas and worries about extraterrestrial capture and the powers lurking just out of sight.
Flame and Steel inside the Capitol
Authors: Belew Kathleen
Published: December 2023

This chapter examines the long history of conspiratorial belief systems in the white power movement, a broad alliance of militant right activists active from the late 1970s to the present. It also examines the category of conspiracy and its efficacy, or lack thereof, in the criminal prosecution of such groups. Seditious conspiracy, or the organized attempt to overthrow the government, has featured in both white power tactics and in attempts to hold such activists accountable for criminal behavior, ranging from a 1987–88 seditious conspiracy trial in Fort Smith, Arkansas to the January 6, 2021, insurrection at the US Capitol.
Epilogue
Authors: Masco Joseph , Wedeen Lisa
Published: December 2023

This epilogue to Conspiracy/Theory explores the terms of epistemic crisis in the twenty-first century. Focusing specifically on the January 6, 2021, insurrection in Washington, DC, the epilogue reviews the multiple conspiratorial projects that informed that violent event. Tracking the differences between authoritarian practices, white supremacists, QAnon believers, and grifters, it underscores the multiple “reality making” techniques informing contemporary politics. The epilogue also reviews the key arguments of the book and considers how the politicization of narrative functions today.