bluuebunny/crossref_metadata_2025 huggingface dataset:
Host genetics influence response to targeted immunotherapy and effector cell capacity to perform key immune functions
Authors: Glassbrook James E , Hackett Justin , Muñiz Maria , Dyson Gregory , Gibson Heather
Published: January 2023

Targeted immunotherapies have revolutionized cancer treatment, markedly improving patient cancer outcomes. Despite this rise to prominence as first line treatments for various malignancies, only a subset of patients respond to targeted immunotherapy. Trastuzumab targets tumor associated antigen (TAA) epidermal growth factor 2 (HER2). Differential response to trastuzumab suggests host genetics may influence response to treatment. To model this interaction, we utilize a genetically heterogeneous Diversity Outbred (DO) mouse model in an F1 cross (DOxBALB/c)F1. These genetically diverse mice (n=126) were orthotopically implanted with TUBO (BALB/c-syngeneic tumor) and treated with αNeu (7.16.4) mAb therapy. Like the human population, we observe a divergent response to therapy. Via genetic linkage analysis, we identify loci that correlate to a robust response. We confirm these loci in vivo using recombinant inbred collaborative cross (CC) strains containing/lacking driver loci (CCxBALB/c)F1. These loci alone are not sufficient to fully account for durable response to therapy; however, here we identify strains that uniformly eliminate tumor and conversely, are consistently refractory to treatment. Utilizing tissues from these strains, we evaluate canonical mechanisms of mAb therapy and show that tumor doubling time correlates with bone marrow derived macrophage capacity to phagocytose opsonized tumor in vitro via confocal microscopy. To better understand which cell populations of tumor infiltrate are expressing transcripts from these loci, we perform transcriptomic analysis on putative responder/non-responder strains, allowing us to see key differences in tumor infiltrating immune cell populations.

Supported by NIH R37 CA220482, DMC Foundation, P30 CA022453
Anti-TIGIT antibodies promote immune activation relevant to targeting stem-like and tumor-specific T cells in combination with anti-PD-1
Authors: Sivick Gauthier Kelsey E , Piovesan Dana , de Groot Amber E , Reiner Gabrielle L , Schweickert Patrick G , Soriano Ferdie , Chen Ada , Singh Hema , Zhao Xiaoning , Seitz Lisa , Reddy Anita , Young Stephen W , Walker Nigel , Walters Matthew J
Published: January 2023

TIGIT is an inhibitory receptor expressed primarily on NK and T cell subsets, and binding to its cognate receptor ligand, CD155, results in multiple mechanisms of immunosuppression. Blocking the TIGIT-CD155 interaction in the context of cancer promotes anti-tumor immunity. We characterized cellular subsets that TIGIT blockade may impact and the pharmacology of two anti-TIGIT antibodies - representing functional (AB308) and non-functional (AB154) Fc domain classes - undergoing clinical evaluation. Surrogate antibodies were leveraged to interrogate TIGIT biology in mouse syngeneic tumor models. Human tumor-infiltrating lymphocytes from a variety of cancer types expressed appreciable levels of TIGIT on relevant immune populations, including Tregs and CD8+ T cells with tumor reactive or pre-dysfunctional stem-like phenotypes. Both antibodies potently bound TIGIT and blocked the TIGIT-CD155 interaction as well as displayed the predicted phenotypes in terms of Fcγ receptor (FcγR) engagement. In line with FcγRIII binding, AB308 demonstrated a capacity to induce ADCC against TIGIT-expressing target cells. Combination of anti-TIGIT antibodies with other therapeutic approaches that promote T cell activation resulted in enhanced immune responses. In mice, while combining Fc-silent or Fc-enabled anti-mouse TIGIT antibody with anti-PD-1 resulted in greater tumor growth inhibition than with anti-PD-1 alone, the activity of Fc-enabled anti-TIGIT was associated with intratumoral Treg depletion. These data provide a rationale for combination with immune-activating agents and support ongoing clinical evaluation of AB154 and AB308 with biomarker strategies focused on understanding the role of Fc functionality.
Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation
Authors: Habel Jennifer R , Chua Brendon Y , Kedzierski Lukasz , Selva Kevin J , Damelang Timon , Haycroft Ebene R , Nguyen Thi H O , Koay Hui-Fern , Nicholson Suellen , McQuilten Hayley , Jia Xiaoxiao , Allen Lilith F , Hensen Luca , Zhang Wuji , van de Sandt Carolien E , Neil Jessica A , Amanant Fatima , Krammer Florian , Wragg Kathleen , Juno Jennifer A , Wheatley Adam K , Tan Hyon-Xhi , Pell Gabrielle , Audsley Jennifer , Reynaldi Arnold , Thevarajan Irani , Denholm Justin , Subbarao Kanta , Davenport Miles P , Hogarth Mark , Godrey Dale I , Cheng Allen C , Tong Steven Y C , Bond Katherine , Williamson Deborah A , James Fiona , Holmes Natasha E , Smibert Olivia C , Trubiano Jason A , Gordon Claire L , Chung Amy W , Whitehead Claire , Kent Stephen J , Lappas Martha , Rowntree Louise C , Kedzierska Katherine
Published: January 2023

Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides key insight to innate T cell and NK cell perturbations occurring in pregnant women with COVID-19, which will potentially inform patient management and education for those with COVID-19 during pregnancy.

Supported by National Health and Medical Research Council, Australia
Role of innate lymphoid cells on experimental sepsis-induced cognitive decline.
Authors: Giridharan Vijayasree Vayalanellore , Tripathi Ashutosh , Madeshiya Amit , Pillai Anilkumar , Petronilho Fabricia , Dal-Pizzol Felipe , Barichello Tatiana
Published: January 2023

Background

Sepsis is a disordered host immune reaction to pathogen invasion that leads to organ dysfunction, high mortality, and long-term consequences. More than 50% of sepsis survivors often suffer from severe and long-term cognitive deficits. We previously demonstrated in vivo microglial activation and neuroinflammation associated with cognitive deficits in an experimental model of sepsis. Recent studies have demonstrated the role of innate lymphoid cells (ILCs) in aging and neurodegeneration-induced cognitive loss. ILCs are enriched at barrier surfaces and regulate inflammation and tissue homeostasis in a disease condition. Here we aimed to explore the role of ILCs subtypes on experimental sepsis-induced cognitive deficits.

Methods

Male, 50-day-old C57BL/6 mice were subjected to cecal ligation and perforation (CLP) surgery to induce sepsis or sham surgery as a control group. At 10 days after sepsis, assessment of cognition was performed using novel object recognition (NOR) task. The ILCs subtypes ILC1, ILC2, and ILC3 were evaluated in the spleen, meninges, and choroid plexus (CP) using multicolor flow cytometry.

Results

Sepsis groups demonstrated cognitive decline as measured by decreased recognition index as compared to the control group. In the periphery, the spleen from the sepsis group demonstrated increased ILC1 and ILC3 levels as compared to control groups. In brain barriers, we observed increased accumulation of ILC2 subtype in CP in the sepsis group. However, there was no difference in the meningeal accumulation of ILCs between control and sepsis groups.

Conclusion

Targeting group 2 innate lymphoid cells may provide a new strategy to combat sepsis-associated long-term cognitive deficits.

Supported by Alzheimer’s Association grant to TB - AARGDNTF-19-619645. NIH/NIA grant to TB - 1RF1AG072491-01.
Role of Macrophage accumulation activates NLRP3 inflammasome induced IL-18 pathway in EoE pathogenesis
Authors: Sekhar Yadavalli Chandra , Venkateshaiah Sathisha Upparahalli , Lokanatha Oruganti , Mishra Anil
Published: January 2023

Objective

Most studies implicated eosinophilic esophagitis (EoE) to the induced esophageal eosinophilia mediated inflammation and fibrosis. However, yet the initial mechanism of allergen-induced eosinophils generation is yet not understood. Our current study provides stepwise pathway operating following the interaction of allergen and antigen presenting cells to induce EoE pathogenesis.

Methods

We performed immunostaining, RT-PCR measure transcript levels and Masson trichrome staining for collagen accumulation.

Results

We show that allergen-challenge promotes induced macrophage accumulation and epithelial cells hyperplasia in esophagus. Further, we observed that NLRP3 is induced in both macrophage and epithelial cells. The NLRP3 is the source of IL-18 and we show induced levels of IL-18 in allergen challenge mice that generate tissue eosinophilia in experimental model of EoE. Further, we observed a similar induced NLRP3 in the accumulated macrophage and epithelial cells along with induced IL-18 in the esophageal biopsies of human EoE. Mechanistically, to substantiate the role of macrophages, epithelial cells, and IL-18 role in EoE pathogenesis, we experimentally induced EoE in wild type, GM-CSF−/−, IL-18−/− mice. We show a similar NLRP3 expression with no IL-18 induction in IL-18−/− mice compare to induced NLRP3 and IL-18 in wild-type and significantly reduced NLRP3 and IL-18 in GM-CSF−/− mice. The NLRP3 regulated IL-18 induction or reduction is consistent with the tissue accumulated eosinophila and promoting esophageal remodeling and fibrosis in murine model of EoE.

Conclusions

The findings show that epithelial cells and macrophage derived NLRP3 regulated IL-18 is critical in promoting EoE pathogenesis.

Supported by NIH grant R01 AI080581
Complementary target engagement and functional assays to probe NLRP3 inflammasome pathway antagonism
Authors: O’Brien Martha A , Robers Matt , Teske Kelly , Corona Cesear , Vasta Jim , Wilkinson Jennifer , Lam Ngan , Hoffman Kaitlin Dunn , Cali James , Lazar Dan
Published: January 2023

Inflammasomes are critical to the innate immune system and implicated in numerous chronic and acute inflammatory diseases. Having tools to screen inflammasome modulatory drugs is critical, especially for the NLRP3 inflammasome that is triggered by a wide array of stimuli. We have developed three cell-based methods for quantifying inflammasome function: a NanoBRET™ NLRP3-specific target engagement assay, a caspase-1 activity assay and an IL-1β release assay. For the NLRP3 target engagement assay, cells are transfected with a NLRP3-Nanoluc construct and incubated with a cell-permeable, fluorescent NLRP3 binder (tracer), generating a bioluminescent resonance energy transfer (BRET) signal. The homogeneous caspase-1 and IL-1β assays can be run directly with cells in culture or with transferred culture medium, enabling application of both luminescent assays to the same cell wells via split-sample analysis. Using all three assays, we tested a series of reported NLRP3 inhibitors, including MCC950, oridonin, NBC6, NBC19, CY09, OXSi2 and OLT1177™ (dapansutrile). MCC950 inhibition of caspase-1 activity and IL-1β release was demonstrated in human and mouse cell models. We used LPS-primed THP-1 cells treated with nigericin for testing the series of inhibitors. The NLRP3 target engagement assay used HEK293 cells in suspension in non-binding plates. All three assays demonstrated good inhibition for MCC950, oridonin, NBC6, NBC19 and CY09 with rank order potency consistent with published results. We did not detect inhibition with OxSi2 or OLT1177™. These three assays enable screening for inflammasome antagonists and provide a mechanistic platform for characterizing NLRP3 inflammasome inhibitors.
CD28 signaling strength regulates the cell fate of TCF-1+ PD-1+ CD8 T cells
Authors: Humblin Etienne , Van der Heide Verena , Filipescu Dan , Lu Ashley , Selvan Myvizhi , Gumus Zeynep , Bernstein Emily , Chipuk Jerry , Homann Dirk , Kamphorst Alice O
Published: January 2023

During chronic infections and cancer, CD8 T cells that recognize pathogens/tumors can persist in a dysfunctional state characterized by high expression of the inhibitory receptor Programmed Cell Death (PD)-1. T cell factor (TCF)-1+ PD-1+ progenitor exhausted cells (Tpex) maintain the antigen-specific T cell pool by self-renewal and differentiation into effector-like TCF-1neg PD-1+ CD8 T cells. Previous studies described that among PD-1+ CD8 T cells, only Tpex respond to PD-1 blockade therapy. However, the molecular mechanisms that support Tpex self-renewal or differentiation are not understood. Tpex have high CD28 expression and we demonstrated that CD28 costimulation is required for response to PD-1 targeted therapy. To better understand the role of CD28 on Tpex, we evaluated how reduction or abrogation of CD28 signaling impacted virus-specific CD8 T cells in mice infected with lymphocytic choriomeningitis virus (LCMV). During established chronic infection, deletion of both Cd28 alleles resulted in reduction of Tpex and TCF-1neg subsets. In contrast, when CD28 signaling was reduced (deletion of one allele), TCF-1neg PD-1+ CD8 T cells decreased, but the number of Tpex was not affected. RNA sequencing and metabolic assays revealed that sustained CD28 signaling during persistent antigen stimulation is required to maintain mitochondrial fitness of Tpex. Our work supports the novel hypothesis that CD28 signaling strength modulates Tpex fate decision through metabolic regulation. Our data also suggest continuous CD28 signaling is required for long-term maintenance of antigen-specific PD-1+ CD8 T cells. These findings have important implications for checkpoint therapy in cancer.
Newly identified role for the transcription factor Foxp1 in natural killer cells
Authors: Canaday Laura M , Koty Amos , del Valle Kamila Andino , Cai Mingjun , Seelamneni Harsha , Krishnamurthy Durga , Waggoner Stephen
Published: January 2023

Natural killer (NK) cells are innate lymphocytes critical for defense against pathogenic microbes and tumors. To understand dysfunction of NK cells in disease and to facilitate effective use of NK cells as therapeutic agents in the clinic, there is a critical need to ascertain the molecular mechanisms that regulate acquisition of optimum functionality of these cells. The functional maturation of NK cells is controlled by an incompletely defined network of transcription factors, which was recently expanded to implicate numerous factors, including Foxp1, that have never been studied in these cells. We show that mice with conditional deletion of the transcription factor Foxp1 in the NK cell lineage have substantially reduced frequencies of NK cells. The remaining NK cells in these mice exhibit an immature phenotype with reduced capacity to kill tumor target cells. The identification of a role of Foxp1 in development of highly functional NK cells is significant for the development of new strategies to promote or engineer highly functional NK cells to treat patients with tumors or infections.

Supported by R01 AI148080
Defining the transcriptional regulation of NR2F6 in CD4+ T helper cell responses
Authors: Wilson Adrianna N , Campbell Sean , Lu Qun , Mosure Sarah A , He Yuanjun , Bdiri Bilel , Kamenecka Theodore M , Solt Laura A
Published: January 2023

NR2F6, an orphan member of the nuclear receptor superfamily of ligand-regulated transcription factors, plays an important role in CD4+ T cell differentiation and effector function. As a transcriptional repressor, NR2F6 can directly repress expression of the pro-inflammatory cytokines IL-2, IL-17A, IL-21, and IFNγ. Our overexpression data is consistent with this, demonstrating NR2F6 represses IL-17A production in TH17 cells, indicating it also may play a role in autoimmune regulation. Furthermore, genetic experiments have demonstrated the ability of NR2F6 to reduce tumor burden and develop host-protective immunological memory, a consequence of it acting as an immune checkpoint in effector T cells. Collectively, these data suggest that modulation of NR2F6 activity may have important clinical applications for autoimmune and cancer immune therapy. To date, no synthetic or endogenous ligands have been identified that modulate its activity and little is known about its transcriptional function at the molecular level. Here through integrating NR2F6 overexpression and cytokine profiling studies with -omics based approaches, such as RNAseq using T cell specific NR2F6 knockouts, we are working to elucidate NR2F6’s transcriptional function in T cells. Additionally, efforts to identify NR2F6 selective small molecules is underway so we can address how ligand modulation of NR2F6 alters its function. These experiments will help define the molecular mechanisms of NR2F6, which are poorly understood, and determine its niche in cancer immunotherapy and autoimmunity.

Supported by R01 CA225890
IL-35 suppresses pathogenic T cell response in atopic dermatitis by inhibiting PSAT1 activation
Authors: Lim Hyo Jung , Lee Jong Yeong , Choi Jin kyeong
Published: January 2023

Interleukin 35 (IL-35) is a member of the IL-12 family and immune-suppressive cytokine and a critical regulator of immunity during autoimmune and infectious diseases. However, it is unclear whether IL-35 can control skin inflammation by regulating the biosynthesis of biomolecules. Here, we demonstrated that IL-35 ameliorated atopic dermatitis (AD), a Th2-mediated inflammatory disease, by inhibiting activated phosphoserine aminotransferase 1 (PSAT1). We DNCB/DFE-induced AD mouse model, monitored progression by ear thickness and histology, and investigated whether IL-35 treatment would suppress AD. Mice treated with IL-35 developed mild or low skin inflammation and disease protection correlated with expansion of Foxp3+ Treg cells with concomitant suppression of Th2 and Th1/2 responses. We further show that IL-35 regulates alterations in glycolytic metabolism in AD skin inflammation. Importantly, the IL-35 mediated suppression of Th2 and Th1/2 cells and its amelioration of AD correlated with inhibition of serine biosynthesis pathways such as PSAT1 in the skin. These results suggest that IL-35 inhibits Th2 and Th1/2 cell differentiation and proliferation by directly regulating PSAT1 immune metabolites in atopic dermatitis. Therefore, the development of targeted therapy for serine-dependent metabolic pathways via IL-35 would be an effective therapeutic strategy for AD.

Supported by 21st Century Medical Science Creative Human Resource Development Center
Ameliorative role of AhR ligands in concanavalin-induced liver injury is due to increased miR-100 expression leading to mTOR downregulation and promoter hydroxymethylation
Authors: Cannon Alkeiver S , Nagarkatti Prakash , Nagarkatti Mitzi
Published: January 2023

The promiscuous aryl hydrocarbon receptor (AhR) has long been the target of immunological studies due to its expression on many immune cells. However, the specific mechanisms underlying the role of AhR activation in inflammatory disease has not been elucidated. We employed a murine model of immune cell-mediated liver injury, comparable to autoimmune hepatitis (AIH) in humans, by intravenously injecting 12.5 mg/kg of Concanavalin A (ConA) and treating one hour later via intraperitoneal injection with an AhR ligand: 10 μg/kg 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or 50 μg/kg 6-formylindolo[3,2-b] carbazole (FICZ). Our studies showed that both ligands improved the clinical parameters of AIH in this model. 24 hours after challenge, liver mononuclear cells were harvested, and total RNA and DNA were isolated. We examined the underlying mechanisms by conducting small RNA-sequencing and discovered dysregulation of many miRNAs. Of note, miR-100 was significantly upregulated, and we found this molecule to contain a dioxin-responsive element (DRE) in its promoter region. Further, we conducted methylated and hydroxymethylated DNA immunoprecipitation sequencing on CD45+ cells in this model and found distinct methylation profiles between each of the groups. Specifically, we observed increased hydroxymethylation in both treatment groups as compared to the ConA+Vehicle group in the promoter of mTOR, a direct target of miR-100. These data suggest that AhR activation reduces liver injury by upregulating miR-100 and reducing mTOR activity. Additionally, hydroxymethylation of the mTOR promoter may contribute to the changes observed upon AhR activation, thus lending credence for a role of hydroxymethylation in cell differentiation.

Supported by NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788 and R01AI123947, R01AI160896 and R01AI123947-04S1
Genome-wide CRISPR screens reveal metabolic and transcriptional regulation of BTN3A and cancer susceptibility to Vγ9Vδ2 T cell targeting
Authors: Mamedov Murad R , Vedova Shane , Freimer Jacob W , Sahu Avinash Das , Chen Peixin Amy , Ramesh Amrita , Hanspers Kristina , Nguyen Vinh Q , Adams Erin J , Marson Alexander
Published: January 2023

γδ T cells are potent anti-cancer effectors with potential to target tumors broadly, independent of neoantigens or HLA-background. γδ T cells can sense conserved cell stress signals prevalent in transformed cells, although the mechanisms governing how γδ T cells sense and kill stressed target cells remain poorly characterized. Vγ9Vδ2 T cells – the most abundant subset of human γδ T cells – recognize a protein complex containing butyrophilin 3A1 (BTN3A1), a ubiquitously expressed cell surface protein that is activated by phosphoantigens abundantly produced by tumor cells. Here we performed genome-wide CRISPR screens in target cancer cells to identify pathways that regulate: (1) γδ T cell activity with a functional co-culture killing screen, and (2) BTN3A1 cell surface expression in a phenotypic screen. Multilayered regulation of BTN3A1 expression was uncovered: transcriptional regulation (IRF1, CTBP1, ZNF217, RUNX1), intracellular trafficking, sialylation, oxidative phosphorylation (OXPHOS), purine metabolism, and other metabolic pathways. Consistent with these results, we found upregulated BTN3A1 on cells undergoing an energy crisis due to glucose deprivation, glycolysis inhibition, or OXPHOS inhibition. Furthermore, we discovered that this BTN3A1 upregulation was induced by activation of the AMP-activated protein kinase (AMPK). Also, CRISPR screen-derived gene expression signatures correlated with higher survival in low-grade glioma patients whose tumors had high Vγ9Vδ2 T cell infiltration. Uncovering this AMPK-dependent mechanism of metabolic stress-induced ligand activation deepens our understanding of γδ T cell stress surveillance and suggests new avenues to enhance γδ T cell anti-cancer activity.

M.R.M. is a Cancer Research Institute (CRI) Irvington Fellow supported by CRI and was funded by the Human Vaccines Project Michelson Prize for Human Immunology.
An Antibody Neutralization Determinant on Domain III and the First α-Helical Domain in the Stem-Anchor Region of Tembusu Virus Envelope Protein
Authors: Yang Baolin , Meng Runze , Feng Chonglun , Huang Jingjing , Li Qiong , Wang Xiaoyan , Zhang Dabing
Published: January 2023

Previous studies identified three neutralizing epitopes on domains I, II, and III of the Tembusu virus (TMUV) envelope (E). More evidence is needed to understand the molecular basis of Ab-mediated neutralization and protection against TMUV. In this study, we observed a neutralizing mAb, 6C8, that neutralized TMUV infection primarily by inhibiting cell attachment. In immunofluorescence assays, 6C8 recognized the premembrane and E proteins coexpressed in HEK-293T cells, but failed to react with premembrane or E expressed individually. Epitope mapping identified nine E protein residues positioned on BC/EF loops and F/G strands in domain III and the first α-helical domain in the stem region. Further investigation with mutant viruses showed that 6C8 pressure resulted in mutations at residues 330 of BC loop and 409 of the first α-helical domain, although 6C8 only exhibited a moderate neutralizing activity in BHK-21 cells and a weak protective activity in BALB/c mice and Shaoxing duck models. Mutations A330S and T409M conferred high- and low-level 6C8 resistance, respectively, whereas the combination of A330S and T409M mutations conferred moderate-level 6C8 resistance. As a result, a quasispecies comprising three groups of antigenic variants appeared in BHK-21 cell–derived viral stocks after repeated passages of TMUV strain Y in the presence of 6C8 treatment. Taken together, these findings have raised a concern about Ab-induced antigenic variations in vivo, and they have revealed information concerning the conformational structure of the 6C8 epitope and its role in constraint on antigenic variations. The present work contributes to a better understanding of the complexity of the TMUV immunogen.
The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer
Authors: Choi Yeonseok , Noh Jae Myoung , Shin Sun Hye , Lee Kyungjong , Um Sang-Won , Kim Hojoong , Pyo Hongryull , Ahn Yong Chan , Jeong Byeong-Ho
Published: January 2023

Purpose This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer.Materials and Methods We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development.Results The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development.Conclusion The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.
“The First Language in My Head”: Student Attitudes to L2 English and L1 Slovene
Authors: Kavalir Monika , Poteko Ina
Published: January 2023

With the global spread of English, young people are exposed to it while still acquiring their first language. As the impact of English in Slovenia is relatively under-researched, this study investigates how often and in what situations university students in Slovenia use English, and what attitudes they have to it compared to Slovene. The results are based on 365 respondents, all students of the Faculty of Arts, University of Ljubljana, who filled out an online questionnaire. The results show that Slovene still dominates in everyday communication, but that English has become an essential skill which goes beyond the traditional function of a foreign language. In addition, many respondents already feel it to be an additional first language, with a sizable group reporting a preference for English as their intimate language.
Neologisms of English Origin in Present-Day Slovak
Authors: Ološtiak Martin , Rešovská Soňa
Published: January 2023

The aim of the paper is to analyse post-1989 Anglicisms in present-day Slovak. Central concepts of the study are neologisms (new items in the lexicon of a language), present-day Slovak (the Slovak language from 1989 onwards), borrowing (one of several ways of lexical enrichment) and adaptation (the process of adapting loans into Slovak as a recipient language). The most extensive part consists of sections devoted to particular adaptation processes on the levels of phonology, orthography, morphology, word-formation, semantics and pragmatics. Finally, the paper addresses the issues of the variability and synonymy of English borrowings in Slovak.
Biyo ve ekolojik sanat bağlamında Yedinci Kıta
Authors: ÖZESKİCİ Evrim
Published: January 2023

Günümüz sanatında bilimsel metotların, teknolojik araç ve gereçlerin kullanıldığı gözlemlenmiştir. Araştırmanın amacı; biyo ve ekolojik sanatın neden ortaya çıktığını araştırmaktır. Ozan Atalan, Eloise Hawser, Pakui Hardware ve Simon Starling gibi sanatçılar araştırmanın kapsam ve sınırlılıklarını oluşturmaktadır. Ayrıca araştırmada ekolojik sanatın tarihsel gelişiminden bahsedilmiştir. Ekolojik sanatın insan ve doğa ilişkisindeki önemi üzerinde durulmuştur. Araştırmaya açıklık getiren sorular şunlardır: Biyo ve ekolojik sanatın güncel sanattaki yansımaları nelerdir? Sanatçıları biyo sanat uygulamalarına iten sebepler nelerdir? 16. İstanbul Bienali’nin biyo ve ekolojik sanatla nasıl bir ilişkisi vardır? Bu sorulara cevap aranması; güncel sanat örneklerinin nasıl ve ne şekilde ele alındığına ilişkin ışık tutacağı umulmaktadır.
Analysis and Characterization of Municipal Solid Wastes Generated in a Community in the Northern Philippines
Authors: Ngohayon J. M. , Tulagan J.
Published: January 2023

The residential community of Potia in the Northern Philippines experiences various problems arising from mismanaged municipal solid waste. Hence, a waste analysis and characterization study on the generated municipal solid wastes was conducted to determine the municipal solid waste generation data which can be used for planning and formulation of potential solutions. For three consecutive days, the generated municipal solid wastes were gathered from the sample which included residential sources, commercial sources (food establishments, service centers, general stores, and markets), industrial sources, and institutional sources (institutions and health units). The total generated municipal solid waste in Potia is about 508.30 kg.day-1 of which most were contributed by the residential sources (70.59%), followed by commercial (25.09%), industrial (2.64%), and institutional (1.70%). The overall composition of the generated MSW is also dominated by biodegradable waste (76.90%), followed by residual waste (14.66%), recyclable waste (7.35%), and special waste (1.08%). The total volume of daily generated MSW is about 3.37 m3.day-1.
Understanding of a Veiled Illness: Evaluation of Polycystic Ovarian Syndrome awareness (PCOS) in Young Female Students of Karachi.
Authors: Tariq Sana , Bhatti Dr Najia , Isran Dr Basma Zia
Published: January 2023

Introduction: PCOS is a major endocrinological syndrome that affects females and impairs hormonal stability thus having an impact on the normal functioning of some body systems. This has affected 6-20% of the female population of reproductive age and hence its diagnosis is important. 
Methods: This is a retrospective cross-sectional observational study. A total of 151 females were enrolled; after signing an informed consent form, females were asked a few questions about their general health, comorbidities, and generalized menstruation history. The last part of the questionnaire contains common signs and symptoms of polycystic ovarian disease to assess awareness. The data was analyzed in the statistical package of social sciences (SPSS) version 2021.Result:  The participants were asked about 7 signs of PCOS. 9.3% (n=14) were facing irregular periods, heavy bleeding was experienced by 16.6% (n=25) participants. Facial hair growth has occurred in 13.2% (n=20) of participants. 15.2% (n=23) had oily scalp and dandruff. Participants were also asked if they were aware of some major risk factors of PCOS. 15.9% (n=24) knew that PCOS can cause infertility, and 7.3% (n=11) said PCOS causes Anovulatory cycles. 41.7% knew that lifestyle modification can help reduce adverse effects of the syndrome.
Conclusion:  the majority of study participants indicated decreased awareness of PCOS and its major risk factors, Hence there is a dire need for awareness as it is rather ignored.
Effective role of olive oil use on lipid profile, blood pressure and blood glucose in subjects of metabolic syndrome
Authors: Safdar Ali Shaikh  , Afsheen Illahi Shaikh  , Dr. Lubna Naz
Published: January 2023

Study was taken with an object to investigate the role of oil extracted from olives on lipid profile, blood pressure and glucose level in subjects having metabolic syndrome. A total of 115 subjects of metabolic syndrome according to International Diabetes Federation criteria, aged between 20-40 years were included. Lipid profile, blood pressure and fasting glucose levels were performed at base line. 30ml of olive oil per day in divided doses 15 ml in the morning and 15 ml in the evening was given to these subjects for six weeks. Then lipid profile, blood pressure and fasting glucose level were performed and compared with base line values. Significant decrease was observed in total cholesterol, low density lipoprotein cholesterol, triglycerides and increase in high density lipoprotein cholesterol, all P values < 0.01. Nonsignificant low level of fasting blood sugar was observed. Significant decrease in systolic and diastolic blood pressure at P value < 0.01 was observed. It is concluded that use of olive oil caused improvement in lipid profile and blood pressure measurement in metabolic syndrome subjects significantly while nonsignificant decrease was observed in fasting blood glucose.
Powdery Mildew A Disease of Grapes And The Fungicides Mode of Action: A Review
Authors: Uddin Mueen , Tareen Juma Khan , Ahmed Faheem , Adnan Faisal , Bazai Mohammad Jafar , Fareed Syed Rehan , Kakar Hidayatullah
Published: January 2023

Powdery mildew caused by Uncinula necator (Schw.) Burr. is one of the widespread fungal diseases of grapes that have caused economic losses through poor fruit set and low yield substantially. To decrease the inoculum potential, a disease management program must be undertaken early in the season which is imperative to reduce late-season disease problems. Because, without early control of the infection of powdery mildew, often lead to severe problem in the late season. Elemental sulfur was the foremost antifungal utilized for the control of powdery mildew which is still in use as an effective and cheap fungicide for vineyards. Sterolbiosynthesis inhibitors (SI), also called SI fungicides, are the latest products to control powdery mildew effectively. For efficient use of fungicides with no or less resistance to the pathogen, it is appropriate to spray fungicides having different mechanisms of action which are specific in function, and for more efficacy, use a mixture of such fungicides that have no harmful impact on plant growth and environment. So, for effective control of powdery mildew, a protective spray of fungicide before bloom and a subsequent spray of systemic fungicides at the time of berry formation ensure healthy and higher grapes yield. This paper reviewed the powdery mildew infection in grapevines and its effect on yield losses with details of fungicides’ mechanism of action and newly developed fungicides having broad spectrum activities.
Real-time temperature detection and Mask entry system
Authors: J Gobinath , kumar Udhaya , Raiyyan V Mohammed , P Logeshwaran P
Published: January 2023

Corona virus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus that causes illness in the Respiratory system in humans. Covid-19 affected our day-to- day life and still, it is continuing to mutate. Though we have discovered vaccines for the treatments, we can’t stop them from spreading. To prevent us from Covid-19, we have to wear a mask and maintain Social distance in public places. Here, we are making an Embedded system device that automatically detects the temperature of a person and checks whether the person wears a mask or not in public places such as Hospitals, Shopping Malls, Stations, etc. The Government of India has made wearing face masks compulsory but the people don't wear masks in public places. To create awareness among the public, these types of devices would help. Many Face detection models have been developed using different approaches and algorithms. The proposed approach in this paper was developed to avoid mask-less people from entering a desired places by detecting face masks using Deep Learning, Keras library, Tensor Flow and Computer Vision. MLX90614 ESF Non-Contact Human Body Infrared Temperature Measurement Module is used to detect the temperature of a person without contact. Adriano is used as a Microprocessor. If either a person doesn’t wear a mask or the temperature of that person is above normal, then it detects it and starts making a sound (alarm) using Buzzer. If a person wears a mask and the temperature of that person is normal, then it detects it and allows that person to Enter.
Ai Based Dual Authentication System
Authors: Gopinath S , Pragadeswaran S , Subaranjani P , Mounitha R , Parameshwari N
Published: January 2023

Artificial intelligence (AI) has demonstrated huge potential in a various real-world applications. However, some significant considerations like fairness, transparency and trustworthiness are still challenging when applying AI to trust-oriented applications such as E-voting. In this project, we aim to facilitate the consolidation of AI ecosystems by developing a blockchain-based traceable self-tallying E-voting system. The proposed system presents a novel voting system by using Fingerprint of Aadhar card. In E-voting system an voter can vote from anywhere as there will be two or more levels of authenticity checks. The system will act as registering module on activating switch by the super admin. For registering module, followed by the fingerprint verification. The system permits the elector to cast their vote, block chain technology comes into existence that is integrated within the machine. Each vote is added into each block encrypted by 256-bit SHA hash codes, the hashed block cannot be tampered by any individual as more security is added to the system. By adopting Blockchain within the distribution of information will scale back one in every of the cheating sources of database manipulation. The proposed mechanism of voting using Blockchain not only serves the election conducting bodies but also the voters who get notified in case of any meddling with their votes before the counting announcement.
POTENCIAL DIGITALIZACIÓN EN MIPYMES GUAYAS – INVESTIGACIÓN EMPÍRICA
Authors: Brito Ochoa María Paulina , Sarmiento Torres Ingrid , Vásquez Luna Luz Elvira , González González Rosa
Published: January 2023

Los emprendedores enfrentaron la digitalización de manera abrupta debido a la pandemia COVID-19, en su intento por promover la relación con los clientes de manera ágil. La oportunidad que representa la inserción digital en las Pymes como una forma de mejorar la gestión y a la vez generar más valor al cliente es evidente. El presente trabajo plantea como objetivo analizar la influencia de las ventajas del emprendimiento digital en la digitalización de los emprendimientos, basado en muestra de 151 emprendimientos ubicados en la provincia del Guayas, Ecuador, empleando el modelo de actitud hacia el uso del emprendimiento digital (Franco et al., 2021) basado en tres factores: eficiencia, relación con los clientes y comportamiento colaborativo. Los resultados del enfoque del modelo de ecuaciones estructurales (SEM) muestran que dos de los tres factores tienen una influencia positiva y significativa en la potencial digitalización de los emprendedores. Es interesante observar que el principal impacto en el potencial la digitalización de los emprendimientos procede de la relación que se establece con los clientes.
Effect of Indole Acetic Acid (IAA) by Serratia marcescens strain MBC1 on Soybean (Glycine max L.) Germination
Authors: Ismawanti Ayu , Nurcahyani Endang , Farizi Salman , Sumardi Sumardi
Published: January 2023

Indole Acetic Acid (IAA) is one type of hormone that can stimulate plant growth. IAA hormone is able to accelerate plant growth, especially in the early stages of growth. IAA hormones are not always found in plants, one of which can be found in microorganisms. Rhizobacteria group have the ability to produce IAA hormones. This study aims to determine whether the IAA produced by Serratia marcescens strain MBC1 is able to accelerate the germination process of soybean seeds (Glycine max L.). The results of the Analysis of Variance (ANOVA) giving the production of IAA Serratia marcescens strain MBC1 of 8.31 ppm and 9.35 ppm to soybean seed germination significantly increased root length and stem length. The increase in germination from the administration of IAA Serratia marcescens MBC1 was still smaller than the positive control using synthetic IAA with a concentration of 8 ppm which was able to significantly increase soybean germination.
Response of Cattleya sp. Orchid Planlet In vitro Selection Results Against Drought Stress with Polyethyleneglycol (PEG) 6000
Authors: Sabatini Aura Priscilla , Nurcahyani Endang , Yulianty Yulianty , Agustrina Rochmah
Published: January 2023

Orchid Cattleya sp. is famous for ornamental plants, known as the queen of flower. The water content is very much needed, so that drought conditions do not become a barrier in its cultivation. Cattleya sp. plantlets can be resistant to drought stress through in vitro culture selection with PEG 6000. The purpose of this study was to determine the proportion of live plantlets that were tolerant to drought stress and to analyze the of the plantlet Cattleya sp. that experienced drought stress after being selected with PEG 6000 included: visualization of plantlets, chlorophyll a, b, and total content and stomata index. This research was conducted in a completely randomized design consisting of 1 factor, namely PEG 6000 with 5 levels: 0%, 5%, 10%, 15% and 20% with 5 repetitions. The homogeneity of variance was tested using Levene's test at a 5% significance level, followed by One-Way ANOVA at a 5% significance level, then if the data showed a significant difference, it was followed by a Significant Difference Test at a 5% significance level. The results of this study showed that the proportion of live plantlets was 60% at a concentration of 20% PEG 6000. The Cattleya sp. plantlets a, b, total chlorophyll’s and the stomatal indekx all decrease in response to the increasing PEG 6000 concentration.
Perception of Barbell Velocity: Can Individuals Accurately Perceive Changes in Velocity?
Authors: Shaw Matthew , Thompson Stephen , Myranuet Per Aslak , Tonheim Håvard , Nielsen Johnny , Steele James
Published: January 2023

The aim of the study was to investigate whether resistance-trained participants can accurately predict changes in barbell velocity, specifically in the deadlift exercise, without feedback from velocity based training (VBT) devices. Seventeen participants (16 male, 1 female; age = 24.7 ± 3.8) were randomized in a counterbalanced, crossover design two experimental sessions that consisted of three sets of Deadlift at 60-and-80% one-repetition maximum (1RM). The number of repetitions were determined by the participants as they were asked to terminate each set when they felt the barbell velocity had reduced by 20%, relative to repetition one. A binomial mixed effects regression model was used to assess the accuracy of participants ability to stop after reaching at least 20% velocity loss. Participants tended to underestimate their proximity to 20% velocity loss and thus had relatively low probability of correctly stopping after reaching this threshold. There was only a 10.49% probability that people could perceive at least 20% velocity loss greater than chance (i.e., 50% probability). Our data, suggests that most participants cannot accurately perceive changes in velocity without exposure to augmented feedback.
الصفات المظهرية لـثلاثة أجناس من الفصيلة الخبازية بمفهومها الواسع Malvaceae s.l. في مديرية طورالباحة، محافظة لحج، اليمن
Authors: Mohammed Nora Mohammed Al-Saqaf , Al-Hawshabi Othman Saad Saeed
Published: January 2023

تناولت الدراسة الحالية الصفات المظهرية لثلاثة أجناس من الفصيلة الخبازية بمفهومها الواسع Malvaceae s.l.، في مديرية طورالباحة – محافظة لحج – اليمن، وذلك خلال الفترة من أغسطس 2020 حتى يناير 2022م، إذ جُمْعِت عينات نباتية مثالية لكل نوع نباتي موجود في منطقة الدراسة. تم مناقشة الصفات المظهرية ذات الأهمية، كما تم سرد مرادفات الأسماء العلمية والأسماء المحلية لكل الأنواع المدروسة وانتشارها في منطقة الدراسة، وتم عمل مفتاح تصنيفي للتفرقة بين الأجناس الثلاثة، كذلك تمت مراجعة التسمية العلمية واستحداثها باستخدام التقسيم الحديث الذي تم فيه إحالة الفصيلة الخبازية Malvaceae إلى تحت فصيلة Malvoideae ضمن الفصيلة الخبازية بمفهومها الواسع Malvaceae s.l.. اثبتت الدراسة أن الصفات المظهرية الخضرية والتكاثرية للثلاثة الأنواع التي تنمو برياً في منطقة الدراسة وهي Cienfuegosia welshii ، Gossypium arboreum و Senra incana ذات قيمة عالية في التمييز بينها.
PREMATURE ONSET OF STROKE IN KHAT CHEWERS IN ADMITTED CASES TO ADEN HOSPITALS
Authors: Al-sobehi Reyad Mohamed A. , Basselm Omer Abobeker
Published: January 2023

Khat chewing is a common habit in Yemen and east African countries. Millions of people chew khat especially young adult male chew khat leaves daily for its euphoric and energetic effects and for the increase of alertness due to action of cathinone (amphetamine like substance) which lead to increase of blood pressure, heart rate and incidence of AMI. Khat use is widespread in some parts of Yemen, even among children. The prevalence of khat chewing has been estimated at 80% for males and 50% for females in the capital Sana'a at age fifteen and above. The aim of the study was done to earlier sage onset of stroke in khat chewing with relation to other risk factors of stroke. This study was conducted during the period from January 2022 to Jun. 2022, during which 150 patients admitted with stroke. The basic information was collected through special questionnaires for this purpose. The khat chewing group was 83 case compromised 55.3%. The study showed that there was a statistically significant relationship between khat chewing and the age group of less than 55 years age (P - 0.000).