bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Socioeconomic Vulnerability Index Using two Agricultural Communities Exposed to Climate Change: A Case Study in Wanathawilluwa in Puttlam District of Sri Lanka
Authors: Demel M. S. V. , Udayanga N. W. B. A. L. , Gajanayake B. , Hapuarachchi B. , Perera D.
Published: October 2022

The importance of vulnerability and adaptive capacity has been frequently emphasized in explaining the societal aspects of climate change over the last few years. Developments in vulnerability research and consequent adaptation policies, have become a top priority in many countries. With the understanding of the significant importance of agriculture, numerous climate change assessments have been conducted to explore the vulnerability status of agricultural communities, whose livelihood is mostly dependent on natural resources. However, such studies are highly limited in Sri Lanka and the current study was aimed at developing a Socioeconomic Vulnerability Index (SeVI) for two climate change affected agricultural communities in Wanathawilluwa Divisional Secretariat Divisions (DSD) using the concept of “Sustainable Livelihoods Approach” under five specific assets, namely (1) human; (2) social; (3) physical; (4) natural and (5) financial. Fifty households from two Grama-Niladhari Divisions (GN) were surveyed to collect data on three vulnerability dimensions and 17 socioeconomic indicators. The SeVI aggregate was developed as a composite indicator index, where a relative weight was assigned to each indicator with a view of obtaining weighted average index scores. In addition, pentagons were developed for each community by analysing the five assets under 17 indicators. Results suggested that Mangalapura farming community (GN Division) was relatively more vulnerable and most exposed to natural hazards. This study suggests SeVI as a viable approach to assist the policy-makers to identify the most vulnerable communities to climate change and thereby improve the early warning systems. Further, this SeVI can be promoted as a simple but effective tool for comparing socioeconomic vulnerability in hazard prone regions towards climate change.
Influence of Employee’s Anxiety on Human Factor Dimensions and Successful Change Implementation: Evidence from Nigeria
Authors: Kuforiji Aramide Arinola , Tobi Ariyo Andrew
Published: October 2022

This study investigated the moderating effects of employees’ anxiety on the relationship between human factor dimensions and the success of change implementation initiatives. The study employed a cross-sectional survey research design and administered a structured questionnaire to employees of four selected food and beverage firms in Lagos State, Nigeria. The findings showed that employees’ anxiety has a statistically insignificant moderating effect on the relationship between human factor dimensions and change implementation success. The study concluded that employees' anxiety has multifaceted effects on change implementation in organisations. It may negatively impact the success of change implementation and may have an insignificant effect on change initiatives. therefore, it is recommended that in order to enhance the success of change initiatives, employees’ anxiety should be given adequate consideration at the planning staged of the change implementation.
Calpains Released from Necrotic Tumor Cells Enhance Antigen Cross-Presentation to Activate CD8+ T Cells In Vitro
Authors: Shields Nicholas J , Peyroux Estelle M , Campbell Katrin , Mehta Sunali , Woolley Adele G , Counoupas Claudio , Neumann Silke , Young Sarah L
Published: October 2022

The initiation of CD8+ T cell responses against dead cell–associated Ags is tightly regulated, facilitating adaptive immunity against pathogens and tumors while preventing autoimmunity. It is now well established that dying cells actively regulate the generation of CD8+ T cell responses via the release or exposure of damage-associated molecular patterns. However, it is unclear whether nonproteasomal proteases (activated in stressed and dying cells) can influence the availability of Ags for cross-presentation. Using a mouse model of immunogenic necrosis, we investigated the role of tumor-derived proteases in the priming of CD8+ T cells. We demonstrate that proteases released from necrotic tumor cells can degrade whole-protein Ag, generating proteolytic intermediates that are efficiently cross-presented by dendritic cells and enhance CD8+ T cell cross-priming. We identify a dominant role for calpain proteases, which are activated during necrotic cell death induced by severe heat shock. Mechanistically, proteolytic intermediates generated by tumor-derived proteases associate with necrotic tumor cell debris, which acts as a vehicle for Ag transfer that facilitates highly efficient cross-presentation in dendritic cells. Our results suggest that proteolytic systems activated in Ag donor cells during cell death may influence the availability of antigenic substrates for cross-presentation, thereby regulating the antigenicity of cell death.
Negative Cross-Talk between TLR2/4-Independent AMPKα1 and TLR2/4-Dependent JNK Regulates S. pneumoniae–Induced Mucosal Innate Immune Response
Authors: Matsuyama Shingo , Komatsu Kensei , Lee Byung-Cheol , Tasaki Yukihiro , Miyata Masanori , Xu Haidong , Shuto Tsuyoshi , Kai Hirofumi , Li Jian-Dong
Published: October 2022

Streptococcus pneumoniae is major cause of otitis media (OM) and life-threatening pneumonia. Overproduction of mucin, the major component of mucus, plays a critical role in the pathogenesis of both OM and pneumonia. However, the molecular mechanisms underlying the tight regulation of mucin upregulation in the mucosal epithelium by S. pneumoniae infection remain largely unknown. In this study, we show that S. pneumoniae pneumolysin (PLY) activates AMP-activated protein kinase α1 (AMPKα1), the master regulator of energy homeostasis, which is required for S. pneumoniae–induced mucin MUC5AC upregulation in vitro and in vivo. Moreover, we found that PLY activates AMPKα1 via cholesterol-dependent membrane binding of PLY and subsequent activation of the Ca2+– Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ) and Cdc42–mixed-lineage protein kinase 3 (MLK3) signaling axis in a TLR2/4-independent manner. AMPKα1 positively regulates PLY-induced MUC5AC expression via negative cross-talk with TLR2/4-dependent activation of MAPK JNK, the negative regulator of MUC5AC expression. Moreover, pharmacological inhibition of AMPKα1 suppressed MUC5AC induction in the S. pneumoniae–induced OM mouse model, thereby demonstrating its therapeutic potential in suppressing mucus overproduction in OM. Taken together, our data unveil a novel mechanism by which negative cross-talk between TLR2/4-independent activation of AMPKα1 and TLR2/4-dependent activation of JNK tightly regulates the S. pneumoniae PLY-induced host mucosal innate immune response.
Modern Clinical Mycobacterium tuberculosis Strains Leverage Type I IFN Pathway for a Proinflammatory Response in the Host
Authors: Shankaran Deepthi , Arumugam Prabhakar , Vasanthakumar Ragavendran P , Singh Anjali , Bothra Ankur , Gandotra Sheetal , Rao Vivek
Published: October 2022

Host phagocytes respond to infections by innate defense mechanisms through metabolic shuffling to restrict the invading pathogen. However, this very plasticity of the host provides an ideal platform for pathogen-mediated manipulation. In the human (THP1/THP1 dual/PBMC-derived monocyte-derived macrophages) and mouse (RAW264.7 and C57BL/6 bone marrow–derived) macrophage models of Mycobacterium tuberculosis infection, we have identified an important strategy employed by clinical lineages in regulating the host immune–metabolism axis. We show greater transit via the macrophage phagosomal compartments by Mycobacterium tuberculosis strains of lineage: M. tuberculosis lineage 3 is associated with an ability to elicit a strong and early type I IFN response dependent on DNA (in contrast with the protracted response to lineage: M. tuberculosis lineage 1). This augmented IFN signaling supported a positive regulatory loop for the enhanced expression of IL-6 consequent to an increase in the expression of 25-hydroxycholesterol in macrophages. This amplification of the macrophage innate response-metabolic axis incumbent on a heightened and early type I IFN signaling portrays yet another novel aspect of improved intracellular survival of clinical M. tuberculosis strains.
Nexinhib20 Inhibits Neutrophil Adhesion and β2 Integrin Activation by Antagonizing Rac-1–Guanosine 5′-Triphosphate Interaction
Authors: Liu Wei , Cronin Chunxia G , Cao Ziming , Wang Chengliang , Ruan Jianbin , Pulikkot Sunitha , Hall Alexxus , Sun Hao , Groisman Alex , Chen Yunfeng , Vella Anthony T , Hu Liang , Liang Bruce T , Fan Zhichao
Published: October 2022

Neutrophils are critical for mediating inflammatory responses. Inhibiting neutrophil recruitment is an attractive approach for preventing inflammatory injuries, including myocardial ischemia-reperfusion (I/R) injury, which exacerbates cardiomyocyte death after primary percutaneous coronary intervention in acute myocardial infarction. In this study, we found out that a neutrophil exocytosis inhibitor Nexinhib20 inhibits not only exocytosis but also neutrophil adhesion by limiting β2 integrin activation. Using a microfluidic chamber, we found that Nexinhib20 inhibited IL-8–induced β2 integrin–dependent human neutrophil adhesion under flow. Using a dynamic flow cytometry assay, we discovered that Nexinhib20 suppresses intracellular calcium flux and β2 integrin activation after IL-8 stimulation. Western blots of Ras-related C3 botulinum toxin substrate 1 (Rac-1)–GTP pull-down assays confirmed that Nexinhib20 inhibited Rac-1 activation in leukocytes. An in vitro competition assay showed that Nexinhib20 antagonized the binding of Rac-1 and GTP. Using a mouse model of myocardial I/R injury, Nexinhib20 administration after ischemia and before reperfusion significantly decreased neutrophil recruitment and infarct size. Our results highlight the translational potential of Nexinhib20 as a dual-functional neutrophil inhibitory drug to prevent myocardial I/R injury.
Duck CD8+ T Cell Response to H5N1 Highly Pathogenic Avian Influenza Virus Infection In Vivo and In Vitro
Authors: Dai Manman , Sun Hui , Zhao Li , Wu Qingxin , You Bowen , Xu Fengxiang , Liao Jiayu , Zhu Sufang , Li Ziwei , Yao Yongxiu , Nair Venugopal , Liao Ming
Published: October 2022

Domestic ducks are the important host for H5N1 highly pathogenic avian influenza virus (HPAIV) infection and epidemiology, but little is known about the duck T cell response to H5N1 AIV infection. In infection experiments of mallard ducks, we detected significantly increased CD8+ cells and augmented expression of cytotoxicity-associated genes, including granzyme A and IFN-γ, in PBMCs from 5 to 9 d postinfection when the virus shedding was clearly decreased, which suggested the importance of the duck cytotoxic T cell response in eliminating H5N1 infection in vivo. Intriguingly, we found that a CD8high+ population of PBMCs was clearly upregulated in infected ducks from 7 to 9 d postinfection compared with uninfected ducks. Next, we used Smart-Seq2 technology to investigate the heterogeneity and transcriptional differences of the duck CD8+ cells. Thus, CD8high+ cells were likely to be more responsive to H5N1 AIV infection, based on the high level of expression of genes involved in T cell responses, activation, and proliferation, including MALT1, ITK, LCK, CD3E, CD247, CFLAR, IL-18R1, and IL-18RAP. More importantly, we have also successfully cultured H5N1 AIV-specific duck T cells in vitro, to our knowledge, for the first time, and demonstrated that the CD8high+ population was increased with the duck T cell activation and response in vitro, which was consistent with results in vivo. Thus, the duck CD8high+ cells represent a potentially effective immune response to H5N1 AIV infection in vivo and in vitro. These findings provide novel insights and direction for developing effective H5N1 AIV vaccines.
Persistent Antigen Harbored by Alveolar Macrophages Enhances the Maintenance of Lung-Resident Memory CD8+ T Cells
Authors: Lobby Jenna L , Uddbäck Ida , Scharer Christopher D , Mi Tian , Boss Jeremy M , Thomsen Allan R , Christensen Jan P , Kohlmeier Jacob E
Published: October 2022

Lung tissue-resident memory T cells are crucial mediators of cellular immunity against respiratory viruses; however, their gradual decline hinders the development of T cell–based vaccines against respiratory pathogens. Recently, studies using adenovirus (Ad)-based vaccine vectors have shown that the number of protective lung-resident CD8+ TRMs can be maintained long term. In this article, we show that immunization of mice with a replication-deficient Ad serotype 5 expressing influenza (A/Puerto Rico/8/34) nucleoprotein (AdNP) generates a long-lived lung TRM pool that is transcriptionally indistinct from those generated during a primary influenza infection. In addition, we demonstrate that CD4+ T cells contribute to the long-term maintenance of AdNP-induced CD8+ TRMs. Using a lineage tracing approach, we identify alveolar macrophages as a cell source of persistent NP Ag after immunization with AdNP. Importantly, depletion of alveolar macrophages after AdNP immunization resulted in significantly reduced numbers of NP-specific CD8+ TRMs in the lungs and airways. Combined, our results provide further insight to the mechanisms governing the enhanced longevity of Ag-specific CD8+ lung TRMs observed after immunization with recombinant Ad.
Inhibitory and Stimulatory Effects of IL-32 on HIV-1 Infection
Authors: Nasser Hesham , Takahashi Naofumi , Eltalkhawy Youssef M , Reda Omnia , Lotfi Sameh , Nasu Kanako , Sakuragi Jun-ichi , Suzu Shinya
Published: October 2022

The proinflammatory cytokine IL-32 is elevated in the plasma and tissues of HIV-1–infected individuals. However, its significance in HIV-1 infection remains unclear because IL-32 inhibits and stimulates viral production in monocyte-derived macrophages (MDMs) and CD4+ T cells, respectively. In this study, we initially found that the inhibitory effect on human MDMs depends on SAMHD1, a dNTP triphosphohydrolase that inhibits viral reverse transcription. IL-32 increased the unphosphorylated active form of SAMHD1, which was consistent with the reduced expression of the upstream cyclin-dependent kinases. Indeed, IL-32 lost its anti–HIV-1 activity in MDMs when SAMHD1 was depleted. These results explain why IL-32 inhibits HIV-1 in MDMs but not CD4+ T cells, because SAMHD1 restricts HIV-1 in noncycling MDMs but not in cycling CD4+ T cells. Another unique feature of IL-32 is the induction of the immunosuppressive molecule IDO1, which is beneficial for HIV-1 infection. In this study, we found that IL-32 also upregulates other immunosuppressive molecules, including PD-L1, in MDMs. Moreover, IL-32 promoted the motility of MDMs, which potentially facilitates intercellular HIV-1 transmission. Our findings indicate that IL-32 has both the direct inhibitory effect on HIV-1 production in MDMs and the indirect stimulatory effects through phenotypic modulation of MDMs, and they suggest that the stimulatory effects may outweigh the inhibitory effect because the window for IL-32 to inhibit HIV-1 is relatively confined to SAMHD1-mediated reverse transcription suppression in the viral life cycle.
Identification of HLA-E Binding Mycobacterium tuberculosis–Derived Epitopes through Improved Prediction Models
Authors: Ruibal Paula , Franken Kees L M C , van Meijgaarden Krista E , van Wolfswinkel Marjolein , Derksen Ian , Scheeren Ferenc A , Janssen George M C , van Veelen Peter A , Sarfas Charlotte , White Andrew D , Sharpe Sally A , Palmieri Fabrizio , Petrone Linda , Goletti Delia , Abeel Thomas , Ottenhoff Tom H M , Joosten Simone A
Published: October 2022

Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, posing great social and economic burden to affected countries. Novel vaccine approaches are needed to increase protective immunity against the causative agent Mycobacterium tuberculosis (Mtb) and to reduce the development of active TB disease in latently infected individuals. Donor-unrestricted T cell responses represent such novel potential vaccine targets. HLA-E-restricted T cell responses have been shown to play an important role in protection against TB and other infections, and recent studies have demonstrated that these cells can be primed in vitro. However, the identification of novel pathogen-derived HLA-E binding peptides presented by infected target cells has been limited by the lack of accurate prediction algorithms for HLA-E binding. In this study, we developed an improved HLA-E binding peptide prediction algorithm and implemented it to identify (to our knowledge) novel Mtb-derived peptides with capacity to induce CD8+ T cell activation and that were recognized by specific HLA-E-restricted T cells in Mycobacterium-exposed humans. Altogether, we present a novel algorithm for the identification of pathogen- or self-derived HLA-E-presented peptides.
Casting a Wide NET
Authors: Kaplan Mariana J
Published: October 2022

This Pillars of Immunology article is a commentary on “Neutrophil extracellular traps kill bacteria,” a pivotal article written by V. Brinkmann, U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D. S. Weiss, Y. Weinrauch, and A. Zychlinksy, and published in Science, in 2004. https://www.science.org/doi/10.1126/science.1092385. The Journal of Immunology, 2022, 209: 843–844.
Molecular Basis for the Recognition of HIV Nef138-8 Epitope by a Pair of Human Public T Cell Receptors
Authors: Ma Keke , Chai Yan , Guan Jiawei , Tan Shuguang , Qi Jianxun , Kawana-Tachikawa Ai , Dong Tao , Iwamoto Aikichi , Shi Yi , Gao George F
Published: October 2022

Cross-recognized public TCRs against HIV epitopes have been proposed to be important for the control of AIDS disease progression and HIV variants. The overlapping Nef138-8 and Nef138-10 peptides from the HIV Nef protein are HLA-A24–restricted immunodominant T cell epitopes, and an HIV mutant strain with a Y139F substitution in Nef protein can result in immune escape and is widespread in Japan. Here, we identified a pair of public TCRs specific to the HLA-A24–restricted Nef-138-8 epitope using PBMCs from White and Japanese patients, respectively, namely TD08 and H25-11. The gene use of the variable domain for TD08 and H25-11 is TRAV8-3, TRAJ10 for the α-chain and TRBV7-9, TRBD1*01, TRBJ2-5 for the β-chain. Both TCRs can recognize wild-type and Y2F-mutated Nef138-8 epitopes. We further determined three complex structures, including TD08/HLA-A24-Nef138-8, H25-11/HLA-A24-Nef138-8, and TD08/HLA-A24-Nef138-8 (2F). Then, we revealed the molecular basis of the public TCR binding to the peptide HLA, which mostly relies on the interaction between the TCR and HLA and can tolerate the mutation in the Nef138-8 peptide. These findings promote the molecular understanding of T cell immunity against HIV epitopes and provide an important basis for the engineering of TCRs to develop T cell–based immunotherapy against HIV infection.
NPAT Supports CD8+ Immature Single-Positive Thymocyte Proliferation and Thymic Development
Authors: Cui Zejin , Zhao Fan , Chen Xiaoping , Li Jiahui , Jin Xuexiao , Han Yongmei , Wang Lie , Zhou Yiting , Lu Linrong
Published: October 2022

Thymocytes need to proliferate into a significant cell mass to allow a subsequent selection process during the double-positive (DP) stage. However, it is not clear at what stage this massive cell proliferation occurs. Immature CD8 single-positive (ISP) cells are a well-defined thymocyte subpopulation. However, the function of this cell subset has not yet been characterized. In this study, we analyzed the transcription pattern of mouse ISP cells and observed higher expression levels of cell cycling genes. We also found out that ISP cells exhibited the highest cell proliferative capacity among thymocytes in different developmental stages. Nuclear protein ataxia-telangiectasia (NPAT/p220) is one of the highly expressed cell cycling genes in ISP cells, which is known to play a critical role in coordinating histone gene expression necessary for rapid cell proliferation. Selective deletion of NPAT at the ISP stage led to reduced thymus size and significant loss of DP cells, secondary to reduced histone gene expression and impaired ISP cell proliferation capacity. A block of thymocyte development at the ISP stage was also observed, which was due to increased IL-7R expression. Continuous IL-7R signal served as a compensating mechanism for cell proliferation upon NPAT deletion, but in turn inhibited the expression of transcription factors TCF-1 and LEF-1, which is essential for the transition of ISP to DP cells. In summary, our study revealed the proliferation capacity of the ISP subpopulation during thymocyte differentiation as well as a vital role of NPAT in this developmental stage.
Deficiency of p53 Causes the Inadequate Expression of miR-1246 in B Cells of Systemic Lupus Erythematosus
Authors: Zhang Qing , Liu Yu , Liao Jieyue , Wu Ruifang , Zhan Yi , Zhang Peng , Luo Shuangyan
Published: October 2022

Underexpression of p53 is considered the leading cause of the decreased miR-1246 expression in B cells of systemic lupus erythematosus (SLE) patients, yet the exact mechanism of action still remains unclear. To further explore the molecular mechanism of p53 upregulating miR-1246 expression, we targeted the methylation and acetylation of histone H3 in the miR-1246 promoter region of SLE B cells. We found that increased histone H3 trimethylation at Lys27 (H3K27me3) and decreased histone H3 acetylation at Lys9 and Lys14 (H3K9/K14ac) in the miR-1246 promoter region are essential for the low expression of miR-1246 in SLE B cells. p53 can promote miR-1246 transcription by recruiting Jumonji domain–containing protein 3 (JMJD3), E1A-binding protein p300 (EP300), and CREB-binding protein (CBP) to bind to the miR-1246 promoter, downregulating H3K27me3 and upregulating H3K9/K14ac. Furthermore, early B cell factor 1 (EBF1), CD40, CD38, and X box binding protein-1 (XBP-1) expression levels in SLE B cells transfected with p53 expression plasmid were significantly decreased, whereas autoantibody IgG production in autologous CD4+ T cells cocultured with overexpressed p53 SLE B cells was reduced. Collectively, our data suggest that the reduction of p53 decreases miR-1246 expression via upregulation of H3K27me3 and downregulation of H3K9/14ac, which in turn results in SLE B cell hyperactivity.
Cutting Edge: The Expression of Transcription Inhibitor GFI1 Is Induced by Retinoic Acid to Rein in Th9 Polarization
Authors: Friesen Leon , Kostlan Raymond , Liu Qingyang , Yu Hao , Zhu Jinfang , Lukacs Nicholas , Kim Chang H
Published: October 2022

IL-9, produced mainly by specialized T cells, mast cells, and group 2 innate lymphoid cells, regulates immune responses, including anti-helminth and allergic responses. Polarization of naive CD4 T cells into IL-9–producing T cells (Th9s) is induced by IL-4 and TGF-β1 or IL-1β. In this article, we report that the transcription factor growth factor–independent 1 transcriptional repressor (GFI1) plays a negative role in mouse Th9 polarization. Moreover, the expression of GFI1 is controlled by liganded RARα, allowing GFI1 to mediate the negative effect of retinoic acid on IL-9 expression. The Gfi1 gene has multiple RARα binding sites in the promoter region for recruiting nuclear coactivator steroid receptor coactivator-3 and p300 for histone epigenetic modifications in a retinoic acid–dependent manner. Retinoic acid–induced GFI1 binds the Il9 gene and suppresses its expression. Thus, GFI1 is a novel negative regulator of Il9 gene expression. The negative GFI1 pathway for IL-9 regulation provides a potential control point for Th9 activity.
Immune Subtypes and Immune Landscape Analysis of Endometrial Carcinoma
Authors: Liang Leilei , Zhu Yunshu , Li Jian , Zeng Jia , Yuan Guangwen , Wu Lingying
Published: October 2022

Some patients with endometrial cancer (EC) suffer from limited survival benefits after immunotherapy, suggesting that there may be a specific pattern associated with immunotherapy. Immune-related genes were extracted from The Cancer Genome Atlas databases. We analyzed the differences among immune subtypes (ISs) in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, immune checkpoint-related genes, immunotherapy, and chemotherapy. We applied dimensionality reduction and defined the immune landscape of EC. Then, we used the Weighted Gene Co-Expression Network Analysis package to identify the coexpression modules of these immune genes. Finally, hub genes were selected and detected by quantitative PCR and immunohistochemistry. We obtained three ISs. There were differences in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, and immune checkpoint–related genes among the ISs. Regarding immunotherapy and chemotherapy, the IS2 subtypes were more sensitive to programmed cell death protein 1 inhibitors. In addition, different positions in the immune landscape map exhibited different prognostic characteristics, providing further evidence of the ISs. The IS2 subtypes were significantly positively correlated with yellow module gene list, indicating a good prognosis with high score. SIRPG and SLAMF1 were identified as the final characteristic genes. The quantitative PCR and immunohistochemistry results showed that the expression levels of SIRPG and SLAMF1 were low in human EC tissue. In this study, we identified three reproducible ISs of EC. The immune landscape analysis further revealed the intraclass heterogeneity of the ISs. SIRPG and SLAMF1 were identified to be associated with progression, suggesting that they may be novel immune-related biomarkers of EC.
Breaking the Paradigm: Selection of Self-Reactive Natural Antibodies
Authors: Baumgarth Nicole
Published: October 2022

This Pillars of Immunology article is a commentary on “Positive Selection of Natural Autoreactive B Cells,” a pivotal article written by K. Hayakawa, M. Asano, S. A. Shinton, M. Gui, D. Allman, C. L. Stewart, J. Silver, and R. R. Hardy, and published in Science, in 1999. https://doi.org/10.1126/science.285.5424.113.
Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation
Authors: Shook Lydia L , Fourman Lindsay T , Edlow Andrea G
Published: October 2022

Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2–positive mothers for neurodevelopmental and cardiometabolic sequelae.
Single-Cell Immunobiology of the Maternal–Fetal Interface
Authors: Miller Derek , Garcia-Flores Valeria , Romero Roberto , Galaz Jose , Pique-Regi Roger , Gomez-Lopez Nardhy
Published: October 2022

Pregnancy success requires constant dialogue between the mother and developing conceptus. Such crosstalk is facilitated through complex interactions between maternal and fetal cells at distinct tissue sites, collectively termed the “maternal–fetal interface.” The emergence of single-cell technologies has enabled a deeper understanding of the unique processes taking place at the maternal–fetal interface as well as the discovery of novel pathways and immune and nonimmune cell types. Single-cell approaches have also been applied to decipher the cellular dynamics throughout pregnancy, in parturition, and in obstetrical syndromes such as recurrent spontaneous abortion, preeclampsia, and preterm labor. Furthermore, single-cell technologies have been used during the recent COVID-19 pandemic to evaluate placental viral cell entry and the impact of SARS-CoV-2 infection on maternal and fetal immunity. In this brief review, we summarize the current knowledge of cellular immunobiology in pregnancy and its complications that has been generated through single-cell investigations of the maternal–fetal interface.
Natural Antibodies Alert the Adaptive Immune System of the Presence of Transformed Cells in Early Tumorigenesis
Authors: Rawat Kavita , Soucy Shannon M , Kolling Fred W , Diaz Kiara Manohar , King William T , Tewari Anita , Jakubzick Claudia V
Published: October 2022

Recent studies have revealed a critical role for natural Abs (NAbs) in antitumor immune responses. However, the role of NAbs in cancer immunosurveillance remains unexplored, mainly because of the lack of in vivo models that mimic the early recognition and elimination of transforming cells. In this article, we propose a role for NAbs in alerting the immune system against precancerous neoantigen-expressing cells immediately after they escape intrinsic tumor suppression mechanisms. We identify four distinct reproducible, trackable, MHC-matched neoantigen-expressing cell models that do not form tumors as the end point. This amplified readout in the critical window prior to tumor formation allows investigation of new mediators of cancer immunosurveillance. We found that neoantigen-expressing cells adoptively transferred in NAb-deficient mice persisted, whereas they were eliminated in wild-type mice, indicating that the circulating NAb repertoire alerts the immune system to the presence of transformed cells. Moreover, immunity is mounted against immunogenic and nonimmunogenic neoantigens contained in the NAb-tagged cells, regardless of whether the NAb directly recognizes the neoantigens. Beyond these neoantigen-expressing model systems, we observed a significantly greater tumor burden in chemically and virally induced tumor models in NAb-deficient mice compared with wild-type mice. Restoration of the NAb repertoire in NAb-deficient mice elicited the recognition and elimination of neoantigen-expressing cells and cancer. These data show that NAbs are required and sufficient for elimination of transformed cells early in tumorigenesis. These models can now be used to investigate how NAbs stimulate immunity via recognition receptors to eliminate precancerous cells.
PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality
Authors: Pandian Nagakannan , Kanneganti Thirumala-Devi
Published: October 2022

Innate immunity is the first response to protect against pathogens and cellular insults. Pattern recognition receptors sense pathogen- and damage-associated molecular patterns and induce an innate immune response characterized by inflammation and programmed cell death (PCD). In-depth characterization of innate immune PCD pathways has highlighted significant cross-talk. Recent advances led to the identification of a unique inflammatory PCD modality called PANoptosis, which is regulated by multifaceted PANoptosome complexes that are assembled by integrating components from other PCD pathways. The totality of biological effects observed in PANoptosis cannot be accounted for by any other PCD pathway alone. In this review, we briefly describe mechanisms of innate immune cell death, including molecular mechanisms of PANoptosis activation and regulation. We also highlight the PANoptosomes identified to date and provide an overview of the implications of PANoptosis in disease and therapeutic targeting. Improved understanding of innate immune-mediated cell death, PANoptosis, is critical to inform the next generation of treatment strategies.
A journey inside the elderly-onset primary Sjögren’s syndrome, looking for useful tips for the geriatrician
Authors: Manzo Ciro , Castagna Alberto , Ruotolo Giovanni
Published: October 2022

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease where xerophthalmia, xerostomia and presence of anti-SSA and anti-SSB antibodies are typical features. Its prevalence is higher in over-65 aged population than in other age groups. In the elderly, pSS diagnosis comes up against a whole series of critical points that may favor its misdiagnosis. The aim of our article is to discuss the most relevant of them: the frequent occurrence of a seronegative subset, the presence of systemic features not related to sicca syndrome, the sicca syndrome as iatrogenic manifestation and the possibility of a biopsy false negative of labial salivary glands.
Lie Symmetry Analysis of Seventh Order Caudrey-Dodd- Gibbon Equation
Authors: Hariom Sharma  , Rajan Arora
Published: October 2022

In the present paper, seventh order Caudrey-Dodd-Gibbon (CDG) equation is solved by Lie symmetry analysis. All the geometry vector fields of seventh order KdV equations are presented. Using Lie transformation seventh order CDG equation is reduced into ordinary
differential equations. These ODEs are solved by power series method to obtain exact solution. The convergence of the power series is also discussed.
On the geometric mean of the values of positive multiplicative arithmetical functions
Authors: Hassani Mehdi , Esfandiari Mohammadreza
Published: October 2022

In this paper we obtain asymptotic expansion for the geometric mean of the
values of positive strongly multiplicative function $f$ satisfying
$f(p)=\alpha(d)\,p^d+O(p^{d-\delta})$ for any prime $p$ with $d$ real and
$\alpha(d),\delta>0$.
A family of non-Volterra quadratic operators corresponding to permutations
Authors: Jamilov U. U.
Published: October 2022

In the present paper we consider a family of non-Volterra quadratic
stochastic operators depending on a parameter $\alpha$ and study their
trajectory behaviors. We find all fixed points for a non-Volterra quadratic
stochastic operator on a finite-dimensional simplex. We construct some Lyapunov
functions. A complete description of the set of limit points is given, and we
show that such operators have the ergodic property.
Effectiveness of Skill Development Programmes under DDUGKY Scheme in Kancheepuram District
Authors: M. J Deepa
Published: October 2022

As India moves undeviating towards becoming a global knowledge economy, it must meet the rising hope of its youth. Skill development has a pivotal role in this highly competitive world in order to cater to the aspirations of its young population. The objective of this article focuses on the skill development programmes under the Deen Dayal Upadhyaya Grameen Kaushalya Yojana (DDU-GKY) scheme and the various factors affecting skill development programmes and employability and finally to conclude whether DDU-GKY scheme is effective in Kancheepuram district. The data for the research was collected from the PIAs in Kancheepuram District. The total population of the study is 1856, out of which 154 sample respondents were chosen using simple random sampling. The statistical tools used were Kruskal Wallis test, One way ANOVA, Chi Square test, Mann Whitney U test and One sample t test. The major findings of the study were Skill mismatch and mobilizations have serious impact on the skill development programmes under DDU-GKY scheme, followed by infrastructure. Also domain knowledge and communication has found to have major importance on employability of the respondents. Based on the analysis, Mobilization has a very serious impact on the effectiveness of the scheme. Present study brings into light that; even though there is a good implementation of the scheme in the Kancheepuram district, they are not up to the expectations in certain points. There is room for further improvement in terms of mobilization and resultant placement.
Nhận xét các trường hợp cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ sản Trung ương
Authors: Phạm Huy Hiền Hào , Vũ Đình Tuấn , Nguyễn Quang Minh
Published: October 2022

Mục tiêu: Mô tả đặc điểm lâm sàng và cận lâm sàng của bệnh nhân cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ sản Trung ương.

Đối tượng và phương pháp nghiên cứu: Nghiên cứu hồi cứu trên 51 bệnh nhân bệnh nhân được cắt tử cung hoàn toàn sau LEEP tại Bệnh viện Phụ Sản Trung ương, từ tháng 1 năm 2017 đến tháng 12 năm 2020.

Kết quả: Xét nghiệm tế bào cổ tử cung bình thường và ASCUS, LSIIL có 95,65% tổn thương mô bệnh học từ CIN-II trở lên, kết quả sinh thiết chỉ phát hiện ra 19,6% trường hợp CIN-III và 3,92 ung thư cổ tử cung. Trong khi đó, khi làm LEEP phát hiện 64,92% ung thư cổ tử cung (19,6 CIN-III, 45,06 CIS và 19,6% ung thư xâm nhập). Trên bệnh phẩm cắt tử cung, có 3,92% CIN-III, 27,45% ung thư cổ tử cung (13,73% CIS, 1,96% AIS, 11,76% ung thư cổ tử cung xâm nhập).

Kết luận: Xét nghiệm tế bào cổ tử cung trong những trường hợp tế bào bình thường, ASCUS và LSIL không tương ứng với tổn thương mô bệnh học; LEEP phát hiện tổn thương ung thư cổ tử cung cao hơn so với sinh thiết; tỷ lệ tổn thương nặng trên bệnh phẩm cắt tử cung thấp, nhưng tổn thương mức độ càng cao thì còn tồn tại sau điều trị LEEP càng tăng.
Ứng dụng kỹ thuật array CGH trong chẩn đoán trước sinh một số bất thường nhiễm sắc thể tại Bệnh viện Phụ sản Hà Nội
Authors: Đinh Thúy Linh , Hoàng Hải Yến , Phạm Thế Vương , Trần Thị Minh Thu , Nguyễn Đức Nghĩa , Nguyễn Tài Đức , Nguyễn Duy Ánh
Published: October 2022

Trong chẩn đoán trước sinh các bất thường nhiễm sắc thể (NST), kỹ thuật nuôi cấy tế bào ối hiện vẫn là tiêu chuẩn vàng. Tuy nhiên, chỉ phát hiện được các bất thường với kích thước > 5 Mb (trên 5 triệu cặp Base). Kỹ thuật array CGH (Microarray-based comparative genomic hybridization) có khả năng đánh giá trên toàn bộ 24 NST giúp phát hiện các bất thường mất cân bằng của NST bao gồm các trường hợp lệch bội, mất hoặc nhân đoạn của NST. Hơn nữa, kỹ thuật array CGH cho phép phát hiện các bất thường của NST ngay cả khi không có định hướng trong chẩn đoán.

Mục tiêu: Xác định tỷ lệ bất thường một số nhiễm sắc thể qua kỹ thuật array CGH tại Bệnh viện Phụ sản Hà Nội.

Đối tượng, phương pháp nghiên cứu: 306 thai phụ có tuổi thai 17 - 28 tuần có chỉ định chọc hút nước ối tại Bệnh viện Phụ sản Hà Nội từ 10/2020 - 09/2021, mẫu nước ối được thực hiện đồng thời 2 kỹ thuật: array CGH và nuôi cấy tế bào ối.

Kết quả: Kỹ thuật karyotype phát hiện được 35/306 (11,4%) bất thường nhiễm sắc thể, trong khi đó array CGH phát hiện được 51/306 (16,7%). Array CGH phát hiện 25 trường hợp bất thường lệch bội, tương đương karyotype. Với các bất thường mất đoạn/nhân đoạn lớn, kỹ thuật array phát hiện được 9 trường hợp, trong khi đó karyotype phát hiện được 8 trường hợp; với các mất đoạn/nhân đoạn nhỏ, array CGH phát hiện được 16 trường hợp trong khi karyotype chỉ phát hiện được 1 trường hợp.

Kết luận: Array CGH là xét nghiệm có độ chính xác cao, phát hiện được các trường hợp bất thường cấu trúc nhiễm sắc thể ở mức độ mất đoạn/nhân đoạn nhỏ mà kỹ thuật karyotype không phát hiện được.
Đặc điểm lâm sàng, cận lâm sàng thai phụ nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt đới Trung ương
Authors: Trần Danh Cường , Đặng Công Việt , Lê Chí Quang , Đặng Quang Hùng , Nguyễn Thị Thu Hà , Nguyễn Quốc Khánh
Published: October 2022

Đặt vấn đề: Tổ chức Y tế thế giới đã công bố đại dịch toàn cầu do coronavirus 2019 (COVID-19) vào tháng 3 năm 2020. Kể từ đó, dịch bệnh đã phát triển nhanh chóng và lan rộng ra khắp thế giới, virus xâm nhập vào tất cả các đối tượng, mọi độ tuổi, kể cả phụ nữ có thai. Chẩn đoán, xử trí và tiên lượng thai phụ nhiễm SARS-CoV-2 có ý nghĩa quan trọng. Mục tiêu: Mô tả đặc điểm lâm sàng, cận lâm sàng của các thai phụ nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt Đới Trung ương.

Đối tượng: Những thai phụ nhập viện và được chẩn đoán nhiễm SARS-CoV-2 tại Bệnh viện Phụ sản Trung ương và Bệnh viện Nhiệt Đới Trung ương từ tháng 12/2021 đến tháng 2/2022.

Phương pháp: Nghiên cứu mô tả tiến cứu.

Kết quả: Tuổi trung bình của thai phụ trong nghiên cứu là 30,65 ± 6,00; trong đó nhóm tuổi 20 - 34 chiếm tỷ lệ cao nhất (71,67%). Tuổi thai trung bình trong nghiên cứu là 31,97 ± 6,98 tuần. Đa số (85%) các thai phụ nhiễm SARS-CoV-2 trong nghiên cứu chưa được tiêm vaccin. Triệu chứng nhiễm SARS-CoV-2 thường gặp nhất ở thai phụ trong nghiên cứu là ho (76,67%), sốt (55%) và khó thở (36,67%). Đa số thai phụ nhiễm SARS-CoV-2 trong nghiên cứu có tăng giá trị CRP (78,9%) và tăng D-Dimer (94,82%) tại thời điểm nhập viện.

Kết luận: Các thai phụ nhiễm SARS-CoV-2 trong nghiên cứu có ít nhất một triệu chứng lâm sàng: ho, sốt, khó thở. Các thai phụ nhiễm SARS-CoV-2 có xu hướng tăng giá trị CRP và D-Dimer máu.
Thoát vị hoành bẩm sinh, cập nhật vấn đề chẩn đoán, điều trị trước và sau sinh
Authors: Lê Minh Trác
Published: October 2022

Thoát vị hoành là bệnh lý mất tính liên tục trong quá trình phát triển của cơ hoành qua đó các tạng trong phúc mạc di chuyển lên khoang lồng ngực qua các lỗ của cơ hoành, đây là dị tật bẩm sinh gặp khoảng 2,5 - 3,5 ca trên 10.000 trẻ sinh sống. Trẻ mắc thoát vị hoành bẩm sinh thường kèm với suy hô hấp ở nhiều mức độ khác nhau vì thiểu sản phổi và tăng áp phổi, tỉ lệ tử vong từ 20% - 60% dù là ở các quốc gia phát triển. Mục tiêu: 1) Mô tả cơ chế bệnh sinh và các phương pháp chẩn đoán thoát vị hoành; 2) Cập nhật những bằng chứng can thiệp trước, sau sinh và một số yếu tố liên quan.
Đánh giá kết quả điều trị chảy máu sau đẻ bằng phương pháp can thiệp nội mạch
Authors: Phan Hoàng Giang , Vũ Đức Thành , Trần Văn Giang , Trương Hồng Đức , Nguyễn Xuân Hiền , Vũ Đăng Lưu
Published: October 2022

Mục tiêu: Đánh giá tính hiệu quả của phương pháp can thiệp nội mạch trong điều trị chảy máu sau đẻ.

Đối tượng và phương pháp nghiên cứu: Kết quả được phân tích ở 30 bệnh nhân chảy máu sau đẻ được điều trị bằng phương pháp can thiệp nội mạch từ tháng 1 năm 2019 đến tháng 11 năm 2021. Thành công lâm sàng được định nghĩa là ngừng chảy máu sau lần can thiệp đầu tiên mà không cần can thiệp hay phẫu thuật lại.

Kết quả: Trong số 30 bệnh nhân có 19 bệnh nhân mổ lấy thai (63,3%), 11 bệnh nhân đẻ thường (37,7%), số lượng khối hồng cầu truyền trung bình là 3,88 đơn vị. Tỷ lệ thành công về mặt kỹ thuật là 100%, tỷ lệ thành công trên lâm sàng 83,3% (25 trên 30). Có 5 trường hợp thất bại, 1 trường hợp can thiệp nội mạch lại (3,3%), 2 trường hợp phải phẫu thuật lại (6,7%), 2 trường hợp tử vong (6,7%). Kiểm soát được chảy máu sau can thiệp là 93,3% (28 trên 30). Thời gian hết ra máu âm đạo trung bình là 4,4 ngày, thời gian nằm viện trung bình là 8,1 ngày.

Kết luận: Can thiệp nội mạch cho thấy an toàn và hiệu quả cao trong điều trị chảy máu sau đẻ. Do đó, đây là một biện pháp hỗ trợ hoặc thay thế cho cắt tử cung cầm máu trong điều trị chảy máu sau đẻ.
Xử trí bảo tồn thành công trường hợp vỡ tử cung tự phát ở tuổi thai 18 tuần
Authors: Đinh Thị Hiền Lê , Nguyễn Thị Hồng Nhung , Cao Thị Thúy Hà , Nguyễn Hữu Công , Dương Việt Bắc
Published: October 2022

Vỡ tử cung sinh non là một biến chứng rất hiếm của thai kỳ mà hầu hết các trường hợp đều xảy ra khi có tiền sử phẫu thuật tử cung. Tỷ lệ mắc bệnh ở bà mẹ và trẻ sơ sinh là đáng kể. Thông thường, thai kỳ phải được chấm dứt để cứu cả mẹ và trẻ sơ sinh, nếu có thể.

Chúng tôi báo cáo trường hợp một bệnh nhân bị vỡ tử cung trước khi chuyển dạ ở tuổi thai 18 tuần phức tạp. Phẫu thuật cấp cứu khẩn cấp với xử trí bảo tồn tử cung và tiếp tục theo dõi thai kỳ đến 32 tuần 3 ngày.

Trong một số rất hiếm trường hợp vỡ tử cung khi tuổi thai nhỏ, xử trí bảo tồn dường như là một giải pháp có thể chấp nhận được để kéo dài tuổi thai để hạn chế các biến chứng liên quan đến sinh non.
Trends in Area, Production and Productivity of Wheat Cultivation at Global Level
Authors: R Ritu
Published: October 2022

The present study was conducted on trend analysis of wheat production in India and Afghanistan. The study was based on secondary data collected from various published and unpublished sources in India, Afghanistan and at the global level from 2000-19. The present study was undertaken to know the growth rate in area, production and productivity of wheat in India and Afghanistan which were found positive during 2019-20. The findings of this study have far-reaching implications that will have a significant impact on the planning, execution, and design of appropriate methodologies in order to achieve meaningful and fruitful demonstration results not only for wheat growers, but also for other sectors that essentially provide feedback to agencies involved in various demonstration programmes. It explicitly emphasises the relevance of frontline demonstration in increasing farmer production, returns and reduce the extension and technology gap.
KETERLIBATAN PEMERINTAH DESA DALAM MENDUKUNG PENINGKATAN KUALITAS PENDIDIKAN DI DESA POLEWALI KECAMATAN SINJAI SELATAN
Authors: Hasdinawati  , Syamsuddin  , Salman
Published: October 2022

Penelitian ini bertujuan untuk mengetahui keterlibatan pemerintah desa dalam mendukung peningkatan kualitas pendidikan di Desa Polewali Kecamatan Sinjai Selatan Kabupaten Sinjai. Tipe Penelitian ini adalah Kualitatif. teknik pengumpulan data yaitu observasi, wawancara dan dokumentasi.informan penelitian ini adalah Kepala Desa Polewali, Sekertaris Desa Polewali, Staff Pemerintah Desa Polewali, Ketua BPD Desa Polewali dan Masyarakat. Teknik analisis data dilakukan dengan cara pengumpulan data, reduksi data,penyajian data dan penarikan kesimpulan.

            Berdasarkan hasil penelitian, penulis berkesimpulan bahwa keterlibatan pemerintah desa dalam mendukung peningkatan kualitas pendidikan di Desa Polewali sudah terlaksana meskipun belum sepenuhnya maksimal baik dalam akses pendidikan, sarana dan prasarana pendidikan maupun beban biaya pendidikan Keterlibatan pemerintah desa dalam mendukung kualitas pendidikan di Desa Polewali dalam akses pendidikan belum sepenuhnya terlaksana secara maksimal, hal ini dibuktikan dengan masih banyaknya masyarakat yang putus sekolah diakibatkan oleh akses jalan dengan kondisi rusak ditambah jarak tempuh dari rumah kesekolah juga lumayan jauh. Adapun penyelenggaraan dan pembangunan sarana dan prasarana pendidikan dengan penyelengaraan paud, TK/TPA Madrasah non formal dan pembangunan WC SDN 244 Jenna, talud SDN 244 jenna dan TBM sebesar ini menunjukkan bahwa keterlibatan pemerintah desa dalam meningkatkan kualitas pendidikan di Desa Polewali secara sarana dan prasarana telah terlaksana.Demikian halnya dengan keterlibatan pemerintah desa dalam mendukung peningkatan kualitas pendidikan di desa polewali dalam membantu beban biaya pendidikan sudah terlaksana hal ini dibuktikan dengan membantu beban biaya pendidikan masyarakat hal ini dibuktikan dengan beberapa bantuan yang telah di berikan kepada masyarakat salahsatu bantuannya yaitu berupa pembagian ikan air tawar (ikan nila) secara gratis untuk dibudidayakan dalam rangka peningkatan pendapatan masyarakat dan mengurangi beban biaya pendidikan.