bluuebunny/crossref_metadata_2025 huggingface dataset:
Relevance of resident memory T (TRM) cells in antitumor immunity and response to cancer immunotherapy
Authors: Mami-Chouaib Fathia , Damei Isabelle , Corgnac Stéphanie
Published: November 2024

CD8+CD103+ TRM cells accumulate in human lung tumors and are associated with a favorable prognosis and response to immune checkpoint blockade (ICB). However, a large fraction of human solid tumors is only weakly infiltrated by TRM, and the reason of this TRM desert is not explained. Defining the molecular signals that give rise and maintain TRM cells within the tumor microenvironment (TME) and the mechanisms that potentiate antitumor TRM functions are important challenges. Data obtained in pre-clinical mouse tumor models demonstrate that knocking-out CD103 impairs antitumor T-cell immunity and response to ICB and therapeutic peptide vaccine. Immunization of melanoma-bearing mice with the cancer vaccine results in a dramatic decrease in the percentage of CD103+ TRM cells among CD8+ tumor-infiltrating T lymphocytes (TIL). Algorithm analyses applied to spectral cytometry data of TIL show that upon activation with the peptide vaccine a TRM subset gives rise to tumor-specific effector T cells. The mechanisms associated with the decrease in CD103 expression on CD8+ TIL and lead to a TRM differentiation shift will be presented as well as the role of TGF-beta in CD8+ TRM formation and persistence. Our data demonstrate that tumor CD8+CD103+ TRM are capable of mounting a potent antitumor immunity, and suggest that a fine balance between diverse signals in the tumor ecosystem is required to induce their differentiation and thereby optimize response to immunotherapy.
Low-dose mIL-2/CD25 alters the composition and reduces the frequency of autoreactive T cell subsets in inflamed islets from NOD mice
Authors: Põder Janika , Malek Thomas
Published: November 2024

To enhance Treg-targeted IL-2-dependent therapy for autoimmunity, we developed a fusion protein of mouse (m) IL-2 linked to CD25. mIL-2/CD25 has a long half-life, acts as a selective agonist for the high-affinity IL-2R, at a low dose (LD) preferentially targets Tregs and is more effective than IL-2 at limiting autoimmunity in models of type 1 diabetes (T1D) and lupus. To explore the mechanism for T1D suppression, we assessed the effect of LD-mIL-2/CD25 on the global islet immune landscape in female NOD mice with scRNA-seq and flow cytometry. In the pancreas, LD mIL-2/CD25 reduced CD4+Foxp3- and CD8+ T cells, especially effector-phenotypic and highly proliferating CD8+ T cells, but increased Tregs, particularly ST2+ eTregs, and ILC2s. In addition, a CD8+ T cell subset expressing an exhaustion-related gene signature was identified. TCR repertoire analysis revealed multiple dominant clonotypes associated with effector-phenotypic CD4+Foxp3- and CD8+ T cells in untreated diseased NOD mice, which were reduced by LD mIL-2/CD25. Consistent with this finding, peptide-MHC tetramer staining showed that LD mIL-2/CD25 reduced autoantigen-reactive CD4+ and CD8+ T cells in islets. Our findings suggest that Tregs regulate autoimmunity in NOD mice in part by limiting the expansion of autoreactive T cells. Moreover, mIL-2/CD25 may also function through Tregs to promote exhaustion of CD8+ T cells, and this may reflect an active mechanism by which Tregs regulate some autoreactive T cells.
Immature Dendritic Cell therapy in early life promotes peripheral tolerance of autoreactive T cells delaying onset and incidence of T1D.
Authors: Orozco Figueroa Stephanie , Reynolds Hayley , Bettini Matt
Published: November 2024

Type 1 Diabetes (T1D) is a complex autoimmune disease characterized by T cells mediating the destruction of insulin-secreting ß-cells in the pancreatic islets of Langerhans. Evidence suggests both central and peripheral T cell tolerance mechanisms fail in the development of T1D. The non-obese diabetic (NOD) mouse model is a spontaneous model of T1D that shares many characteristics to human disease. Studies in adult pre-diabetic NOD mice using immature dendritic cells (iDCs) as therapy result in delaying disease onset and, in some cases, lowering disease incidence. The mechanism by which DCs confer protection to diabetes is largely unknown, but is thought to occur in an antigen-independent manner; driven by tolerogenic cytokines. Broadly, DCs are also known to induce peripheral tolerance by activation induced cell death, anergy and inducing the development of regulatory T cells (iTregs). In the past twenty years, the existence of a neonatal window of tolerance has highlighted the importance of tolerogenic mechanisms to prevent autoimmunity. Therefore, we hypothesized DC therapy administered at a neonatal stage in NOD mice will result in protection to the development of T1D. Our studies treating NOD mice with iDCs from an early point in life demonstrate that donor iDCs migrate to the pancreatic draining lymph nodes, modulate the microenvironment diminishing islet T cell infiltration and T cell activation, culminating in a significant delay in the onset and incidence of T1D.
Trabectedin modulates the glioma innate and adaptive immune microenvironment in vivo
Authors: Nazzaro Matthew , Rajappa Prajwal , Currier Mark , Glaspell Andrea , Behbehani Gregory , Cripe Timothy
Published: November 2024

Low-grade gliomas (LGG) are the most common brain tumor in adolescents and young adults. LGG are neglected in the field of research due to their low relative risk compared to high-grade glioblastoma despite their potential to malignantly transform into fatal high-grade gliomas (HGG). Therefore, there is a necessity to investigate and develop novel therapeutics to combat the progression of glioma. Malignant progression of glioma is associated with an accumulation of immunosuppressive myeloid cells that impair anti-tumor T cell function. Trabectedin is an FDA approved chemotherapy used in the treatment of soft tissue sarcoma. Beyond its chemotherapeutic properties, Trabectedin has been shown to selectively deplete monocytes and macrophages, but its role in the modulating the brain TME has not yet been investigated. Here, we utilized mass cytometry (CyTOF) to investigate the impact of Trabectedin on the glioma immune TME as well as the global immune system in the immunocompetent, transgenic RCAS/t-va murine glioma model which recapitulates the progression of low to high-grade glioma. Trabectedin significantly reduced bone-marrow derived myeloid cells in the glioma TME as well as splenic macrophages and monocytes. Further, Trabectedin increased the proportion of tumor-infiltrating T cells. In conclusion, Trabectedin immunomodulates the glioma TME in vivo and could potentially enhance the efficacy of immunotherapies by overcoming myeloid-driven immunosuppressive resistance.
Microbial experience influences B16 melanoma tumor growth
Authors: Busalacchi Marlee , Bunda Nicholas , Pullen Johnna , Groeber Hanna , Morrison Cody , Renkema Kristin
Published: November 2024

Cancer immunity research is traditionally conducted with specific pathogen-free (SPF) mice, which mimic the immune system of a human newborn. This poses a challenge for research aimed at understanding immune responses relevant to humans. We utilized a mouse model to investigate microbial experience impacts on immune population dynamics and responses. By cohousing SPF C57Bl/6 mice with pet store mice, we generated a cohoused (CoH) mouse that more accurately reflects the impact of microbial experience on the human immune system. We hypothesized that CoH mice would mount a more effective anti-tumor response when compared to SPF mice. We challenged the mice with sub-cutaneous B16 melanoma to measure both tumor growth and immune responses. Interestingly, CoH tumor grew more slowly, and tumor weights were significantly reduced when compared to SPF mice on days 7 and 10 post-injection. We investigated CD8+ T cell and monocyte/macrophage phenotypes in various tissues, including the tumors. Control of tumor growth may be related to the observed differences in CD8+ T cell activation profiles and monocyte/macrophage differentiation found in CoH mice. Collectively, our results indicate that microbial experience influences anti-tumor immunity and that cohoused mouse models may prove to have valuable translational applications for future cancer immunity research.
Modulating the epigenetic interplay in exhausted CD8 T cells for effective immunotherapy
Authors: Yousif Amir , Saadey Abbey , Lowin Ava , Castillo Chelsea , Saini Ankita , Chan Wing , Alinari Lapo , Webb Amy , Oltz Eugene , Ghoneim Hazem
Published: November 2024

Epigenetic imprinting of terminal exhaustion in chronically stimulated CD8 T cells is a major impediment to T cell immunotherapies during chronic viral infections or cancer. Foundational work establishes that exhausted CD8 T cells (TEX) acquire heritable DNA methylation programs that silence genes critical for T cell stemness/function, restraining responses to immune checkpoint blockade (ICB). However, the molecular interplay between histone post-translational modifications and de novo DNA methylation during the progression to terminal exhaustion remains poorly understood. To address this, we employ our novel in vitro model of human T cell dysfunction and the chronic LCMV infection model to reveal a temporal linkage in which progressive histone changes prime the acquisition of de novo DNA methylation in TEX. Via a selective inhibitor or CRISPR editing in human CD8 T cells, we identify specific histone-modifying enzymes as key epigenetic drivers that orchestrate DNA methylation programming during terminal exhaustion. Notably, targeting the histone-modifying enzymes reinvigorated effector function and cytotoxicity in dysfunctional human T cells. Moreover, combined epigenetic therapy and anti-PD-L1 enhanced the ICB responses of both progenitor and cytolytic TEX during chronic viral infection. Collectively, our findings reveal novel epigenetic drivers of CD8 T cell dysfunction, supporting therapeutic potential of targeting the epigenetic crosstalk underpinning T cell exhaustion.
Crispr-Cas9 screen identifies potential novel regulators of CD8+ T cell dysfunction.
Authors: Holcomb Erin , Jiang Long , Tate Akshay , Pearson Ashley , Wang Zhuwen , Elaimy Ameer , James Jadyn , Huber Amanda , Green Michael
Published: November 2024

CD8+ T cells directly target and kill cancer cells and are required for effective antitumor immunity. However, CD8+ T cells may become dysfunctional when exposed to chronic antigen stimulation during cancer. Dysfunction is characterized by reduced proliferation, increased expression of inhibitory receptors, and impaired effector function, yet the genetic mechanisms controlling dysfunction remain poorly understood. To address this gap, we have developed an ex vivo restimulation model that recapitulates features of CD8+ T cell dysfunction seen within the tumor microenvironment. By coupling this system with genome-wide CRISPR-Cas9 loss of function screening, we have identified eIF4G2, a non-canonical protein translation factor, which may play a novel role in the progression of CD8+ T cells to a dysfunctional state. Deletion of eIF4G2 restored CD8+ T cell survival and proliferation during chronic restimulation conditions in vitro. Transcriptomic and flow cytometric analyses revealed that eIF4G2 controls expression of genes contributing to oxidative stress and a dysfunctional phenotype in vitro. Future studies will focus on characterizing the mechanistic and functional roles of this protein translation factor in vivo, as well as translating this model to primary human CD8+ T cells. In summary, we have uncovered eIF4G2 as a novel potential regulator of CD8+ T cell dysfunction and targeting eIF4G2 may improve antitumor immunity and immunotherapy efficacy.
The regulatory role of the transcription factor HEB in Myc-overexpressing T-cell Acute Lymphoblastic Leukemia
Authors: Tousinas Georgios , Lewis Cody , Tracy Melissa , Arnovitz Stephen , Emmanuel Akinola Olumide , Khazaie Khashayarsha , Bergsagel Leif , Gounari Fotini
Published: November 2024

Acute Lymphoblastic Leukemia (ALL) is the most common cancer among children in the US. Approximately 5% of T-cell ALL (T-ALL) cases involve acquired focal chromosomal duplications encompassing a region downstream of the Myc oncogene, characterized as a Notch1-dependent Myc enhancer (N‑Me). The lack of mouse models with such N‑Me duplications has limited our ability to study the molecular mechanisms of the disease. We found that mouse leukemias resulting from conditional aberrant activation of β-catenin with simultaneous ablation of the transcription factor HEB in CD4+CD8+ double positive thymocytes bear N‑Me duplications. The ablation of HEB fundamentally changes the mechanism of leukemogenesis induced by the simple activation of β-catenin, which is characterized by TCRα-Myc/Pvt1 reciprocal translocations. Based on the finding that HEB binds N-Me at a site that overlaps Notch-1 binding and the conserved motifs of other regulators, we propose that HEB has a central regulatory role in the oncogenic process. We hypothesize that HEB binding regulates the access of transcription regulators to N-Me, rationing Myc expression. Loss of HEB in the context of activated β-catenin enables access of these regulators to N-Me, and triggers super-enhancer properties and changes in chromatin conformation, leading to excessive Myc expression and leukemogenesis. Ultimately, the proposed study aspires to determine the role of HEB in the initiation, progression, and treatment of human T-ALL
High throughput assay for detection of antibodies targeting multiple subunit membrane proteins of human neuron synapse in vitro
Authors: Li Quanzhen , Yang Shuwei , Muellner Julius , Lin Dan , Feng Feifei , Xie XiaoXia , Mai Zihao
Published: November 2024

Synapses are essential to the transmission of nervous impulses from one neuron to another. There are more than 1000 multiple-subunit membrane proteins in synapse. Some of them are drug targets and/or autoantigens. Most autoantibodies against synapse membrane proteins recognize conformation of extracellular domains. Based on known structures and predicted structures by chatGPT, we used N-methyl-D-aspartate (NMDA)receptor as model for quantitative assay in vitro. In order to keep the native form of the extracellular domains of NMDA receptor, we modified some amino acids in transmembrane domains and intracellular domains, establishing a stable cell line expressing cluster NMDA receptor used to sensitively detect autoantibody in human serum and cerebrospinal fluid. We also prepared stable NMDA receptor tetramer complex from the stable cell line and prepared monoclonal antibodies (mAB) against subunit GluN1 and GluN2. Based on tetramer complex and mABs, we established a method to quantitatively detect antibodies from clinical samples.
Selective small-molecule PKC-theta inhibitors effectively block TCR-mediated activation of naïve peripheral blood and tissue resident memory T cells
Authors: Whitener Robert , Harden Jamie , Hofland Hans , Patel Jeegar
Published: November 2024

Immune mediated inflammatory diseases constitute a diverse set of illnesses in which an aberrant immune response damages self-tissue. While progress has been made in treating these conditions, there continues to be room for improvement. Patients diagnosed with T cell mediated disorders (TMDs) such as atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease often respond well to broadly-acting immunosuppressive drugs, most of which come with significant side-effects, further highlighting the need for more targeted approaches. Compared to other family members, the protein kinase c - theta isoform (PKCt) expression is highly restricted to T cells, is critical to downstream signaling of the TCR complex, and represents an attractive therapeutic target for TMDs. Here, we report results from novel small molecule inhibitors (SMIs) which are highly specific for PKCt. In an in-vitro model of TCR-mediated activation of human PBMCs, our SMIs potently prevented activation of both CD4 and CD8 T cells without affecting cellular viability. Similarly, in in-vitro models of whole primary human skin biopsies under Th1, Th2, and Th17 inducing conditions, tissue resident memory T cells failed to activate and release pro-inflammatory cytokines after PKCt inhibition. Taken together, we have identified multiple novel SMIs of PKCt which are highly potent and highly selective, representing a potential new therapeutic strategy for patients with T-cell mediated inflammatory disease.
Variation in the single cell epigenomic and transcriptomic profiles in response to seasonal influenza vaccination: A comparison between healthy young and older adults
Authors: Ravichandran Sathyabaarathi , Ucar Duygu , Marches Radu , Chaussabel Damien , A. Kuchel George , Banchereau Jacques
Published: November 2024

Older adults exhibit reduced responses to influenza vaccines than young adults. However, the underlying immunological features responsible for this age-related decline remains limited. In our study, we recruited 35 older (>65 years) and 7 young (26-39 years) adults, administered standard or high-dose seasonal influenza vaccines in 2017 and 2018. We assessed antibody responses to H1N1, H3N2, and Influenza B strains using a hemagglutination inhibition(HAI) assay at baseline and on Day35 post-vaccination. We then performed scRNAseq and snATACseq on 10 healthy older and 7 young adults on Day1, Day7, and Day35 to probe innate and adaptive immune responses. Post-vaccination, significant increases in HAI antibody titers were observed for all strains in both age groups, albeit with variability in responses among healthy older adults. Analyses of scRNAseq and snATACseq data revealed distinct innate and adaptive immune signatures in healthy young and older adults, reflecting age-related differences in influenza vaccine responses. Previously, we identified a unique baseline immune phenotype associated to weak Prevnar™ responses in older adults, suggesting it might serve as an aging signature. This baseline phenotype feature is characterized by increased expression of CYTOX genes, increased CD16+ NK and TH17 cell frequency, and decreased TH1 cell frequency. We further assessed the relevance of these characteristics in the context of age-related influenza vaccine responses.
Ubiquitination of Hemocyanin Mediated by a Mitochondrial E3 Ubiquitin Ligase Regulates Immune Response in Penaeus vannamei
Authors: Zhang Xiaojun , Zhang Zhaoxue , Zheng Zhihong , Yao Defu , Zhao Yongzhen , Liu Qingyun , Lin Zhongyang , Zhang Yueling
Published: November 2024

Ubiquitination is a critical posttranslational modification that regulates host immune responses to pathogens. In this study, we investigated the ubiquitination of hemocyanin (PvHMC [Penaeus vannamei hemocyanin]) mediated by the mitochondrial E3 ubiquitin ligase (PvMulan) in shrimp Penaeus vannamei. We characterized distinct ubiquitination patterns of PvHMC in response to different pathogen challenges, both in vitro and in vivo. Specifically, we found that Vibrio parahaemolyticus infection led to an increase in PvMulan, which resulted in K48-linked ubiquitination and subsequent proteasomal degradation of PvHMC. In contrast, PvMulan primarily enhanced the SUMOylation of PvHMC, bolstering its immune functions against white spot syndrome virus challenges. Inhibition of PvMulan-mediated PvHMC ubiquitination significantly affected the proliferation of V. parahaemolyticus and the survival rate of infected shrimps. This study sheds light on the role of hemocyanin ubiquitination in immune regulation, illustrating its dual function in response to distinct pathogens.
Disability research in African Network for Evidence-to-Action in Disability affiliated countries
Authors: Kahonde Callista K. , Mji Gubela
Published: November 2024

Background: The African Network for Evidence-to-Action in Disability (AfriNEAD) is a leading role player in Africa promoting evidence-informed policies and practices for disability inclusion on the continent. This article presents findings of a desktop review that explored trends of disability research in the AfriNEAD affiliated countries.Objectives: The review explored trends of research that has been published by members of the disability research community who are contributing to AfriNEAD Conferences.Method: A Google scholar search was conducted using names of researchers who presented articles at the first six AfriNEAD Conferences, recording peer-reviewed journal publications by each author according to the eight AfriNEAD research focus areas. This was followed by a hand search of all articles published in the African Journal of Disability from AfriNEAD affiliated countries.Results: There is an exponential increase in the number of peer reviewed journal publications from AfriNEAD affiliated countries over the last two decades. Collaborations are common among authors within the same African country. International collaborations are common among authors from Africa with authors from the Global North.Conclusion: African researchers need to network and collaborate more across Africa, to promote disability research in countries where research is scarce and to focus more on research areas that are not receiving attention.Contribution: The desktop exploration is a first step for AfriNEAD to get a baseline understanding of published disability research in the countries affiliated to the network. Further research is required to understand these trends and to provide evidence necessary to address the identified gaps.
A sociotheological interpretation of Genesis 50:25 in a Zimbabwean context
Authors: Mwandayi Canisius
Published: November 2024

Migration to foreign lands is as old as the biblical stories of Abraham leaving his native land, Ur of the Chaldeans to go to a land that God was to show him. Concomitant with migration, however, is the possibility of death in the new habitat and oftentimes important decisions are made on how to fund the funerals. In the case of Zimbabwean diasporas, this has seen the rise in popularity of funeral insurance companies such as Diaspora Insurance and the GoFundMe initiatives. While the issue of funding funerals appears to be the primary thing that people are seized with when a funeral strikes, the most salient aspects would be issues of religion and culture. This article endeavours to show how, despite the challenging economic environment, the costly repatriation of dead relatives can best be appreciated through a sociotheological interpretation of Genesis 50:25. In other words, Genesis 50:25 can be used as a mirror to understand the value people place on issues of religion and culture. It is thus my argument that the religious background of the actors as well as their socio-cultural setting are critical in making important decisions regarding the place of interment as well as influencing the funding logistics to take the corpse to the desired resting place.Contribution: As the death toll continues to rise of diasporas who would have gone offshore in search of a reprieve from the economic challenges that have become almost an indelible mark of Zimbabwe, issues around the values of traditional religion and culture continue to come to the fore. This research adds a voice to the ongoing religious and political dialogue in Zimbabwe in so far as it seeks to explain and understand the underlying reasons behind the costly repatriation of deceased relatives through a sociotheological reading of Genesis 50:25.
Evaluating factors influencing youth participation in agricultural enterprises: Implications for food security and agribusiness
Authors: Giwu Ongama , Mdoda Lelethu , Ntlanga Samuel S. , Loki Olwethu
Published: November 2024

Background: Agriculture is crucial for economic growth, yet youth engagement in agricultural enterprises is declining due to concerns related to perceived profitability, resource access, and social stigmas. Understanding these determinants is vital for fostering youth interest in agriculture and promoting sustainable rural development and food security.Aim: This study examines the factors affecting youth engagement in agricultural enterprises in Umzimvubu Local Municipality, South Africa, and their implications for food security and agribusiness.Setting: Addressing youth unemployment and enhancing agriculture’s contribution to gross domestic product (GDP) require understanding barriers to youth participation. This study was conducted in Umzimvubu Local Municipality, South Africa.Methods: A structured questionnaire was administered to 210 youths through stratified random sampling. Descriptive statistics and a univariate probit regression model were used for analysis.Results: Findings indicate male dominance in agriculture, with educational background positively correlating with participation. Single youths showed greater interest than married counterparts. Challenges like land availability and a lack of financial support hinder engagement. Significant determinants include age, education, farming skills, social group membership, and household revenue, while factors like household size, gender, and limited access to credit negatively impact willingness to participate.Conclusion: Addressing financial barriers through improved access to loans is essential to enhance youth involvement. Policies should cater to youth-specific traits and environmental challenges to build a resilient agricultural sector driven by young innovators.Contribution: The study emphasises the need for a comprehensive policy framework collaboratively developed by the government, the Department of Agriculture, and non-governmental organisations.
Prevalence of Low Bone Mineral Density and Associated Risk Factors among Patients with Systemic Lupus Erythematosus: A Retrospective Observational Study
Authors: Aloudah Norah , Alsuwaidan Salem , Malhis Alaa , Alanazi Deemah , Alghamdi Taghreed , Alsaqqa Mashael , Al Ghanim Nayef
Published: November 2024

Objectives:

The objective of this study was to determine the prevalence of low bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) and evaluate potential risk factors.

Methods:

A retrospective observational study of 144 patients with SLE who had at least one BMD test through dual-energy X-ray absorptiometry (DEXA) scan was conducted at King Saud Medical City and Prince Sultan Military Medical City in Riyadh, Saudi Arabia, between April 19, 2022, and April 18, 2023. Multivariate linear regression analyses were performed to determine the risk factors for low BMD.

Results:

The study included 144 SLE patients. The prevalence of low BMD was 53.3%. Low bone mass prevalence (defined as a Z-score <−2.0 in premenopausal women and men younger than 50 years), osteopenia, and osteoporosis were 29.9%, 13.2%, and 10.4%, respectively. There were 5.6% patients with fragility fractures, 75% vertebral fractures, and 25% peripheral fractures. Older age, postmenopausal status, arthritis, and high cumulative glucocorticoid dose were associated with low BMD. Immunosuppressive agents are protected against low BMD. In multivariate linear regression analyses, postmenopausal status remained a risk factor for low BMD.

Conclusions:

Patients with SLE are at a high risk of having low BMD. The majority exhibit low bone mass rather than osteopenia or osteoporosis, with the most common fractures occurring in the vertebrae. Notably, postmenopausal status represents a major risk factor for low BMD in patients with SLE.
Assessment of Salivary Flow Rate and Salivary PH in Subjects with Smoked, Smokeless, and Combined form of Tobacco Habits (Epidemiological-Based Study)
Authors: Sethi Kavleen K. , Srivastava Sunita , Sinha Abhishek , Mishra Anuj , Iqbal Haider , Srivastava Tanmay
Published: November 2024

Background:

Saliva is a complicated secretion of the oral cavity and is the first fluid to be exposed to the toxic components of tobacco products. Saliva undergoes structural and functional changes due to tobacco use throughout time. As a result, measurements of salivary flow rate (SFR) and pH were made in subjects with habit of smokeless, smoked, and combined forms of tobacco habits.

Methodology:

The study was conducted in a dental institute. Subjects with the habit of smoking, smokeless, and combined forms of habits were included in this study. Schirmer tear strips and pH strips were used to assess SFR and pH.

Results:

On comparison of SFR between control and habit groups, a statistically significant reduction of SFR was observed in habit groups. On comparison of salivary pH, a statistically significant decrease was observed in smokeless and smoked form of tobacco usage group when compared with the control group. Duration, frequency, and exposure also alter SFR and pH. Significant gradual decline in resting salivary flow rate levels with increase in duration of tobacco usage and increase in number of packs consumed/day was observed.

Conclusion:

The role of salivary flow and pH is to maintain oral and dental health. Based on the results of this study, we concluded that long-term habits, whether smokeless, smoking, or combined tobacco habit, significantly reduce SFR and pH. These alterations can render oral mucosa more vulnerable to various oral diseases.
Quality of Life and Healthcare Seeking Behavior among Internal Migrant Laborers in Coimbatore, India: A Community-based Analytical Cross-sectional Study
Authors: Aparnavi P , Malarkodi M , Ramanathan Sivagami , Sambandan Madhavi , Shanmugam Jeevithan , Kumar Mohan , Priya Shanmuga , Narayanan Seetharaman , Rathinamoorthy Ramesh
Published: November 2024

Background:

Globalization and urbanization have increased international and internal migration. However, migrants are still not absorbed into the local communities and remain vulnerable groups. Hence, the present study aimed to determine the quality of life (QoL) and healthcare-seeking behavior (HCSB) of internal migrant laborers in Coimbatore, Tamil Nadu.

Methodology:

An analytical cross-sectional study was conducted in the year 2023 among 321 migrant laborers residing for a minimum duration of 6 months in Coimbatore. A pre-tested questionnaire was used to collect data on socio-demography, QoL (using the WHO BREF scale), HCSB, and healthcare expenses. Ethical clearance was obtained from the institutional ethical committee. Informed written consent was obtained from the participants. Data were analyzed using SPSS version 27. Mann–Whitney U test and Kruskal–Wallis test were used to compare QoL across socio-demographics and HCSB.

Results:

The overall QoL score was 61, and those in social and environmental domains were also above 60. The QoL was higher in the environmental and social domains than in the physical and psychological domains. Females, married people, those currently living with their family, those working in the organized sector, and those in higher socio-economic status had better QoL than their counterparts. Per capita income had a positive correlation with physical, psychological, and environmental aspects of life. About 68% of those who used private sector healthcare services had catastrophic health expenditures (CHEs).

Conclusion:

The overall QoL among migrant laborers was moderate. Migrants preferring formal healthcare enjoyed better QoL. Major CHE was for delivery, and hence, the barriers to accessing free government services are to be explored.
Nutritional Guidelines for Patients with Type 1 Diabetes Mellitus and its Adherence- A Narrative Review
Authors: Kaushik Anu , Rekhi Tejmeet K. , Puri Seema , Tandon Nikhil
Published: November 2024

Nutritional guidelines are of importance in directing food choices of T1D patients. The objective is to summarise existing nutritional recommendations and examine its adherence by T1D patients. Literature was searched on dietary guidelines in T1D using electronic databases PubMed, Science Direct, Scopus, Google Scholar, in English and 29 papers were selected. As per ADA, EASD, ISPAD, and ICMR guidelines, energy recommendations for T1D are based on ideal body weight to prevent overweight and obesity. The safe amounts of carbohydrates, protein and fat includes 50–55%, 15–20% and 25–30% of total energy respectively with fiber intake recommended at 20–30 g/day. Vitamin and mineral supplementation are beneficial in the presence of deficiency. Adherence to nutritional recommendations was suboptimal but better in those who were frequently consulting a dietician. As suboptimal dietary adherence leads to poor glycaemic control, nutritional guidelines must be followed to manage T1D and prevent or delay diabetic complications.
Assessment of Correlation Between Glycaemic Variability Indices and Measures of Hypoglycaemia in Patients with Type 2 Diabetes Mellitus
Authors: Suresh Arjun , Kumar Bhargavi , Boopathy Sindhumalini , Thangavelu Saravanan
Published: November 2024

Introduction:

Diabetes mellitus is a global health burden, and India is regarded as the diabetes capital of the world. Glycaemic variability (GV) is an established risk factor for hypoglycaemia (plasma glucose concentration <70 mg/dL) and a notorious risk factor for diabetes complications. The primary aim of the study was to assess the correlation between the GV indices, HbA1c levels, and measures of hypoglycaemia in patients with type 2 DM (T2DM).

Methods:

In this cross-sectional study, continuous glucose monitoring (CGM) was done for a period of 14 days in T2DM patients (n = 50). The GV indices were determined from the readings obtained from the CGM monitor. Spearman’s rank correlation coefficient was used for correlation analyses. The area under the receiver operating characteristics (ROC) curve was used to assess the effectiveness of the various GV indices in predicting hypoglycaemia.

Results:

A total of 50 T2DM patients had a mean (SD) age of 61.84 ± 11.88 years. Among the GV indices, high blood glucose index (HBGI), average daily risk range (ADRR), and continuous overall net glycaemic action (CONGA) had a significantly positive correlation with HbA1c levels. Average episodes of nocturnal hypoglycaemia in 8 hours of night-time had a statistically significant negative correlation with the HbA1c levels (correlation coefficient: −0.301, P = 0.034). In addition, low blood glucose index (LBGI) was found to be the best predictor for the risk of hypoglycaemia in 24 hours and nocturnal hypoglycaemia.

Conclusion:

Various GV indices are associated with HbA1c levels and are better predictors of hypoglycaemia.
О качественном анализе одного класса вольтеровских квадратично-стохастических операторов с непрерывным временем
Authors: Rasulov Xaydar Raupovich
Published: November 2024

В данной статье изучен непрерывный аналог одного класса вольтеровских квадратично-стохастических операторов с непрерывным временем. Проведен качественный анализ операторов, найдены численные и аналитические решения. Сравнены аналитические решения с численным решением, и доказано, что траектория оператора стремится к положению равновесия. Также изучены четырнадцать крайних операторов и результаты приведены в виде таблицы.
Библиография: 23 названия.
О глобальных решениях квазилинейных дифференциальных неравенств второго порядка
Authors: Kon'kov Andrej Alexandrovich , Shishkov Andrey Evgenievich
Published: November 2024

Рассматриваются дифференциальные неравенства вида
$$
- \operatorname{div} A (x, \nabla u)\geqslant f(u)\quad в\quad {\mathbb R}^n,
$$
где $n \geqslant 2$ и $A$ - каратеодориева функция, удовлетворяющая условиям равномерной эллиптичности
$$
C_1|\xi|^p\leqslant\xi A (x, \xi),
\qquad |A (x, \xi)| \leqslant C_2 |\xi|^{p-1},
\qquad C_1, C_2 > 0,
\qquad p > 1,
$$
для почти всех $x \in {\mathbb R}^n$ и всех $\xi \in {\mathbb R}^n$.
Для неотрицательных решений этих неравенств получены точные условия отсутствия нетривиальных решений.
Библиография: 17 названий.
Evaluation of the Usability and User Experience of the Jaminan Kesehatan Nasional Mobile Application in Indonesia
Authors: Handasari Savira Putri , Wulandari Respati , Haikal
Published: November 2024

Objectives: The National Health Insurance (Jaminan Kesehatan Nasional or JKN) mobile application represents an administrative transformation of health social insurance in Indonesia. The application’s user base has quadrupled in the past 2 years. The study aimed to evaluate the usability and user experience of the JKN mobile application in Indonesia.Methods: The study administered an online survey featuring the System Usability Scale (SUS) questionnaire alongside a user experience assessment. The survey was disseminated via social media and garnered responses from 370 participants. The variables examined included usability and user experience, specifically focusing on attractiveness, perspicuity, efficiency, dependability, stimulation, and novelty. Data analysis was performed descriptively, and the results were benchmarked.Results: The JKN mobile application had an average SUS score of 60.9 ± 13.47 (adjective rating “good,” Grade “F,” acceptability rating of “low marginal,” and a percentile range of 34). User experience testing yielded the following results: attractiveness (1.09 ± 1.09), perspicuity (1.05 ± 1.17), efficiency (1.07 ± 1.20), dependability (1.03 ± 1.12), stimulation (0.88 ± 1.20), and novel-ty (0.58 ± 1.09). The benchmark for the JKN mobile application placed the user experience in the “below average” category.Conclusions: The evaluation of the usability and user experience of the JKN mobile application was generally positive. However, there is a need to improve the usability and all parameters of the user experience. Broader-scale research is needed to explore the factors that influence usage and user experience to promote the adoption of the JKN application and increase user satisfaction.
Vaccine Logistics Management Information System at Public Health Facilities in Amhara Region, Ethiopia: A Performance Evaluation
Authors: Mekonen Zelalem Tilahun , Cho Denny J. , Nadeem Simon Peter , Garza-Reyes Jose Arturo , Fenta Teferi Gedif
Published: November 2024

Objectives: This study aimed to evaluate the performance of vaccine logistics management information systems at public health facilities in Amhara Region, Ethiopia.Methods: An institution-based concurrent explanatory mixed design was used at public health facilities in Amhara Region, Ethiopia. In total, 102 health facilities were selected using the multi-stage, stratified, random-sampling proportionate-to-size method. Data were collected using a structured data abstraction checklist from vaccine logistics management information system records. Additionally, experiences of Expanded Program for Immunization focal persons were gathered through interviewer-administered questionnaires.Results: Among the 102 health facilities surveyed, 99 (97.1%) provided vaccination services during the study period. On the day of the visit, the average availability and utilization rates of 15 vaccine logistics management information system forms were 44.1% and 40.5%, respectively. The mean inventory accuracy for tracer vaccines stood at 58.3% ± 45.1%. The overall average accuracy percentages for urban and rural vaccine request form reports were 73.4% and 69.6%, respectively.Conclusions: The performance of vaccine logistics management information systems in these public health facilities was suboptimal. Key issues identified include inconsistent use of recording forms, shortages of reporting forms, lack of digitalization, poor data quality, and a shortage of qualified staff. These findings underscore the urgent need for standardization of the vaccine logistics management information system and enhancement of data quality.
Cancer-related Keywords in 2023: Insights from Text Mining of a Major Consumer Portal
Authors: Jeong Wonjeong , Song Eunkyoung , Jeong Eunzi , Oh Kyoung Hee , Lee Hye-Sun , Jun Jae Kwan
Published: November 2024

Objectives: With the growing importance of monitoring cancer patients’ internet usage, there is an increasing need for technology that expands access to relevant information through text mining. This study analyzed internet articles from portal sites in 2023 to identify trends in the information available to cancer patients and to derive meaningful insights.Methods: This study analyzed 19,578 news articles published on Naver, a major Korean portal site, from January 1, 2023, to December 31, 2023. Natural language processing, text mining, network analysis, and word cloud analysis were employed. The search term “am” (Korean for “cancer”) was used to identify keywords related to cancer.Results: In 2023, an average of 1,631 cancer-related articles were published monthly, with a peak of 1,946 in September and a low of 1,371 in February. A total of 132,456 keywords were extracted, with “cure” (2,218 occurrences), “lung cancer” (1,652), and “breast cancer” (1,235) being the most frequent. Term frequency-inverse document frequency analysis ranked “struggle” (1064.172) as the most significant keyword, followed by “lung cancer” (839.988) and “breast cancer” (744.840). Network analysis revealed four distinct clusters focusing on treatment, celebrity-related issues, major cancer types, and cancer-causing factors.Conclusions: The analysis of cancer-related keywords in 2023 indicates that news articles often prioritize gossip over essential information. These findings provide foundational data for future policy directions and strategies to address misinformation. This study underscores the importance of understanding the nature of cancer-related information consumed by the public and offers insights to guide official policies and healthcare practices.
The State of Human Papillomavirus (HPV) Vaccination Among Secondary School Adolescents in Nnewi, Nigeria Prior to Free Routine HPV Vaccine Rollout
Authors: Duru Chinefo G , Ugochukwu Ebelechuku F , Onubogu Chinyere U , Uchie Simon N , Mbachu Chioma NP
Published: November 2024

Background: Human papillomavirus (HPV) has been linked to various cancers of the genital, oropharyngeal, and anal regions in both sexes. 
Objective: To assess the vaccination rate and factors influencing the uptake of the HPV vaccine among secondary school students in Nnewi, Nigeria, prior to the introduction of free HPV vaccine in the routine national immunisation program.
Methods: A cross-sectional, descriptive survey was conducted among male and female students aged 10 to 18 years in public and private secondary schools between April and July 2023. A total of 200 participants were recruited using multi-stage sampling. Data on relevant sociodemographic characteristics, awareness about the HPV vaccine, details of HPV vaccination and reasons for not vaccinating were collected using pretested interviewer-administered questionnaires.
Results: Nearly two-thirds (62.0%) of participants were aged 15 to 18 years. Sixty-five per cent had not previously heard about HPV infection or the HPV vaccine. However, only 3 (1.5%) female participants reported receiving the HPV vaccine. Significant associations were found between awareness of HPV infection and HPV vaccination status (p = 0.006). The major reasons for not receiving the HPV vaccine were a lack of information about the vaccine (100%), where to get the vaccine (27.9%]), and the cost of the vaccine (6.0%).
Conclusion: The study revealed a low level of awareness about HPV infection or vaccine and a very low HPV vaccination rate among the participants. Public enlightenment and advocacy about HPV and the HPV vaccine should be prioritised to enhance knowledge and uptake after the free HPV vaccine rollout.
The Impact of Hydroxyurea Therapy on Clinical and Haematological Parameters in Children with Sickle Cell Anaemia
Authors: Oni Nathaniel O , Ogundeyi Mojisola M , Dedeke Iyabo O , Adebola Muhktar B , Olanrewaju DUrotoye M
Published: November 2024

Background: Sickle cell anaemia (SCA) is an inherited genetic disorder of the erythrocyte that is frequently encountered worldwide. Hydroxyurea is a myelosuppressive and sickle cell disease-modifying agent.
Objective: To determine the effects of six months of treatment with hydroxyurea on the clinical and haematological parameters of children with SCA.
Methods: A longitudinal study involving 58 subjects was used. Clinical and haematological parameters were recorded at recruitment and intervals within six months of the commencement of hydroxyurea. Pre- and post-HU therapy data were compared.
Results: There was a significant reduction in the frequency of vaso-occlusive crises, acute chest syndrome, hospitalisations, stroke and blood transfusions (p<0.001 respectively). Haemoglobin F value and packed cell volume increased from a median (IQR) of 6.6% (6.0) to 15.9% (7.6) and from 22.0% (3.9) to 27.0% (3.5), respectively (p<0.001 in each case).
Conclusion: This study reports significant improvement in the clinical and haematological profiles of children with SCA following hydroxyurea therapy. Due to its proven clinical and haematological advantages, hydroxyurea should be globally adopted to manage SCA in children.
A Retrospective Study of the Prevalence and Pattern of Intraventricular Haemorrhage Among Preterm Neonates in Makurdi, Nigeria
Authors: Michael Aondoaseer A , Adikwu Morgan G , Ochoga Martha O
Published: November 2024

Background: Globally, an estimated 2.5 million newborns died in the first month of life in 2018, with preterm birth complications as the leading cause of death. Preterm neonates who survive are at greater risk of a range of short-term and long-term morbidities. Intraventricular haemorrhage (ICH) is an important cause of brain damage in premature newborns.
Objective: To determine the prevalence, risk factors, pattern and outcomes of intraventricular haemorrhage amongst the preterm neonates in a tertiary facility.
Methods: A six-year (Jan 2018-Dec 2023) retrospective study was carried out at the Special Care Baby Unit (SCBU) of the Benue State University Teaching Hospital, Makurdi. The hospital records of all preterm neonates admitted into the unit during the period under review were retrieved and assessed using the study proforma.
Results:  A total of 121 preterm neonates were admitted with a male-to-female ratio of 1.1:1. The majority, (93; 76.9%) of the neonates had the first brain scan within the first seven days of life, while 10.7% had the scan between 8 and 14 days. Intraventricular haemorrhage was observed in 39 (32.2%), while 82 (67.8%) had normal brain scans. The severity pattern revealed Grade I, Grade II, and Grade III haemorrhages in 16.5%, 10.7%, and 5%, respectively. There were seven deaths accounting for 17.9% mortality.
Conclusion: Intraventricular haemorrhage in preterm neonates is a silent cause of mortality among preterm neonates. Proactive measures are needed to prevent the condition and manage affected babies.
Clinical and Laboratory Profile, Parental Perception and Management of Micropenis in Childhood: Experience at a Referral Centre in Abidjan, Cote d'Ivoire
Authors: Dainguy Marie E , Micondo Kouame H , Oyenusi Elizabeth E , Kouako Cyprien , Abodo Jacko R , Amorissani Folquet M
Published: November 2024

Background: Micropenis is a congenital condition that is part of the group of disorders of sex differentiation (DSD). It is a condition that has not received much attention among children in our environment.
Objective: To describe the epidemiological, clinical profile, and therapeutic profile of children with micropenis and the management outcome.
Methods: This was a descriptive, retrospective study of children with micropenis at the Paediatric unit of the Military Hospital, Abidjan, over six years (May 2016 to June 2022).
Results: A total of 70 children with micropenis were studied. The mean age was 9.3±3.9 years (1 month to 15 years). About one-third (30%) of the children were obese. The mean penile length was 2.55 ±0.65 cm (1 cm to 4 cm). In more than three-quarters of the cases, the mothers discovered a small-sized penis and anxiety in 91.4% of the parents. In the majority of cases (62.9%), the aetiology was unknown, while primary and central hypogonadism were observed in 24.3% and 11.4%, respectively. Affected children received testosterone treatment with favourable outcomes in all cases. The mean increase in penile length was 2.68 cm ± 0.97 (minimum of +1 cm and maximum of 6 cm).
Conclusion: It is essential to raise awareness about micropenis among the population and health personnel to reduce undue anxiety in parents and children.