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1.
Ann Rheum Dis ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986577

RESUMO

OBJECTIVES: Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. METHODS: We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (Irg1)-deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation. RESULTS: We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of Irg1 and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, Irg1-deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. CONCLUSION: In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.

2.
ACG Case Rep J ; 11(7): e01438, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39021713

RESUMO

Mucosal-associated lymphoid tissue (MALT) is a low-grade lymphoma derived from marginal zone B cells in extranodal tissue. Gastric MALT lymphoma is frequently seen; however, duodenal MALT lymphoma is rare, and there is no standardized knowledge up to date about the management of the disease. We present a case of a 56-year-old woman with gastric and duodenal MALT lymphoma.

3.
Bull Math Biol ; 86(7): 82, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837083

RESUMO

Many neurodegenerative diseases (NDs) are characterized by the slow spatial spread of toxic protein species in the brain. The toxic proteins can induce neuronal stress, triggering the Unfolded Protein Response (UPR), which slows or stops protein translation and can indirectly reduce the toxic load. However, the UPR may also trigger processes leading to apoptotic cell death and the UPR is implicated in the progression of several NDs. In this paper, we develop a novel mathematical model to describe the spatiotemporal dynamics of the UPR mechanism for prion diseases. Our model is centered around a single neuron, with representative proteins P (healthy) and S (toxic) interacting with heterodimer dynamics (S interacts with P to form two S's). The model takes the form of a coupled system of nonlinear reaction-diffusion equations with a delayed, nonlinear flux for P (delay from the UPR). Through the delay, we find parameter regimes that exhibit oscillations in the P- and S-protein levels. We find that oscillations are more pronounced when the S-clearance rate and S-diffusivity are small in comparison to the P-clearance rate and P-diffusivity, respectively. The oscillations become more pronounced as delays in initiating the UPR increase. We also consider quasi-realistic clinical parameters to understand how possible drug therapies can alter the course of a prion disease. We find that decreasing the production of P, decreasing the recruitment rate, increasing the diffusivity of S, increasing the UPR S-threshold, and increasing the S clearance rate appear to be the most powerful modifications to reduce the mean UPR intensity and potentially moderate the disease progression.


Assuntos
Conceitos Matemáticos , Modelos Neurológicos , Neurônios , Doenças Priônicas , Resposta a Proteínas não Dobradas , Resposta a Proteínas não Dobradas/fisiologia , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Doenças Priônicas/fisiopatologia , Neurônios/metabolismo , Humanos , Animais , Dinâmica não Linear , Simulação por Computador , Príons/metabolismo , Análise Espaço-Temporal , Apoptose
4.
Cell Death Dis ; 15(5): 369, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806478

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3ß. While STAT3α is predominantly described as an oncogenic driver, STAT3ß has been suggested to act as a tumor suppressor. To elucidate the role of STAT3ß in AML, we established a mouse model of STAT3ß-deficient, MLL-AF9-driven AML. STAT3ß deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3ß. Accordingly, STAT3ß-deficient leukemia cells displayed enhanced sensitivity to blockade of IFN signaling through both an IFNAR1 blocking antibody and the JAK1/2 inhibitor Ruxolitinib. Analysis of human AML patient samples confirmed that elevated expression of IFN-inducible genes correlated with poor overall survival and low STAT3ß expression. Together, our data corroborate the tumor suppressive role of STAT3ß in a mouse model in vivo. Moreover, they provide evidence that its tumor suppressive function is linked to repression of the STAT1-mediated IFN response. These findings suggest that the STAT3ß/α mRNA ratio is a significant prognostic marker in AML and holds crucial information for targeted treatment approaches. Patients displaying a low STAT3ß/α mRNA ratio and unfavorable prognosis could benefit from therapeutic interventions directed at STAT1/IFN signaling.


Assuntos
Leucemia Mieloide Aguda , Fator de Transcrição STAT3 , Animais , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Camundongos , Transdução de Sinais , Interferons/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Camundongos Endogâmicos C57BL , Receptor de Interferon alfa e beta/metabolismo , Receptor de Interferon alfa e beta/genética , Linhagem Celular Tumoral , Nitrilas , Pirazóis , Pirimidinas
5.
Cureus ; 16(3): e56528, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646333

RESUMO

Introduction Obesity is a pandemic causing a significant burden on healthcare systems and carries increased morbidity and mortality. One of the options for managing obesity is endoscopic intragastric balloon (IGB) insertion. The aim of the study is to assess the efficacy, tolerance, and side effects of IGB insertion in overweight and obese patients. Methods This is a cross-sectional retrospective study that includes 71 patients who underwent IGB insertion from 2015 to 2019 at King Hamad University Hospital (KHUH), Kingdom of Bahrain. Records of these patients were accessed to assess the percentage of weight loss at the time of balloon removal, complications, and tolerance of the procedure. Furthermore, telephonic interviews were conducted to enquire about side effects and the satisfaction of the procedure. Results A total of 57 patients were included in the weight loss analysis. Thirteen patients did not tolerate the balloon, and one patient had a balloon rupture. The patients experienced a significant reduction in weight upon balloon removal with a mean of 9.74 ± 8.71 kg (p-value of <0.001) and percentage total body weight loss of 10.48 ± 8.07 (p-value of <0.001). A significant reduction was also seen in the body mass index of 3.67 ± 3.57 (p-value of <0.001). The most frequent side effects were nausea, vomiting, and abdominal pain. No major complications or mortalities occurred. Conclusion Intragastric balloons are effective in establishing weight loss. Among patients who tolerated the procedure, the most frequently reported side effects were nausea, vomiting, and abdominal pain.

6.
ACS Appl Eng Mater ; 1(11): 3040-3052, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38031538

RESUMO

Disinfection of water is essential to prevent the growth of pathogens, but at high levels, it can cause harm to human health. Therefore, accurate monitoring of disinfectant concentrations in water is essential to ensure safe drinking water. The use of multiple disinfectants at different stages in water treatment plants makes it necessary to also identify the type and concentrations of all of the disinfectant species present. Here, we demonstrate an effective approach to identify and quantify multiple disinfectants (using the example of free chlorine and potassium permanganate) in water using single-walled carbon nanotube (SWCNT)-based reagent-free chemiresistive sensing arrays. Facile fabrication of chemiresistive devices makes them a popular choice for the implementation of sensor arrays. Our sensing array consists of functionalized and unfunctionalized (blank) SWCNT sensors to distinguish the disinfectants. The distinct responses from the different sensors at varying concentrations and pH can be fitted to the mathematical model of a Langmuir adsorption isotherm separately for each sensor. Blank and functionalized sensors respond through different mechanisms that result in varying responses that are concentration- and pH-dependent. Chemometric techniques such as principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) were used to analyze the sensor data. PCA showed an excellent separation of the analytes over five different pHs (5.5, 6.5, 7.5, 8.5, and 9.5). PLS-DA provided excellent separability as well as good predictability with a Q2 of 94.26% and an R2 of 95.67% for the five pH regions of the two analytes. This proof-of-concept solid-state chemiresistive sensing array can be developed for specific disinfectants that are commonly used in water treatment plants and can be deployed in water distribution and monitoring facilities. We have demonstrated the applicability of chemiresistive devices in a sensor array format for the first time for aqueous disinfectant monitoring.

7.
Digit Health ; 9: 20552076231203649, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791140

RESUMO

Objective: Augmented reality (AR) is a relatively new technology that merges virtual and physical environments, augmenting one's perception of reality. AR creates a computer-generated environment that evokes a unique perception of reality, where real and virtual objects are registered with one another, which operates interactively and in real time. Recently, the medical application of AR technology has dramatically increased with other assisted technologies, from training to clinical practice. The ability to manipulate the real environment extensively has given AR interventions an advantage over traditional approaches. In this study, we aim to conduct a systematic review of the use of AR to have a better understanding of how the use of AR may affect patients with mental health-related conditions when combined with gamification. Method: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching Pubmed and Web of Science databases. Results and Conclusion: We identified 48 relevant studies that fulfill the criteria. The studies were grouped into four categories: Neurodevelopmental disorders, anxiety and phobia, psychoeducation & well-being, and procedural & pain management. Our results revealed the effectiveness of AR in mental health-related conditions. However, the heterogeneity and small sample sizes demonstrate the need for further research with larger sample sizes and high-quality study designs.

8.
PLoS One ; 18(4): e0284157, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37104371

RESUMO

Since November 2019, most countries across the globe have suffered from the disastrous consequences of the Covid-19 pandemic which redefined every aspect of human life. Given the inevitable spread and transmission of the virus, it is critical to acknowledge the factors that catalyse transmission of the disease. This research investigates the relation of the external demographic parameters such as total population, population density and weighted population density on the spread of Covid-19 in Malaysia. Pearson correlation and simple linear regression were utilized to identify the relation between the population-related variables and the spread of Covid-19 in Malaysia using data from 15th March 2020 to 31st March 2021. As a result, a strong positive significant correlation between the total population and Covid-19 cases was found. However, a weak positive relationship was found between the density variable (population density and weighted population density) and the spread of Covid-19. Our findings suggest that the transmission of Covid-19 during lockdown (Movement Control Order, MCO) in Malaysia was more readily explained by the demographic variable population size, than population density or weighted population density. Thus, this study could be helpful in intervention planning and managing future virus outbreaks in Malaysia.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Malásia/epidemiologia , Densidade Demográfica , SARS-CoV-2 , Pandemias/prevenção & controle , Controle de Doenças Transmissíveis
9.
Nutrients ; 14(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36235867

RESUMO

Helicobacter pylori (H. Pylori) infection is the main bacterial cause of several gastrointestinal disorders. This study aims to estimate the prevalence of H. pylori infection in a population of Bahraini adults seeking care in gastroenterology clinics in a tertiary care hospital in the Kingdom of Bahrain and examine the association between dietary habits and other factors with H. pylori infection. The study is a hospital-based retrospective, cross-sectional analytical study that included 200 participants. H. pylori infection prevalence among the studied group was 55.5%, and it was significantly higher among participants with a high school education or less (44.1%). Among dietary habits, the mean of frequency of green tea, coffee and honey intake was significantly lower among the H. pylori infected participants compared to their non-infected counterparts. H. pylori infection was significantly higher among participants with vitamin D deficiency (63.6%) compared to participants with normal vitamin D (30%) (p = 0.001) and each unit decrease in serum vitamin D was associated with an increased risk of infection by 1.1 times (OR = 1.1; 95% CI: 1.05, 1.18; p < 0.001). The study revealed that high educational levels, consumption of honey, green tea, and coffee, as well as normal serum vitamin D level, were independent protectors against H. pylori infection. Additional studies are needed to estimate the prevalence and predisposing factors of H. pylori infection in the general population.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Barein/epidemiologia , Café , Estudos Transversais , Comportamento Alimentar , Infecções por Helicobacter/microbiologia , Humanos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Chá , Vitamina D
10.
Toxics ; 10(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36287880

RESUMO

(1) Background: Arsenic (As) is a common drinking water contaminant that is regulated as a carcinogen. Yet, As is a systemic toxicant and there is considerable epidemiological data showing As adversely impacts reproductive health. This study used data from a birth cohort in Bangladesh (2008−2011) to examine associations between drinking water As levels and reproductive outcomes. (2) Methods: Pregnant individuals (n = 1597) were enrolled at <16 weeks gestation and drinking water As was measured. Participants with live births (n = 1130) were propensity score matched to participants who experienced miscarriage (n = 132), stillbirth (n = 72), preterm birth (n = 243), and neonatal mortality (n = 20). Logistic regression was used to examine drinking water As recommendations of 50, 10, 5, 2.5, and 1 µg/L on the odds of adverse birth outcomes. (3) Results: The odds of miscarriage were higher for pregnant women exposed to drinking water ≥2.5 versus <2.5 µg As/L [adjusted odds ratio (OR) 1.90, 95% Confidence Interval (CI): 1.07−3.38)]. (4) Conclusions: These preliminary findings suggest a potential threshold where the odds of miscarriage increases when drinking water As is above 2.5 µg/L. This concentration is below the World Health Organizations and Bangladesh's drinking water recommendations and supports the re-evaluation of drinking water regulations.

11.
STAR Protoc ; 3(3): 101653, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36065293

RESUMO

By their capacity to induce peripheral T cell tolerance, dendritic cells (DCs) present a promising target cell and therapeutic strategy for treatment of several autoimmune diseases including multiple sclerosis (MS). This protocol describes how to determine the tolerogenic capacities of DCs in the context of the murine MS model, experimental autoimmune encephalomyelitis (EAE). We provide a step-by-step instruction for EAE induction, antigen-loaded bone-marrow-derived-DC (BM-DC) generation, adoptive cell transfer, and analysis of DC-mediated changes in regulatory T cell populations. For complete details on the use and execution of this protocol, please refer to Vogel et al. (2022).


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Transferência Adotiva , Animais , Antígenos , Células Dendríticas , Encefalomielite Autoimune Experimental/terapia , Camundongos , Linfócitos T Reguladores
12.
Environ Res ; 214(Pt 1): 113845, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35830911

RESUMO

BACKGROUND: Pregnancy is a sensitive time for maternal cardiovascular functioning and exposures to arsenic or manganese may adversely affect blood pressure (BP). OBJECTIVES: This study examined the associations between arsenic and manganese exposures and maternal BP measured during pregnancy. Effect modification by pre-pregnancy body mass index (BMI) was evaluated. METHODS: Pregnant women (N = 1522) were recruited for a prospective cohort study in Bangladesh (2008-2011). Exposure to arsenic and manganese was measured in drinking water at <16 weeks gestation and toenails at one-month postpartum. Systolic and diastolic BP were measured monthly. Linear mixed models estimated mean BP and differences in mean BP over gestation for arsenic or manganese exposures and adjusted for covariates. RESULTS: Arsenic levels had an increasing dose-response association with maternal BP after 25 weeks gestation. Effect modification was observed for BMI. Participants with lower BMI (<23 kg/m2) exposed to 50 µg/L arsenic had 2.83 mmHg (95% CI:1.74-3.92) greater mean systolic and 1.96 mmHg (95% CI: 1.02-2.91 mmHg) diastolic BP compared to those exposed to ≤ 1 µg/L arsenic at 40 weeks gestation. Participants with higher BMI (≥23 kg/m2) showed a greater mean systolic BP of 5.72 mmHg (95% CI: 3.18-8.27 mmHg) and diastolic BP change of 6.09 mmHg (95% CI: 4.02-8.16 mmHg) at 40 weeks gestation when exposed to 50 µg/L compared to ≤ 1 µg/L arsenic. Participants with lower BMI exposed to drinking water manganese in the 2nd quartile (181-573 µg/L) had 1.04 mmHg higher mean diastolic BP (95% CI: 0.01-2.07 mmHg) at 40 weeks gestation compared to those in the 1st quartile (0.5-180 µg/L). CONCLUSION: Arsenic exposures during pregnancy were consistently associated with increased average maternal systolic and diastolic BP. The effect of manganese on BP was less consistent.


Assuntos
Arsênio , Água Potável , Pressão Sanguínea , Feminino , Humanos , Íons , Manganês , Gravidez , Estudos Prospectivos
13.
J Hepatol ; 77(4): 991-1004, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35750136

RESUMO

BACKGROUND & AIMS: Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis. METHODS: TREM-2 expression was analyzed in the livers of patients with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC), and in mouse models of cholestasis. Wild-type (WT) and Trem-2 deficient (Trem-2-/-) mice were subjected to experimental cholestasis and gut sterilization. Primary cultured Kupffer cells were incubated with lipopolysaccharide and/or ursodeoxycholic acid (UDCA) and inflammatory responses were analyzed. RESULTS: TREM-2 expression was upregulated in the livers of patients with PBC or PSC, and in murine models of cholestasis. Compared to WT, the response to bile duct ligation (BDL)-induced obstructive cholestasis or alpha-naphtylisothiocyanate (ANIT)-induced cholestasis was exacerbated in Trem-2-/- mice. This was characterized by enhanced necroptotic cell death, inflammatory responses and biliary expansion. Antibiotic treatment partially abrogated the effects observed in Trem-2-/- mice after BDL. Experimental overexpression of TREM-2 in the liver of WT mice downregulated ANIT-induced IL-33 expression and neutrophil recruitment. UDCA regulated Trem-1 and Trem-2 expression in primary cultured mouse Kupffer cells and dampened inflammatory gene transcription via a TREM-2-dependent mechanism. CONCLUSIONS: TREM-2 acts as a negative regulator of inflammation during cholestasis, representing a novel potential therapeutic target. LAY SUMMARY: Cholestasis (the reduction or cessation of bile flow) causes liver injury. This injury is exacerbated when gut-derived bacterial components interact with receptors (specifically Toll-like receptors or TLRs) on liver-resident immune cells, promoting inflammation. Herein, we show that the anti-inflammatory receptor TREM-2 dampens TLR-mediated signaling and hence protects against cholestasis-induced liver injury. Thus, TREM-2 could be a potential therapeutic target in cholestasis.


Assuntos
Colestase , Glicoproteínas de Membrana , Receptores Imunológicos , Ácido Ursodesoxicólico , Animais , Antibacterianos , Anti-Inflamatórios , Colestase/complicações , Inflamação , Interleucina-33 , Lipopolissacarídeos , Fígado , Glicoproteínas de Membrana/genética , Camundongos , Receptores Imunológicos/genética , Receptor Gatilho 1 Expresso em Células Mieloides , Ácido Ursodesoxicólico/farmacologia
14.
Case Rep Gastroenterol ; 16(1): 264-269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35702444

RESUMO

Pseudomelanosis of the upper gastrointestinal tract is a rare diagnosis of undetermined significance, most commonly affecting the duodenum. Endoscopically, it is characterized by dark spickled pigmentation . Its development has been linked to certain conditions and medications. Involvement of the stomach is extremely rare with very few cases reported in the literature to date. We report an 85-year-old male who is known to have type 2 diabetes mellitus, dyslipidemia, iron deficiency anemia, and chronic kidney disease who underwent an esophagogastroduodenoscopy for evaluation of upper gastrointestinal bleeding and was found to have gastric and duodenal pseudomelanosis confirmed by biopsy. It is an extremely rare benign condition, but metastatic melanoma has to be ruled out, as was done in this case.

15.
Front Immunol ; 13: 695576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514976

RESUMO

Aberrant innate immune responses to the gut microbiota are causally involved in the pathogenesis of inflammatory bowel diseases (IBD). The exact triggers and main signaling pathways activating innate immune cells and how they modulate adaptive immunity in IBD is still not completely understood. Here, we report that the PI3K/PTEN signaling pathway in dendritic cells enhances IL-6 production in a model of DSS-induced colitis. This results in exacerbated Th1 cell responses and increased mortality in DC-specific PTEN knockout (PTENΔDC) animals. Depletion of the gut microbiota using antibiotics as well as blocking IL-6R signaling rescued mortality in PTENΔDC mice, whereas adoptive transfer of Flt3L-derived PTEN-/- DCs into WT recipients exacerbated DSS-induced colitis and increased mortality. Taken together, we show that the PI3K signaling pathway in dendritic cells contributes to disease pathology by promoting IL-6 mediated Th1 responses.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Células Dendríticas , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais
16.
Sci Rep ; 12(1): 5083, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35332192

RESUMO

The challenge of accurately short-term forecasting demand is due to model selection and the nature of data trends. In this study, the prediction model was determined based on data patterns (trend data without seasonality) and the accuracy of prediction measurement. The cumulative number of COVID-19 affected people in some ASEAN countries had been collected from the Worldometers database. Three models [Holt's method, Wright's modified Holt's method, and unreplicated linear functional relationship model (ULFR)] had been utilized to identify an efficient model for short-time prediction. Moreover, different smoothing parameters had been tested to find the best combination of the smoothing parameter. Nevertheless, using the day-to-day reported cumulative case data and 3-days and 7-days in advance forecasts of cumulative data. As there was no missing data, Holt's method and Wright's modified Holt's method showed the same result. The text-only result corresponds to the consequences of the models discussed here, where the smoothing parameters (SP) were roughly estimated as a function of forecasting the number of affected people due to COVID-19. Additionally, the different combinations of SP showed diverse, accurate prediction results depending on data volume. Only 1-day forecasting illustrated the most efficient prediction days (1 day, 3 days, 7 days), which was validated by the Nash-Sutcliffe efficiency (NSE) model. The study also validated that ULFR was an efficient forecasting model for the efficient model identifying. Moreover, as a substitute for the traditional R-squared, the study applied NSE and R-squared (ULFR) for model selection. Finally, the result depicted that the prediction ability of ULFR was superior to Holt's when it is compared to the actual data.


Assuntos
COVID-19 , COVID-19/epidemiologia , Previsões , Humanos , Modelos Lineares
17.
Cell Rep ; 38(8): 110420, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35196494

RESUMO

Dendritic cells (DCs) induce peripheral T cell tolerance, but cell-intrinsic signaling cascades governing their stable tolerogenesis remain poorly defined. Janus Kinase 1 (JAK1) transduces cytokine-receptor signaling, and JAK inhibitors (Jakinibs), including JAK1-specific filgotinib, break inflammatory cycles in autoimmunity. Here, we report in heterogeneous DC populations of multiple secondary lymphoid organs that JAK1 promotes peripheral T cell tolerance during experimental autoimmune encephalomyelitis (EAE). Mice harboring DC-specific JAK1 deletion exhibit elevated peripheral CD4+ T cell expansion, less regulatory T cells (Tregs), and worse EAE outcomes, whereas adoptive DC transfer ameliorates EAE pathogenesis by inducing peripheral Tregs, programmed cell death ligand 1 (PD-L1) dependently. This tolerogenic program is substantially reduced upon the transfer of JAK1-deficient DCs. DC-intrinsic IFN-γ-JAK1-STAT1 signaling induces PD-L1, which is required for DCs to convert CD4+ T cells into Tregs in vitro and attenuated upon JAK1 deficiency and filgotinib treatment. Thus, DC-intrinsic JAK1 promotes peripheral tolerance, suggesting potential unwarranted DC-mediated effects of Jakinibs in autoimmune diseases.


Assuntos
Antígeno B7-H1 , Encefalomielite Autoimune Experimental , Janus Quinase 1 , Linfócitos T Reguladores , Animais , Autoimunidade , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Células Dendríticas/metabolismo , Tolerância Imunológica , Janus Quinase 1/imunologia , Janus Quinase 1/metabolismo , Camundongos , Tolerância Periférica
18.
SN Comput Sci ; 3(2): 135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35072102

RESUMO

Emotion classification in text has growing interest among NLP experts due to the enormous availability of people's emotions and its emergence on various Web 2.0 applications/services. Emotion classification in the Bengali texts is also gradually being considered as an important task for sports, e-commerce, entertainments, and security applications. However, It is a very critical task to develop an automatic emotion classification system for low-resource languages such as, Bengali. Scarcity of resources and deficiency of benchmark corpora make the task more complicated. Thus, the development of a benchmark corpus is the prerequisite to develop an emotion classifier for Bengali texts. This paper describes the development of an emotional corpus (hereafter called 'BEmoC') for classifying six emotions in Bengali texts. The corpus development process consists of four key steps: data crawling, pre-processing, labelling, and verification. A total of 7000 texts are labelled into six basic emotion categories such as anger, fear, surprise, sadness, joy, and disgust, respectively. Dataset evaluation with 0.969 Cohen's κ score indicates the close agreement between the corpus annotators and the expert. The analysis of evaluation also represents that the distribution of emotion words obeys Zipf's law. Moreover, the results of BEmoC analysis shown in terms of coding reliability, emotion density, and most frequent emotion words, respectively.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34626791

RESUMO

Macrophages are professional phagocytes, indispensable for maintenance of tissue homeostasis and integrity. Depending on their resident tissue, macrophages are exposed to highly diverse metabolic environments. Adapted to their niche, they can contribute to local metabolic turnover through metabolite uptake, conversion, storage and release. Disturbances in tissue homeostasis caused by infection, inflammation or damage dramatically alter the local milieu, impacting macrophage activation status and metabolism. In the case of persisting stimuli, defective macrophage responses ensue, which can promote tissue damage and disease. Especially relevant herein are disbalances in lipid rich environments, where macrophages are crucially involved in lipid uptake and turnover, preventing lipotoxicity. Lipid uptake is to a large extent facilitated by macrophage expressed scavenger receptors that are dynamically regulated and important in many metabolic diseases. Here, we review the receptors mediating lipid uptake and summarize recent findings on their role in health and disease. We further highlight the underlying pathways driving macrophage lipid acquisition and their impact on myeloid metabolic remodelling.


Assuntos
Inflamação/genética , Lipídeos/genética , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Transporte Biológico/genética , Homeostase/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia
20.
J Healthc Inform Res ; 6(1): 72-90, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34549163

RESUMO

The aim of this study is to analyse the coronavirus disease 2019 (COVID-19) outbreak in Bangladesh. This study investigates the impact of demographic variables on the spread of COVID-19 as well as tries to forecast the COVID-19 infected numbers. First of all, this study uses Fisher's Exact test to investigate the association between the infected groups of COVID-19 and demographical variables. Second, it exploits the ANOVA test to examine significant difference in the mean infected number of COVID-19 cases across the population density, literacy rate, and regions/divisions in Bangladesh. Third, this research predicts the number of infected cases in the epidemic peak region of Bangladesh for the year 2021. As a result, from the Fisher's Exact test, we find a very strong significant association between the population density groups and infected groups of COVID-19. And, from the ANOVA test, we observe a significant difference in the mean infected number of COVID-19 cases across the five different population density groups. Besides, the prediction model shows that the cumulative number of infected cases would be raised to around 500,000 in the most densely region of Bangladesh, Dhaka division.

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