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Ayoub Ali Alshaikh,1,* Syed Esam Mahmood,1,* Fatima Riaz,1,* Ahmed Shubayli Assiri,2,* Majdoleen A Abdulrahman,3,* Mohammed Yahya Althwabi Asiri,3,* Ghadeer Redha Abdullah Alnakhli,4,* Mohanad Qasem A Alshabab,3,* Saud Saeed Abdullah Alsaleh,5,* Majed Yahya Alshahrani,6,* Amnah Saad H Alharthi,7,* Amar Abdullah Al Qahtani7,* 1Department of Family & Community Medicine, College of Medicine, King Khalid University, Abha, 62529, Saudia Arabia; 2Consultant Family Medicine, Ministry of Health, Aseer Region, Abha, Saudia Arabia; 3Saudi Board of Family Medicine, Abha, Saudi Arabia; 4Saudi Board of Pediatric Neurology, Abha, Saudi Arabia; 5Saudi Board of Internal Medicine, Abha, Saudi Arabia; 6Saudi Board of General Medicine, Abha, Saudi Arabia; 7College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia*These authors contributed equally to this workCorrespondence: Syed Esam Mahmood, Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia, Email smahmood@kku.edu.saIntroduction: Many studies report a lack of public awareness of the risk factors and complications of Diabetes Mellitus. Adequate glycemic control is crucial in preventing or delaying the onset of type 2 diabetes complications, and medication adherence is one of the key factors in achieving this goal. This study aimed to measure the knowledge about diabetes mellitus and practices regarding lifestyle factors and diabetes management in the study population in the Aseer region, of Saudi Arabia.Material and Methods: A descriptive cross-sectional survey was conducted in Abha, a city in the Aseer region of Saudi Arabia. The general population of 18 years of age and above, who were residing in the study area during the period of study, ie, January 2023 to June 2023, were included. The questionnaire was distributed through social media and e-mail for data collection. The descriptive variables were presented using frequency, percentage, and graphs. Pearson’s chi-square test was used at a 5% level of significance. Multivariate tests were applied to further explore the findings of univariate analysis. The data were analyzed using SPSS version 20.0.Results: Out of the total 348 participants, a higher proportion was males (56.3%). About 78.7% of the participants were ever diagnosed with diabetes mellitus and 21.3% were never diagnosed with diabetes mellitus. Nearly 31.6% knew that the major cause of diabetes mellitus was obesity and 31.3% knew that it was a hereditary disease. About 42.2% of respondents exercised regularly and 27.6% were smokers. Adherence to prescribed anti-diabetic medications was seen in 63.2% of the respondents. Self-alterations in the timing and dose of prescribed anti-diabetic drugs were seen in 36.5% and 34.8%, respectively. About 60.1% had a moderate level of self-rated knowledge about Diabetes Mellitus, and 27.6% and 12.4% had good and poor self-rated knowledge levels of Diabetes mellitus, respectively. On multivariate analysis, the age group 60– 69 years had significant variations as compared to the other age groups on DM, bachelor’s degree holders had significant variations as compared to other education variables, being married had significant differences as compared to those unmarried, those employed had significant variations as compared to the other occupation categories, and smokers had a significant impact on DM as compared to non-smokers.Conclusion: Findings indicated less number of respondents exercised regularly, low adherence to prescribed anti-diabetic medications and low levels of self-rated knowledge of diabetes mellitus. Enhancing the patients’ knowledge of diabetes mellitus and improving their self-management and adherence to its medications is necessary through public health education.Keywords: adherence, diabetes mellitus, management, aseer region

Gadolinium-based contrast agents (GBCAs) are used in around 40 % of MRI procedures. Despite initial perceptions of minimal risk, their long-term use has emphasized the need to reduce toxicity and develop more efficient GBCAs with extended blood retention. Advancements in nanomaterials have led to improved GBCAs, enhancing MRI diagnostics. This study synthesizes and characterizes nanostructured gadolinium(III) micelles as superior MRI contrast agents. The complexes, [Gd(L)2], where L is a ligand of the N-alkyl-N-methylglucamine surfactant series (L8, L10 or L12, L10), form nanostructured micelles in aqueous solution. Gd(L8)2 and Gd(L10)2 relaxivities remained stable across concentrations. Compared to Gd-DTPA, Gd(III) micelles showed enhanced T1-weighted MRI contrast. Gd(L12)2 micelles exhibited cytotoxicity against B16F10 melanoma cells (IC 50 42.5 ± 2.2 μM) and L292L929 fibroblasts (IC 50 52.0 ± 2.5 μM), with a selectivity index of 1.2. In vivo application in mice brain T2-weighted images suggests nanostructured Gd(III) micelles are promising MRI contrast agents for targeting healthy organs or tumors., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2 HKO ) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2 HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1., (© 2024. The Author(s).)

The Aluminum alloy AA7075 workpiece material is observed under dry finishing turning operation. This work is an investigation reporting promising potential of deep adaptive learning enhanced artificial intelligence process models for L 18 (6 1 3 3 ) Taguchi orthogonal array experiments and major cost saving potential in machining process optimization. Six different tool inserts are used as categorical parameter along with three continuous operational parameters i.e., depth of cut, feed rate and cutting speed to study the effect of these parameters on workpiece surface roughness and tool life. The data obtained from special L 18 (6 1 3 3 ) orthogonal array experimental design in dry finishing turning process is used to train AI models. Multi-layer perceptron based artificial neural networks (MLP-ANNs), support vector machines (SVMs) and decision trees are compared for better understanding ability of low resolution experimental design. The AI models can be used with low resolution experimental design to obtain causal relationships between input and output variables. The best performing operational input ranges are identified for output parameters. AI-response surfaces indicate different tool life behavior for alloy based coated tool inserts and non-alloy based coated tool inserts. The AI-Taguchi hybrid modelling and optimization technique helped in achieving 26% of experimental savings (obtaining causal relation with 26% less number of experiments) compared to conventional Taguchi design combined with two screened factors three levels full factorial experimentation., (© 2024. The Author(s).)

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.

Epithelioid inflammatory myofibroblastic sarcoma, a variant of the inflammatory myofibroblastic tumor, is a rare tumor that is not well described in the radiologic literature. We present a case of a 14-year-old male adolescent who presented with fever, fatigue, and weight loss symptoms and was found to have an abdominal mass on contrast enhanced CT. Initial differentials included lymphoma, pheochromocytoma, desmoid, and sarcoma, and pathological evaluation revealed an epithelioid inflammatory myofibroblastic sarcoma. The mass was separate from the surrounding structures of the left upper abdomen with unique radiologic features not previously described in the literature. Prior literature examples of epithelioid inflammatory myofibroblastic sarcoma described a heterogenous, enhancing lobulated mass, and our case was a lobulated, avidly enhancing homogenous mass on CT with surrounding inflammation and avid uptake on PET/CT. In addition to the imaging features, we describe the surgical findings, the pathologic features of the tumor, and the oncologic treatment of this patient. This case highlights the importance of including rare tumors such as epithelioid inflammatory myofibroblastic sarcoma as a potential differential consideration of an avidly enhancing homogenous abdominal mass in an adolescent., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objectives: Prostate cancer is characterized by diverse genetic mutations that influence disease progression and treatment response. This study was launched to explore the genetic basis of prostate cancer patients., Methods: We employed Next Generation Sequencing (NGS) to analyze 14 cancer-susceptible genes in prostate cancer patients., Results: Our study identified genetic mutations in BRCA1, BRCA2, TP53, and PMS2. In BRCA1 gene, we identified two pathogenic mutations, c.181T>G (p.Cys61Gly) and c.2457delC (p.Ala819fs), found in 10 patients, along with three benign mutations, c.5357T>G (p.Leu1786Arg), c.1111T>C (p.Leu371Pro), and c.1201C>G (p.Thr401Arg), present in 13, 11, and 15 patients, respectively. For the BRCA2 gene, one pathogenic mutation, c.6275_6276del (p.Val2092fs), was detected in 10 patients, and four benign mutations, c.5347A>T (p.Met1783Leu), c.5198A>G (p.Asp1733Gly), c.5158A>G (p.Thr1720Ala), and c.5117G>C (p.Gly1706Ala), were found in 17, 21, 34, and 12 patients, respectively. In the TP53 gene, we found two pathogenic mutations, c.1014_1015insT (p.Glu339Ter) and c.916C>T (p.Arg306Ter), in 10 and 11 patients, respectively, and two benign mutations, c.311T>C (p.Ser104Pro) and c.1129C>T (p.Arg377Cys), in 8 and 9 patients, respectively. Lastly, the PMS2 gene exhibited 16 benign mutations. Notably, the detected pathogenic mutations are rare in the broader Asian population according to the gnomAD database. Functional analyses using RT-qPCR and immunohistochemistry showed decreased expression of BRCA1, BRCA2, and TP53 in samples with pathogenic mutations, corroborating their impact on tumor suppressor function. Furthermore, drug sensitivity analysis revealed that BRCA1 and BRCA2 mutations are associated with increased sensitivity to a range of chemotherapeutic agents, supporting the concept of synthetic lethality. However, TP53 did not significantly impact drug sensitivity., Conclusion: This comprehensive analysis emphasizes the critical roles of BRCA1, BRCA2, TP53, and PMS2 in prostate cancer pathogenesis and highlights the importance of population-specific genetic screening., Competing Interests: None., (AJTR Copyright © 2024.)

Background: The high mortality rate associated with coronary heart disease has led to state-of-the-art non-invasive methods for cardiac diagnosis including computed tomography and magnetic resonance imaging. However, stenosis computation and clinical assessment of non-calcified plaques has been very challenging due to their ambiguous intensity response in CT i.e. a significant overlap with surrounding muscle tissues and blood. Accordingly, this research presents an approach for computation of coronary stenosis by investigating cross-sectional lumen behaviour along the length of 3D coronary segments., Methods: Non-calcified plaques are characterized by comparatively lower-intensity values with respect to the surrounding. Accordingly, segment-wise orthogonal volume was reconstructed in 3D space using the segmented coronary tree. Subsequently, the cross sectional volumetric data was investigated using proposed CNN-based plaque quantification model and subsequent stenosis grading in clinical context was performed. In the last step, plaque-affected orthogonal volume was further investigated by comparing vessel-wall thickness and lumen area obstruction w.r.t. expert-based annotations to validate the stenosis grading performance of model., Results: The experimental data consists of clinical CT images obtained from the Rotterdam CT repository leading to 600 coronary segments and subsequent 15786 cross-sectional images. According to the results, the proposed method quantified coronary vessel stenosis i.e. severity of the non-calcified plaque with an overall accuracy of 83%. Moreover, for individual grading, the proposed model show promising results with accuracy equal to 86%, 90% and 79% respectively for severe, moderate and mild stenosis. The stenosis grading performance of the proposed model was further validated by performing lumen-area versus wall-thickness analysis as per annotations of manual experts. The statistical results for lumen area analysis precisely correlates with the quantification performance of the model with a mean deviation of 5% only., Conclusion: The overall results demonstrates capability of the proposed model to grade the vessel stenosis with reasonable accuracy and precision equivalent to human experts., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with irritable bowel syndrome (IBS) experience not only a detrimental impact on their physical health but also a significant influence on their psychological well-being. This study aimed to assess the prevalence of IBS among university students, investigating the sociodemographic and lifestyle factors influencing its onset. Furthermore, it explored the potential impact of psychological factors such as depression, anxiety, and overall well-being on the prevalence of IBS. A cross-sectional analytical study was conducted at Saudi Arabian universities in November and December 2023. To collect data, an anonymous, validated, predesigned questionnaire was used. The diagnosis of IBS was carried out using the validated Arabic version of the Rome IV questionnaire. We used the Arabic version of the World Health Organization Well-being Index to assess the participants' well-being. We used the Arabic version of the Hospital Anxiety and Depression Scale (HADS) to identify people who show clinically significant symptoms of anxiety and depression. Our study included a total of 379 university students, 46.7% were female 86.0% of participants resided in urban areas, and 7.2% had been previously diagnosed with IBS. The prevalence of IBS among participants was found to be 31.9%. We observed a significant association between marital status and IBS (χ2 = 3.95, P = .047). Furthermore, the highest prevalence of IBS was observed among students majoring in literary and scientific disciplines (χ2 = 0.952, P = .049). Individuals with IBS demonstrate a significantly higher prevalence of anxiety (71.90% vs 41.09%, P < .001) and depression (64.46% vs 42.64%, P < .001) compared to those without IBS. Furthermore, people with IBS had a slightly higher prevalence of poor well-being (38.84%) compared to those without IBS (33.72%), but this association was not statistically significant. In multivariate analysis, having a family history of IBS [OR = 1.75 (95% CI, 1.06-2.87), P = .029] having borderline anxiety [OR = 7.58, 95% CI (2.12-27.06), P = .012] and anxiety [OR = 16.07, 95% CI (4.57-56.52), P < .001], and depression [OR = 2.97, 95% CI (1.13-7.83), P = .010] were the main significant predictors of IBS among university students. The high prevalence of IBS among university students was associated with a family history of IBS as well as depression and anxiety. Increasing awareness, multidisciplinary support, and access to mental health services is required to ensure university students' well-being., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In the wake of rapid industrialization and burgeoning transportation networks, the escalating demand for fossil fuels has accelerated the depletion of finite energy reservoirs, necessitating urgent exploration of sustainable alternatives. To address this, current research is focusing on renewable fuels like second-generation bioethanol from agricultural waste such as sugarcane bagasse. This approach not only circumvents the contentious issue of food-fuel conflicts associated with biofuels but also tackles agricultural waste management. In the present study indigenous yeast strain, Clavispora lusitaniae QG1 (MN592676), was isolated from rotten grapes to ferment xylose sugars present in the hemicellulose content of sugarcane bagasse. To liberate the xylose sugars, dilute acid pretreatment was performed. The highest reducing sugars yield was 1.2% obtained at a temperature of 121 °C for 15 min, a solid-to-liquid ratio of 1:25 (% w/v), and an acid concentration of 1% dilute acid H 2 SO 4 that was significantly higher (P < 0.001) yield obtained under similar conditions at 100 °C for 1 h. The isolated strain was statistically optimized for fermentation process by Plackett-Burman design to achieve the highest ethanol yield. Liberated xylose sugars were completely utilized by Clavispora lusitaniae QG1 (MN592676) and gave 100% ethanol yield. This study optimizes both fermentation process and pretreatment of sugarcane bagasse to maximize bioethanol yield and demonstrates the ability of isolated strain to effectively utilize xylose as a carbon source. The desirable characteristics depicted by strain Clavispora lusitaniae shows its promising utilization in management of industrial waste like sugarcane bagasse by its conversion into renewable biofuels like bioethanol., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dementia is characterized by a progressive loss of cognitive abilities, and diagnosing its early stages Mild Cognitive Impairment (MCI), is difficult since it is a transitory state that is different from total cognitive collapse. Recent clinical research studies have identified that balance impairments can be a significant indicator for predicting dementia in older adults. Accordingly, the current research focuses on finding innovative postural balance-based digital biomarkers by using wearable inertial sensors and pre-screening of MCI in home settings using machine learning techniques. For this research, sixty subjects (30 cognitively normal and 30 MCI) with waist-mounted inertial sensor performed balance tasks in four different standing postures: eyes-open, eyes-closed, right-leg-lift, and left-leg-lift. The significant balance biomarkers for MCI identification are discovered by our research, demonstrating specific characteristics in each of these four states. A robust feature selection approach is ensured by the multi-step methodology that combines the strengths of Filter techniques, Wrapper methods, and SHAP (Shapley Additive exPlanations) technique. The proposed balance biomarkers have the potential to detect MCI (with 75.8% accuracy), as evidenced by the results of machine learning algorithms for classification. This work adds to the growing body of literature targeted at enhancing understanding and proactive management of cognitive loss in older populations and lays the groundwork for future research efforts aimed at refining digital biomarkers, validating findings, and exploring longitudinal perspectives., (© 2024. The Author(s).)

Allergic asthma is a widely prevalent inflammatory condition affecting people across the globe. T cells and their secretory cytokines are central to the pathogenesis of allergic asthma. Here, we have evaluated the anti-inflammatory impact of dimethyl fumarate (DMF) in allergic asthma with more focus on determining its effect on T cell responses in allergic asthma. By utilizing the ovalbumin (OVA)-induced allergic asthma model, we observed that DMF administration reduced the allergic asthma symptoms and IgE levels in the OVA-induced mice model. Histopathological analysis showed that DMF treatment in an OVA-induced animal model eased the inflammation in the nasal and bronchial tissues, with a particular decrease in the infiltration of immune cells. Additionally, RT-qPCR analysis exhibited that treatment of DMF in an OVA-induced model reduced the expression of inflammatory cytokine (IL4, IL13, and IL17) while augmenting anti-inflammatory IL10 and Foxp3 (forkhead box protein 3). Mechanistically, we found that DMF increased the expression of Foxp3 by exacerbating the expression of nuclear factor E2-related factor 2 (Nrf2), and the in-vitro activation of Foxp3+ Tregs leads to an escalated expression of Nrf2. Notably, CD4-specific Nrf2 deletion intensified the allergic asthma symptoms and reduced the in-vitro iTreg differentiation. Meanwhile, DMF failed to exert protective effects on OVA-induced allergic asthma in CD4-specific Nrf2 knock-out mice. Overall, our study illustrates that DMF enhances Nrf2 signaling in T cells to assist the differentiation of Tregs, which could improve the anti-inflammatory immune response in allergic asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cen, Li, Li, Zhang, Riaz, Zhao, Wei and Pan.)

Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship and/or publication of this article.

The lentil ( Lens culinaris Medikus ssp. Culinaris) is a self-pollinating, diploid (2n = 2X = 14) crop with a genome size of 4 Gbp. The present study was conducted to provide a database for the evaluation of lentil antioxidant capacity, nutritional quality, and biochemical attributes. For these purposes, lentil germplasm, including 100 exotic and local genotypes from different agro-climatic zones of Pakistan, was collected. Significant variation ( p  < 0.05) was found among the genotypes under investigation using the Tukey HSD test. Ascorbate peroxidase was highest in ALTINOPARK (2,465 Units/g s. wt.), catalase in LPP 12110 (5,595 Units/g s. wt.), superoxide dismutase in LPP 12105 (296.75 Units/g s. wt.), and peroxidase in NIAB Masoor 2002 (3,170 Units/g s. wt.). Furthermore, NLM 15016 had a maximum total antioxidant capacity of 15.763 mg/g s. wt. The maximum values of total soluble sugars (83.93 mg/g. s. wt.) and non-reducing sugars (74.79 mg/g. s. wt.) were noticed in NLM 15015. The highest reducing sugars were detected in ILL 8006 (45.68 mg/g. s. wt.) ascorbic acid in LPP 12182 (706 μg/g s. wt.), total phenolic content in NLI 17003 (54,600 μM/g s. wt.), and tannins in NLI 17057 (24,563 μM/g s. wt.). The highest chlorophyll a (236.12 μg/g s. wt.), chlorophyll b (317 μg/g s. wt.), total chlorophyll (552.58 μg/g s. wt.), and lycopene (10.881 μg/g s. wt.) were found in NLH 12097. Maximum total carotenoids were revealed in the local approved variety Markaz 2009 (17.89 μg/g s. wt.). Principal component analysis (PCA), correlation analysis (Pearson's test), and agglomerative hierarchical clustering (AHC) were performed to detect the extent of variation in genotypes. In cluster analysis, all genotypes were categorized into three clusters. Cluster II genotypes showed remarkable divergence with cluster III. According to PCA, the contribution of PC-I regarding tested nutritional parameters toward variability was the highest (39.75%) and indicated positive factor loading for the tested nutritional and biochemical parameters. In conclusion, genotype X 2011S 33-34-32 can be used by the food industry in making pasta, multigrain bread, and snacking foods due to its high protein content for meat alternative seekers. Identified genotypes with high nutritional attributes can be utilized to improve quality parameters in the respective lentil breeding lines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Riaz, Hameed and Asghar.)

Background: Crohn's disease (CD) is characterized by granulomatous inflammation of the digestive tract. Diagnosing CD involves assessing clinical symptoms, radiological and endoscopic findings, and histopathological evidence. Although previously considered a disease in developed countries, CD is increasing in developing nations, but challenges exist in diagnosing CD promptly. This study aims to report diagnostic parameters for early and correct CD diagnosis in Pakistan., Methodology: A retrospective analysis from June 2016 to August 2023 of 22 CD patients was done, by data from medical records, questionnaires completed at diagnosis, and telephonic interviews. Baseline demographic and clinical characteristics were assessed, and patients were categorized using the Montreal classification., Results: CD was diagnosed in 22 patients, with a 1:1 male-to-female ratio with a mean age of 33 years (range 15-55 years). Symptoms at presentation included abdominal pain (95.5%), watery diarrhea (86.4%), fever (31.8%), rectal bleeding (54.5%), and weight loss (81.8%) with 68% having symptoms for over 12 months before diagnosis. Disease characteristics were diverse, with various patterns of involvement and histopathological findings., Conclusions: In resource-limited countries like Pakistan, the timely diagnosis of CD presents a significant healthcare challenge. Therefore, it is necessary to tackle these complex problems by enhancing diagnostic capabilities, raising medical awareness, and improving access to healthcare resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Buffaloes are considered animals of the future with the ability to survive under unfavorable conditions. However, the lack of access to superior germplasm poses a significant challenge to increasing buffalo production. Resveratrol has been shown to improve oocyte quality and developmental competence in various animals during in vitro embryo development. However, limited information is available on the use of resveratrol to improve the in vitro maturation and development competence of Nili Ravi buffalo oocytes. Therefore, the current study aimed to investigate the influence of different concentrations of resveratrol on the maturation, fertilization, and development of buffalo oocytes under in vitro conditions. Oocytes were collected from ovaries and subjected to in vitro maturation (IVM) using varying concentrations of resveratrol (0 µM, 0.5 µM, 1 µM, 1.5 µM, and 2 µM), and the maturation process was assessed using a fluorescent staining technique. Results indicated no significant differences in oocyte maturation, morula rate, and blastocyst rate among the various resveratrol concentrations. However, the cleavage rate notably increased with 1 µM and 1.5 µM concentrations of resveratrol (p < 0.05). In conclusion, the study suggests that adding 1 µM of resveratrol into the maturation media may enhance the cleavage and blastocyst hatching of oocytes of Nili Ravi buffaloes. These findings hold promise for advancing buffalo genetics, reproductive performance, and overall productivity, offering potential benefits to the dairy industry, especially in Asian countries., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Sjögren's syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome. In general, adding a methyl group to DNA is linked with the inhibition of genes because it changes the chromatin structure. DNA methylation changes the fate of multiple immune cells, such as it leads to the transition of naïve lymphocytes to effector lymphocytes. A lack of central epigenetic enzymes frequently results in abnormal immune activation. Alterations in epigenetic modifications within immune cells or salivary gland epithelial cells are frequently detected during the pathogenesis of SjS, representing a robust association with autoimmune responses. The analysis of genome methylation is a beneficial tool for establishing connections between epigenetic changes within different cell types and their association with SjS. In various studies related to SjS, most differentially methylated regions are in the human leukocyte antigen (HLA) locus. Notably, the demethylation of various sites in the genome is often observed in SjS patients. The most strongly linked differentially methylated regions in SjS patients are found within genes regulated by type I interferon. This demethylation process is partly related to B-cell infiltration and disease progression. In addition, DNA demethylation of the runt-related transcription factor (RUNX1) gene, lymphotoxin-α (LTA), and myxovirus resistance protein A (MxA) is associated with SjS. It may assist the early diagnosis of SjS by serving as a potential biomarker. Therefore, this review offers a detailed insight into the function of DNA methylation in SjS and helps researchers to identify potential biomarkers in diagnosis, prognosis, and therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Riaz, Wang, Pu, Liang, Wu, Pan, Song, Yang, Zhang, Wu, Han, Tang and Wang.)

Metastatic disease, a leading and lethal indication of deaths associated with tumors, results from the dissemination of metastatic tumor cells from the site of primary origin to a distant organ. Dispersion of metastatic cells during the development of tumors at distant organs leads to failure to comply with conventional treatments, ultimately instigating abrupt tissue homeostasis and organ failure. Increasing evidence indicates that the tumor microenvironment (TME) is a crucial factor in cancer progression and the process of metastatic tumor development at secondary sites. TME comprises several factors contributing to the initiation and progression of the metastatic cascade. Among these, various cell types in TME, such as mesenchymal stem cells (MSCs), lymphatic endothelial cells (LECs), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), T cells, and tumor-associated macrophages (TAMs), are significant players participating in cancer metastasis. Besides, various other factors, such as extracellular matrix (ECM), gut microbiota, circadian rhythm, and hypoxia, also shape the TME and impact the metastatic cascade. A thorough understanding of the functions of TME components in tumor progression and metastasis is necessary to discover new therapeutic strategies targeting the metastatic tumor cells and TME. Therefore, we reviewed these pivotal TME components and highlighted the background knowledge on how these cell types and disrupted components of TME influence the metastatic cascade and establish the premetastatic niche. This review will help researchers identify these altered components' molecular patterns and design an optimized, targeted therapy to treat solid tumors and restrict metastatic cascade., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Riaz, Zhang and Pan.)

Purpose of Review: This review highlights important changes in our understanding of triple-negative breast cancer. It highlights important novel approaches in treatment and reviews predicts potential challenges facing the treatment of triple-negative breast cancer., Recent Findings: There is a clear shift away from chemotherapy-centric approaches to the treatment of breast cancer, and instead, a move towards incorporating immune checkpoint inhibitors, antibody-drug conjugates, and other targeted therapies. There is a focus on understanding biomarkers and leveraging novel targets in drug development., Summary: It is now standard of care to use neoadjuvant combination immunotherapy-chemotherapy in patients with Stage 1 and 2 breast cancers. Chemo-immunotherapy combinations when appropriate biomarkers are present (PD-L1) are standard first-line therapy in metastatic triple-negative breast cancer. Antibody-drug conjugates are now a mainstay in the treatment of this disease. These findings have shifted the treatment paradigm of the treatment of triple-negative breast cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Patients with inborn errors of immunity (IEI) are predisposed to severe recurrent/chronic infections, and often require hospitalization, resulting in substantial burden to patients/healthcare systems. While immunoglobulin replacement therapies (IgRTs) are the standard first-line treatment for most forms of IEI, limited real-world data exist regarding clinical characteristics and treatment costs for patients with IEI initiating such treatment. This retrospective analysis examined infection and treatment characteristics in US patients with IEI initiating IgRT with immune globulin infusion (human), 10% (IG10%). Healthcare resource utilization (HCRU) and associated costs before and after treatment initiation were compared. Additionally, the impact of COVID-19 on infection diagnoses was evaluated., Methods: Patients with IEI initiating IG10% between July 2012 and August 2019 were selected from Merative MarketScan Databases using diagnosis/prescription codes. Patients were followed 6 months before and after first IG10% claim date. Demographic and clinical characteristics were described. Treatment characteristics and HCRU before and after IG10% initiation were compared. Infection diagnoses during 2020 and 2019 (March-December) were compared., Results: The study included 1,497 patients with IEI diagnoses (mean age = 43.4 years) initiating IG10%, with frequently reported comorbidities like asthma (32.1%). Following IG10% initiation, fewer severe infection diagnoses (11.6% vs 19.9%), fewer infection-related inpatient (10.8% vs 19.5%) and outpatient services (71.6% vs 79.9%), and lower infection-related total healthcare costs ($7,849 vs $13,995; p  < 0.001)-driven by lower inpatient costs ($2,746 vs $9,900)-were observed than before. Fewer patients had infection diagnoses during COVID-19 (22.8%) than the prior year (31.2%)., Conclusion: Patients with IEI are susceptible to severe infections leading to high disease burden and treatment costs. Following IG10% initiation, we observed fewer infections, lower infection-related treatment costs, and shift in care (inpatient to outpatient) leading to significant cost savings. Among patients with IEI, 27% fewer infection diagnoses were observed during the early COVID-19 lockdown period than the prior year.

Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder with a significant global impact, affecting approximately 50 million individuals, and projections estimate that up to 152 million people will be affected by 2050. AD is characterized by beta-amyloid plaques and tau tangles in the brain, leading to cognitive decline., Summary: Recent research on AD has made significant strides, including the development of an "amyloid clock" biomarker that tracks AD progression through positron emission tomography (PET) scans. Surf4 and other genes have been discovered to play a role in regulating beta-amyloid toxicity, while inhibiting the enzyme hexokinase-2 has shown positive results in preclinical studies. New brain mapping techniques have identified early brain-based causes of cognitive changes in AD, and biomarkers such as neuronal pentraxin protein Nptx2 and astrocytic 7-subunit of the nicotinic acetylcholine receptors (7nAChRs) show potential for early detection. Other approaches, such as replenishing the enzyme Tip60, selectively degrading the modified protein p-p38 with PRZ-18002, and targeting the protein voltage-dependent anion channel-1 (VDAC1), have shown promise in enhancing cognitive function and preventing pathophysiological alterations linked to AD. Baseline blood samples and other biomarkers such as urine formic acid, p-tau 198, microRNAs, and glial fibrillary acidic protein (GFAP) have also been discovered for early detection and intervention of AD. Additionally, recent FDA approvals for medications such as aducanumab and lecanemab provide options for reducing AD symptoms and improving function, while clinical trials for dementia vaccines show promise for the nasal and beta-amyloid 40 vaccines as well as vaccinations targeting tau., Key Messages: These advancements in AD research, including biomarker discovery and the development of disease-modifying treatments, are crucial steps towards improving the lives of those affected by AD and finding a cure for this debilitating disease., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)