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Some researchers claim that Muslim scholars do not emphasize the importance of Bayt al-Maqdis as strongly as they do upon the two holy cities of Islam, Makkah and Madinah. Even when they do, their writings are mixed with weak and forged narrations. Additionally, their efforts aimed to strengthen the political position of certain caliphs. In the current regional situation, some Muslims radically and literally interpret the hadith out of context to support the liberation of Bayt al-Maqdis. They believe that participating in jihadi group is a noble effort, even if it involves suicide bombings. Based on these issues, this article explores the efforts of scholars in hadith scholarship related to Bayt al-Maqdis. Specifically, it examines the perspective of a prominent hadith scholar, Imam al-Bukhari, in his initiative to compile hadiths, which he placed in different chapters of his book al-Jāmi’ al-Ṣaḥīḥ. This study employs a library research approach involving content analysis. The findings of this study reveal that numerous Muslim scholars have contributed significantly to Islamic scholarship in Bayt al-Maqdis through writing and the dissemination of knowledge. Specifically, they compiled hadiths about Bayt al-Maqdis in certain books and chapters. Imam al-Bukhari documented 12 narrations related to Bayt al-Maqdis in 9 books and 13 chapters. This study selected one hadith that is almost identical but is placed under four different chapters. This illustrates the unique way a single narration, both textually and contextually, can explain the significance and position of Bayt al-Maqdis in Islam from diverse and interesting perspectives. This study recommends continuing the exploration of hadiths related to Bayt al-Maqdis to examine various other forms of Tarājim. This will help the Muslim community, in particular, to understand the hadith texts comprehensively while simultaneously refuting the argument that Islam neglects this third holy city.

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100–AY.44 and Omicron BA.1–BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01, HLA-A*26:01, and HLA-B*53:01, and relatively protected from disease, such as HLA-A*31:01, HLA-B*40:01, HLA-B*44:03, and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8+ epitope diversity that putatively impacts much of the United States population.

Big data classification is a challenging task because most known classification methods need a long time and a lot of processing resources to execute such a task and use the vast amount of available data. In this paper, we propose a novel big data classification method that leverages the power of the KNN classifier and the efficiency of the ensemble learning technique to create a new method capable of performing classification tasks on big data efficiently. The proposed method picks tiny data chunks at random from a big dataset, with each chunk including random examples of a small number of randomly selected features. A weak KNN classifier is employed on each data chunk to perform classification on new (unseen) data, and the majority voting rule is used to reach the final classification decision based on the outcomes of the weak classifiers. The proposed method has a constant classification time, according to the time complexity analysis. Furthermore, the proposed method was found to be more efficient on a single node than existing methods, some of which run on a large cluster of nodes. Because of its speed and enhanced performance, the proposed method can be considered an ideal classifier for handling complex data types such as Geospatial data, Big trajectory data, and Big Data in general.

Multiple myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of Granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T cells from patients with MM more closely resembles TCR-activated CD8+ T cells from age-matched controls than their resting counterparts.

OBJECTIVES/GOALS: Our goal was to distinguish SARS-CoV-2 CD8+ T cell epitopes of spike, membrane, and nucleocapsid products in 27 of the most frequent HLA-Aand -B alleles.We hypothesize that differences mediated by variation in SARS-CoV-2 and host HLA genetics affect the differential clinical severity and presentation of acute infection and PASC. METHODS/STUDY POPULATION: Genomic sequences of SARS-CoV-2 variants were blasted against the original Wuhan strain using Ensembl’s SARS-CoV-2 browser. We examined 16 COVID variants: 2 Alpha (B.1 and B.1.1.7), 5 Delta (AY.100, AY.25, AY.3, AY.3.1, and AY.44), and 9 Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, and XBB.1.5), sequenced from the Louisiana patient population. cDNA sequences were translated using the Expasy tool. To predict MHC-I epitope binding, we used the Immune Epitope Database and Analysis Resource, via TepiTool utilizing the IEDB recommended default prediction and the 27 most frequent HLA-A and -B alleles. In silico peptide docking was conducted on FoldX, utilizing HLA-B*15:01 structures (n= 7) from the Protein Data Bank. RESULTS/ANTICIPATED RESULTS: CD8+ epitope conservation was estimated at 87.6-96.5% in S, 92.5-99.6% in M, and 94.6-99% for N. As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1- XBB.1.5 S epitopes experienced decreased predicted binding, as compared to ~ 3% and ~15% in Delta AY.100-AY.44 and Omicron BA.1-BA.5 respectively. Additionally, we identified several novel candidate haplotypes that may be susceptible to severe disease, notably HLA-A*32:01, -A*26:01, -B*58:01, and -B*53:01, and relatively protected from disease, such as -A*01:01, -A*02:01,-A*31:01, -B*15:01, -B*40:01, -B*44:03, and -B*57:01. In silico analysis of COVID peptides and HLA-B*15:01, a common allotype in the United States, largely matched predicted binding patterns. DISCUSSION/SIGNIFICANCE: To elicit long term COVID-19 immunity and prevent PASC, it is important to understand the relationship between T-cells, viral variants, and HLA genetics. This project is one of the first to explore the interaction between CD8+ epitope diversity and viral genetics for the majority of the United States population.

A laboratory experiment was carried out under the laboratory natural conditions of Seed Technology Laboratory, Department of Field Crops, College of Agriculture, University of Anbar, Iraq, during year of 2017, to study the effect of seed priming (concentrations of potassium chloride solution KCl i.e. 0, 15, 20, 25 and 30 mg L-1) on germination and seedling vigor of two sorghum cultivars (Rabih and Inkath). The experiment was carried out in factorial experiment in completely randomized design (CRD) with four replications. The main results of this study were as follow; Rabih cultivar significantly superior Inkath cultivar and resulted in the highest values of germination speed and final germination percentages, radical length and seedling vigor index. While, Inkath cultivar resulted in the highest values of plumel length. Germination and seedling vigor parameters were significantly enhanced as increasing concentration of potassium chloride (KCl) as seed priming from 0 to 15 and 20 mg L-1. Conversely, increasing concentration of KCl as seed priming from 25 to 30 and 20 mg L-1 significantly decreased germination and seedling vigor parameters. It could be concluded that priming seeds of Rabih sorghum cultivar in 20 mg KCl L-1 for 24 hours to enhance germination and seedling vigor characters. [ABSTRACT FROM AUTHOR]

Emotion has impact on individuals’ ways of thinking and actions. It can be manifested physically and verbally. Studies indicate that male and female behaviours are dissimilars in emotional coping and reactions. Studies also underline the presence of internal and external factors, which related to stress and anxiety that can influence women’s emotions. The failure of dealing with emotional burdens and battles can be devastating as it gives negative impacts to the individuals and community’s quality of life and well-being. The aim of this article is to highlight the importance of emotional coping skill by examining the stories of women in the Quran.Verses of the Quran related to the stories of Maryam in the Quran and exegeses are compiled and analysed thematically. This article explores the personality of Maryam, the mother of Prophet Isa through the lens of life challenges and important elements and references in emotional coping. It classifies Maryam’s life into four phases starting from her infancy to motherhood. Through those phases, Maryam underwent hardships and contested with the Israilites’ tradition and challenges. This article concludes there are six important points in emotional coping skills that can empower women while dealing with life challenges and predicaments. They are: (i) stronghold of faith; (ii) consistency in religious ritual and submission; (iii) continuous efforts in purifying of soul; (iv) living in isolation or physically separating from toxic environment; (v) seeking for external moral and physical supports; and (vi) sharpening essential life skills and strategies.

The research aims to show the histopathological changes caused by Intistinal protozoa in differ tissues in the body (liver, lung, intesitant) infection in laboratory animals (1 Week, 2 Week, 1 Month, 2 Month). Histopathological examination of liver, lung, Intesitant showed the presence of degeneration and necrotic hepatic cyts and emphysema in alveolar alveoli in the lung and mucinous degeneration in the cell epithelium cell intestinal glands, distortion of vill in intestine.

This research aimed to studying the pathological effects of intestinal parasite Entanebahistolytica& Giardia lamblia on the Hemoglobin concentration and number of WBCs in the albino mice by measuring the concentration Hb and number of WBCs after oral adminstratier of the parasites and various concentrations of (1000, 10,000.100000) and periods fixed time (week, two weeks, a month, two months) It was the follow-up changes that occur in different concentrations of these parasites, this study shows increase in the number of WBCs and decrease in the Hb..

Service-Learning or the learning based on service is defined as a method of teaching and learning strategy which optimized experiences in serving the community. Although this practice of teaching and learning has given positive impacts; practitioners and researchers alike are still uneven in their consent regarding the best way to define and characterize the concept of Service-Learning. The main focus of this article is to analyze the key elements in the definition about Service Learning. This article will discuss and elaborate on the concept of Service Learning into four main parts, namely; a general explanation of Service-Learning, different kinds of participation in Service-Learning, the approaches in Service-Learning and the impacts of Service-Learning. In confronting the challenges of the 21st century learning strategy, the implementation of Service- Learning as a learning process based on experiences is timely because it provides students with a strong knowledge for the content of the course, the skills required by the market career, also in instilling positive values required for community development and community change.

Abstract Objective MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR. Results The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.

Multiple Myeloma (MM) is preceded by the clinically stable condition monoclonal gammopathy of undetermined significance (MGUS). Critical immune events that discriminate MGUS from newly diagnosed MM (ND)MM patients remain unknown, but may involve changes in the regulatory T cell (Treg) compartment that favor myeloma growth. To address this possibility, we used mass cytometry and the unsupervised clustering algorithm Flow self-organizing map (FlowSOM) to interrogate the distribution of multiple subsets within CD25+CD127low/negTreg in matched bone marrow (BM) and peripheral blood (PB) of MGUS and NDMM patients. Both mass cytometry and flow cytometry confirmed a trend toward prevalence of CD39−Treg within the Treg compartment in BM and PB of NDMM patients compared to CD39−Treg in MGUS patients. FlowSOM clustering displayed a phenotypic organization of Treg into 25 metaclusters that confirmed Treg heterogeneity. It identified two subsets which emerged within CD39−Treg of NDMM patients that were negligible or absent in CD39−Treg of MGUS patients. One subset was found in both BM and PB which phenotypically resembled activated Treg based on CD45RO, CD49d, and CD62L expression; another subset resembled BM-resident Treg based on its tissue-resident CD69+CD62L−CD49d− phenotype and restricted location within the BM. Both subsets co-expressed PD-1 and TIGIT, but PD-1 was expressed at higher levels on BM-resident Treg than on activated Treg. Within BM, both subsets had limited Perforin and Granzyme B production, whilst activated Treg in PB acquired high Perforin and Granzyme B production. In conclusion, the use of mass cytometry and FlowSOM clustering discovered two discrete subsets of CD39−Treg which are discordant in MGUS and NDMM patients and may be permissive of myeloma growth which warrants further study. Understanding the regulatory properties of these subsets may also advance MGUS and MM diagnosis, prognosis, and therapeutic implications for MM patients.

Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD.

Background: Mental health is a critical aspect of overall well-being, influencing how individuals think, feel, and perform. Mental health among healthcare students has become a major concern, drawing attention due to its profound impact on their welfare, academic performance, and ability to effectively interact with patients. This paper aimed to explore the experiences of undergraduate healthcare students facing mental health challenges at Qatar University. With a focus on understanding the factors contributing to mental health issues and exploring their coping mechanisms, the research also sought to identify students' recommendations for institutional support to improve their mental well-being., Methods: A qualitative approach using semi-structured face-to-face interviews was employed to collect data. A purposive sampling method was used to recruit students from five healthcare disciplines- Medicine, Dentistry, Pharmacy, Health Sciences and Nursing- who had self-reported mild to moderate depressive symptoms based on the Patient Health Questionnaire (PHQ-9) and Depression Anxiety and Stress Scale (DASS21). A total of 15 interviews were conducted, recorded, and transcribed verbatim, with thematic analysis used to identify key themes., Results: Several themes emerged from the interviews, including academic pressure, social isolation, anxiety, coping mechanisms, fear of failure, and stigma surrounding mental health support. Academic pressure was consistently reported as a major stressor, contributing to anxiety and emotional strain. Social isolation further exacerbated mental health challenges, while many students highlighted a lack of well-established coping strategies. Stigma related to seeking mental health support was a significant barrier, preventing students from accessing available services., Conclusion: The study highlights the mental health challenges faced by healthcare students, emphasizing the need for effective institutional mental health support. Addressing academic pressures, enhancing self-coping mechanisms and social support systems, and reducing the stigma around mental health care are essential steps toward improving student well-being., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: All methods were carried out in accordance with relevant guidelines and regulations (Declaration of Helsinki). All experimental protocols were approved by the Institutional Review Board (IRB) at Qatar University (QU-IRB1797-EA/23 January 2023). Informed consent was obtained from all subjects and/or their legal guardian(s). Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Several mechanisms were postulated to reduce drilling problems, improve hole cleaning characteristics, and keep the bit in good condition for the second usage. This study was conducted on Majnoon Field in southeastern Iraq to optimize the bit and drilling parameters. The results indicated that the 16" SFD75D bit proved the preferred bit for both vertical and deviated wells due to its directional capabilities. MMD and MME were the best bit types for 12.25" and 8.5" sections and proved more successful than the FX and EQ types. The maximum weight on bit (WOB), Round per Minute (RPM), mud weight, and flow rate must be 25.45-73 klbs, 50-179.22, 10.5-10.8 ppg, and 662-940 gpm respectively, according to the drilling section. The wells with the J-shape showed a better penetration rate (increased 50-100%) and steadier torque than those with the S-shape for all drilling sections, with some deviations in the Shiranish, Sadi, and Tanuma Formations. The wells in the south have a sliding percentage of drilling hours more than in the north of the Field, and the inclination of the wells in the south was generally more stable and had lower hydraulics requirements than in the north of the Field., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study aimed to evaluate the positional and morphological changes in the temporomandibular joint (TMJ) in adult patients with skeletal Class I malocclusion treated with fixed orthodontic appliances (FAs) and clear aligners (CAs), both with and without premolar extractions., Methods: This retrospective study involved 120 adult patients divided into non-extraction and extraction groups, each further subdivided equally into those treated with FAs and CAs. Cone beam computed tomography (CBCT) was used to assess the TMJ measurements before (T0) and after treatment (T1). Statistical analyses were conducted to compare the mean changes in intra- and inter-groups. A significance level of p ≤ 0.05 was considered., Results: In the non-extraction group, specifically in FAs, significant increases were observed in TMJ parameters; anteroposterior condylar position (APCP) and mediolateral condylar inclination (MCI). Conversely, significant decreases were noted in vertical condylar position (VCP) and vertical condylar inclination (VCI). In the extraction group, significant increases were noted in APCP and anterior joint space (AJS), while posterior joint space (PJS) and anteroposterior condylar joint position (APCJP) decreased. For inter-group comparisons, the extraction group showed significant increases in APCP in FAs compared to CAs, and a significant decrease in APCJP in FAs compared to CAs., Conclusion: FAs significantly impact condylar positions and joint spaces, especially in extraction cases. Monitoring TMJ parameters during orthodontic treatment is crucial to ensure positive outcomes and prevent TMJ disorders (TMDs). These findings may guide the selection of orthodontic appliances based on individual malocclusion characteristics., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of the China Medical University School of Stomatology approved this study (Ethics Approval No. CMUKQ-2024-019). All methods adhered to the principles of the Declaration of Helsinki. Informed consent was obtained from all participants prior to their inclusion in the study. To protect patient confidentiality, all identifiable information was removed from CBCT data, and anonymized datasets were used. Only the research team accessed securely stored data, adhering to ethical and regulatory standards. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Objectives: This study aims to assess the alterations in condylar positioning in adult skeletal Class I patients with unilateral posterior crossbite after microimplant-assisted rapid palatal expansion (MARPE) treatment., Methods: This retrospective study involving 30 participants (10 males, 20 females) average age 22.9 ± 4.2 years and they ranged in age from (18.1 to 30.9 years) who treated with a customized microimplant-supported rapid palatal expander. Pre-expansion and post comprehensive orthodontic treatment CBCT images (20-26 ±2.1months) were analyzed to assessed the condylar changes before and after treatment. We measured the temporomandibular joint (TMJ) in 3D in terms of: (1) the position, angle and tilt of the mandibular condyles; (2) how centralized the condyles were in their particular mandibular fossae; and (3) the volume of the TMJ and TMJ spaces. To evaluate the differences between the T1 and T2 samples, we used the paired t-test and the Wilcoxon signed rank test., Results: Before treatment, minor differences were noted in the anterior joint space (AJS), superior joint space (SJS), and anteroposterior condylar joint position (APCJP) between the crossbite and non-crossbite sides, though these differences were not statistically significant. Post-treatment, the condyles on both sides assumed a more posterior position, yet significant asymmetry in the AJS persisted (P < .05). The crossbite-side condyle also showed a tendency to rotate toward the non-crossbite side in the anteroposterior direction. While MARPE affected specific aspects of condylar positioning, achieving complete alignment remained challenging., Conclusion: This study provides insightful observations on the enduring impacts of MARPE on TMJ spaces and position in adult patients suffering from a unilateral posterior crossbite., Competing Interests: Declaration of competing interest I confirm that there are no conflicts of interest associated with this article. Please consider this as the formal statement regarding the absence of conflicts of interest., (Copyright © 2025. Published by Elsevier Masson SAS.)

Objective: This study aimed to assess the effect of implantation of fresh human amniotic membranes (HAM) on bone consolidation during distraction bone lengthening., Methods: Ten New Zealand white rabbits were used in this study. For each rabbit, we performed a diaphyseal tibial osteotomy after installing a single-plane distraction external fixator. Rabbits were divided into 2 groups (n = 5): an osteotomy and rapid lengthening of 2.8 mm/days (negative control (NC) group) or an osteotomy with implantation of fresh HAM and rapid lengthening of 2.8 mm/days (HAM group). We carried out a rapid lengthening at a rate of 2 turns/day for 7 days and a single turn on the 8th day knowing that one turn corresponds to an elongation of 1.4 mm. The total elongation obtained was 21 mm corresponding to 20-25 % of the length of the rabbit's tibia. A radiological study was carried out on 4 and 8 weeks after the end of lengthening. Micro-computed tomography (μ-CT) analysis was carried out 8 weeks after the end of the lengthening and after the sacrifice of the rabbits associated with histological analyses., Results: For the HAM group, radiographic analysis showed that all cases consolidated with a homogeneous callus visible at 1 month after lengthening, and complete corticalization was demonstrated at μ-CT analysis. Histological staining exhibited thick continuous cortices with intramedullary fibro adipose tissue with a medulla rich in hematopoietic cells., Conclusion: The results show that HAM affects the stimulation of bone consolidation during bone lengthening by distraction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial conflicts or interpersonal connections that could have appeared to influence the work reported in this study., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Etrasimod (ADP334) is an oral, once-daily, selective sphingosine 1-phosphate (S1P) 1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis and in development for the treatment of immune-mediated inflammatory diseases. Interaction between S1P and its five receptor subtypes (S1P 1 -S1P 5 ) plays a role in several physiologic systems, including the cardiovascular and immune systems. Since differences in S1PR binding and downstream intracellular signaling could contribute to distinct profiles of drug efficacy and safety, we directly compared the S1P 1-5 selectivity profile of etrasimod to three marketed S1PR modulators: fingolimod, ozanimod, and siponimod. Using both heterologous expression systems and human umbilical vein endothelial cells that spontaneously express S1P 1 , we profiled key S1P 1 downstream signaling pathways and found that etrasimod had similar potency to the other tested S1PR modulators in promoting β-arrestin recruitment and S1P 1 internalization. However, etrasimod was notably less potent than other S1PR modulators in assays measuring S1P 1 -mediated G protein activation (GTPγS binding and cAMP inhibition). Relatively lower potency of etrasimod in inducing G protein signaling corresponded to significantly diminished activation of human cardiac G protein-coupled inwardly rectifying potassium channels when compared to ozanimod. Together with pharmacokinetic properties, this pharmacologic profile of etrasimod may contribute to the positive benefit risk profile of etrasimod observed during the phase III ELEVATE UC 52 and ELEVATE UC 12 trials in patients with moderately to severely active ulcerative colitis., (© 2024 Pfizer. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Objectives: Ozone (O 2 -O 3 ) nucleolysis is emerging as a promising minimally invasive therapy for treating lumbosciatica due to herniated discs. This study aims to evaluate changes in pain and functional abilities before and after ozone disc nucleolysis in patients with lumbar disc herniation (LDH)., Materials and Methods: This study included 34 patients (15 males, 19 females; age range 17-76, average age 46.7 ± 11.2 years) treated between April 2018 and May 2022. A single dose of an O 2 -O 3 mixture (5 ml, 30 µg/ml) was injected into the disc under fluoroscopic guidance via a lateral approach, followed by an additional periradicular injection of the same mixture (5 ml) combined with a corticosteroid (2 ml). Pain and patient satisfaction were assessed using the VAS score and modified MacNab criteria, while MRI findings evaluated treatment-related changes, including herniated disc surface and disc height., Results: VAS scores indicated pain improvement in 85% of patients, with 82% achieving satisfactory outcomes per modified MacNab criteria. Patients under 50 years of age showed greater responsiveness to ozone therapy. Central LDH responded more favorably than larger foraminal herniations, and hernias with a larger surface area than the average also showed better outcomes. No complications were observed., Conclusion: Ozone therapy is a cost-effective, simple, and safe minimally invasive technique that provides significant pain relief and functional improvement. It may be a reliable and competitive treatment option for patients with persistent symptoms after conservative treatment and before considering surgical intervention. Key Points •Ozone nucleolysis provides a minimally invasive treatment for lumbosciatica with reduced recovery time. •Injecting oxygen-ozone into the disc decreases its volume and inflammation, easing nerve pressure. •Initial results show significant pain relief and improved mobility in patients following treatment. •This method appears safe, with fewer complications than traditional surgery for herniated discs., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

This study investigates the integration of Ti 3 C 2 T x (MX) and Ag/Ti 3 C 2 T x (Ag/MX) nanocomposites into polylactic acid membranes to enhance hydrophilicity and impart antibacterial properties, targeting hospital wastewater treatment. MX and silver nanoparticles are known for their hydrophilicity and antimicrobial capabilities, were synthesized and incorporated into PLA; a green polymer. The impact of nanocomposite concentration on the membrane's chemical structure, morphology, and overall performance were characterized using various PLA membrane properties and to evaluate the nanocomposite's performance in enhancing pure water flux and antibacterial efficacy. The pure water permeability increased from 1512 L m -2  h -1  bar -1 to 3108 L m -2  h -1  bar -1 in PLA/AgMX4 compared to PLA. Furthermore, a total bacteria count (TBC) rejection of up to 97 % was obtained using the PLA/AgMX4 membrane. The results demonstrated significant improvements in PLA/AgMX membranes compared to pristine PLA, showing a large potential for hospital wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The use of clear aligners (CAs) for orthodontic treatment has substantially increased in recent decades. However, limited empirical evidence exists regarding their potential effects on the temporomandibular joint (TMJ). The aim of this study was to assess the effect of maxillary molar distalization on the positional and dimensional TMJ parameters between CAs and conventional fixed orthodontic appliances (FAs) in skeletal class II malocclusion., Methods: This is a retrospective cohort study examined 70 adult patients with skeletal class II malocclusion with similar baseline characteristics based on American Board of Orthodontics (ABO) discrepancy index scores. The patients were treated by maxillary distalization movement by CAs or FAs, of which there were two equal groups of 35 patients were included in each group. CBCTs on TMJs were performed before and after treatment through Anatomage Invivo Dental 6.0. The measured parameters included inclination, position, condyle and articular fossa dimensions, and the volumetric joint spaces., Results: In both groups, linear measurements of the maxillary molar position revealed significant improvement after treatment (P < 0.001). Regarding TMJ parameters, intra-group comparisons revealed significant changes in FA group in the anterioposterior condylar inclination and condylar position across the three planes. Additionally, the pretreatment-centric condylar position in the glenoid fossa was 45.7% and 40% in the CA and FA groups, respectively. After treatment, these percentages changed to 51.4% and 31.4%, respectively. In inter-group comparisons, significant changes were noted in the mediolateral condylar position, which was more inward in the FA group than the CA group., Conclusion: The FA group had more significant dimensional and positional changes in the mandibular condyle than the CA group; nevertheless, the changes are considered clinically negligible., Competing Interests: Declarations Ethics approval and consent to participate This retrospective cohort study was reviewed and approved by the Regional Review Board of China Medical University Stomatological Hospital, Shenyang, Liaoning, China (registration no. CMUKQ-2022-059) and also met the ethical principles of the World Medical Association Declaration of Helsinki. All participants provided informed consent to participate in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Biological communication system for neurological disorder patients is similar to the Brain Computer Interface in a way that it facilitates the connection to the outside world in real time. The interdisciplinary field of Electroencephalogram based message depiction is gaining importance as it assists the paralysed person to communicate. In the proposed method a novel approach of feature extraction is done by Empirical Mode Decomposition on non- stationary & non-linear kind of EEG signal. EMD helps in the effective time frequency analysis by disintegrating the EEG signal in the form of six Intrinsic Mode Functions with help of the frequency components. In all nine features are extracted from the decomposed IMFs so as to predict the states or messages of the patient. The above computed features are then served to the Deep Neural Network to perform the classification. The performance of suggested method is studied through applying it to the acquired database generated by the designed hardware as well as also in real time message depiction. The maximum classification accuracy 97% for the acquired database & 85% in real time are obtained respectively by comparative analysis. The command messages generated from the proposed system helps the person suffering from neurological disorder to establish the communication link with the outside world in an efficient way. Thus, the proposed novel method shows better performance in real time message depiction purpose as related to other existing methods., (© 2024. The Author(s).)

Intervertebral disc degeneration (IDD) is one of the most frequent causes of low back pain. No treatment is currently available to delay the progression of IDD. Conservative treatment or surgical interventions is only used to target the symptoms of IDD rather than treat the underlying cause. Currently, numerous potential therapeutic strategies are available, including molecular therapy, gene therapy, and cell therapy. However, the hostile environment of degenerated discs is a major problem that has hindered the clinical applicability of such approaches. In this regard, the design of drugs using alternative delivery systems (macro-, micro-, and nano-sized particles) may resolve this problem. These can protect and deliver biomolecules along with helping to improve the therapeutic effect of drugs via concentrating, protecting, and prolonging their presence in the degenerated disc. This review summarizes the research progress of diagnosis and the current options for treating IDD., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A novel method for discovery of adulteration in edible oil is proposed based on concept of refractive index and electronic sensors. The research work focusses on two distinct methodologies like employing datasets and implementing a fumigation technique that integrates real-time hardware for testing Edible oil Impurities. In the first method, the dataset taken into consideration contains spectral data collected using Advanced ATR-MIR Spectroscopy for pure oil and various levels of adulteration with Vegetable oil. Each and every edible oil has a certain value of refractive index. When such oils are contemned in a change adding adulterants, the value of its refractive indices also changes. This value of refractive index serves as a feature for testing the oil and helps us in detecting the adulteration. If Oil is adulterated with vegetable oils, the refractive index will be lower and with animal fats, the refractive index will be higher than that of pure Oil. While in Fumigation Method a hardware module is develop in which adulterated & pure oil samples are heated at 40-50 °C for 4.66 min and the volatiles that are generated by varying gas concentrations are forcefully passed through to the MEMS Gas Sensor-MISC-2714 and Multichannel Gas sensor. The conductance of the sensors changes according to the gases sensed by the sensors contributes to features extraction. The conductance value serves as a feature for the classifier to determine whether the sample is highly, moderately, or lowly contaminated. Thus, in proposed methods we use different algorithms based on machine learning like KNN, Random Forest, CATBOOST and XGBOOST to accurately reveal the adulteration. Amongst all the applied algorithm Random Forest (RF) Classifier & XGBOOST algorithm outperform well and gives 100% accuracy. The proposed work is used for identifying food adulteration in edible food products which helps us to feed Society with high-quality food., (© 2024. The Author(s).)

Digital pathology has emerged as a revolutionary field, transforming traditional diagnostic practices by integrating advanced imaging technologies, computational tools, and artificial intelligence (AI). Adopting digital slides over conventional glass slides enables high-resolution imaging, facilitating remote consultations, second opinions, and telepathology. The digitalization of pathology laboratories enhances workflow efficiency and allows for large-scale data storage, retrieval, and analysis, paving the way for developing robust diagnostic algorithms. One of the most transformative aspects of digital pathology is its synergy with AI and machine learning (ML). These technologies have enabled the automation of repetitive processes, including diseased feature detection, biomarker quantification, and tissue segmentation. This has decreased inter-observer variability and increased diagnostic accuracy. AI-driven algorithms are particularly beneficial in complex cases, assisting pathologists in detecting subtle patterns that might be missed through manual examination. Furthermore, digital pathology plays a critical role in personalized medicine by enabling the precise characterization of tumors, which leads to targeted therapy decisions. Integrating digital pathology with genomics and other omics data holds promise for a more holistic understanding of diseases, driving innovation in diagnostics and treatment. However, the transition to digital pathology is challenging. Issues such as data standardization, regulatory compliance, and the need for robust IT infrastructure must be addressed to realize its full potential. This review provides a detailed examination of these advances, their clinical applications, and the challenges faced in the widespread adoption of digital pathology. As the field continues to evolve, it is poised to play a pivotal role in shaping the future of diagnostics, offering new possibilities for improving patient outcomes. This comprehensive review explores the significant advances in digital pathology, highlighting its impact on diagnostics, research, and patient care., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fatima et al.)

Stroke prediction remains a critical area of research in healthcare, aiming to enhance early intervention and patient care strategies. This study investigates the efficacy of machine learning techniques, particularly principal component analysis (PCA) and a stacking ensemble method, for predicting stroke occurrences based on demographic, clinical, and lifestyle factors. We systematically varied PCA components and implemented a stacking model comprising random forest, decision tree, and K-nearest neighbors (KNN).Our findings demonstrate that setting PCA components to 16 optimally enhanced predictive accuracy, achieving a remarkable 98.6% accuracy in stroke prediction. Evaluation metrics underscored the robustness of our approach in handling class imbalance and improving model performance, also comparative analyses against traditional machine learning algorithms such as SVM, logistic regression, and Naive Bayes highlighted the superiority of our proposed method., (© 2024. The Author(s).)

Magnesium (Mg), an essential mineral abundantly present within the human body, is intricately involved in a multitude of biochemical processes vital for maintaining health and overall well-being. This review aims to delve into the multifaceted impact of Mg on human health, exploring its physiological functions, dietary sources, and potential health implications of deficiency or insufficiency. Mg plays a pivotal role in various physiological processes, including energy metabolism, muscle contraction, protein synthesis, and DNA synthesis. It acts as a cofactor for more than 300 enzymatic reactions, facilitating the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) for energy production. Moreover, Mg is essential for the proper functioning of ion channels, particularly calcium channels, influencing nerve transmission and muscle relaxation. Mg is naturally found in a wide array of foods, with green leafy vegetables, whole grains, nuts, seeds, and legumes being particularly rich sources. Additionally, certain fortified foods and dietary supplements provide supplemental Mg intake. Deficiency or insufficiency of mg can have profound implications for health. Inadequate mg levels have been associated with increased risks of various chronic diseases, including hypertension, type 2 diabetes, osteoporosis, and cardiovascular diseases. Furthermore, mg deficiency may manifest as symptoms such as muscle weakness, fatigue, tremors, and irregular heartbeat. Numerous studies have elucidated the relationship between mg intake and the risk of developing chronic diseases. For instance, epidemiological evidence suggests that higher mg intake is associated with a reduced risk of hypertension, possibly due to its vasodilatory effects and influence on blood pressure regulation mechanisms. Similarly, mg has been implicated in the pathophysiology of type 2 diabetes, with mg deficiency contributing to insulin resistance and impaired glucose metabolism. Furthermore, adequate mg intake is crucial for maintaining bone density and reducing the risk of osteoporosis, as mg plays a vital role in bone mineralization and bone health. Understanding the importance of mg in human physiology underscores the significance of ensuring adequate mg intake through diet or supplementation. Healthcare professionals play a critical role in educating individuals about the importance of incorporating mg-rich foods into their diets and considering mg supplementation when necessary, particularly for individuals at risk of deficiency or those with chronic diseases. Mg is an indispensable mineral with far-reaching implications for human health. Its involvement in various physiological processes underscores its importance in maintaining overall health and well-being. Ensuring adequate mg intake is essential for preventing deficiency-related health complications and reducing the risk of chronic diseases. Further research is warranted to elucidate the optimal strategies for mg supplementation and its potential therapeutic applications in disease prevention and management., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fatima et al.)

Objective: This study aimed to explore the relationship between three-dimensional (3D) measurements of the hyoid bone (HB) and pharyngeal airway space (PAS) in relation to sagittal and vertical malocclusion., Methods: A total of 368 cone-beam computed tomography (CBCT) scans were classified into three skeletal groups (Class I, II, and III) and subdivided by vertical growth patterns (hypodivergent, normodivergent, and hyperdivergent). PAS dimensions, including nasopharyngeal, oropharyngeal, hypopharyngeal, and total airway spaces, were measured in surface area, volume, minimum constricted area (MCA), length, and width, HB position and dimension were analyzed in 3D using InVivo 6.0.3 and Dolphin 11.8 software. Data were analyzed using two-way ANOVA, and Bonferroni post-hoc tests, with P ≤ 0.05 considered significant., Results: The study found that patients with skeletal Class III and hypodivergent growth pattern had the highest sagittal position of the hyoid bone, while those with skeletal Class II and hyperdivergent pattern had the lowest hyoid length. Nasopharyngeal airway space width was significantly lower in skeletal Class III patients, while volume and area were lower in hyperdivergent patients. Oropharyngeal and hypopharyngeal dimensions were also affected by skeletal class and growth pattern, with hyperdivergent patients having the lowest values. Total pharyngeal volume, area, and minimum constricted area were also affected, with hyperdivergent patients having the lowest values and skeletal Class II patients having the lowest minimum constricted area., Conclusion: Pharyngeal airway dimensions and hyoid bone parameters vary with malocclusions. The hyoid bone's position influences the airway, identifying patients at risk for airway obstruction and sleep-disordered breathing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Language-appropriate outcome measurements help to improve health equity. The purpose of this study was to translate and validate the Cohen-Hoberman Inventory of Physical Symptoms (CHIPS) in Nepali for Bhutanese refugee utilization., Methods: English-Nepali forward and back translations of CHIPS were completed by an official translator and evaluated by three content experts. A scaled rubric measured the following constructs: neurogenic stress response (NSR), somatic stress response (SSR), and visceral stress response (VSR). Data were analyzed using SPSS 26.0., Results: The Nepali version of CHIPS reported good content validity, strong internal consistency (Cronbach's α  = .94), and inter-rater reliability (ICC = 0.91). Kappa statistic reported 88% to 96% agreement. Constructs of NSR (0.91), SSR (0.94), and VSR (0.94) reported strong internal consistency., Conclusions: The Nepali translated version of CHIPS showed strong validity and reliability for utilization in the Bhutanese refugee population and improves health access to outcome measurements for a vulnerable population., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bacterial infections continue to pose a global health challenge, driven by antibiotic resistance and septicemia. This study aimed to assess the diagnostic utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in bacterial infections versus non-infectious causes of inflammation., Methods: A prospective study included 164 adult patients who were divided into two groups: a group of patients with confirmed bacterial infections and a second group of patients with other diagnoses (inflammatory pathologies, neoplasms, venous thromboembolic diseases, etc.). NLR and PLR values were compared between the bacterial infection group and the non-infectious causes group and the diagnostic performances of NLR and PLR for detecting bacterial infections were evaluated in comparison with other infection markers., Results: NLR and PLR were significantly higher in bacterial infections (p < 10 ^-6 ), and NLR was correlated positively with inflammation markers. NLR and PLR demonstrated significant potential in diagnosing bacterial infections, with an AUC of 0.72 and 0.60, respectively, using the following cutoff values: 4.3 for NLR and 183 for PLR., Conclusion: These findings underscore the importance of NLR and PLR as adjunctive tools for bacterial infection diagnosis., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Anoun J et al.)

Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids - termed oxa-iboga - defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists in vitro and in vivo, but exhibit atypical behavioral features compared to standard kappa opioid agonists. Oxa-noribogaine induces long-lasting suppression of morphine, heroin, and fentanyl intake after a single dose or a short treatment regimen, reversal of persistent opioid-induced hyperalgesia, and suppression of opioid drug seeking in rodent relapse models. As such, oxa-iboga compounds represent mechanistically distinct iboga analogs with therapeutic potential., (© 2024. The Author(s).)

A 34-year-old woman at 18 weeks' gestation experienced shortness of breath and palpitations after receiving her first dose of doxorubicin for right-sided invasive ductal breast carcinoma. Telemetry monitoring found frequent runs of nonsustained ventricular tachycardia that was treated with metoprolol tartrate. No further arrhythmias occurred with subsequent doses of chemotherapy., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

BACKGROUND Submental intubation, a technique often considered a good alternative for managing the airway in challenging maxillofacial surgical scenarios, plays a pivotal role in providing accessibility to the surgical site and ensuring airway safety, particularly in cases involving facial fractures. This innovative approach not only grants surgeons adequate access to the operative field but also mitigates potential complications associated with traditional intubation methods, making it a valuable tool in dealing with complex facial trauma cases. CASE REPORT A 37-year-old man arrived at the Emergency Department (ED) with a severe facial injury caused from a traumatic incident involving a falling concrete wall, resulting in severe facial injuries that included multiple lacerations and abrasions on his face and body. The patient presented with multiple facial and body lacerations and abrasions, necessitating prompt medical intervention. The ED team swiftly treated the facial lacerations, controlled the bleeding, stabilized the patient, and proceeded to secure the airway through orotracheal intubation. Following stabilization, the patient was transferred to the operation theater (OT) for further management of his extensive pan-facial fractures under general anesthesia, utilizing the submental intubation technique for airway management. CONCLUSIONS Despite its limited use, submental intubation is a good option for some maxillofacial surgeries, offering a less intrusive approach to airway management and presenting an alternative pathway to the conventional endotracheal intubation technique. Its ability to streamline procedures, enhance patient outcomes, and reduce complications underscores the importance of considering submental intubation as a valuable tool in dealing with complex maxillofacial cases.

Background: Among the causes of the progression of intervertebral disc (IVD) degeneration (IDD) is the loss of nutrient intake to the IVD through the microcirculation disruption of the subendplate. Also, the vertebral body fracture intervenes in the degeneration the adjacent IVD. This research aimed to create an animal model of IDD using these 2 strategies., Methods: Thirty male Sprague-Dawley rats were split into 3 groups: a control group, a middle vertebral body injury (MI) associated with ethanol injection (MI + EtOH) group, and an MI associated with phosphate-buffered saline injection group. A vertebral body fracture with or without endplate injection of ethanol was generated by either drilling a hole in the center of a caudal rat vertebral body to form a fracture with an unabated endplate or drilling a hole in the center of a rat coccygeal vertebral body with endplate injection of ethanol to establish a vertebral body fracture with endplate damage. X-ray, macroscopic, histologic, and biochemical evaluations were utilized to assess IDD at weeks 3 and 6., Results: According to X-ray findings, the MI + EtOH group demonstrated a significant decrease in intervertebral space height over time in comparison to the 2 other groups. The water content also was significantly decreased. Macroscopic and histological analysis demonstrated progressive degenerative changes in the IVD of the MI + EtOH group., Conclusions: The caudal vertebra fracture with ethanol injection is more likely to induce degeneration of adjacent IVD. This model effectively reproduced IDD, which may serve as a theoretical basis for future clinical intervention for IDD., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The MDM2 oncogene is amplified and/or overexpressed in various human cancers and elevated expression of MDM2 protein acts as a survival factor promoting cancer progression through both p53-dependent and -independent pathways. Here, we report a novel small-molecule chemical compound (MX69-102) that we identified to induce MDM2 protein degradation, resulting in reactivation of p53, inhibition of XIAP, and potent cell growth inhibition and apoptosis in MDM2-overexpressing acute lymphoblastic leukemia (ALL) in vitro and in vivo. We have previously identified a compound (MX69) that binds to the MDM2 C-terminal RING domain and induces MDM2 protein degradation. In the present study, we performed structural modifications of MX69 and selected analog MX69-102, showing increased MDM2-targeting activity. MX69-102 exhibited significantly enhanced inhibitory and apoptotic effects on a group of MDM2-overexpressing ALL cell lines in vitro with IC 50 values of about 0.2 μM, representing an approximately 38-fold increase in activity compared to MX69. MX69-102 also showed effective inhibition on xenografted human MDM2-overexpressing ALL in SCID mice. Importantly, MX69-102 had minimal or no inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in vivo in animal models. Based on the strong inhibitory and apoptotic activity against MDM2-overexpressing ALL, along with minimal or no toxicity to normal cells/tissues, MX69-102 is a candidate for further development as a novel MDM2-targeted therapeutic drug for refractory/MDM2-overexpressing ALL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes., Objective: The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions., Methods: The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset., Results: A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance., Conclusion: We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic., (© 2024 S. Karger AG, Basel.)