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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.)

Desalination processes frequently require a lot of energy to generate freshwater and energy, which depletes resources. Their reliance on each other creates tension between these two vital resources. Herein, hierarchical MXene nanosheets and bismuth vanadate (Ti 3 C 2 /BiVO 4 )-derived microcapsules were synthesized for a photothermal-induced photoredox reaction for twofold applications, namely, solar-driven water evaporation and hydrogen (H 2 ) production. For this purpose, flexible aerogels were fabricated by introducing Ti 3 C 2 /BiVO 4 microcapsules in the polymeric network of natural rubber latex (NRL-Ti 3 C 2 /BiVO 4 ), and a high evaporation rate of 2.01 kg m -2 h -1 was achieved under 1-kW m -2 solar intensity. The excellent performance is attributed to the presence of Ti 3 C 2 /BiVO 4 microcapsules in the polymeric network, which provides balanced hydrophilicity and broadband sun absorption (96 %) and is aimed at plasmonic heating with microscale thermal confinement tailored by heat transfer simulations. Notably, localized plasmonic heating at the catalyst active sites of the Ti 3 C 2 /BiVO 4 heterostructure promotes enhanced photocatalytic H 2 production evolved after 4 h of reaction is 9.39 μmol, which is highly efficient than pure BiVO 4 and Ti 3 C 2 . This method turns the issue of water-fuel crisis into a collaborative connection, presenting avenues to collectively address the anticipated demand rather than fostering competition., 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 Inc. All rights reserved.)

In the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), statins are the primary pharmacologic intervention for ASCVD risk reduction. Statins have proven efficacy and safety in reducing cardiovascular events and total mortality in patients with and without clinically evident ASCVD. The purpose of this brief review is to provide a stepwise approach to lipid management, including lifestyle recommendations and medical therapy. We first review the main available approaches to lipid lowering and their mechanisms of action. We then summarise the findings of large randomised controlled trials investigating the benefit of statin therapy from 1994 to the present. The available statins are then reviewed, along with their main pharmacologic properties and potential adverse effects. Although statins are generally well tolerated, certain patients may require dose adjustments or alternative treatments because of side-effects. In patients not achieving adequate lipid control on a maximally tolerated statin, nonstatin medications, including ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, provide enhanced low-density lipoprotein cholesterol reduction and cardiovascular benefits, especially in high-risk patients inadequately managed with statins alone. We review the role of triglyceride-lowering agents, including fibric acid derivatives and icosapent ethyl. We then deal with special populations, including those with hepatic steatosis, chronic kidney disease, pregnancy, and heart failure. This field continues to progress, and novel therapies are under active investigation, including an oral PCSK9 inhibitor and molecular therapies targeting lipoprotein(a), angiopoietin-like protein 3, and apolipoprotein CIII. We can look forward to exciting developments that will have major impacts on patient health and management., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In 1948, the indirect ophthalmoscope revealed full intra-ocular retinoblastoma, documented on paper with coloured pencils. At SickKids, eCancerCare RB (eCC RB ) digital drawings and timeline have facilitated patient care, education, and research., Methods: Each child's eCC RB timeline shows treatments and dates. The Swimmer RB tool presents eCC RB data for research with time "0" start of intervention. Any tumour treatment after the intervention indicates recurrence; no cancer treatments indicate complete response. To further quantify the impact of retinoblastoma on child/family, we arbitrarily assigned a "consequence" score to each standard treatment (i.e., focal = 1, intra-arterial chemotherapy = 3, enucleation last eye = 30). Retrospective control eCC RB patients were matched to study participants by similar "propensity" scores before time "0." Postintervention scores indicated effectiveness., Results: eCC RB included 700 patients with retinoblastoma treated between 2001 and 2023 at SickKids. Swimmer RB facilitated comparing eCC RB patients treated with single- versus triple-drug intra-arterial chemotherapy. In the phase 1 Chemoplaque Clinical Trial, Swimmer RB analysis compared number of treatments before and after the Chemoplaque. Consequence scores quantitating negative outcomes will be refined by quality-of-life studies including those with lived experience. DEPICT HEALTH (DEPICT) on the cloud-hosted technology will soon replace eCC RB (now-outdated technology), offering digital retinoblastoma care to the world., Discussion: eCC RB (only in SickKids) is the time-tested prototype for DEPICT on the cloud. DEPICT brings digital retinal drawings, timeline, research, and clinical consultation to full view for families as partners in retinoblastoma care. DEPICT will be offered through the International Retinoblastoma Consortium to any site caring for children with retinoblastoma., (Copyright © 2024. Published by Elsevier Inc.)

Leukemia is a type of blood cell cancer that is in the bone marrow's blood-forming cells. Two types of Leukemia are acute and chronic; acute enhances fast and chronic growth gradually which are further classified into lymphocytic and myeloid leukemias. This work evaluates a unique deep convolutional neural network (CNN) classifier that improves identification precision by carefully examining concatenated peptide patterns. The study uses leukemia protein expression for experiments supporting two different techniques including independence and applied cross-validation. In addition to CNN, multilayer perceptron (MLP), gated recurrent unit (GRU), and recurrent neural network (RNN) are applied. The experimental results show that the CNN model surpasses competitors with its outstanding predictability in independent and cross-validation testing applied on different features extracted from protein expressions such as amino acid composition (AAC) with a group of AAC (GAAC), tripeptide composition (TPC) with a group of TPC (GTPC), and dipeptide composition (DPC) for calculating its accuracies with their receiver operating characteristic (ROC) curve. In independence testing, a feature expression of AAC and a group of GAAC are applied using MLP and CNN modules, and ROC curves are achieved with overall 100% accuracy for the detection of protein patterns. In cross-validation testing, a feature expression on a group of AAC and GAAC patterns achieved 98.33% accuracy which is the highest for the CNN module. Furthermore, ROC curves show a 0.965% extraordinary result for the GRU module. The findings show that the CNN model is excellent at figuring out leukemia illnesses from protein expressions with higher accuracy., (© 2024. The Author(s).)

Magnesium is an essential nutrient for various physiological processes and becomes even more vital during pregnancy, contributing to muscle relaxation, bone development, electrolyte balance, and blood pressure regulation. Despite the fact that the dietary sources of magnesium are diversified, it is still challenging to obtain it in sufficient quantities during pregnancy. We have elucidated its interactions and its specific impact on maternal-fetal health in different research publications. Magnesium also interacts synergistically with other micronutrients like calcium, vitamin D, potassium, zinc, iron, and vitamin B6, emphasizing its significance in promoting optimal outcomes for both the mother and the fetus. Inadequate magnesium intake during pregnancy has been linked to complications like gestational diabetes, preeclampsia, preterm birth, and low birth weight. Therefore, there should be an emphasis on the importance of maintaining adequate magnesium levels through a balanced diet and supplementation. This research therefore studies the complex mechanisms of micronutrient interactions and their specific impacts on maternal-fetal health to enhance prenatal care practices., Competing Interests: All the authors declare no conflict of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

This article examines the ethics of research design and the initiation of a study (e.g., recruitment of participants) involving refugee participants. We aim to equip investigators and members of IRBs with a set of ethical considerations and pragmatic recommendations to address challenges in refugee-focused research as it is developed and prepared for IRB review. We discuss challenges including how refugees are being defined and identified; their vulnerabilities before, during, and following resettlement that impacts their research participation; recruitment; consent practices including assent and unaccompanied minors; and conflicts of interest. Ethical guidance and regulatory oversight provided by international bodies, federal governments, and IRBs are important for enforcing the protection of participants. We describe the need for additional ethical guidance and awareness, if not special protections for refugee populations as guided by the National Institutes of Health (NIH) Guiding Principles for Ethical Research., (© 2024 The Authors. Ethics & Human Research published by Wiley Periodicals LLC on behalf of The Hastings Center.)

Cyclin A2 (CCNA2) is a master regulatory gene of the cell cycle that is normally silenced in postnatal mammalian cardiomyocytes. We have previously demonstrated that it can induce significant cardiac repair in both small and large animals when delivered to the heart via a viral vector. To date, whether CCNA2 gene delivery can induce cytokinesis in isolated cardiomyocytes from adult human hearts has not been investigated. Therefore, we designed a human gene therapy vector featuring a replication-deficient, E1/E3-deleted human adenovirus five encoding human CCNA2 driven by the cardiac Troponin T promoter to enable the expression of CCNA2 in freshly isolated human cardiomyocytes. Utilizing time-lapse microscopy live imaging of cultured adult human cardiomyocytes isolated from a 21-year-old male, 41-year-old female, and 55-year-old male, we now report that human adult cardiomyocytes can be induced to undergo complete cytokinesis in response to CCNA2 gene delivery with preservation of sarcomere integrity in the resulting daughter cells. To elucidate the mechanistic underpinnings of CCNA2-dependent gene regulation in governing cardiomyocyte cytokinesis, we conducted single nucleus transcriptomics (snRNA-seq, 10X Genomics) analysis in hearts isolated from adult transgenic mice that constitutively express CCNA2 in cardiomyocytes (CCNA2-Tg) and non-transgenic mice (nTg). Remarkably, we identified a subpopulation of cardiomyocytes enriched with cytokinesis, proliferative, and reprogramming genes in hearts obtained from CCNA2-Tg mice as compared to hearts obtained from nTg mice. We also performed bulk RNA sequencing of human adult and fetal hearts, and we identified key reprogramming genes that are involved in CCNA2-induced cytokinesis. These results provide a compelling path forward for the clinical development of cardiac regenerative therapy based on strategic manipulation of the cardiomyocyte cell cycle.

Precision Medicine is being increasingly used in the developed world to improve health care. While several Precision Medicine (PM) initiatives have been launched worldwide, their implementations have proven to be more challenging particularly in low- and middle-income countries. To address this issue, the "Personalized Medicine in North Africa" initiative (PerMediNA) was launched in three North African countries namely Tunisia, Algeria and Morocco. PerMediNA is coordinated by Institut Pasteur de Tunis together with the French Ministry for Europe and Foreign Affairs, with the support of Institut Pasteur in France. The project is carried out along with Institut Pasteur d'Algérie and Institut Pasteur du Maroc in collaboration with national and international leading institutions in the field of PM including Institut Gustave Roussy in Paris. PerMediNA aims to assess the readiness level of PM implementation in North Africa, to strengthen PM infrastructure, to provide workforce training, to generate genomic data on North African populations, to implement cost effective, affordable and sustainable genetic testing for cancer patients and to inform policy makers on how to translate research knowledge into health products and services. Gender equity and involvement of young scientists in this implementation process are other key goals of the PerMediNA project. In this paper, we are describing PerMediNA as the first PM implementation initiative in North Africa. Such initiatives contribute significantly in shortening existing health disparities and inequities between developed and developing countries and accelerate access to innovative treatments for global health., 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. Published by Elsevier Inc.)

This study explored parents' attitudes towards vaccinating their children against COVID-19 and the rate of vaccine hesitancy in Oman. A cross-sectional, online, self-administered questionnaire, previously validated and administered between June 2021 and May 2022, was used. The questionnaire consisted of nine items. Parents of children younger than 12 years were eligible for participation. A total of 384 participants, including 207 males (54%), completed the questionnaire, resulting in an 86% response rate (384/447). The results showed that 69% of participants were hesitant to vaccinate their children aged 1-11 years. In parents of children aged 1-4 years, vaccination status was significantly associated with vaccine hesitancy (odds ratio [OR], 0.116; 95% confidence interval [CI], 0.044-0.306; p = 0.001). Furthermore, after multivariable analysis, compared to the fathers, mothers were significantly less likely to be associated with vaccine hesitancy (OR, 0.451; 95% CI, 0.240-0.848; p = 0.013).

Introduction: Mental health issues among undergraduate health-care students are a growing concern. This research aims to explore the frequency of mental health issues among health-care students in medicine, dentistry, pharmacy, nutrition, biomedical sciences, nursing, and public health at Qatar University., Methods: Ethics approval was obtained from the institutional review board. A total of 1,378 health-care students were invited to participate. Data were collected online using two validated questionnaires including the Patient Health Questionnaire (PHQ-9) to assess symptoms of depression, and Depression, Anxiety, and Stress Scale (DASS-21), and two open-ended questions investigating risk factors and recommendations for enhancing institutional support., Results: A total of 270 health-care students completed the survey; 227 female, and 43 male students. According to PHQ-9 cut-off values, 37.7% of students had mild depression symptoms, 25.5% moderate, 14.8% moderately severe and 10% severe symptoms. DASS-21 responses revealed 34.7% displayed severe to extremely severe anxiety symptoms, 15.4% severe to extremely severe stress symptoms and 21% severe to extremely severe depression symptoms. Students aged 18-21 years had significantly higher depression (p=0.03) and stress scores (p=0.05). Qatari students had significantly higher anxiety scores (p=0.05). Responses to open-ended questions were categorized into sub-themes and grouped together into broader themes. Most students reported exam stress and workload as key factors contributing to their negative mental health. Participants' recommendations included reducing academic workload through better curricular planning, providing training to faculty to better support students with mental health issues, and improving mental health services., Conclusion: This study showed a significant percentage of respondents reported symptoms of stress, anxiety, and depression during undergraduate studies. Participants represent the future healthcare force for the country and there is a need to identify and support students with mental health issues through close monitoring, and work with all stakeholders to improve student support services., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Hayk O et al.)

Large amount of sulphur is released by the combustion of fossil fuels in the form of So X which affects human health and leads to acid rain. To overcome this issue, it is essential to eliminate sulphur moieties from heterocyclic organo-sulphur compounds like Dibenzothiophene (DBT) present in the petrol. In this study Surface enhanced Raman scattering (SERS) spectroscopy is used to analyze the desulfurizing activity of Tsukamurella paurometabola bacterial strain. The most prominent SERS peaks observed at 791, 837, 944 and 1032 cm -1 , associated to C-S stretching, are solely observed in dibenzothiophene and its metabolite-I (DBTS) but absent in 2-Hydroxybiphenyl (metabolite-II) and extraction sample of supernatant as a result of biodesulfurization. Moreover, the SERS peaks observed at 974 (characteristic peak of benzene ring) and 1015 cm -1 is associated to C-C ring breathing while 1642 and 1655 cm -1 assigned to CC bonds of aromatic ring. These peaks are only observed in 2-Hydroxybiphenyl (metabolite-II) and extraction sample of supernatant as a result of biodesulfurization. Notably, these peaks are absent in the Dibenzothiophene and its metabolite-I which indicate that aromatic ring is carrying sulfur in this fraction. Moreover, multivariate data analytical tools like principal component analysis (PCA) and PCA-loadings are applied to further differentiate between dibenzothiophene and its metabolites that are Dibenzothiophene sulphone (metabolite-I) and 2-Hydroxybiphenyl (metabolite-II)., 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.)

One of the frequent causes of low back pain is intervertebral disc degeneration (IDD), which is followed by discogenic pain. Some significant risk factors that have been linked to the onset and progression of IDD include age, mechanical imbalance, changes in nutrition and inflammation. According to recent studies, five types of animal models are established for producing IDD: the spontaneous models, the puncture models, the biomechanical models, the chemical models and the hybrid models. These models are crucial in studying and understanding IDD's natural history and identifying potential treatment targets for IDD. In our study, we'll talk about the technical aspects of these models, the time between model establishment and the apparition of observable degradation, and their potential in various research. Each animal model should be compared to the human natural IDD pathogenesis to guide future research efforts in this area. By improving knowledge and appropriate application of various animal models, we seek to raise awareness of this illness and further translational research., Competing Interests: There are no conflicts of interest between the authors to declare., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

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., Competing Interests: Authors RR and SL are employed by the company BioInfoExperts, LLC. The remaining 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 Kim, Elnaggar, Varnado, Feehan, Tauzier, Rose, Lamers, Sevalia, Nicholas, Gravois, Fort, Crabtree and Miele.)

Since its discovery over 35 years ago, MDM2 has emerged as an attractive target for the development of cancer therapy. MDM2's activities extend from carcinogenesis to immunity to the response to various cancer therapies. Since the report of the first MDM2 inhibitor more than 30 years ago, various approaches to inhibit MDM2 have been attempted, with hundreds of small-molecule inhibitors evaluated in preclinical studies and numerous molecules tested in clinical trials. Although many MDM2 inhibitors and degraders have been evaluated in clinical trials, there is currently no Food and Drug Administration (FDA)-approved MDM2 inhibitor on the market. Nevertheless, there are several current clinical trials of promising agents that may overcome the past failures, including agents granted FDA orphan drug or fast-track status. We herein summarize the research efforts to discover and develop MDM2 inhibitors, focusing on those that induce MDM2 degradation and exert anticancer activity, regardless of the p53 status of the cancer. We also describe how preclinical and clinical investigations have moved toward combining MDM2 inhibitors with other agents, including immune checkpoint inhibitors. Finally, we discuss the current challenges and future directions to accelerate the clinical application of MDM2 inhibitors. In conclusion, targeting MDM2 remains a promising treatment approach, and targeting MDM2 for protein degradation represents a novel strategy to downregulate MDM2 without the side effects of the existing agents blocking p53-MDM2 binding. Additional preclinical and clinical investigations are needed to finally realize the full potential of MDM2 inhibition in treating cancer and other chronic diseases where MDM2 has been implicated. SIGNIFICANCE STATEMENT: Overexpression/amplification of the MDM2 oncogene has been detected in various human cancers and is associated with disease progression, treatment resistance, and poor patient outcomes. This article reviews the previous, current, and emerging MDM2-targeted therapies and summarizes the preclinical and clinical studies combining MDM2 inhibitors with chemotherapy and immunotherapy regimens. The findings of these contemporary studies may lead to safer and more effective treatments for patients with cancers overexpressing MDM2., (Copyright © 2024 by The Author(s).)

Introduction: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143&#95;1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings., 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. Published by Elsevier Inc.)

Objective: This study sought to three-dimensionally (3D) evaluate the maxillomandibular basal bone and dentoalveolar widths using cone-beam computed tomography (CBCT) scans in adult Chinese populations with different vertical and sagittal facial skeletal patterns whilst no apparent posterior dental crossbite., Materials and Methods: The retrospective cross-sectional comparative study enrolled CBCT images of 259 adult patients (125 males and 134 females). The subjects were divided into the hyperdivergent(n = 82), hypodivergent(n = 88), and normodivergent(n = 89) groups based on the Jarabak ratio (S-GO/N-Me), which were further divided into three subgroups of skeletal Class I, II and III, based on both the ANB angle and AF-BF parameters. ANOVA was used to analyze the extracted data of the studied groups. The intra- and inter-observer reliability was analyzed using the intra-class correlation coefficient (ICC)., Results: In all three vertical facial skeletal patterns, the skeletal Class II had significantly smaller mandibular basal bone width compared to skeletal Class I and Class III, both at the first molar and first premolar levels. The skeletal Class III seemed to have smaller maxillary basal bone width compared to skeletal Class I and Class II malocclusions; however, a significant difference was found only in the normodivergent pattern. As for the dentoalveolar compensation, it was most notable that in the hypodivergent growth pattern, the skeletal Class II had significantly smaller maxillary dentoalveolar width compared to the Class I and Class III groups, both at the first molar and first premolar levels., Conclusions: Based on the sample in the present study, skeletal Class II has the narrowest mandibular basal bone regardless of the vertical facial skeletal pattern., Clinical Relevance: For Chinese adults with no apparent transverse discrepancy, the maxillomandibular basal bone and dentoalveolar widths are revealed in specific categories based on different vertical and sagittal facial skeletal patterns. In diagnosis and treatment planning, particular attention should be paid to skeletal Class II for possibly existing mandibular narrowing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Raman spectroscopy is reliable tool for analyzing and exploring early disease diagnosis related to body fluids, such as blood serum, which contain low molecular weight fraction (LMWF) and high molecular weight fraction (HMWF) proteins. The disease biomarkers consist of LMWF which are dominated by HMWF hence their analysis is difficult. In this study, in order to overcome this issue, centrifugal filter devices of 30 kDa were used to obtain filtrate and residue portions obtained from whole blood serum samples of control and breast cancer diagnosed patients. The filtrate portions obtained in this way are expected to contain the marker proteins of breast cancer of the size below this filter size. These may include prolactin, Microphage migration inhabitation factor (MIF), γ-Synuclein, BCSG1, Leptin, MUC1, RS/DJ-1 present in the centrifuged blood serum (filtrate portions) which are then analyzed by the SERS technique to recognize the SERS spectral characteristics associated with the progression of breast cancer in the samples of different stages as compared to the healthy ones. The key intention of this study is to achieve early-stage breast cancer diagnosis through the utilization of Surface Enhanced Raman Spectroscopy (SERS) after the centrifugation of healthy and breast cancer serum samples with Amicon ultra-filter devices of 30 kDa. The silver nanoparticles with high plasmon resonance are used as a substrate for SERS analysis. Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) models are utilized as spectral classification tools to assess and predict rapid, reliable, and non-destructive SERS-based analysis. Notably, they were particularly effective in distinguishing between different SERS spectral groups of the cancerous and non-cancerous samples. By comparing all these spectral data sets to each other PLSDA shows the 79 % accuracy, 76 % specificity, and 81 % sensitivity in samples with AUC value of AUC = 0.774 SERS has proven to be a valuable technique for the rapid identification of the SERS spectral features of blood serum and its filtrate fractions from both healthy individuals and those with breast cancer, aiding in disease diagnosis., 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.)

Methicillin-resistant Staphylococcus aureus (MRSA) is gram positive bacteria and leading cause of a wide variety of diseases. It is a common cause of hospitalized and community-acquired infections. Development of increasing antibiotic-resistance by methicillin-resistant S. aureus (MRSA) strains demand to develop alternate novel therapies. Bacteriophages are now widely used as antibacterial therapies against antibiotic-resistant gram-positive pathogens. So, there is an urgent need to find fast detection techniques to point out phage susceptible and resistant strains of methicillin-resistant S. aureus (MRSA) bacteria. Samples of two separate strains of bacteria, S. aureus, in form of pellets and supernatant, were used for this purpose. Strain-I was resistant to phage, while the other (strain-II) was sensitive. Surface Enhanced Raman Spectroscopy (SERS) has detected significant biochemical changes in these bacterial strains of pellets and supernatants in the form of SERS spectral features. The protein portion of these two types of strains of methicillin-resistant S. aureus (MRSA) in their relevant pellets and supernatants is major distinguishing biomolecule as shown by their representative SERS spectral features. In addition, multivariate data analysis techniques such as principal component analysis (PCA) and a partial least squares-discriminant analysis (PLS-DA) were found to be helpful in identifying and characterizing various strains of S. aureus which are sensitive and resistant to bacteriophage with 100% specificity, 100% accuracy, and 99.8% sensitivity in case of SERS spectral data sets of bacterial cell pellets. Moreover, in case of supernatant samples, the results of PLS-DA model including 95.5% specificity, 96% sensitivity, and 96.5% accuracy are obtained., 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. Published by Elsevier B.V.)

Neurosteroids have been implicated in the pathophysiology of post-traumatic stress disorder (PTSD). Allopregnanolone is reduced in subsets of individuals with PTSD and has been explored as a novel treatment strategy. Both direct trauma exposure and witnessed trauma are risk factors for PTSD; however, the role of neurosteroids in the behavioral outcomes of these unique experiences has not been explored. Here, we investigate whether observational fear is associated with a reduced capacity for endogenous neurosteroidogenesis and the relationship with behavioral outcomes. We demonstrated that mice directly subjected to a threat (foot shocks) and those witnessing the threat have decreased plasma levels of allopregnanolone. The expression of a key enzyme involved in endogenous neurosteroid synthesis, 5α-reductase type 2, is decreased in the basolateral amygdala, which is a major emotional processing hub implicated in PTSD. We demonstrated that genetic knockdown or pharmacological inhibition of 5α-reductase type 2 exaggerates the behavioral expression of fear in response to witnessed trauma, whereas oral treatment with an exogenous, synthetic neuroactive steroid gamma-aminobutyric acid-A receptor positive allosteric modulator with molecular pharmacology similar to allopregnanolone (SGE-516 [tool compound]) decreased the behavioral response to observational fear. These data implicate impaired endogenous neurosteroidogenesis in the pathophysiology of threat exposure, both direct and witnessed. Further, these data suggest that treatment with exogenous 5α-reduced neurosteroids or targeting endogenous neurosteroidogenesis may be beneficial for the treatment of individuals with PTSD, whether resulting from direct or witnessed trauma., (© 2024 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy., Methods: Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired t tests were applied to establish statistically significant differences across the measured variables., Results: Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer., Conclusion: We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

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.

The ability of surface-enhanced Raman spectroscopy (SERS) to generate spectroscopic fingerprints has made it an emerging tool for biomedical applications. The objective of this study is to confirm the potential use of Raman spectroscopy for early disease diagnosis based on blood serum. In this study, a total of sixty blood serum samples, consisting of forty from diseased patients and twenty (controls) from healthy individuals, was used. Because disease biomarkers, found in the lower molecular weight fraction, are suppressed by higher molecular weight proteins, 50 kDa Amicon ultrafiltration centrifugation devices were used to produce two fractions from whole blood serum consisting of a filtrate, which is a low molecular weight fraction, and a residue, which is a high molecular weight fraction. These fractions were then analyzed, and their SERS spectral data were compared with those of healthy fractions. The SERS technique was utilized on blood serum, filtrate and residue of patients with tuberculosis to identify characteristic SERS spectral features associated with the development of disease, which can be used to differentiate them from healthy samples using silver nanoparticles as a SERS substrate. For further analysis, the effective chemometric technique of principal component analysis (PCA) was used to qualitatively differentiate all the analyzed samples based on their SERS spectral features. Partial least squares discriminant analysis (PLS-DA) accurately classified the filtrate portions of healthy and tuberculosis samples with 97% accuracy, 97% specificity, 98% sensitivity, and an area under the receiver operating characteristic (AUROC) curve of 0.74., Competing Interests: The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)