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This study was conducted to evaluate the quality of frozen chicken meat received at government hos-pitals in Assiut city, Egypt, during hot and cold seasons. A total of 308 chicken meat samples were collected randomly and subjected to sensory, chemical, physical and microbiological testing. The findings showed that frozen chicken meat samples examined during the cold season had a better sen-sory evaluation than those examined during the hot season. The mean values of the physical quality tests, which included pH, drip loss, and water-holding capacity (WHC), were 6.12±0.017, 4.13±2.8, and 63.60±0.55 in the hot season and 5.9±0.013, 3.32±3.09, and 81.28±0.48 in the cold season, re-spectively. The total bacterial count, psychrotrophic count, total yeast and mould counts were 6.9×105±8.7×104, 1.1×106±1.0×105, 3.9×104±3.8×103, and 7.4×104±2.7×103 CFU/g in the hot season and 4.4×104±2.2×103, 1.9×105±1.6×104, 1.4×104±2.0×103, and 3.8×104±3.1×103 CFU/g in the cold season, respectively. These findings indicate that temperature has a significant impact on meat quality; the frozen chicken meat samples examined in the cold season were in better condition than those examined in the hot season. It is necessary to maintain sanitary hygienic conditions during handling, packaging, storage and distribution particularly in the hot season.

Introduction Individuals with co-occurring mental and physical health issues have worse health outcomes in both domains. Integration improves outcomes and aligns with patient preference, but health services tend to be siloed. The Mental Health in Medicine Clinic (MHiM) supports patients receiving inpatient or outpatient medical or surgical care at a tertiary academic hospital in Toronto, Canada. The predominantly virtual clinic has an interdisciplinary team offering services via stepped care, matching patient need with service intensity. Measurement-based care (MBC), the systematic evaluation of patient reported outcomes, was not initially used routinely in the clinic, but its implementation may improve treatment decision-making and may be useful in allocating patients within a stepped care model. Objectives 1) To describe the stepped care model, referral patterns, diagnoses, and level of care provided since implementation of stepped care. 2) To conduct a quality improvement initiative to implement MBC in the clinic, with a goal of 50% of patients completing at the time of first assessment and prior to discharge from the clinic. Methods We reviewed the electronic medical record for referral source, diagnoses, and level of stepped care within the clinic. We conducted semi-structured interviews with stakeholders (clinicians, administrative staff, patients) to explore barriers to implementation of MBC. Interviews were analyzed for themes around barriers and facilitators to MBC. Plan, Do, Study, Act cycles were carried out around change concepts informed by stakeholder interviews and relevant literature. Results The MHiM clinic began operations in August 2020. The clinic operated on a physician-only model until March 2022 and then shifted to a stepped care model with an interdisciplinary team. The most frequent referral sources were internal medicine, COVID19 clinics, consultation-liaison psychiatry, red blood cell disorders clinic and cardiology. Since the implementation of stepped care, 250 referrals were assessed. 58% of new referrals were assessed by the psychiatrist, 42% were managed by the NP, and 25% consulted with the social worker. Referrals consisted of trauma and stress-related disorders (32%), depression (21%) or anxiety disorders (20%). Personality, substance use, and psychotic disorders accounted for less than 10% of referrals combined. Some patients did not have any diagnosis (6%). Results from the quality improvement initiative to implement MBC will also be presented. Conclusions The MHiM clinic provides an integrated care pathway addressing comorbid mental and physical health conditions. We describe a novel stepped care model and the implementation of MBC. Future directions include ongoing quality improvement of MBC and its integration within the clinic to assess and re-assess service intensity. Disclosure of Interest None Declared

Background: The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture. Objective: This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system. Methods: Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish's behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET's impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored. Results: The lethal concentration (LC50) of MET estimated using Finney's probit technique was 3.77 mg/L. The fish's behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure. Conclusion: According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated. [ABSTRACT FROM AUTHOR]

In the present work, the morphological, optical, and gas-sensing properties of La0.67Ca0.2Ba0.13Fe0.97M0.03O3 (M = Ti, Cr, and Mn) nano-powders prepared via the auto-combustion route, were investigated. TEM images prove the nanoscale particle size of all the samples. Optical studies confirm the semiconductor behavior of the studied materials. The response of the prepared nano-powders towards the presence of two gas-reducing agents (ethanol and acetone) was investigated. From the resistance ratio under air and gas, it was possible to determine the response to different gases and deduce that La0.67Ca0.2Ba0.13Fe0.97Ti0.03O3 presents the highest responses to ethanol and acetone. Likewise, we deduced that the prepared materials were able to detect low concentrations of ethanol and acetone gases.

Abstract Background Deep learning techniques excel at identifying tumor-infiltrating lymphocytes (TILs) and immune phenotypes in hematoxylin and eosin (H&E)-stained slides. However, their ability to elucidate detailed functional characteristics of diverse cellular phenotypes within tumor immune microenvironment (TME) is limited. We aimed to enhance our understanding of cellular composition and functional characteristics across TME regions and improve patient stratification by integrating H&E with adjacent immunohistochemistry (IHC) images. Methods A retrospective study was conducted on patients with Human Papillomavirus-positive oropharyngeal squamous cell carcinoma (OPSCC). Using paired H&E and IHC slides for 11 proteins, a deep learning pipeline was used to quantify tumor, stroma, and TILs in the TME. Patients were classified into immune inflamed (IN), immune excluded (IE), or immune desert (ID) phenotypes. By registering the IHC and H&E slides, we integrated IHC data to capture protein expression in the corresponding tumor regions. We further stratified patients into specific immune subtypes, such as IN, with increased or reduced CD8+ cells, based on the abundance of these proteins. This characterization provided functional insight into the H&E-based subtypes. Results Analysis of 88 primary tumors and 70 involved lymph node tissue images reveals an improved prognosis in patients classified as IN in primary tumors with high CD8 and low CD163 expression (p = 0.007). Multivariate Cox regression analysis confirms a significantly better prognosis for these subtypes. Conclusions Integrating H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability, and improves patient stratification in HPV( + ) OPSCC.

Abstract Background The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture. Objective This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system. Methods Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish’s behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET’s impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored. Results The lethal concentration (LC50) of MET estimated using Finney’s probit technique was 3.77 mg/L. The fish’s behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure. Conclusion According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.

Abstract Background Pseudomonas putida is a pathogenic bacterium that induces great losses in fishes, including Nile tilapia (Oreochromis niloticus). Currently, the application of nanomaterials in aquaculture practices has gained more success as it endows promising results in therapies compared to traditional protocols. Objective Therefore, the current perspective is considered the first report to assess the anti-bacterial efficacy of titanium dioxide nanogel (TDNG) against Pseudomonas putida (P. putida) in Nile tilapia. Methods The fish (n = 200; average body weight: 47.50±1.32 g) were allocated into four random groups (control, TDNG, P. putida, and TDNG + P. putida), where 0.9 mg/L of TDNG was applied as bath treatment for ten days. Results Outcomes revealed that P. putida infection caused ethological alterations (surfacing, abnormal movement, and aggression) and depression of immune-antioxidant variables (complement 3, lysozyme activity, total antioxidant capacity, superoxide dismutase, and reduced glutathione content). Additionally, a substantial elevation in hepatorenal biomarkers (aspartate and alanine aminotransferases and creatinine) with clear histopathological changes and immuno-histochemical alterations (very weak BCL-2 and potent caspase-3 immuno-expressions) were seen. Surprisingly, treating P. putida-infected fish with TDNG improved these variables and obvious restoration of the tissue architectures. Conclusion Overall, this report encompasses the key role of TDNG as an anti-bacterial agent for controlling P. putida infection and improving the health status of Nile tilapia.

Abstract In recent years, the development of antitumor drugs has been dedicated to natural products. Amygdalin is a natural herbal cyanoglycoside that has anticarcinogenic effect on many types of cancers once hydrogen cyanide (HCN) is released. The main objective of the present study is to synthesize and investigate the potential of carboxymethyl chitosan nanoparticles (CMC NPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer and normal cell lines. In this study, carboxymethyl chitosan nanoparticles encapsulated with amygdalin (CMC-Am NPs) were prepared and characterized through their particle size, surface charge, chemical structure and dielectric properties. Also, the invitro drug release of amygdalin from CMC NPs was studied. Additionally, the cytotoxcity of the amygdalin and CMC-loaded amygdalin NPs were evaluated through MTT assay. The results showed that the prepared CMC-loaded amygdalin NPs exhibited a small particle size of 129 nm, high zeta potential value of − 43 mV and confirmed the amygdalin stability and compatibility with CMC NPs. Furthermore, the CMC NPs demonstrated sustained release of amygdalin during 24 h. Moreover, compared to free amygdalin, amygdalin-loaded CMC NPs have significant anti-cancerous effect on human colon HCT-116 and breast MCF-7 cancer cell lines while being safe on normal cells BJ1. In conclusion, CMC NPs can be employed as an efficient drug delivery vehicle for controlled and sustained amygdalin release with enhanced cytotoxicity on malignant cells without harming normal cells.

Abstract Despite the high prevalence of primary headaches, the role of food in modifying clinical characteristics among migraine patients is often overlooked. The aim is to detect the correlation between adopting unhealthy dietary habits and migraine severity and identify foods that have a greater chance of triggering specific subtypes of migraine. The present study was a cross-sectional analytical study that was conducted at Kasralainy Hospital, Cairo University, headache clinic at Alexandria University Hospital, and Al-Azhar University Hospitals from January to June 2020. We included 124 patients fulfilling the ICHD-3 criteria for migraine. A full clinical profile for migraine headaches was reported using a headache sheet applied to the Al-Azhar University headache unit. A nutritionist obtained data collected about dietary habits using many reliable scales and questionnaires such as food frequently sheets questionnaire. Logistic regression and Pearson correlation coefficients have been used to identify foods that are more likely to be associated with increased clinical features of migraine. Our participants reported that the fried meat, fried chicken, processed meats, fava beans, falafel, aged cheese “Pottery salted cheese” and “Rummy cheese”, salted-full fatty cheese “Damietta cheese”, citrus fruits, tea, coffee, soft drinks, nuts, pickles, chocolate, canned foods, sauces, ice cream, smoked herring, in addition to the stored food in the refrigerator for many days were significantly associated with the diagnosis of chronic migraine CM compared to episodic migraine (EM). Margarine, pickles, and smoked herring were significantly associated with the diagnosis of migraine with aura (MA) compared to migraine without aura (MO). Adopting unhealthy eating habits was a more prevalent dietary consumption pattern among people with chronic migraines compared to those with episodic migraine.

Physical clogging of porous media plays an important role in controlling their hydraulic conductivity. This study investigates how uniformly graded medium-to-coarse sand in a reservoir’s bed performs in response to the inflow of turbid water with fine suspended sediments. Different particle sizes, heads, and concentrations were simulated to cover a range of hydrologic conditions. A 1D sand column was used with three bed material sizes and three suspended particle sizes. Seven particle size ratios were tested under a constant head. Four heads and three suspended sediment concentrations are also evaluated. It was concluded that the decline in the relative hydraulic conductivity of the bed material is directly proportional to the ratio of sediments-to-bed particle sizes. Increasing the concentration of suspended sediments accelerated the rate of clogging, while bigger heads increased the depth of clogging. The study highlights how physical clogging affects the water balance in surface reservoirs and threatens the safety of dams.

Nile tilapia, Oreochromis niloticus, (2.00 ± 0.02 g) were reared in 16 70-L tanks (40 individual/tank) and fed diets (approx. 345 g/kg protein, approx. 87 g/kg crude fat) containing 0 (CTL), 75 (PH-75), 150 (PH-150), and 300 (PH-300) mg/kg phytol (n = 4). After 60 days of feeding (4% daily), growth performance, humoral immune parameters, and gut bacteria were analyzed. Also, hepatic antioxidant parameters were determined before and after the fish were transported in plastic bags for 6 hr. The results showed that PH-75 exhibited the highest final weight (P

This study aimed to determine the antimicrobial effects of ethanolic extracts of Ulva sp. and garlic (Allium sativum) powder ethanolic extracts against Vibrio harveyi in vitro. The stimulatory effects of Ulva sp. extract (UE) and garlic powder extract (GPE) on the growth performance and innate immune responses of white-leg shrimp, Litopenaeus vannamei, and their challenge against V. harveyi infection were also investigated. A commercial shrimp diet (36.1% protein) was enriched with 0.5, 1.0 and 2.0 g UE/kg diet and 2, 4 and 6 g GPE/kg diet, whereas the control group was free of any supplement. Health juveniles of L. vannamei (average weight 2-3 g) were distributed in 21 fiberglass reinforced plastic (FRP) tanks (500-L capacity) at a stocking density of 300 animals/tank to represent each treatment in triplicate. The animals were fed ad libitum on the experimental diets up to satiety four times daily for 60 days. The phytochemical analysis of ethanolic extracts of Ulva sp. and garlic powder evoked their richness of several bioactive compounds showing significant antibacterial activity against V. harveyi. The GPE exhibited a higher inhibition zone than that of the UE. The supplemented diets did not significantly affect weight gain %, final weight, feed conversion ratio, specific growth rate and survival rates of white shrimp compared to those fed on the control diet. Significant increases were observed in total haemocyte count, phagocytosis and phagocytic index of all treatments compared with the control group. There were significant increases in serum total protein, acid phosphatase activity, alkaline phosphatase, lysosomal enzyme activity, phenoloxidase activity and superoxide dismutase activity with offered diets with increasing the levels of ethanolic extracts of Ulva sp. and garlic powder up to 2.0 g UE/kg diet and 6 g GPE/kg diet, respectively. The ethanolic extraction of Ulva sp. and garlic powder-supplemented diet groups, particularly at treatments of 2.0 and 6 g GPE/kg diet, respectively, significantly reduced the shrimp mortality induced by V. harveyi infection when compared with the control group. The net results evoked that ethanolic extraction of Ulva sp. (2.0 g UE/kg) and garlic powder (6 g GPE/kg diet) enhanced the immune response and disease resistance of the white-leg shrimp, L. vannamei. It is also noted that the GPE is more efficient than the UE in vitro and in vivo investigations., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The liver has a distinctive capacity to regenerate, yet severe acute injury can be life-threatening if not treated appropriately. Inflammation and oxidative stress are central processes implicated in the pathophysiology of acute livery injury. NOX isoforms are important enzymes for ROS generation, NF-κB and NLRP3 activation, its inhibition could be vital in alleviating acute liver injury (ALI). Here in our study, we used apocynin, a natural occurring potent NOX inhibitor, to exploreits potential protective effect against thioacetamide (TAA)-induced ALI through modulating crucial oxidative and inflammatory pathways. Rats were injected once with TAA (500 mg/kg/i.p) and treated with apocynin (10 mg/kg/i.p) twice before TAA challenge. Sera and hepatic tissues were collected for biochemical, mRNA expression, western blot analysis and histopathological assessments. Pretreatment with apocynin improved liver dysfunction evidenced by decreased levels of aminotransferases, ALP, GGT and bilirubin. Apocynin reduced mRNA expression of NOX1 and NOX4 which in turn alleviated oxidative stress, as shown by reduction in MDA and NOx levels, and elevation in GSH levels andcatalase and SOD activities. Moreover, apocynin significantly reduced MPO gene expression. We also demonstrate that apocynin ameliorated inflammation through activating IκBα and suppressing IKKα, IKKβ, NF-κBp65 and p-NF-κBp65, IL-6 andTNF-α. Additionally, apocynin potentiated the gene expression of anti-inflammatory IL-10 and reduced levels of hepatic NLRP3, Caspase-1 and IL-1β. These results suggest that apocynin protects against ALI in association with the inhibition of NOX1 and NOX4 and regulating oxidative and inflammatory pathways., 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 Ltd. All rights reserved.)

Background: Enhancing the prognosis and treatment outcomes of oral cancer relies heavily on its early detection. This study aims to establish a connection between serum and salivary dipeptidyl peptidase-4 (DPP-4) levels and oral squamous cell carcinoma (OSCC), comparing them with oral potentially malignant lesions (OPMLs) and control subjects and validating salivary DPP-4 as a diagnostic marker for the early detection of oral cancer., Methodology: Forty-five systemically healthy individuals were categorized into three groups: Group I consisted of 15 patients diagnosed with OSCC, Group II comprised 15 patients with OPMLs (including leukoplakia and oral lichen planus), and Group III included 15 participants without any oral mucosal lesions. Serum and whole unstimulated salivary samples were collected from all participants to assess DPP-4 levels using an enzyme-linked immunosorbent assay (ELISA) kit. Receiver operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy of DPP-4., Results: Both serum and salivary DPP-4 levels were highest in the healthy group, followed by OPMLs, and lowest in the OSCC group, with statistically significant differences observed. ROC analysis demonstrated excellent diagnostic accuracy of salivary DPP-4 in distinguishing OSCC from healthy individuals, OPMLs from healthy individuals, and OSCC from OPMLs, with accuracies of 100%, 100%, and 96.67%, respectively. Salivary DPP-4 levels also exhibited a statistically significant correlation with OSCC grades., Conclusions: DPP-4 appears to play a protective, anti-oncogenic role in maintaining oral tissue health. The remarkable diagnostic accuracy of both serum and salivary DPP-4 in discriminating between OSCC, OPMLs, and healthy controls suggests its potential utility as a well-established marker for early oral cancer diagnosis. Salivary DPP-4, being non-invasive, could serve as a convenient chair-side diagnostic tool for the early detection of OSCC., Clinical Trial Registration: The study was retrospectively registered on clinicaltrial.gov with NCT06087042, date of registration (first posted date): 17/10/2023., (© 2024. The Author(s).)

VEXAS syndrome is an X-linked monogenic disease with adult-onset inflammatory disease and myeloid dysplasia, with clinical presentation ensuing in the fifth decade of life or later. Inflammatory symptoms associated with VEXAS syndrome are treated with several lines of therapy, eventually requiring allogeneic hematopoietic cell transplantation (allo-HCT). No evidence from randomized controlled trials exists on allo-HCT versus other treatments in patients not responding to front-line therapy(ies). We show results of a systematic review/meta-analysis (SR/MA) following a search using EMBASE, PUBMED/MEDLINE and Web of Science on April 5, 2024. We extracted outcomes based on benefits (overall response rate (ORR), complete remission (CR), event-free survival (EFS) and overall survival (OS), and harms (non-relapse mortality (NRM) and acute and chronic graft-versus-host disease (GVHD)). The search identified 88 studies. Four studies (39 patients) met inclusion criteria. Median follow-up time after allo-HCT ranged from 8 to 18.5 months. Pooled EFS and OS rates were 56% and 86%, respectively. Pertaining to harms, pooled NRM rate was 14%. Pooled rates of acute and chronic GVHD were 42% and 13%, respectively. Allo-HCT is an effective treatment for VEXAS syndrome. We hope these results would increase awareness about this underdiagnosed and underreported disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The development of innovative methods for concealing critical data in multimedia files has exploded in information security in recent years. Cryptography and steganography cannot be used alone to protect data; rather, they can be combined and used in a single system. Audio steganography is among the most important information security techniques. It involves the concealment of information within audio signals to achieve covert communication. This paper introduces a comprehensive technique that integrates chaos Henon, Baker, and Arnold maps for image encryption with audio steganography to create a robust and secure audio steganography technique. First, the target image is encrypted using chaotic maps. Then, it is embeded within the high frequencies of the cover audio signal based on the Inverse Short Time Fourier Transform (ISTFT) to be transmitted to the destination through the channel. By integrating both encryption and concealment techniques, the cover audio signal quality can be preserved. Moreover, the hidden image security and robustness are improved, making the technique resistant to many types of attacks. The simulation results confirm that the suggested technique is robust in the presence of attacks. It achieves a distinct perceptual quality with an appreciated peak signal-to-noise ratio (PSNR) of 91.2 dB and a Mean Square Error (MSE) of 7.5 × 10 -10 . The randomness of the resulting encrypted image has successfully passed the National Institute of Standards and Technology (NIST) statistical test suite., (© 2024. The Author(s).)

Background: The Eastern Mediterranean Region (EMR) faces numerous public health risks caused by biological, chemical, man-made, and natural hazards. This manuscript aimed to assess the multifaceted interventions and strategies used to strengthen the EMR's preparedness capacities to respond properly to current and upcoming health emergencies., Objective: To address these challenges, it is crucial to implement comprehensive and robust strategic risk assessments and health emergency preparedness frameworks. The World Health Organization (WHO) takes a risk-based approach, emphasizing the significance of all-hazards emergency management and the creation of national health risk profiles using the Strategic Toolkit for Assessing Risk (STAR). Furthermore, the International Health Regulations (IHR) Monitoring and Evaluation Framework (MEF) ensures continuous learning and capacity building among Member States, enhancing their ability to manage health emergencies effectively. Key components include State Party Annual Reporting (SPAR), Joint External Evaluation (JEE), After Action Review (AAR), Intra Action Review (IAR), and Simulation Exercises (SimEx). Moreover, initiatives like One Health, Emergency Care Systems, Safe Hospitals, and Public Health Emergency Operations Centers (PHEOCs) reinforce preparedness and response capacities. Risk communication and community engagement (RCCE) strategies play a pivotal role in disseminating timely information and fostering community resilience. Furthermore, the management of Chemical, Biological, and Radiological (CBRN) incidents remains a priority, necessitating collaboration between the public health and security sectors. This comprehensive approach aims to strengthen health systems, reduce risks, and improve emergency response capabilities throughout the EMR, thereby promoting global health security and resilience., Conclusion: The EMR is addressing public health challenges through frameworks like IHR-MEF, and RCCE. It is strengthening emergency care systems, ensuring safe hospitals, and establishing PHEOCs. Proactive measures to address CBRN events and collaboration are enhancing resilience. The inclusion of the One Health approach underscores the EMR's holistic strategy to address the health threats at the human-animal-environment interface. This demonstrates the EMR's commitment to global health security., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elhakim, Hammoud, Gmach, Albadri, Mahrous, Arifi, Abdel Latif, Moussa, Anan, Saidouni, Ghazy, Elkholy, Elsakka and Samhouri.)

Abstract: Although initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine plus rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance after induction is often used. Thus, the open-label, randomized phase 2 ECOG-ACRIN Cancer Research Group E1411 trial was designed to test 2 questions: (1) does addition of bortezomib to BR induction (BVR) and/or (2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012 to 2016, 373 previously untreated patients, 87% aged ≥60 years, were enrolled in this trial. At a median follow-up of 7.5 years, there is no difference in the median PFS of BR compared with BVR (5.5 vs 6.4 years; hazard ratio [HR], 0.90; 90% confidence interval [CI], 0.70-1.16). There were no unexpected additional toxicities with BVR treatment compared with BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide did not significantly improve PFS, with median PFS in R vs LR (5.9 vs 7.2 years; HR, 0.84; 90% CI, 0.62-1.15). Most patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with R alone after BR. Nonetheless, the >5-year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by R maintenance as highly effective initial therapy for older patients with MCL. This trial was registered at www.clinicaltrials.gov as #NCT01415752., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.17 trial evaluated a dose-intensive chemotherapy approach using a single cycle of inpatient R-DICEP (rituximab, dose-intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol-specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R-DICEP or to 3 cycles of R-GDP. The overall response rate (ORR) was 65.6% for R-DICEP and 48.6% for R-GDP. The ASCT rate was 71.9% versus 54.3%, and 1-year progression-free survival rate was 42% versus 32%, respectively, for R-DICEP versus R-GDP. Although the improvement in ORR for R-DICEP versus R-GDP exceeded the pre-specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3-5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The current study was designed to assess the impact of L-carnitine (LC) supplementation in the drinking water of growing Alexandria-line rabbits on performance and physiological parameters. Two hundred eighty-eight 35-day-old rabbits were divided into four groups of twenty-four replicates each (seventy-two rabbits/treatment). The treatment groups were a control group without LC and three groups receiving 0.5, 1, and 1.5 g/L LC in the drinking water intermittently. The results showed that the group receiving 0.5 g LC/L exhibited significant improvements in final body weight, body weight gain, feed conversion ratio, and performance index compared to the other groups. The feed intake remained unaffected except for the 1.5 g LC/L group, which had significantly decreased intake. Hematological parameters improved in all supplemented groups. Compared with those in the control group, the 0.5 g LC/L group showed significant increases in serum total protein and high-density lipoprotein, along with decreased cholesterol and low-density lipoprotein. Compared to other supplemented groups, this group also demonstrated superior carcass traits (carcass, dressing, giblets, and percentage of nonedible parts). In conclusion, intermittent supplementation of LC in the drinking water, particularly at 0.5 g/L twice a week, positively influenced the productivity, hematology, serum lipid profile, and carcass traits of Alexandria-line growing rabbits at 84 days of age.

Background and Aim: The spleen has an essential role in immune responses regulation and is considered the biggest peripheral immune organ. Citicoline is used for various brain disorders management. This study aimed to examine the using possibility of citicoline to treat γ-radiation-induced splenic inflammation in rats., Materials and Methods: Eighteen male albino rats were classified into: Group 1 (control) animals were kept as control. Group 2 (γ-radiation) animals were total-body γ-irradiated with 6 Gy. Group 3 (γ-radiation + citicoline) rats were γ-irradiated with 6 Gy, then injected intraperitoneally with citicoline (300 mg/kg/d) 5 min after irradiation for one week. Levels of TNF-α, IL-1β, iNOS, NF-κB, JAK2, and STAT3 were determined in spleen tissue, along with histopathological examination., Results: Rats exposure to gamma-radiation led to elevation in splenic TNF-α, IL-1β, NF-κB, iNOS, JAK2, and STAT3 levels significantly. Treatment with citicoline after gamma-radiation exposure improved this elevation, and modulated gamma-radiation-induced histopathological alterations., Conclusions: This data showed that citicoline inhibited γ-radiation-induced splenic inflammation via suppressing NF-κB and JAK2/STAT3 signaling pathways in spleen tissue.

Gaucher's disease (GD) is a lysosomal storage disorder characterized by the storage of glucosylceramide in macrophages ("Gaucher cells"), mainly in the reticuloendothelial system. GD type 1 (GD1) is the most common phenotype that usually manifests with hepatosplenomegaly, cytopenias, and bone involvement. Skeletal manifestations are the most debilitating characteristic and result in significant morbidities. We describe a case of GD1, first presented by a nontraumatic bone fracture. The case presentation highlights the importance of considering GD among the differential diagnosis of nontraumatic fractures, avascular necrosis, and infarcts of the bones. Early diagnosis and treatment improve the course of disease and avoid irreversible sequelae., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs., Methods: We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths., Results: A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease., Conclusions: Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Dr. Suarez-Almazor has received consultant fees from participation on advisory boards for Syneos Health and Celgene. All activities are unrelated to this work. Dr. Xerxes Pundole is an employee and shareholder of Amgen, Inc. The remaining authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive., Areas Covered: This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information., Expert Opinion: In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs.

Background: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL)., Patients/methods: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4 + T-cell counts with treatment were measured via Wilcoxon signed-rank tests. Overall response rate (ORR) was defined as the proportion of patients with partial or complete response (PR/CR) per 2014 Lugano classification., Results: We identified 23 patients with HIV-cHL who received a median of 6 cycles of PD-1 blockade: 1 as 1st-line, 6 as 2nd-line, and 16 as ≥3rd-line therapy. Seventeen (74%) patients received monotherapy, 5 (22%) received nivolumab plus brentuximab vedotin, and 1 received nivolumab plus ifosfamide, carboplatin, and etoposide. The median baseline CD4 + T-cell count was 155 cells/µL, which increased to 310 cells/µL at end-of-treatment (P = .009). Three patients had grade 3 imAEs; none required treatment discontinuation. The ORR was 83% with median duration of response of 19.7 months. The median progression-free survival was 21.2 months and did not differ between patients with <200 versus ≥200 CD4 + cells/µL (P = .95)., Conclusion: Our findings support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL., Competing Interests: Disclosure KL and RR: Bristol Myers Squibb-Celgene, Merck, EMD-Serono, Eli Lilly, Janssen, Lentigen, and CTI BioPharma research support through CRADAs with the NCI. DBJ: BMS, Catalyst Biopharma, Iovance, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko—advisory boards or consultancy; BMS and Incyte—research funding. NAW: ChemoCentryx—consultancy and speaker honoraria CK: Ad board/Consulting fee: Novartis, Regeneron, Janssen, Eisai, Daiichi Sankyo, Jazz Pharmaceuticals, Arcus Biosciences, Mirati Therapeutics, Sanofi, Diffuse Pharmaceuticals; Grant Support: Blueprint Medicines, Bristol-Myers Squibb, Daiichi Sankyo, Inc., Debiopharm, Genentech, Inc., Janssen, Karyopharm, Lyell, Novartis Pharmaceuticals, Regeneron, Spectrum TF: ADC therapeutics—speakers bureau; Astrazeneca—Consultancy and Speakers Bureau; Daiichi—Speakers Bureau; Sankyo—Speakers Bureau; Genmab—Consultancy and Speakers Bureau; Karyopharm—Speakers Bureau; Kite/Gilead—Honoraria and Speakers Bureau; MorphoSys—Speakers Bureau; Secura Bio—Speakers Bureau; Juno/Bristol Myers Squibb (BMS)—Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees and Research Funding; Celgene Corporation—Membership on an entity's Board of Directors or advisory committees; Janssen—Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC/Janssen—Honoraria and Membership on an entity's Board of Directors or advisory committees; Seattle Genetics—Membership on an entity's Board of Directors or advisory committees and Research Funding; Takeda—Honoraria, Membership on an entity's Board of Directors or advisory committees and travel expenses; Abbvie—Consultancy and Honoraria; Seagen—Consultancy, Honoraria, travel expenses, and Speakers Bureau; Bayer—honoraria; Portola Pharmaceuticals—research funding; Eisai—research funding; Kyowa Kirin—research funding; Amgen—research funding; Viracta Therapeutics—research funding; Cell Medica—research funding; Roche—research funding; Trillium Therapeutics—research funding; Pfizer—research funding AD: Athos Therapeutics—Current Employment, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees and Patents & Royalties; Attica Sciences—Current Employment, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees and Patents & Royalties; Dyania Health—Consultancy, Current Employment and stocks; Urogen Pharma- Stocks; Alimera Sciences—stocks; Kyn Therapeutics—stocks; Moderna Therapeutics—stocks; Proteas Bioanalystics—stocks and patents and royalties; BMS—consultancy and research funding; AstraZeneca—Consultancy, Other: Travel, accommodations, expenses and Research Funding; Radmetric—consultancy; Seagen—Consultancy and travel, accommodations, expenses; Janssen—consultancy; PACT Pharma—consultancy; Merck—Consultancy and Research Funding; Roche/Genentech—Consultancy and Research Funding; Exelixis—consultancy; Aveo—consultancy; Kite/Gilead—research funding; Jounce Therapeutics—Research funding; Infinity Pharmaceutics—research funding; Seattle Genetics/Astellas—research funding; Immunomedics/Gilead—research funding; Harvard Medical School—patents and royalties to spouse; UCLA—patents and royalties to spouse; Eli Lilly—travel, accommodations, expenses MM: Genentech/Roche—honoraria and speakers bureau, Novartis—honoraria, Sanofi—honoraria, Lexicon—honoraria and Research Funding, Ipsen—Honoraria and Speakers Bureau, Bayer—honoraria, Taiho Pharmaceutical—Honoraria and speakers bureau, Boehringer Ingelheim—honoraria, Eisai—Honoraria, Research Funding and Speakers Bureau, Merck—Honoraria and Research Funding, Exelixis—Honoraria and Speakers Bureau, AstraZeneca/Daiichi Sankyo—Honoraria and Speakers Bureau, Servier—Honoraria and Speakers Bureau, Tersera—Honoraria, QED Therapeutics—Honoraria, Precision Biologics—Research Funding, BMS—research funding, Onyx—research funding, Advanced Accelerator Applciations—research funding, AlphaVax—Research Funding, Duke University—Patents and Royalities DBJ: Advisory boards/consultancy: BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko; Research funding: BMS and Incyte AM: Research funding: Nektar, Tracon Pharma, Regeneron, Tempu slabs; Consultancy and research funding: SpringWorks Therapeutics; Honoraria: Targeted Oncology CD: Advisory Board: GenMab; BeiGene; ADC Pharmaceuticals Research funding: Genentech; Seagen; Astrazeneca AL: Advisory Board—Seagen, Kite Pharma; Consultancy—Research to Practice GS: Advisory Board: BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV, Vial, Syapse, Tempus, Ellipses Pharma; Consultant/Scientific Advisory Board (SAB): Suba Therapeutics, Syapse, Servier, Merck Research Support to institution: Sanofi (iaward), Astrazeneca, Gilead, Helsinn, Lucence, BMS, EMD Serono, Jazz Therapeutics; Speaker: BIO—INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, OLE Forum (Mexico), Seagen, Gilead, Natera, Exelixis, Janssen, Bayer; Data safety monitoring committee honorarium: Mereo; Employment: Spouse employed by Myriad; Writing/Editor fees: Uptodate, Onviv PR: research funding (to institution)—Lilly, Bayer, Telix; speaker's fees—OncLive ARN: Funding to Institution for Trials he is PI on: Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals; Consultant Editor Compensation: JCO Precision Oncology; Travel Compensation from: SITC/ AACR/ Conquer Cancer Foundation/BinayTara Foundation and Foundation Med/Caris Life Sciences; Advisory Board : Foundation Med AFH: Bristol Myers Squibb—research funding, consultancy; Genentech—research funding, consultancy; Merck—research funding, consultancy; Seattle Genetics—research funding, consultancy; KiTE Pharma—research funding; Gilead Sciences—research funding; AstraZeneca—research funding, consultancy; Karyopharm—consultancy; ADC Therapeutics—research funding, consultancy; Takeda—consultancy; Tubulis—consultancy; Regeneron—consultancy; Genmab—consultancy; Pfizer—consultancy; Caribou Biosciences—consultancy; Adicet Bio—consultancy; Abbvie—consultancy; Allogene Therapeutics—consultancy All other authors have nothing to disclose., (Published by Elsevier Inc.)

Addiction is a complex behavioral disorder characterized by compulsive drug-seeking and drug use despite harmful consequences. The prefrontal cortex (PFC) plays a crucial role in cocaine addiction, involving decision-making, impulse control, memory, and emotional regulation. The PFC interacts with the brain's reward system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc). The PFC also projects to the lateral habenula (LHb), a brain region critical for encoding negative reward and regulating the reward system. In the current study, we examined the role of PFC-LHb projections in regulating cocaine reward-related behaviors. We found that optogenetic stimulation of the PFC-LHb circuit during cocaine conditioning abolished cocaine preference without causing aversion. In addition, increased c-fos expression in LHb neurons was observed in animals that received optic stimulation during cocaine conditioning, supporting the circuit's involvement in cocaine preference regulation. Molecular analysis in animals that received optic stimulation revealed that cocaine-induced alterations in the expression of GluA1 subunit of AMPA receptor was normalized to saline levels in a region-specific manner. Moreover, GluA1 serine phosphorylation on S845 and S831 were differentially altered in LHb and VTA but not in the PFC. Together these findings highlight the critical role of the PFC-LHb circuit in controlling cocaine reward-related behaviors and shed light on the underlying mechanisms. Understanding this circuit's function may provide valuable insights into addiction and contribute to developing targeted treatments for substance use disorders., (© 2024. The Author(s).)

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1 -/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mosala, Mpotje, Abdel Aziz, Ndlovu, Musaigwa, Nono and Brombacher.)

Background: Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability., Aim: This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 10 6 once every 2 weeks., Results: The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects., Conclusion: Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts., Competing Interests: The authors declare there are no competing interests., (©2024 El-Akabawy et al.)

The analysis of body motion is a valuable tool in the assessment and diagnosis of gait impairments, particularly those related to neurological disorders. In this study, we propose a novel automated system leveraging artificial intelligence for efficiently analyzing gait impairment from video-recorded images. The proposed methodology encompasses three key aspects. First, we generate a novel one-dimensional representation of each silhouette image, termed a silhouette sinogram, by computing the distance and angle between the centroid and each detected boundary points. This process enables us to effectively utilize relative variations in motion at different angles to detect gait patterns. Second, a one-dimensional convolutional neural network (1D CNN) model is developed and trained by incorporating the consecutive silhouette sinogram signals of silhouette frames to capture spatiotemporal information via assisted knowledge learning. This process allows the network to capture a broader context and temporal dependencies within the gait cycle, enabling a more accurate diagnosis of gait abnormalities. This study conducts training and an evaluation utilizing the publicly accessible INIT GAIT database. Finally, two evaluation schemes are employed: one leveraging individual silhouette frames and the other operating at the subject level, utilizing a majority voting technique. The outcomes of the proposed method showed superior enhancements in gait impairment recognition, with overall F1-scores of 100%, 90.62%, and 77.32% when evaluated based on sinogram signals, and 100%, 100%, and 83.33% when evaluated based on the subject level, for cases involving two, four, and six gait abnormalities, respectively. In conclusion, by comparing the observed locomotor function to a conventional gait pattern often seen in healthy individuals, the recommended approach allows for a quantitative and non-invasive evaluation of locomotion.

Background: In the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting., Methods: A nationwide, population-based, historical cohort study of all people aged 45-80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators., Results: During 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose-response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49-2.69) and 2.09 (95%CI:2.01-2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c>9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years)., Conclusions: Longitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdel-Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The natural product chlorotonil displays high potency against multidrug-resistant Gram-positive bacteria and Plasmodium falciparum. Yet, its scaffold is characterized by low solubility and oral bioavailability, but progress was recently made to enhance these properties. Applying late-stage functionalization, we aimed to further optimize the molecule. Previously unknown reactions including a sulfur-mediated dehalogenation were revealed. Dehalogenil, the product of this reaction, was identified as the most promising compound so far, as this new derivative displayed improved solubility and in vivo efficacy while retaining excellent antimicrobial activity. We confirmed superb activity against multidrug-resistant clinical isolates of Staphylococcus aureus and Enterococcus spp. and mature transmission stages of Plasmodium falciparum. We also demonstrated favorable in vivo toxicity, pharmacokinetics and efficacy in infection models with S. aureus. Taken together, these results identify dehalogenil as an advanced lead molecule., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Venetoclax is a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor approved as continuous monotherapy and in combination with rituximab as fixed-treatment duration for relapsed and refractory chronic lymphocytic leukemia (R/R CLL). DEVOTE was a 24-week, multicenter observational study (NCT03310190) evaluating the safety, healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) of patients initiating venetoclax for R/R CLL in Canada. Overall, 89 patients received 1 dose of venetoclax; 80% had prior exposure (42% resistant) to ibrutinib. Biochemical tumor lysis syndrome (TLS) occurred in five patients. We observed differences in hospitalization across Canadian provinces including in patients at low risk for TLS with no clear impact on TLS incidence. Additionally, a rapid and sustained improvement in several domains of HRQoL was observed during venetoclax initiation. Early adoption of venetoclax was mainly for R/R CLL patients with few treatment options; nonetheless, acceptable toxicity and a positive impact on HRQoL were observed.

Moringa oleifera (MO), a cultivated species of the Moringa, is known for its high concentration of essential nutrients that promote growth. To assess its impact on rabbits' gut morphometric, behavioural, and physiological parameters, a study was conducted using sixty growing male white New Zealand rabbits at 40 days old. The rabbits were divided into four groups and supplemented with dried MO leaves at varying levels (0%, 0.5%, 1% and 2% of body weight) for four weeks. The results revealed significant increases in organ weights, such as liver and intestinal length, and the height of intestinal villi and crypt depth in the large intestine. The muscular layer's and submucosa's thickness also increased in different parts of the intestine in rabbits fed with MO compared to the control group. No significant effect was observed on the caecum mucosa depth. Interestingly, no significant differences were found in body weight or weight gain between the Moringa supplementation groups and the control group. However, rabbits offered 0%, 0.5% and 1% MO spent more time feeding and resting than those given 2% MO. The grooming and sniffing percentage remained unaffected by Moringa supplementation. Regarding blood parameters, rabbits that received MO leaves in their diet showed improvements in red blood cell count, haemoglobin levels, packed cell volume, white blood cell count, neutrophil count, total protein, globulin, and A/G ratio. Moreover, there was a significant decrease in malondialdehyde levels and an increase in glutathione and high-density lipoprotein levels, indicating an antioxidative effect. Overall, the study concluded that MO leaves supplementation in the rabbit diet positively influenced the rabbits' health by modulating the immune system, improving histological aspects of the intestine, liver, and spleen, and enhancing physiological parameters through its antioxidative properties., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The increasing prevalence of mental disorders among youth worldwide is one of society's most pressing issues. The proposed methodology introduces an artificial intelligence-based approach for comprehending and analyzing the prevalence of neurological disorders. This work draws upon the analysis of the Cities Health Initiative dataset. It employs advanced machine learning and deep learning techniques, integrated with data science, statistics, optimization, and mathematical modeling, to correlate various lifestyle and environmental factors with the incidence of these mental disorders. In this work, a variety of machine learning and deep learning models with hyper-parameter tuning are utilized to forecast trends in the occurrence of mental disorders about lifestyle choices such as smoking and alcohol consumption, as well as environmental factors like air and noise pollution. Among these models, the convolutional neural network (CNN) architecture, termed as DNN1 in this paper, accurately predicts mental health occurrences relative to the population mean with a maximum accuracy of 99.79%. Among the machine learning models, the XGBoost technique yields an accuracy of 95.30%, with an area under the ROC curve of 0.9985, indicating robust training. The research also involves extracting feature importance scores for the XGBoost classifier, with Stroop test performance results attaining the highest importance score of 0.135. Attributes related to addiction, namely smoking and alcohol consumption, hold importance scores of 0.0273 and 0.0212, respectively. Statistical tests on the training models reveal that XGBoost performs best on the mean squared error and R -squared tests, achieving scores of 0.013356 and 0.946481, respectively. These statistical evaluations bolster the models' credibility and affirm the best-fit models' accuracy. The proposed research in the domains of mental health, addiction, and pollution stands to aid healthcare professionals in diagnosing and treating neurological disorders in both youth and adults promptly through the use of predictive models. Furthermore, it aims to provide valuable insights for policymakers in formulating new regulations on pollution and addiction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RS declared a shared affiliation with the author PK to the handling editor at the time of review., (Copyright © 2024 Dhariwal, Sengupta, Madiajagan, Patro, Kumari, Abdel Samee, Tadeusiewicz, Pławiak and Prakash.)

Introduction: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalization and often results in death. Patients hospitalized in the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological indicators for the diagnosis of AHF., Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to diagnose AHF. Important risk variables for AHF diagnosis were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) feature selection. To test the efficacy of the suggested prediction model, Extreme Gradient Boosting (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP were used to assess the importance and influence of the model's incorporated risk factors., Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group ( p  < 0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH), and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls ( p  < 0.05). When XGBoost was used in conjunction with LASSO to diagnose AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF., Conclusion: The results of this study showed that XAI combined with ML could successfully diagnose AHF. SHAP descriptions show that advanced age, low platelet count, high RDW-SD, and PDW are the primary hematological parameters for the diagnosis of AHF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yilmaz, Yagin, Colak, Toprak, Abdel Samee, Mahmoud and Alshahrani.)

Background: The COVID-19 pandemic has been noted to decrease access to maternal health and family planning services globally. However, evidence from the Middle East and North Africa region is very scarce and limited. We qualitatively explored women's experiences in accessing maternal health and family planning services during the COVID-19 lockdown months in the two Egyptian governorates of Port Said and Souhag., Methods: Using a case study design, semi-structured phone interviews were conducted with a total of 40 women aged 18-35 years from Port Said and Souhag governorates in Egypt. Interviews explored women's experiences in accessing maternal health and family planning services during COVID-19 lockdown months, their coping strategies, and impact of challenges and/or coping strategies on participants and their families. The collected data was analyzed manually using qualitative thematic analysis., Results: Many participants were unable to access maternal health and family planning services during COVID-19 lockdown due to fear of contracting the virus, closure of health facilities, changing service hours, family planning method or drug stock-outs, and/or financial constraints. The above challenges in accessing services along with coping strategies that some women and their families used exposed women to additional health risks, including unintended pregnancies, and posed several social, emotional, and financial burdens to many., Conclusions: The COVID-19 pandemic and associated lockdown measures undermined women's access to maternal and family planning services and interfered with their ability to achieve their reproductive goals. The paper concludes with a number of recommendations to ensure access to maternal and family planning services at times of crisis. Those recommendations include: (1) adapting reliable guidelines from humanitarian settings, (2) providing adequate guidance to healthcare providers and the public to tackle fears and misinformation, (3) making self-care products available such as oral contraceptive pills, vaginal rings and self- administered injectables, (4) involving other health professionals in the provision of maternal and family planning services through task-sharing/shifting, (5) expanding the use of telemedicine and/or digital health services especially to those living in remote areas and (6) raising policymakers' awareness of the centrality of reproductive rights and the importance of protecting them at all times., (© 2024. The Author(s).)

The dietary effects of the green microalga Tetraselmis suecica (TS) on the growth, digestive enzymes, immune and antioxidant responses, genes expression, and disease resistance of Nile tilapia (Oreochromis niloticus) fingerlings were investigated. This microalga was mixed with the diet' ingredients at doses of 0.0 (the control), 5, 10, 15, and 20 g/kg diet and then fed to fish daily for 84 days. After the feeding trial, fish were experimentally challenged with Aeromonas sobria, infection and fish mortalities were recorded for another 10 days. Dietary TS significantly (p < 0.05) enhanced growth, digestive enzymes activities, and blood proteins, particularly at the level of 15 g/kg diet. Feeding the fish on 15 TS/kg feed exhibited highest mRNA expressions of GH and IGF-1 genes as well as SOD, CAT, and GPx genes compared to other TS groups. Moreover, highest levels of hepatic antioxidant and immune indices were found in the treatment of 15 g TS/kg feed. Significant downregulation of IL-1β and IL-8 genes expression and significant upregulation of IL-10 gene expression were observed in TS-fed fish, principally in fish groups fed on 15-20 g TS/kg feed. Conversely, hepatic malondialdehyde levels, blood glucose, and the activities of transaminases (ALT and AST) were significantly (p < 0.05) decreased in fish fed with 15-20 g TS/kg diet. Serum bactericidal activity against A. sobria was significantly higher in TS-fed fish groups, and its highest levels were found in treatments of 15-20 g/kg diet. Of interest, the survival rates of fish groups fed diets with 10-20 g TS/kg feed were higher after the challenge with A. sobria infection than the control group. Accordingly, we can conclude that supplementing fish diets with a 15 g TS/kg diet enhanced the growth, antioxidant and immune activities, and resistance of Nile tilapia fingerlings to possible A. sobria infection., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be detected when there are enough macroscopic changes in tumor volume, which limits the usability of radiological response criteria in evaluating earlier stages of disease response and necessitates much time to lapse for gross changes to be notable. One promising approach is to incorporate dynamic changes in circulating tumor DNA (ctDNA), which occur early in the course of therapy and can predict tumor responses weeks before gross size changes manifest. However, several issues need to be addressed before recommending the implementation of ctDNA response criteria in daily clinical practice such as clinical, biological, and regulatory challenges and, most importantly, the need to standardize/harmonize detection methods and ways to define ctDNA response and/or progression for precision oncology. Herein, we review the use of liquid biopsy (LB) to evaluate response in solid tumors and propose a plan toward standardization of LB-RECIST., (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Purpose: Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment., Materials and Methods: We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches., Results: Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS., Conclusion: This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.

Introduction: The transition towards remote healthcare has been rapidly accelerated in recent years due to a number of factors, including the COVID-19 pandemic, however, few studies have explored service users' views of remote mental healthcare, particularly in community mental health settings., Methods: As part of a larger study concerned with the development of a remotely delivered psychosocial intervention, a survey was conducted with service users with psychosis ( N  = 200) from six NHS trusts across England to gain cross-sectional data about service users' opinions and attitudes towards remote interventions and explore how digital access varies across different demographic groups and geographical localities., Results: The majority of service users had access to technological devices and a quiet space to receive care. Age was a key factor in motivation to engage with remote care as older participants had less access to technological devices and the internet, and reported less confidence to learn how to use new technologies compared to younger participants. Differences in access and attitudes towards remote care were found across the different geographical localities. Over half of the participants (53.1%) preferred a hybrid model (i.e., mixture of face-to-face and remotely delivered treatment), with only 4.5% preferring remote treatment exclusively. Factors that both encourage and deter service users from engaging with remote care were identified., Conclusions: The findings of this study provide important information about the environmental and clinical barriers that prevent, or limit, the uptake of remotely delivered care for people with psychotic disorders. Although service users often have the ability and capacity to receive remote care, providers need to be cognisant of factors which may exacerbate digital exclusion and negatively impact the therapeutic alliance., Competing Interests: The authors declare that this research was conducted for the purpose of developing a novel remotely delivered healthcare software called Remote DIALOG+. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kuhn, Abdel-Halim, Healey, Bird, Elliot and McNamee.)

Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication and the occurrence of stereotyped and repetitive behaviors. Several studies have reported altered cytokine profiles in ASD and hence may serve as potential diagnostic biomarkers of the disorder. This study aims to identify diagnostic biomarkers for ASD in a well-defined study cohort in Qatar., Methods: We measured the protein levels of 45 cytokines in the plasma samples of age- and gender-matched children (2-4 years) with ASD (n = 100) and controls (n = 60) using a Luminex multiplex assay. We compared the differences in the levels of these cytokines between the two study groups and then fitted the significantly altered cytokines into a logistic regression model to examine their diagnostic potential for ASD., Results: We found elevated levels of IFN-γ, FGF-2, IL-1RA, and IL-13 and reduced levels of eotaxin, HGF, IL-1 alpha, IL-22, IL-9, MCP-1, SCF, SDF-1 alpha, VEGFA, and IP-10 in the plasma of children with ASD compared to controls. Furthermore, we observed that elevated levels of IFN-γ (odds ratio (OR) = 1.823; 95% (confidence interval) CI = 1.206, 2.755; p = 0.004) and FGF-2 (OR = 2.528; 95% CI = 1.457, 4.385; p < 0.001) were significantly associated with increased odds of ASD, whereas reduced levels of eotaxin (OR = 0.350; 95% CI = 0.160, 0.765; p = 0.008) and HGF (OR = 0.220; 95% CI = 0.070, 0.696; p = 0.010) were significantly associated with lower odds of ASD relative to controls. The combination of these four cytokines revealed an area under the curve (ROC-AUC) of 0.829 (95% CI = 0.767, 0.891; p < 0.001), which demonstrates the diagnostic accuracy of the four-cytokine signature., Conclusions: Our results identified a panel of cytokines that could discriminate between children with ASD and controls in Qatar. In addition, our findings support the predominance of a Th1 immune phenotype in ASD children and emphasize the need to validate these results in larger populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nour-Eldine, Manaph, Ltaief, Abdel Aati, Mansoori, Al Abdulla and Al-Shammari.)