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Mona Hmoud AlSheikh,1 Rania G Zaini,2 Muhammad Zafar Iqbal1 1Medical Education Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Medical Education Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Mona Hmoud AlSheikh, Physiology Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, Tel +966 50 498 1912, Email monaalsheikh@gmail.com; msheikh@iau.edu.saPurpose: This study aimed at developing a national consensus on entrustable professional activities (EPAs) for Saudi undergraduate medical education and mapping them with the “Saudi Meds” competency framework.Methods: A three phased approach was used. Phase 1 consisted of identifying and developing EPAs; Phase 2 consisted of building a national consensus on developed EPAs (validation process); and Phase 3 consisted of mapping the validated EPAs with the Saudi Meds competency framework. Nominal group and modified Delphi techniques were used to develop consensus on EPAs. Classical test theory-based item analysis was conducted to establish validity and reliability of finalized EPAs.Results: Fifteen expert medical educationists and 109 academic leaders from 23 medical schools participated in the validation process. The study achieved a consensus on 10 core EPAs with an overall reliability (Cronbach’s Alpha) of 0.814. The item-total correlation ranged from 0.341 to 0.642.Conclusion: This study results in a national consensus on generic, comprehensive and region-specific EPAs that have been mapped with Saudi Meds competency framework. Our study is the first step in the direction of facilitating EPA-based curricular reforms in Saudi medical schools.Keywords: competency-based medical education, undergraduate training, entrustable professional activities, competency framework, Saudi Meds

Hong Su,1 Xin Song,1 Juan Li,2 Muhammad Zubair Iqbal,2 Samuel Selorm Fiati Kenston,1 Zhen Li,1 Aiguo Wu,2 Min Ding,3 Jinshun Zhao1 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, Medicine School of Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China; 2Key Laboratory of Magnetic Materials and Devices, Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, People’s Republic of China; 3Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA Introduction: Newly synthesized Janus-structured Fe3O4-TiO2 nanoparticles (NPs) appear to be a promising candidate for the diagnosis and therapy of cancer. Although the toxicity of individual Fe3O4 or TiO2 NPs has been studied extensively, the toxicity of Janus Fe3O4-TiO2 NPs is not clear. Methods: In this study, the biosafety of both Janus Fe3O4-TiO2 NPs (20–25 nm) and the maternal material TiO2 NPs (7–10 nm) were evaluated in Sprague Dawley rats after one intravenous injection into the tail vein. Healthy rats were randomly divided into one control group and six experimental groups. Thirty days after treatment, rats were killed, then blood and tissue samples were collected for hematological, biochemical, element-content, histopathological, and Western blot analysis. Results: The results show that only a slight Ti element accumulation in the heart, spleen, and liver could be found in the Janus Fe3O4-TiO2 NP groups (P>0.05 compared with control). However, significant Ti element accumulation in the spleen, lungs, and liver was found in the TiO2 NP-treated rats. Both Fe3O4-TiO2 NPs and TiO2 NPs could induce certain histopathological abnormalities. Western blot analysis showed that both NPs could induce certain apoptotic or inflammatory-related molecular protein upregulation in rat livers. A certain degree of alterations in liver function and electrolyte and lipid parameters was also observed in rats treated with both materials. However, compared to Janus structure Fe3O4-TiO2 NP-treated groups, TiO2 NPs at 30 mg/kg showed more severe adverse effects. Conclusion: Our results showed that under a low dose (5 mg/kg), both NP types had no significant toxicity in rats. Janus NPs certainly seem less toxic than TiO2 NPs in rats at 30 mg/kg. To ensure safe use of these newly developed Janus NPs in cancer diagnosis and therapy, further animal studies are needed to evaluate long-term bioeffects. Keywords: Fe3O4-TiO2 NPs, Janus structure NPs, TiO2 NPs, accumulation, inductively coupled plasma mass spectrometry, ICP-MS, biodistribution, nanomedicine

AIM OF THE STUDY: This study was conducted to document the ethnoveterinary medicinal (EVM) practices for the treatment of different parasitic diseases of livestock in Cholistan desert, Pakistan. MATERIALS AND METHODS: An initial reconnaissance survey (rapid rural appraisal) among the local shepherds was conducted to identify the traditional healers. Information was collected from the traditional healers using a well-structured questionnaire through open-ended interviews and guided dialogue technique. RESULTS: The parasitic diseases reported in livestock were: tick and lice infestation, mange, myiasis and helminthiasis. A total of 77 ethnoveterinary practices comprising of 49 based on plant usage and 28 based on dairy products, chemicals and other organic matter were documented. A total of 18 plant species representing 14 families were documented to treat the parasitic diseases. The plants included: Aerva javanica (Amaranthaceae), Aizoon carariense (Aizoaceae), Azadirachta indica (Meliaceae), Brassica campestris (Cruciferae), Capparis decidua (Capparaceae), Capsicum annuum (Solanaceae), Citrullus colocynthis (Cucurbitaceae), Cyperus rotundus (Cyperaceae), Calligonum polygonoides (Polygonaceae), Eruca sativa (Cruciferae), Ferula assafoetida (Umbelliferae), Haloxylon salicornicum (Chenopodiaceae), Mallotus philippinensis (Euphorbiaceae), Nicotiana tabacum (Solanaceae), Pinus roxburghii (Pinaceae), Salsola baryosma (Chenopodiaceae), Solanum surratens (Solanaceae) and Zingiber officinale (Zingiberaceae). CONCLUSION: The EVM practices documented in this study need to be validated using standard parasitological procedures. Issues that should be addressed are efficacy (vis-à-vis claims made by the respondents), quality, safety and standardization of doses. [ABSTRACT FROM AUTHOR]

Ovarian cancer, predominantly epithelial ovarian cancer (EOC), is a global health concern due to its high mortality rate. Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70% of advanced patients are with recurrent cancer and disease. Bevacizumab is a humanized monoclonal antibody, which blocks VEGF signaling in cancer, inhibits angiogenesis and causes tumor shrinkage, and has been recently approved by the FDA as a monotherapy for advanced ovarian cancer in combination with chemotherapy. Unfortunately, Bevacizumab may also induce harmful adverse effects, such as hypertension, bleeding, arterial thromboembolism, poor wound healing and gastrointestinal perforation. Given the expensive cost and unwanted toxicities, there is an urgent need for predictive methods to identify who could benefit from bevacizumab. Of the 18 (approved) requests from 5 countries, 6 teams using 284 whole section WSIs for training to develop fully automated systems submitted their predictions on a test set of 180 tissue core images, with the corresponding ground truth labels kept private. This paper summarizes the 5 qualified methods successfully submitted to the international challenge of automated prediction of treatment effectiveness in ovarian cancer using the histopathologic images (ATEC23) held at the 26th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) in 2023 and evaluates the methods in comparison with 5 state of the art deep learning approaches. This study further assesses the effectiveness of the presented prediction models as indicators for patient selection utilizing both Cox proportional hazards analysis and Kaplan-Meier survival analysis. A robust and cost-effective deep learning pipeline for digital histopathology tasks has become a necessity within the context of the medical community. This challenge highlights the limitations of current MIL methods, particularly within the context of prognosis-based classification tasks, and the importance of DCNNs like inception that has nonlinear convolutional modules at various resolutions to facilitate processing the data in multiple resolutions, which is a key feature required for pathology related prediction tasks. This further suggests the use of feature reuse at various scales to improve models for future research directions. In particular, this paper releases the labels of the testing set and provides applications for future research directions in precision oncology to predict ovarian cancer treatment effectiveness and facilitate patient selection via histopathological images., 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.)

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T 1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The murine model is invaluable for studying intricate interactions among gut microbes; hosts; and diseases. However; the impact of genetic variations in the murine microbiome; especially in disease contexts such as Klebsiella pneumoniae ( Kp ) infection; still needs to be explored. Kp ; an opportunistic global pathogen; is becoming increasingly prevalent in regions like Asia; especially China. This study explored the role of the gut microbiota during Kp infection using mouse model; including wild-type and rpoS mutants of Kp138; KpC4; and KpE4 from human; maize; and ditch water; respectively. Under stress conditions; RpoS reconfigures global gene expression in bacteria; shifting the cells from active growth to survival mode. Our study examined notable differences in microbiome composition; finding that Lactobacillus and Klebsiella (particularly in WKp138) were the most abundant genera in mice guts at the genus level in all wild-type treated mice. In contrast; Firmicutes were predominant in the healthy control mice. Furthermore; Clostridium was the dominant genus in all mutants; mainly in ∆KpC4; and was absent in wild-type treated mice. Differential abundance analysis identified that these candidate taxa potentially influence disease progression and pathogen virulence. Functional prediction analysis showed that most bacterial groups were functionally involved in biosynthesis; precursor metabolites; degradation; energy generation; and metabolic cluster formation. These findings challenge the conventional understanding and highlight the need for nuanced interpretations in murine studies. Additionally; this study sheds light on microbiome-immune interactions in K. pneumoniae infection and proposes new potential therapeutic strategies.

Tick infestation poses an important challenge to livestock in Pakistan. Farm management practices and environmental variables can influence tick infestation prevalence in animals. To this end, a cross-sectional survey of 96 farms in four different geographical districts (24 farms from each district) was conducted in Punjab, Pakistan, between October 2021 and January 2022. An epidemiological questionnaire was designed focusing on farm management practices and their impact on tick infestations at these farms. Data were collected via in-person interviews. Regional and farm-specific variables' associations were evaluated using Pearson's chi-square test and Fischer's exact test, respectively. A multivariable logistic regression model was used to identify significant risk factors. This study identified that using soft bedding materials, e.g., wheat straw, leaf litter or plain soil posed a significant risk of tick infestation. Additionally, the absence of quarantine measures, open sheds and inadequate drainage were found as contributing factors in univariable analysis. Higher tick prevalence in the hotter seasons highlighted the influence of Punjab's extreme weather on tick infestation. Despite regular veterinary visits and the use of acaricidal drugs, the prevalence of tick infestation at these farms suggested potential drug resistance in the ticks. The study recommended establishing quarantine practices, improving farms' drainage systems and bedding and using a combination of chemical and traditional remedies to tackle drug resistance in ticks. Education and awareness programs on tick-borne diseases and control measures are advocated to reduce the tick infestation burden on animals. Further research on longitudinal studies to better understand tick population dynamics and develop effective acaricides is encouraged. This called for collaborative control efforts among farmers, veterinarians and research institutions.

Bacterial infections present a major global challenge. Penicillin, a widely used antibiotic known for its effectiveness and safety, is frequently prescribed. However, its short half-life necessitates multiple high-dose daily administrations, leading to severe side-effects. Therefore, this study aims to address these issues by developing hydrogels which control the release of penicillin and alleviate its adverse effects. Various combinations of aspartic acid and acrylamide were crosslinked by N', N'-methylene bisacrylamide through a free radical polymerization process to prepare aspartic acid/acrylamide (Asp/Am) hydrogels. The fabricated hydrogels underwent comprehensive characterization to assess physical properties and thermal stability. The soluble and insoluble fractions and porosity of the synthesized matrix were evaluated by sol-gel and porosity studies. Gel fraction was estimated at 88-96%, whereas sol fraction was found 12-4% and porosity found within the 63-78% range for fabricated hydrogel formulations. Maximum swelling and drug release were seen at pH 7.4, demonstrating a controlled drug release from hydrogel networks. The results showed that swelling, porosity, gel fraction, and drug release increased with higher concentrations of aspartic acid and acrylamide. However, integration of N', N'-methylene bisacrylamide exhibited the opposite effect on swelling and porosity, while increasing gel fraction. All formulations followed the Korsymer-Peppas model of kinetics with ' r ' values within the range of 0.9740-0.9980. Furthermore, the cytotoxicity study indicated an effective and safe use of hydrogel because the cell viability was higher than 70%. Therefore, these prepared hydrogels show promise candidates for controlled release of Penicillin and are anticipated to be valuable in clinical applications.

Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn' extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy., (© 2024 Wiley‐VCH GmbH.)

External factors often lead to predictable damage, such as chemical injuries, burns, incisions, and wounds. Bacterial resistance to antibiotics at wound sites underscores the importance of developing hydrogel composite systems with inorganic nanoparticles possessing antibacterial properties to treat infected wounds and expedite the skin regeneration process. In this study, a promising TiO 2 -HAp@PF-127@CBM inorganic and organic integrated hydrogel system was designed to address challenges associated with bacterial resistance and wound healing. The synthesized TiO 2 -hydroxyapatite (HAp) nanocomposites were coated with an FDA-approved PluronicF-127 polymer and combined with a carbomer hydrogel (CBM) to accomplish the final product. The synthesized nanoparticles exhibit enhanced biocompatibility against L929 and HUVECs and cell proliferation effects. To mitigate oxidative stress caused by TiO 2 -induced reactive oxygen species in dark environments for effective antibacterial effects, HAp promotes cell proliferation, expediting wound skin layer formation. CBM binds to inorganic nanoparticles, facilitating their gradual release and promoting wound healing. The reduced inflammation and enhanced tissue regeneration observed in the TiO 2 -HAp@PF-127@CBM group suggest a favorable environment for wound repair. These results align with prior findings highlighting the biocompatibility and wound-healing properties of titanium-HAp-based materials. The ability of the TiO 2 -HAp@PF-127@CBM hydrogel dressing to promote granulation tissue formation and facilitate epidermal regeneration underscores its potential for promoting antibacterial effects and wound healing applications.