Preclinical Human and Murine Models of Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most frequent liver cancer, which account for more than 90 % of all liver cancer cases. It is the fifth leading cause of cancer globally and the second leading cause of cancer-related mortality in men. The availability of competent HCC preclinical models is fundamental to the success of mechanistic studies, molecular target identification, and drug testing. However, there are challenges associated with the use of these models. In this review, we provided updates on various cell lines, animals, and human HCC models, their specific preclinic use and associated potential challenges. Overall, the understanding of the merits and demerits of a particular HCC model will improve model selection for various preclinical studies.

ChatGPT for digital pathology research.

The rapid evolution of generative artificial intelligence (AI) models including OpenAI's ChatGPT signals a promising era for medical research. In this Viewpoint, we explore the integration and challenges of large language models (LLMs) in digital pathology, a rapidly evolving domain demanding intricate contextual understanding. The restricted domain-specific efficiency of LLMs necessitates the advent of tailored AI tools, as illustrated by advancements seen in the last few years including FrugalGPT and BioBERT. Our initiative in digital pathology emphasises the potential of domain-specific AI tools, where a curated literature database coupled with a user-interactive web application facilitates precise, referenced information retrieval. Motivated by the success of this initiative, we discuss how domain-specific approaches substantially minimise the risk of inaccurate responses, enhancing the reliability and accuracy of information extraction. We also highlight the broader implications of such tools, particularly in streamlining access to scientific research and democratising access to computational pathology techniques for scientists with little coding experience. This Viewpoint calls for an enhanced integration of domain-specific text-generation AI tools in academic settings to facilitate continuous learning and adaptation to the dynamically evolving landscape of medical research.

Neighborhood Walkability Is Associated With Lower Burden of Cardiovascular Risk Factors Among Cancer Patients.

Background: Modifiable cardiovascular risk factors constitute a significant cause of cardiovascular disease and mortality among patients with cancer. Recent studies suggest a potential link between neighborhood walkability and favorable cardiovascular risk factor profiles in the general population. Objectives: This study aimed to investigate whether neighborhood walkability is correlated with favorable cardiovascular risk factor profiles among patients with a history of cancer. Methods: We conducted a cross-sectional study using data from the Houston Methodist Learning Health System Outpatient Registry (2016-2022) comprising 1,171,768 adults aged 18 years and older. Neighborhood walkability was determined using the 2019 Walk Score and divided into 4 categories. Patients with a history of cancer were identified through International Classification of Diseases-10th Revision-Clinical Modification codes (C00-C96). We examined the prevalence and association between modifiable cardiovascular risk factors (hypertension, diabetes, smoking, dyslipidemia, and obesity) and neighborhood walkability categories in cancer patients. Results: The study included 121,109 patients with a history of cancer; 56.7% were female patients, and 68.8% were non-Hispanic Whites, with a mean age of 67.3 years. The prevalence of modifiable cardiovascular risk factors was lower among participants residing in the most walkable neighborhoods compared with those in the least walkable neighborhoods (76.7% and 86.0%, respectively). Patients with a history of cancer living in very walkable neighborhoods were 16% less likely to have any risk factor compared with car-dependent-all errands neighborhoods (adjusted OR: 0.84, 95% CI: 0.78-0.92). Sensitivity analyses considering the timing of events yielded similar results. Conclusions: Our findings demonstrate an association between neighborhood walkability and the burden of modifiable cardiovascular risk factors among patients with a medical history of cancer. Investments in walkable neighborhoods may present a viable opportunity for mitigating the growing burden of modifiable cardiovascular risk factors among patients with a history of cancer.

Barbiturate-sulfonate hybrids as potent cholinesterase inhibitors: design, synthesis and molecular modeling studies.

Aim: Design and synthesis of a series of 5-benzylidene(thio)barbiturates 3a-r. Methodology: Evaluation of the inhibitory activity of the new chemical entities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Donepezil as the standard reference. Results & Conclusion: Compound 3r emerged as the most potent AChE inhibitor (IC50 = 9.12 µM), while compound 3q exhibited the highest inhibitory activity against BChE (IC50 = 19.43 µM). Toxicological bioassays confirmed the absence of cytotoxicity for the most potent compounds at the tested doses. Molecular docking analysis demonstrated that the tested derivatives effectively bind to the active sites of both enzymes. Overall, this study sheds light on the potential of barbiturate-sulfonate conjugates as promising drug candidates.

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Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis.

BACKGROUND: Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients. METHODS: We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value. RESULTS: In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%. CONCLUSION: Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.

Artificial Intelligence-Powered Optimization and Milk Permeate Upcycling for Innovative Sesame Milk with Enhanced Probiotic Viability and Sensory Appeal.

Consumer demand for plant-based alternatives drives innovation in nondairy beverages. This study explores the development of a novel sesame milk with enhanced functionality using an artificial neural network (ANN) and milk permeate integration. An ANN model effectively optimized water-based sesame milk (WSM) extraction, maximizing total solids (T.S.) recovery. The ANN model's predicted T.S. yield (99.65%) closely matched the actual value (95.18%), demonstrating its potential for optimizing high-yield production. Furthermore, milk permeate was incorporated (5:1 ratio) to create permeate-based sesame milk (PSM), which supported the growth of lactic acid bacteria, suggesting its potential as a growth medium for future probiotic applications. PSM also displayed superior nutritional value and sensory characteristics compared to WSM. These findings highlight the promise of ANN-powered optimization and milk permeate integration for creating innovative sesame milk alternatives with enhanced probiotic viability and sensory appeal. Future research should focus on ANN optimization of alternative-based-plant milk, including permeate-based sesame milk production, the health benefits of LAB fermentation, and consumer preferences for flavors and textures. Optimizing fermentation and LAB selection remain key for commercial success.

Thirty versus 60-Watt thulium laser enucleation of prostate: Toward the development of low-power anatomical enucleation of the prostate.

Introduction: We aimed to study whether using 30 W versus 60 W thulium enucleation of the prostate (ThuLEP) would affect postoperative outcomes in patients with benign prostatic hyperplasia (BPH). Materials and Methods: We prospectively identified male patients with moderate or severe lower urinary tract symptoms due to BPH. We randomized patients into 30 W (Group 1) or 60 W (Group 2) thulium yag laser with a 550 µm laser fiber and a 26 Fr continuous flow resectoscope. We collected data related to prostate size, enucleation time, morcellation time, laser time, perioperative complications, and 1-year functional outcomes. Results: A total of 120 patients were included, with a mean age of 67 years and a mean prostate size of 105 g. The preoperative characteristics were similar across both groups. The mean operative time was shorter in the 60 W group, 74 ± 27 vs. 91 ± 33 min in the 30 W group (P = 0.001), and the mean laser time was 55 ± 20 in 60 W versus 71 ± 25 in 30 W (P = 0.0001). The mean hospital stay was 1 day in both groups and at 1-year follow-up; there was a similar improvement in mean Qmax and International Prostate Symptom Score symptom scores. Discussion/Conclusion: Both 30 and 60 W ThuLEP provided a safe and comparable outcome with a relatively shorter operative time for the 60 W groups. Perhaps using a 30-W setting would be beneficial in the early learning curve or cases with more bleeding capsular perforators; besides, the financial benefit of manufacturing low-cost low-power devices that may help in the widespread of AEEP.

Complications following surgical treatment of ankle fractures in the elderly: can they be avoided?

Background Following surgical treatment of ankle fractures, geriatric patients face high complication rates (CR) in literature. Commonly used diagnostic and treatment algorithms fail to consider requirements of ageing patients which increases the risk of postoperative complications. Objective Present study critically evaluated surgical management of ankle fractures in patients over 65 years old, with focus on identifying modifiable risk factors and effective comorbidity management strategies. Methods We conducted a retrospective single-center study on patients who underwent surgical treatment of an ankle fracture. Based on their age, participants were divided into non-geriatric patients (NGP<65y) and geriatric patients (GP≥65y). We analyzed overall CR and number of minor and major complications in relation to timing of surgery, biological sex, injury pattern, osteosynthesis, pre-existing medical conditions, and postoperative care. Results 402 patients were included. GP encountered significantly higher overall (p<0.001), minor (p<0.001) and major (p=0.003) complications. They presented more complex, displaced and open fractures. Predominant factor contributing to higher CR in NGP and markedly in GP was concomitant diseases, presenting a strong OR of 19,290 (p<0.001) and 17,022 (p<0.001). Delaying surgery and managing comorbidities preoperatively had a favorable impact. Conclusion We revealed a high significant correlation between pre-existing medical conditions and postoperative results. To ascertain viability of delayed surgery in facilitating additional diagnostics and treatment of comorbidities, further comparative trials with a larger cohort are imperative.

The usage of the autoregressive integrated moving average model for forecasting milk production in Egypt (2022-2025).

Background: Milk is considered one of the most important capital goods and essential sources of animal protein in the diet of the Egyptian family, as well as an effective means to improve the economic condition of farmers, considering this important view, the policymakers need accurate and advance information regarding future supply for planning on the both short and long term. Aim: The study aims to forecast the production of milk in Egypt during the period from 2022 to 2025 using the Autoregressive Integrated Moving Average (ARIMA) model using time series data of milk production (MP) (1970-2021) obtained from the Central Agency for public mobilization and statistics (CAPMS). Methods: Augmented Dickey-Fullar Unit Root test, Partial autocorrelation function (PACF), and Autocorrelation function (ACF) of the time series sequence were used to judge the stationarity of the data. After confirming the stationarity of the data, the appropriate ARIMA model was selected based on certain statistical parameters like significant coefficients, values of adjusted R-squared, Akaike information criteria (AIC), Schwarz criterion (SC), and Standard Error of Regression. After the selection of the model based on the previous parameters, the verification of the model was employed by checking the residuals of the Correlogram-Q-Statistics test. Results: The most fitted model to predict the future levels of MP in Egypt was ARIMA (1, 1, and 3). Conclusion: Using the ARIMA (1, 1, 3) model, it could be forecasted that the production of milk in Egypt would show an increasing trend from 6,152.606 thousand tons in 2022 to 6,360.829 thousand tons in 2025.

Bictegravir/emtricitabine/tenofovir alafenamide as first-line treatment in naïve HIV patients in a rapid-initiation model of care: BIC-NOW clinical trial.

OBJECTIVE: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. RESULTS: Two hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95 P = 0.49]) rates were very high over the 48- week study period. CONCLUSIONS: BIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.

Comparative effectiveness of cervical vs thoracic spinal-thrust manipulation for care of cervicogenic headache: A randomized controlled trial.

BACKGROUND: There is ample evidence supporting the use of different manipulative therapy techniques for Cervicogenic Headache (CgH). However, no technique can be singled as the best available treatment for patients with CgH. Therefore, the objective of the study is to find and compare the clinical effects of cervical spine over thoracic spine manipulation and conventional physiotherapy in patients with CgH. DESIGN, SETTING, AND PARTICIPANTS: It is a prospective, randomized controlled study conducted between July 2020 and January 2023 at the University hospital. N = 96 eligible patients with CgH were selected based on selection criteria and they were divided into cervical spine manipulation (CSM; n = 32), thoracic spine manipulation (TSM; n = 32) and conventional physiotherapy (CPT; n = 32) groups, and received the respective treatment for four weeks. Primary (CgH frequency) and secondary CgH pain intensity, CgH disability, neck pain frequency, neck pain intensity, neck pain threshold, cervical flexion rotation test (CFRT), neck disability index (NDI) and quality of life (QoL) scores were measured. The effects of treatment at various intervals were analyzed using a 3 × 4 linear mixed model analysis (LMM), with treatment group (cervical spine manipulation, thoracic spine manipulation, and conventional physiotherapy) and time intervals (baseline, 4 weeks, 8 weeks, and 6 months), and the statistical significance level was set at P < 0.05. RESULTS: The reports of the CSM, TSM and CPT groups were compared between the groups. Four weeks following treatment CSM group showed more significant changes in primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, neck pain frequency, pain intensity, pain threshold, CFRT, NDI and QoL) than the TSM and CPT groups (p = 0.001). The same gradual improvement was seen in the CSM group when compared to TSM and CPT groups (p = 0.001) in the above variables at 8 weeks and 6 months follow-up. CONCLUSION: The reports of the current randomized clinical study found that CSM resulted in significantly better improvements in pain parameters (intensity, frequency and threshold) functional disability and quality of life in patients with CgH than thoracic spine manipulation and conventional physiotherapy. TRIAL REGISTRATION: Clinical trial registration: CTRI/2020/06/026092 trial was registered prospectively on 24/06/2020.

Pure mucinous adenocarcinoma of the breast with the rare lymphoplasmacytic infiltration: A case report with review of literature.

Key Clinical Message: A unique ER/PR-positive mucinous adenocarcinoma of breast but CK7/CK20 negativity. A rare finding of Lymphoplasmacytic Infiltration is noted. Successful treatment included modified radical mastectomy and tamoxifen-based therapy, leads to remission. Abstract: Mucinous carcinoma, which is characterized by the presence of abundant extracellular mucin, is a rare and distinctive subtype of invasive breast cancer. This subtype accounts for less than 5% of all invasive breast cancers, with pure mucinous carcinoma representing only around 2%. It is most commonly found in older patients, typically in the sixth to early eighth decade of life. We present the case of a 55-year-old female with a 15-year history of a painless, gradually enlarging palpable lump on her left breast. Upon examination, a 5 × 5 cm lump with well-defined margins and a hard consistency was found in the lower outer quadrant of the left breast. Histopathological examination confirmed a diagnosis of Mucinous Adenocarcinoma of the Left Breast. The patient underwent modified radical mastectomy and received adjuvant endocrine therapy with tamoxifen due to hormone receptor-positive status. Mucinous carcinoma of the breast is a unique entity with specific histological features including the presence of extracellular mucin pools. Immunohistochemical staining is crucial for determining hormone receptor status, which can guide treatment decisions. Although surgical intervention is the primary approach, the extent of surgery may vary, ranging from lumpectomy to mastectomy. Adjuvant therapies such as chemotherapy and radiotherapy may also be considered based on individual cases. This case underscores the importance of a multidisciplinary approach in managing rare subtypes of breast cancer, such as mucinous carcinoma. Accurate diagnosis, appropriate surgical intervention, adjuvant therapy, and long-term follow-up are critical components of treatment.

Discernible decline in macroplastic litter inputs to the central eastern Red Sea shoreline during the COVID-19 lockdown.

Plastic debris accumulating on beaches pose a major threat to marine ecosystems. Unexpected events affecting human operations, such as the COVID-19 pandemic, which prompted governments to implement safety measures and restrictions, can serve as an unplanned investigation of anthropogenic pressure on the marine environment. This study aimed to explore deviations in macroplastic delivery rates to the central eastern Red Sea shoreline during three distinct population mobility periods: before, during, and after COVID-19 restrictions, spanning from January 2019 to June 2022. We observed a 50 % reduction in the estimated macroplastic delivery rates during the lockdown, followed by a 25 % increase after restrictions were eased. Seasonal variations in delivery rates were also observed, with higher values during the winter monsoon. Reduced shoreline litter delivery during the pandemic highlights human operations as a cause of macroplastic litter and suggests the potential of temporary measures to reduce plastic pollution in the coastal environment.

The first assessment of marine litter on somalian coast: The case of Liido Beach, mogadishu.

This paper presents the first assessment of marine litter in the Mogadishu coastal area of Somalia. Samples were collected monthly using 100 m × 40 m transect and classified following OSPAR Marine Litter Survey Guide while litter sources were identified using Ocean Conservancy Marine Debris Index. The results showed a total of 119873 items consisting of plastics (89.47%), clothing items (7.53%), and others (3.00%) recovered from Liido Beach. Litter density ranged from 2.19 items/m2 to 14.18 items/m2 with a mean of 6.25 items/m2 and Clean Coast Index (CCI) suggesting that Liido Beach is extremely dirty (>20 items/m2). In addition, the primary sources of marine litter at the beach are local recreational and shoreline activities (54.12%), and dumping (36.61%). The dominance of plastic litter on the beach poses potential threats to marine biodiversity in the Somalia coastal area and the West Indian Ocean. It is recommended that effective strategies and solutions to mitigate litter on the beach and other coastal areas in Somalia should be developed and compensated with public education and awareness campaigns across the country.

DOLAMA 200: Effectiveness and Safety of a Dual Therapy with Dolutegravir Plus Lamivudine in Treatment-Experienced HIV-1 Infected Real World Participants in Spain.

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

Early coronary angioplasty fails to lower all-cause mortality in patients with out-of-hospital cardiac arrest without ST-segment elevation: A systematic review and meta-analysis.

Introduction: Out-of-hospital cardiac arrest (OHCA) is defined as the loss of functional mechanical activity of the heart in association with an absence of systemic circulation, occurring outside of a hospital. Immediate coronary angiography (CAG) with percutaneous coronary intervention is recommended for OHCA with ST-elevation. We aimed to evaluate the effect of early CAG on mortality and neurological outcomes in OHCA patients without ST-elevation. Methods: This meta-analysis and systemic review was conducted as per principles of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) group. A protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, Ref No. = CRD42022327833). A total of 674 studies were retrieved after scanning several databases (PubMed Central, EMBASE, Medline, and Cochrane Central Register of Controlled Trials). Results: A total of 18 studies were selected for the final analysis, including 6 randomized control trials and 12 observational studies. Statistically, there was no significant difference in primary outcome, i.e., mortality, between early and delayed CAG. In terms of the grade of neurological recovery as a secondary outcome, early and delayed CAG groups also showed no statistically significant difference. Conclusion: Early CAG has no survival benefits in patients with no ST elevations on ECG after OHCA.

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images.

IMPLICATIONS: Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.

Effects of first year COVID-19 pandemic on urology practice in three major Arab Countries: Sub-Analysis of a survey by Arab association of urology research group.

BACKGROUND AND OBJECTIVES: The World Health Organization (WHO) declared the coronavirus disease-19 (COVID-19) pandemic on March 11, 2020. The health care system faced tremendous challenges in providing ethical and high-quality care. The impact of COVID-19 on urological practices varied widely worldwide, including in Arab countries. This study aimed to compare the influence of the COVID-19 pandemic on urology practice in Egypt, the KSA, and the UAE during the first year of the pandemic. METHODS: This sub-analysis assessed the demographics and COVID-19's effects on urological practice in terms of adjustments to hospital policy, including outpatient consultations, the management of elective and urgent surgical cases, and the continuation of education across the three countries. The availability of personal protective equipment (PPE) and urologists' emotional, physical, and verbal intimidation during COVID-19 were also compared. RESULTS: Regarding the impact on hospital policy, consultations replaced by telemedicine were significantly higher in the KSA (36.15%), followed by the UAE (33.3%), then Egypt (10.4%) (P = 0.008). Elective cases requiring ICU admission were 65.1% in Egypt, 45.2% in the KSA, and 58.2% in the UAE and were performed only in high-risk patients. PPE was freely available in 20.8% of the Egyptian hospitals compared to 83.3% in the KSA and 81.8% in the UAE. Online courses were significantly higher in Egypt (70.8%), followed by the UAE (53%) and the KSA (41.7%) (P = 0.02). Emotional intimidation was higher than verbal intimidation, representing 80%, 75.9%, and 76% in the UAE, KSA, and Egypt, respectively. CONCLUSION: This sub-analysis outlined significant hospital policy changes across the three Arab countries. Exposure to emotional, verbal, and physical intimidation was observed. The development of teleconsultations and online platforms for educational purposes was observed.