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BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Abstract Background Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. Methods We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. Results Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. Conclusions This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Abstract Introduction Assessing critical thinking disposition is crucial in nursing education to foster analytical skills essential for effective healthcare practice. This study aimed to evaluate the cross-cultural adaptation and validation of the Persian version of the Critical Thinking Disposition Scale among Iranian nursing students. Method A total of 390 nursing students (mean age = 21.74 (2.1) years; 64% female) participated in the study. Face and content validity were established through feedback from nursing students and expert specialists, respectively. Construct validity was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The EFA was used to explore the number of factors and the items that were loading on them. The CFA was used to confirmed the fidnings of the EFA on the same sample. Convergent and discriminant validity were examined, along with reliability through internal consistency and test-retest reliability. Results EFA revealed a two-factor structure, comprising “Critical Openness” and “Reflective Skepticism,” explaining 55% of the total variance. CFA confirmed the model’s fit (χ² = 117.37, df = 43, χ²/df = 2.73, p

Abstract Background When any aspect of patient care is overlooked or delayed, it is known as Missed Nursing Care (MNC), leading to adverse events such as medication errors, infections, increased mortality rates, and poor prognosis. Moral competence is crucial for clinical nurses as it guarantees high-quality patient care in nursing practice. Thus, this study aimed to investigate the correlation between moral competencies and MNC among nurses. Methods This study was conducted with a descriptive-correlational design. The participants in the study were nurses who were currently enrolled at Shahid Beheshti University of Medical Sciences. In order to recruit nurses for the study, a convenience sampling method was implemented. The study tools were completed by a total of two hundred nurses. Research tools included a demographic questionnaire, the Moral Competence of Clinical Nurses Questionnaire, and the Kalisch and Williams Missed Nursing Care (MISSCARE) survey. Ethical consideration This study was approved by the Medical Ethics and Law Research Center of Shahid Beheshti University of Medical Sciences. Results The mean scores of moral competencies and MNC were 151.83 ± 12.60 and 42.71 ± 9.38, respectively. In other words, descriptive statistics showed that the moral competence score was more than 75%, and the MNC score was less than 50%. Also, there was a significant negative correlation between the total scores of moral competencies and MNC (r = -0.38, p

Suayib Yalcin,1 Sahin Lacin,2 Ahmed Omar Kaseb,3 Bora Peynircioğlu,4 Murat Cantasdemir,5 Barbaros Erhan Çil,6 Pervin Hurmuz,7 Ahmet Bülent Doğrul,8 Murat Fani Bozkurt,9 Hüseyin Abali,10 Okan Akhan,4 Halis Şimşek,11 Berksoy Sahin,12 Faruk N Aykan,13 İdris Yücel,14 Gürkan Tellioğlu,15 Fatih Selçukbiricik,2 Philip A Philip16 1Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 2Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey; 3Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA; 4Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 5Department of Radiology, Memorial Şişli Hospital, İstanbul, Turkey; 6Department of Radiology, Koç University Faculty of Medicine, İstanbul, Turkey; 7Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 8Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey; 9Department of Nuclear Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey; 10Department of Medical Oncology, Bahrain Oncology Center, Muharraq, Bahrain; 11Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 12Department of Medical Oncology, Cukurova University Faculty of Medicine, Adana, Türkiye; 13Department of Medical Oncology, Istinye University Faculty of Medicine Bahçeşehir Liv Hospital, İstanbul, Turkey; 14Medicana International Hospital Samsun, Department of Medical Oncology, Samsun, Turkey; 15Department of General Surgery, Koç University Faculty of Medicine, İstanbul, Turkey; 16Department of Medicine, Division of Hematology-Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USACorrespondence: Sahin Lacin, Email sahin.lacin@hotmail.comAbstract: Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40– 50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient’s medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.Keywords: hepatocellular carcinoma, screening, imaging, diagnosis, treatment, immunotherapy, tyrosine kinase inhibitors

Abstract Copper can be susceptible to corrosion in acidic cleaning solutions for desalination system, especially if the solution is highly concentrated or if the cleaning process involves extended exposure to the acid. In the current work, Aloe ferox Mill (AFM extract) can be used as a natural origin corrosion inhibitor for copper in 1.0 M HCl solution. The corrosion mitigation qualities of AFM extract were assessed by means of electrochemical, gravimetric, and surface examinations. AFM extract is a mixed-type inhibitor, based on polarization research findings. The inhibitory effectiveness of AFM extract rises with concentration, reaching its maximum level (93.3%) at 250 mg L–1. The inclusion of AFM extract raises the activation energy for the corrosion reaction from 7.15 kJ mol–1 (blank solution) to 28.6 kJ mol–1 (at 250 mg L–1 AFM extract).

Background and Objective: Job fatigue is considered one of the factors affecting the performance and productivity of workers in work environments. Therefore, the objective of the present study was to investigate the relationship between job fatigue and its dimensions with fine motor skills in the production line workers of Sabzevar Cable Car Company. Materials and Methods: One hundred and forty-eight workers from the production line of Sabzevar Car Company were selected as a sample. The level of occupational fatigue of workers was measured using the standard questionnaire of Excessive Occupational Fatigue. In addition, the manual and sorting skills of workers were estimated through a Board test. To analyze the research data, Spearman's correlation coefficient test was used. Results: The results of the Spearman correlation coefficient test showed that there were negative and significant relationships between job fatigue and the components of hand and finger dexterity skills, including manual skills (r=0.188; P≤0.022) and sorting skill r (r=-0.246; P≤0.003). Additionally, a statistically significant relationship was observed between the dimensions of fatigue and coping skills (P≤0.05). Conclusion: According to the results of the present research study, employers can prevent the occurrence of worker fatigue in industrial environments by providing conditions such as shift breaks and performing short-term activities with low intensity. Otherwise, another way to prevent accidents and the production of defective products is to prevent tired workers from performing fine manual activities such as assembling.

Shadi Chamseddine,1,* Michael LaPelusa,2,* Lianchun Xiao,3 Yehia I Mohamed,1 Sunyoung S Lee,1 Zishuo Ian Hu,1 Rikita I Hatia,4 Manal Hassan,4 James C Yao,1 Dan G Duda,5 Saumil Datar,6 Hesham M Amin,7,8 Ahmed O Kaseb1 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 6Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; 7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 8MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Hesham M Amin, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston, TX, 77030, USA, Tel +1 713 794-1769, Fax +1 713 792-7273, Email hamin@mdanderson.org Ahmed O Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA, Tel +1-713-792-2828, Fax +1 713-745-1163, Email akaseb@mdanderson.orgIntroduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T).Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤ 3.7 μg/L and ≤ 0.9 μg/L, respectively. The Kaplan–Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups.Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036).Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.Keywords: hepatocellular carcinoma, growth hormone, durvalumab, tremelimumab, overall survival, progression-free survival

Although viral hepatocellular carcinoma (HCC) is declining, nonviral HCC, which often is the end stage of nonalcoholic or alcoholic steatohepatitis (NASH, ASH), is on an upward trajectory. Immune checkpoint inhibitors (ICIs) that block the T cell inhibitory receptor PD-1 were approved for treatment of all HCC types. However, only a minority of HCC patients show a robust and sustained response to PD-1 blockade, calling for improved understanding of factors that negatively impact response rate and duration and the discovery of new adjuvant treatments that enhance ICI responsiveness. Using a mouse model of NASH-driven HCC, we identified peritumoral fibrosis as a potential obstacle to T cell-mediated tumor regression and postulated that antifibrotic medications may increase ICI responsiveness. We now show that the angiotensin II receptor inhibitor losartan, a commonly prescribed and safe antihypertensive drug, reduced liver and peritumoral fibrosis and substantially enhanced anti-PD-1-induced tumor regression. Although losartan did not potentiate T cell reinvigoration, it substantially enhanced HCC infiltration by effector CD8+ T cells compared to PD-1 blockade alone. The beneficial effects of losartan correlated with blunted TGF-β receptor signaling, reduced collagen deposition, and depletion of immunosuppressive fibroblasts.

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing Murine Leukemia Virus (MLV) based pseudovirus particles. We demonstrated that NP-101, TQ, and other individual ingredients, including oleic, linoleic, and palmitic acids inhibited SARS-CoV-2 infection in the MLV-based pseudovirus model. A large, randomized phase 2 study of NP-101 is planned in outpatient COVID-19 patients.

Ashokkumar Thirunavukkarasu,1 Mohammed Falji A Alanazi,2 Ahmad Homoud Al-Hazmi,1 Bashayer Farhan ALruwaili,1 Aseel Awad Alsaidan,1 Thamer Alshami M Alruwaili,3 Majed Abdulaziz M Algaed,4 Areej Kaseb Alsharari,4 Ragad Humaidi Alenazi,4 Amal Muteb Alshalan,5 Sultan Muteb Alshalan6 1Department of Family and Community Medicine, College of Medicine, Jouf University, Sakaka, Saudi Arabia; 2Department of Public Health, Hafr Al Batin Health Affairs, Hafr Al Batin, Saudi Arabia; 3Department of Pediatrics, College of Medicine, Jouf University, Sakaka, Saudi Arabia; 4College of Medicine, Jouf University, Sakaka, Saudi Arabia; 5Department of Medicine, King Abdulaziz Specialist Hospital, Sakaka, Saudi Arabia; 6Medical Department, North Medical Tower hospital, Arar, Saudi ArabiaCorrespondence: Ashokkumar Thirunavukkarasu, Department of Family and Community Medicine, College of Medicine, Jouf University, Sakaka, 72388, Saudi Arabia, Tel +966-599739619, Email ashokkumar@ju.edu.saBackground: Consumer perception of and satisfaction with vaccination services is a critical and commonly used indicator for evaluating the quality of services provided by concerned authorities. The present survey assessed maternal perceptions, hesitancy, satisfaction, and factors associated with childhood immunization services provided at the primary health centers (PHCs) of eastern Saudi Arabia.Methods: The current analytical cross-sectional study included mothers of childhood vaccine beneficiaries attending PHCs in Hafr Al-Batin. We collected data related to mothers’ perceptions, hesitancy, and satisfaction using a validated Arabic version of the data collection tool. Factors associated with low and high satisfaction with the immunization services were evaluated using logistic regression analysis. We performed Spearman correlation test to identify the correlation between the perception and satisfaction scores.Results: Of the 675 participants, 87.4% were satisfied with the immunization services provided at the PHCs. The participants’ satisfaction was significantly associated with the immunized child’s age group (adjusted odds ratio [AOR] = 1.89, 95% CI = 1.39– 2.89, p = 0.037) and occupation status (AOR = 1.42, 95% CI = 1.17– 1.74, p = 0.024). Vaccine hesitancy was significantly associated with the mother’s age group (AOR = 1.89, 95% CI of AR = 1.35– 3.39, P = 0.003) and number of children (AOR = 1.42, 95% CI of AR = 1.17– 1.74, P = 0.024), Additionally, we found a significant positive correlation (Spearman’s rho = 0.207, p < 0.001) between perception and satisfaction scores.Conclusion: We recommend targeted health education programs for mothers to improve their perceptions and the importance of all recommended childhood vaccines. Additionally, we suggest continuing maternal satisfaction assessments to enhance and maintain the quality of vaccination services.Keywords: childhood vaccines, adverse effect, satisfaction, hesitancy, perception, Saudi Arabia

Ashraf Omar,1 Ahmed Kaseb,2 Tamer Elbaz,1 Mohamed El-Kassas,3 Amr El Fouly,3 Abdel Fatah Hanno,4 Ahmed El Dorry,5 Ahmed Hosni,6 Amr Helmy,7 Amr S Saad,8 Ashwaq Alolayan,9 Basem Elsayed Eysa,10 Emad Hamada,11 Hamdy Azim,11 Hany Khattab,12 Hesham Elghazaly,8 Hesham Tawfik,13 Hisham Ayoub,14 Hussein Khaled,11 Ibtessam Saadeldin,11 Imam Waked,15 Eman MF Barakat,16 Mahmoud El Meteini,17 Mohamed Hamed Shaaban,6 Mohamed EzzElarab,10 Mohamed Fathy,17 Mohamed Shaker,5 Mohamed Sobhi,5 Mohamed Kamal Shaker,16 Mohamed ElGharib,5 Mohammed Abdullah,11 Mohesn Mokhtar,11 Mostafa Elshazli,18 Omar Mohamed Khaleil Heikal,14 Osama Hetta,5 Reda Mahmoud ElWakil,16 Sameh Abdel Wahab,5 Samir Shehata Eid,19 Yousri Rostom20 On behalf of the Egyptian Liver Cancer Committee Study Group1Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt; 8Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 9Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia; 10Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; 11Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt; 12Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt; 13Department of Oncology, Faculty of Medicine, Tanta University, Tanta Egypt; 14Department of Gastroenterology, Military Medical Academy, Cairo, Egypt; 15Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt; 16Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 17Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 18Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt; 19Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt; 20Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Ashraf Omar, Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt, Email abdelazizashraf@hotmail.comAbstract: Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.Keywords: hepatocellular carcinoma, clinical recommendations, Egyptian society of liver cancer, hepatitis c virus, Egypt, guidelines

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). Results: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73–0.86) but not in female (pooled HR 0.85; 95% CI 0.70–1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59–1.04; 1.02, 95% CI 0.80–1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes. Conclusion: Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted. Impact and implications: While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised. Systematic review registration: PROSPERO CRD42023429625.

Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.

Sentiment analysis becomes an essential part of every social network, as it enables decision-makers to know more about users’ opinions. Arabic sentiment analysis has a small number of datasets relative to English. This paper introduces active learning to the Arabic NLP community and demonstrates its power. Active learning is the process of selecting the data before labelling it to get the best benefits from the labelled data and improve performance. As it takes much time and effort to label large datasets, a better way is to label selected data and get higher performance. This paper applies active learning to the ArSarcasm-v2 dataset, which is labelled for sentiment, sarcasm, and dialect, by using the SAIDS “Sentiment Analysis Informed of Dialect and Sarcasm” model that predicts sarcasm and dialect and then uses them to predict the sentiment of the text. The paper runs multiple active learning experiments with different setups. The paper achieves state-of-the-art performance on ArSarcasm-v2 for sentiment analysis by achieving a 76.71 F1-score using 95% of the training dataset which means that adding some data points makes the performance worse. The paper also demonstrates that by using active learning, we achieve 97%, 99%, and 100% of the highest F1-score reached by all training data using only 10%, 20%, and 27% of the training data respectively. This means that using about one-quarter of the training data attains the same F1-score as using the full training data. As per our knowledge, this is the first paper to introduce active learning to the Arabic NLP community.

Introduction: Achieving a high level of motor learning requires finding an optimal combination of variables and methods. This research aimed to investigate the interactive effect of the focus of attention (internal and external) and learning approach (explicit and implicit) on the retention and transfer of basketball free throw skills.Methods: Forty-eight volunteer male students were randomly assigned to four Explicit Learning - Internal Attention, Explicit Learning - External Attention, Implicit Learning - Internal Attention, and Implicit Learning - External Attention groups. In the acquisition phase, the groups practiced basketball free throws in 6 blocks of 10 trials. 24 hours after the end of the acquisition phase, a retention test and two transfer tests were performed in a block of 10 trials for each test. The first transfer test was performed 10 minutes after the retention test under pressure conditions, and the second transfer test was performed ten minutes after the first transfer test from a 4-meter distance and a 45-degree angle.Results: The results showed that in explicit learning conditions, the external focus of attention and in implicit learning conditions, the internal focus of attention led to better learning in basketball free throw.Conclusion: According to the findings of the present study, the cognitive overload of the explicit learning approach was moderated by providing the external focus of attention instructions. However, in the implicit learning approach, due to the use of analogy learning, little cognitive load is exerted on the learners’ working memory and it is possible to direct their attention to the skill itself or parts of the body that are involved in the execution of skill to achieve the benefits of the internal focus of attention.

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.

Plant architecture includes traits such as plant height, stem diameter, and branching pattern, which have significant impacts on yield and fruit quality. Polyploidization can bring changes in plant architectural traits in different crops along with other agronomic and biochemical attributes; however, the specific physiological and biochemical mechanisms are still unclear. In this study, we utilized five watermelon lines: ‘91E7’, ‘Zhengzhou No. 3’, ‘Fanzu No. 1’, ‘Shenlong’, and ‘Houlv’, along with their corresponding autopolyploid derivatives (diploid, autotriploid, and autotetraploid) to compare plant architecture differences in different polyploidy watermelon plants. The results showed that the growth habits of diploid, triploid, and tetraploid watermelon plants were noticeably different. Triploid and tetraploid watermelon plants had greater stem diameters and larger leaf sizes. The leaf angle was also larger in polyploid watermelons than in their diploid ancestor lines. Although vine length was significantly higher in diploid watermelon, there was no significant difference in node number, indicating that the short vine length was due to the short internodal length. The major differences between diploid and polyploid watermelon plants were found in the branching pattern, as diploid watermelon lines have more branching compared to their polyploid sister lines. Furthermore, we examined the phytohormone content of diploid, triploid, and tetraploid ‘Fanzu No. 1’. The reasons for the selection of this material are its robust growth and profuse branching habit, which cause visible differences among the ploidy levels. Hormone analysis showed distinct variations in abscisic acid in the nodal and stem regions, gibberellin in the auxiliary bud regions, and brassinosteroids in the apical meristematic regions. The correlation coefficient also strongly correlated these hormones with architecture-related traits. Our findings indicated that gibberellin, ABA, and brassinosteroids might be associated with variations in plant architectural traits like branching, vine length, internodal length, stem thickness, and leaf angle among different ploidy levels of watermelon. The exogenous application of GA3 showed a positive effect on branching, whereas ABA showed a negative effect on branching. The application of brassinosteroid at the apical meristem demonstrated its effect on leaf angle, leaf size, and internodal length. The results of this study can provide a theoretical reference and valuable insights into the link between plant architecture and ploidy levels.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59–64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Our aims in this work are the preparation of an ionic liquid based on heterocyclic compounds with Ag nanoparticles and the investigation of its application as an antibacterial and anticandidal agent. These goals were achieved through the fabrication of an ionic liquid based on Ag nanoparticles with 5-Amino-3-(4-fluorophenyl)-N-hexadecyl-7-(4-methylphenyl)-2-H spiro[cyclohexane1,2’-[1,3]thiazolo [4,5-b]pyridine]-6-carbonitrile (P16). The nanostructure of the prepared ionic liquid was characterized using techniques such as FTIR, 1HNMR, 13CNMR, UV, SEM, and TEM. The biological activity of the prepared compound (P16) and its nanocomposites with Ag nanoparticles was tested using five clinical bacteria (Pseudomonas aeruginosa 249; Escherichia coli 141; Enterobacter cloacae 235; Staphylococcus epidermidis BC 161, and methicillin-resistant S. aureus 217), and three Candida species (Candida utilis ATCC 9255; C. tropicalis ATCC 1362, and C. albicans ATCC 20402). The FTIR, 1HNMR, and 13CNMR results confirmed the chemical structure of the synthesized P16 compound. The nanostructure of the prepared ionic liquid was determined based on data obtained from the UV, SEM, and TEM tests. The antibacterial and anticandidal results showed that the biological activity of the compound (P16) was enhanced after the formation of nanocomposite structures with Ag nanoparticles. Moreover, the biological activity of the compound itself (P16) and that of its nanocomposite structure with Ag nanoparticles was higher than that of ampicillin and amphotericin B, which were used as control drugs in this work.

Abstract Seed production for polyploid watermelons is costly, complex, and labor-intensive. Tetraploid and triploid plants produce fewer seeds/fruit, and triploid embryos have a harder seed coat and are generally weaker than diploid seeds. In this study, we propagated tetraploid and triploid watermelons by grafting cuttings onto gourd rootstock (C. maxima × C. mochata). We used three different scions: the apical meristem (AM), one-node (1N), and two-node (2N) branches of diploid, triploid, and tetraploid watermelon plants. We then evaluated the effects of grafting on plant survival, some biochemical traits, oxidants, antioxidants, and hormone levels at different time points. We found significant differences between the polyploid watermelons when the 1N was used as a scion. Tetraploid watermelons had the highest survival rates and the highest levels of hormones, carbohydrates, and antioxidant activity compared to diploid watermelons, which may explain the high compatibility of tetraploid watermelons and the deterioration of the graft zone in diploid watermelons. Our results show that hormone production and enzyme activity with high carbohydrate content, particularly in the 2–3 days after transplantation, contribute to a high survival rate. Sugar application resulted in increased carbohydrate accumulation in the grafted combination. This study also presents an alternative and cost-effective approach to producing more tetraploid and triploid watermelon plants for breeding and seed production by using branches as sprouts.