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Breast cancer is the most common illness among women, accounting for 25% of all diagnoses, as stated by the American Cancer Society. Current research focuses on 43 compounds of styrylquinoline derivatives as potential inhibitors of tubulin to design a new drug that could potentially be effective against breast cancer cells in humans. The target compounds were subjected to a three-dimensional quantitative structure-activity relationship/comparative molecular similarity indices analysis (CoMSIA) approach, where CoMSIA models were used; the best results obtained are (Q 2 = 0.84, R 2 = 0.97, rext2{r}_{\text{ext}}^{2} = 0.91), H-bond acceptor field was discovered to be important for increasing inhibitory activity by examining the contour maps (54%), and it plays a key role in the prediction of anticancer activity. Based on the contour maps of the CoMSIA models, we obtained information that allows us to propose four new molecules with higher cancer inhibitory than the 43 compounds found in the literature. The molecular docking was applied to determine the likely types of binding between the tubulin protein (PDB ID: 4O2B) and the proposed compounds, and the results show that M1 has a higher total score of 6.53 and two interactions with important conventional hydrogen bond type, followed by compound M2 with a total score of 5.74. Furthermore, the designed molecules showed better pharmacokinetic properties based on absorption, distribution, metabolism, excretion, and toxicity properties. Molecular dynamics simulations at 100 ns were conducted to confirm the binding stability of the selected ligands (M1 and M2) with tubulin protein. The simulation parameters used in the current study are root mean square deviation, root mean square fluctuation, H-bond, Rg, solvent accessible surface area, and binding energy. As a result, the designed compounds (ligands M1 and M2) have shown noteworthy potential as a drug candidate for experimental in vivo and in vitro testing due to their potential inhibition of breast cancer. Finally, the study of retrosynthesis in this work facilitates the synthesis of drug candidates.

Muhammad Nadeem,1 Mumtaz Anwar,2 Shahid Adil,3 Wajid Syed,4 Mahmood Basil A Al-Rawi,5 Ayesha Iqbal6,7 1Department of Economics, University of Education, Lahore, Vehari Campus, Pakistan; 2School of Economics, University of the Punjab, Lahore, Pakistan; 3Punjab Resource Improvement and Digital Effectiveness (PRIDE) Project, Planning and Development Board, Government of the Punjab, Punjab, Pakistan; 4Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 6Division of Pharmacy Practice and Policy, School of Pharmacy, University of Nottingham, Nottingham UK; 7Faculty of Medicine and Dentistry, University of Alberta, Edmonton, CanadaCorrespondence: Muhammad Nadeem, Email muhammad.nadeem@ue.edu.pkBackground: Access to safe drinking water, sanitation, and hygiene (WASH) facilities is crucial for health and human rights, impacting nutrition and weight.Methods: Multiple Indicators Cluster Survey (MICS) 2017– 18 has been used in this study to examine the association between WASH and underweight, alongside other factors. Analysis included descriptive statistics, association tests, logistic regression, and population-attributable fractions (PAF).Results: According to results child were 1.8, 1.1 and 1.04 times less likely to be underweight if they had access to improved source of drinking water, improved sanitation and hygiene facilities respectively. The likelihood of child being underweight reduces by 1.4, 1.89, 2.01 and 2.55 times if the household wealth status increases from poorest to second, middle, fourth and richest wealth quintiles, respectively. As the mothers’ education level increases from no schooling to primary, middle, secondary, and higher level, the possibility of child being underweight reduces by 1.22, 1.24, 1.60 and 2.01 times, respectively. Moreover, the likelihood of a child being underweight decreases as the education level of the household head improves. If maternal age is less than 20 or more than 35 years the likelihood of the child being underweight is increased by 1.074 and 1.121 times, respectively. A child is 1.1 times more likely to be underweight if birth spacing is less than 2 years. A child’s risk of being underweight decreases by 1.1 times if they have not experienced diarrhea. A child who has never been breastfed has 1.3 times higher risk of being underweight. The results of Population Attributable Fraction (PAF) indicate that holding the other factors constant, approximately 36.46% burden of underweight was preventable by access to improved drinking water, sanitation, and hygiene practices.Conclusion: Comprehensive strategy is needed that focuses on improving access to safe drinking water, sanitation infrastructure, and hygiene behaviors.Keywords: water, sanitation, hygiene, children, underweight, Pakistan, WASH

Abstract Aging-related sarcopenia is a degenerative loss of strength and skeletal muscle mass that impairs quality of life. Evaluating NUDT3 gene and myogenin expression as new diagnostic tools in sarcopenia. Also, comparing the concomitant treatment of resistance exercise (EX) and creatine monohydrate (CrM) versus single therapy by EX, coenzyme Q10 (CoQ10), and CrM using aged rats. Sixty male rats were equally divided into groups. The control group, aging group, EX-treated group, the CoQ10 group were administered (500 mg/kg) of CoQ10, the CrM group supplied (0.3 mg/kg of CrM), and a group of CrM concomitant with resistance exercise. Serum lipid profiles, certain antioxidant markers, electromyography (EMG), nudix hydrolase 3 (NUDT3) expression, creatine kinase (CK), and sarcopenic index markers were measured after 12 weeks. The gastrocnemius muscle was stained with hematoxylin–eosin (H&E) and myogenin. The EX-CrM combination showed significant improvement in serum lipid profile, antioxidant markers, EMG, NUDT3 gene, myogenin expression, CK, and sarcopenic index markers from other groups. The NUDT3 gene and myogenin expression have proven efficient as diagnostic tools for sarcopenia. Concomitant treatment of CrM and EX is preferable to individual therapy because it reduces inflammation, improves the lipid serum profile, promotes muscle regeneration, and thus has the potential to improve sarcopenia.

Abstract Helminth-derived proteins have immunomodulatory properties, influencing the host’s immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn’s disease.

Abstract Background Parkinson's disease (PD) is a chronic progressive neurodegenerative disabling disease and involves about 1–3% of the worldwide population over the age of 60. A significant prevalence of psychopathological symptoms has been recorded as most patients with PD developed over their disease course neuropsychiatric symptoms such as depression, anxiety, sleep disorders, psychosis, and cognitive and behavioral abnormalities. These non-motor symptoms, which could appear decades before motor ones, become disturbing symptoms during the later phases of the disease. Hence, the current research aims to study depressive symptoms in Parkinson's disease patients. Thirty-six patients with Parkinson’s disease aged from 40 to 65 years (20 males and 16 females) and 36 age and sex-matched controls (19 males and 17 females) were included in the study. Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr scale, Schwab and England’s scale, Mini-Mental State Examination, Cognitive Ability Screening Instrument, and Hamilton Depression Rating Scale were applied to assess depression in both groups. Results Patients were 20 males and 16 females (mean age 52.44 ± 7.45), mean duration of Parkinsonism was 3.88 years. The mean value for Hoehn and Yahr scale was 1.97 ± 1.42, for UPDRS T was 42.41 ± 20.91 and Schwab England's scale was 74.77 ± 17.78. Concerning cognition, MMSE was significantly lower among patients 25.33 ± 3.63, than in the control group and CAS total was significantly lower in patients (16 ± 71.35) than in the control group 9.81 ± 84.62. Conclusion Depressive symptoms are widespread in Parkinson's disease. Depression should be strictly determined and addressed, particularly in patients with more advanced cognitive impairment who are at a higher risk of developing or worsening depression.

Background: Khat has a stimulating and addictive effect and can induce consequences on the health and socioeconomic status of khat chewers. Objectives: This study aims to assess knowledge, attitude, and practice of khat chewing among parents in Jazan and its consequential effect on their children. Methods: This cross-sectional investigation was conducted in the Jazan region of Saudi Arabia. Data was collected via a web-based, self-administered questionnaire measuring demographics, knowledge, attitudes, and practices concerning khat chewing. The Chi-square test or Fisher's exact test was used to assess factors associated with khat chewing among parents and its consequential effect on their children. Results: A total of 724 parents were included. The sample had an overall good knowledge about the health hazards of khat chewing and an attitude against khat chewing. Nonetheless, the number of parents who reported that they had ever tried khat chewing was 200 (27.6%) and 106 parents (14.6%) confirmed that their children were khat chewers. Additionally, 98 (13.5%) parents declared that they practiced khat chewing in front of their children. Higher frequencies of parents who reported providing khat to their children were identified among parents with higher attitude levels that favor khat chewing (P value = 0.04). Conclusions: Efforts should be made to develop targeted preventive and educational strategies to reduce khat chewing among parents who have favorable attitudes toward khat chewing.

A wedding reception in the Malay wedding tradition absolutely must be carried out by the Malay community in the Kepulauan Riau, because there are moral sanctions if someone does not follow the applicable customary law. Apart from that, there is a doctrine for the Malay community in Kepulauan Riau, that a wedding reception is important to hold, if a wedding reception is not held, then one's wedding procession will not be complete. Complexity in these problems often divert the value of the relationship between custom and religion, especially Islam, within the scope of sharia. Starting from the idea that in Islam, everything must be seen for its benefit, this research uses an approach al-Maṣlaḥah Ash-Shatibi. This research uses a type of field research with the nature of descriptive qualitative research. In this research the data used is primary data and secondary data. Primary data comes from data obtained through observation, interviews and documentation. Meanwhile, secondary data comes from internet sites, literature and other media. At the data processing stage there are three activities carried out, namely: editing, coding and tabulation. The results of this research show that if viewed based on al-Maṣlaḥah perspective, Malay wedding reception in Kepulauan Riau is something special taḥsiniyyah. This is because the traditional Malay wedding procession in Kepulauan Riau is only a support for a person's advancement in society and is simply a form of obedience. Abstrak: Resepsi pernikahan dalam tradisi perkawinan melayu mutlak harus dilaksanakan oleh masyarakat melayu di Kepulauan Riau, karena adanya sanksi moral apabila seseorang tidak megikuti hukum adat yang berlaku. Selain itu juga, terdapat doktrin bagi masyarakat melayu di Kepulauan Riau, bahwa resepsi pernikahan menjadi penting untuk dilaksanakan, jika resepsi pernikahan tidak dilaksanakan, maka belum sempurna prosesi pernikahan seseorang. Kompleksitas di dalam problematika tersebut sering kali mengalihkan nilai keterkaitan antara adat dan agama khususnya Islam dalam lingkup syariah. Berangkat dari pemikiran bahwa dalam Islam, segala sesuatu harus dilihat kemaslahatannya, dalam penelitian ini dengan pendekatan al-Maṣlaḥah asy-Syathibi. Penelitian ini menggunakan jenis studi lapangan (field research) dengan sifat penelitian kualitatif deskriptif. Dalam penelitian ini data yang digunakan adalah data primer dan data sekunder. Data primer berasal dari data yang diperoleh melalui observasi, wawancara, dan dokumentasi. Sedangkan data sekunder bersumber dari situs internet, kepustakaan dan media lainnya. Pada tahap pengolahan data ada tiga kegiatan yang dilakukan, yaitu: penyuntingan (editing), pengkodean (coding) dan tabulasi (tabulating). Hasil dari penelitian ini diketahui bahwa jika ditinjau berdasarkan perspektif al-Maṣlaḥah, resepsi pernikahan melayu di Kepulauan Riau merupakan sesuatu yang bersifat taḥsiniyyah. Hal ini karena prosesi pernikahan adat Melayu Kepulauan Riau, hanya menjadi suatu penunjang peningkatan seseorang dalam pergaulannya di masyarakat dan sebagai bentuk kepatuhan semata.

Hui Yee Yeo,1,2 Jacqueline Hui Yi Wong,3 Suz Jack Chan,1 Anna Tiatia Fa’atoese Latu,1 Catherine H Han,4,5 Mudassir Anwar,1 Carlo A Marra1 1School of Pharmacy, University of Otago, Dunedin, New Zealand; 2Clinical Research Center, Hospital Seberang Jaya, Seberang Jaya, Penang, Malaysia; 3Pharmacy Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 4Auckland Oncology, Auckland, New Zealand; 5Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandCorrespondence: Carlo A Marra, School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Tel +64-34797275, Fax +64-34797034, Email carlo.marra@otago.ac.nzPurpose: Despite the importance of acknowledging patient preferences in treatment decision-making, little is known about the treatment preferences and the factors underlying those preferences of breast cancer patients. This study aims explore patient experience and perspective regarding treatment preferences and identify the important determinants that shape these preferences in the context of New Zealand.Patients and Methods: Semi-structured online interviews comprised of six focus group discussions and five individual interviews were performed with 26 breast cancer patients. The interviews were recorded, transcribed, and analyzed using the reflexive thematic analysis approach.Results: Four main themes were derived: (1) positive treatment outcomes; (2) the negative impact of treatment-related side effects on quality of life; (3) treatment accessibility, availability, and timeliness; (4) cost of treatment. Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. Additionally, patients favored treatments with minimal side effects that had minimal impact on their quality of life. There was a notable preference for treatments that were easily accessible and available in a timely manner. However, patients faced challenging decisions in balancing the costs of treatments with their benefits, leading to a consistent preference for treatments supported by government funding or medical insurance to alleviate financial burdens.Conclusion: Our study reveals that breast cancer patients in New Zealand have different perceptions and preferences regarding cancer treatment. Patients frequently find themselves making trade-offs among various attributes of a treatment, aligning these decisions with their personal values and beliefs. By considering these preferences and trade-offs in future studies that measure patient preferences, healthcare professionals can enhance their support for patients in making informed choices that align with their values and priorities. Additionally, healthcare policymakers can develop patient-centered policies that cater to the unique needs and preferences of breast cancer patients.Plain Language Summary: Breast cancer is a significant health concern in New Zealand, affecting both the well-being of patients and their families. Despite advancements in treatment, patient preferences regarding treatment risks and benefits are often neglected. This study aims to bridge this knowledge gap by qualitatively exploring the unique experiences and preferences of breast cancer patients in New Zealand, shedding light on the factors influencing their treatment decisions. The study involved a series of interviews with a group of 26 women living with breast cancer. The interview revealed four main themes that shape patients’ preferences for breast cancer treatment: 1. Positive outcomes: Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. 2. Quality of life: Treatment-related side effects negatively impacted patients’ quality of life, affecting them physically, mentally, emotionally, spiritually, and psychosocially. Patients preferred a treatment that entailed few side effects with minimal impact on their quality of life. 3. Treatment accessibility and timeliness: Patients expressed concerns about administrative complexities, long distances to healthcare facilities, timely treatment, and restricted access to treatment options in the country. There was a notable preference for treatments that were easily accessible and available in a timely manner. 4. Cost of treatment: Balancing the cost of treatments with their benefits posed challenging decisions for patients, who consistently voiced a preference for treatments supported by government funding or medical insurance.The study highlights diverse perspectives and preferences among breast cancer patients in New Zealand about treatment preference. Patients frequently find themselves making trade-offs concerning various attributes of a treatment that align with their individual values and beliefs. Integrating these preferences and trade-offs into future studies and healthcare policies can help healthcare professionals and policymakers better support patients in making informed choices aligned with their values, fostering a more patient-centered healthcare system.Keywords: qualitative research, patient preference, breast cancer, reflexive thematic analysis, treatment preference, treatment decision-making

There is no traffic-related education in the general educational curriculum of Saudi Arabia, and teenagers can acquire a licence without receiving traffic education. Consequently, the lack of sufficient traffic education can be a contributing factor to road traffic crashes (RTCs). This quantitative research study implemented a Structured Traffic Education Program (STEP) among 270 male students, all 18 years old. The study assessed demographic and driving experience characteristics and their association with exposure to car crashes and traffic violations. It is also an intervention study where there is statistical testing between baseline and follow-up data collection mediated by an intervention education program. It also analysed the levels of knowledge and self-reported commitment to traffic rules related to risky driving behaviours (RDBs) before and after implementing STEP. It was found that 66.3 percent of participants started driving at an illegal age, and only 1.5 percent underwent traffic education at a related institution. In addition, 67.8 percent of participants were unlicensed, 45.9 percent received at least one traffic violation, 34.1 percent were the mistaken party (at-fault driver) in crashes, and 56 percent watched drifting scenes out of curiosity or desire to be involved. Using a mobile phone while driving was the most prevalent RDB (77.8%). Saudis, drivers who started driving at an illegal age, car owners, and major traffic violators were significantly associated with causing crashes as the mistaken party (at-fault driver). The STEP program improved knowledge, commitment to traffic rules, and patterns related to RDBs. Additionally, driving licences should not be granted without comprehensive traffic education at driving schools. This study aims to contribute to reducing the epidemic of road traffic injuries (RTIs) and emphasises the importance of incorporating traffic education into school curricula.

Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body’s own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors. We also discuss combining CRC vaccines with monoclonal antibodies, delve into preclinical studies of novel cancer vaccines, and assess the impact of these treatment methods on patient outcomes. This review seeks to provide a deeper understanding of the current state of CRC treatment by evaluating innovative treatments and their potential to redefine the prognosis of patients with CRC.

This case presents a novel occurrence of a de novo BRCA1 gene deletion in a fetus with a cystic hygroma. Chorionic villus sampling (CVS) was performed for chromosome G-banding analysis, demonstrating a normal karyotype: 46, XX. Chromosome microarray analysis performed as a reflex test revealed an 80 kb deletion on 17q21.31, encompassing the BRCA1 gene. Follow-up FISH analysis performed on parental blood samples yielded negative results, confirming that the deletion was de novo in the fetus. Subsequent anatomic ultrasound evaluation showed no identifiable structural defects, and it was concluded that the microdeletion was unlikely to be the cause of the cystic hygroma. Regardless, it will be imperative that the patient’s daughter be appropriately counseled regarding the implications of carrying a BRCA1 deletion and the need for heightened surveillance in adulthood. As BRCA1 genetic testing is traditionally performed on adult patients with informed consent, this case report highlights the need for ongoing conversations and research in the management of incidental fetal diagnosis discovered during routine prenatal testing, as well as the care and counseling of these patients and their families.

Abstract Background Pancreatic ductal adenocarcinomas (PDAC) are characterized by frequent cell cycle pathways aberrations. This study evaluated safety and efficacy of abemaciclib, a cyclin‐dependent kinase 4 and 6 inhibitor, as monotherapy or in combination with PI3K/mTOR dual inhibitor LY3023414 or TGFβ inhibitor galunisertib versus standard of care (SOC) chemotherapy in patients with pretreated metastatic PDAC. Methods This Phase 2 open‐label study enrolled patients with metastatic PDAC who progressed after 1–2 prior therapies. Patients were enrolled in a safety lead‐in (abemaciclib plus galunisertib) followed by a 2‐stage randomized design. Stage 1 randomization was planned 1:1:1:1 for abemaciclib, abemaciclib plus LY3023414, abemaciclib plus galunisertib, or SOC gemcitabine or capecitabine. Advancing to Stage 2 required a disease control rate (DCR) difference ≥0 in abemaciclib‐containing arms versus SOC. Primary objectives for Stages 1 and 2 were DCR and progression‐free survival (PFS), respectively. Secondary objectives included response rate, overall survival, safety, and pharmacokinetics. Results One hundred and six patients were enrolled. Abemaciclib plus galunisertib did not advance to Stage 1 for reasons unrelated to safety or efficacy. Stage 1 DCR was 15.2% with abemaciclib monotherapy, 12.1% with abemaciclib plus LY3023414, and 36.4% with SOC. Median PFS was 1.7 months (95% CI: 1.4–1.8), 1.8 months (95% CI: 1.3–1.9), and 3.3 months (95% CI: 1.1–5.7), respectively. No arms advanced to Stage 2. No new safety signals were identified. Conclusion In patients with pretreated metastatic PDAC, abemaciclib‐based therapy did not improve DCRs or PFS compared with SOC chemotherapy. No treatment arms advanced to Stage 2. Abemaciclib remains investigational in patients with PDAC.

Hui Yee Yeo,1,2 Ai Ch’i Liew,2 Suz Jack Chan,1 Mudassir Anwar,1 Catherine Hye-Won Han,3 Carlo A Marra1 1School of Pharmacy, University of Otago, Dunedin, New Zealand; 2Clinical Research Center, Hospital Seberang Jaya, Penang, Malaysia; 3Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandCorrespondence: Carlo A Marra, School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Tel +64-34797275, Fax +64-34797034, Email carlo.marra@otago.ac.nzObjective: Conventionally, optimal treatment strategies for breast cancer have been largely determined by physicians, with a scant understanding of patients’ treatment values and preferences. Incorporating patient preferences in the decision-making process for breast cancer treatment is gaining recognition and can potentially improve treatment outcomes and compliance. This scoping review aims to synthesize evidence on the key determinants that are most valued by breast cancer patients when deciding on their treatment options.Methods: We searched three electronic databases (PubMed/MEDLINE, SCOPUS, and CINAHL Plus) utilizing a systematic scoping review method. Two reviewers independently screened, applied inclusion criteria, reviewed, and synthesized findings. A mixed-method narrative approach combining the inductive thematic analysis and content analysis methodologies was used to synthesize and summarize the findings.Results: The review included 22 studies, leading to the conceptualization of 5 overarching themes and 17 sub-themes. Among these, the most frequently cited theme was treatment benefits, followed by treatment-related process, treatment-related risk, quality of life, and cost of treatment. Women with breast cancer highly value treatments that offer good effectiveness, prolong survival, prevent recurrence, and maintain quality of life. Patient concerns include treatment-related side effects, safety, the risk of secondary cancer, and direct or indirect out-of-pocket costs. Additionally, patients also consider treatment duration, mode of administration, physician recommendation, and treatment availability and accessibility when deciding on their preferred treatment.Conclusion: The evidence synthesized in this review offers insights into refining breast cancer treatment strategies to align more closely with patient values. Recognizing and integrating patient perspectives in breast cancer care could potentially lead to improved treatment outcomes, enhanced patient compliance, and more personalized care. Healthcare professionals are encouraged to incorporate these key determinants in their treatment decision-making processes, aiming to deliver a patient-centered care that aligns with the unique preferences and values of each patient.Plain Language Summary: Breast cancer is a significant health concern, and treatment decisions have traditionally driven by physicians, often without due consideration for patients’ preferences in their treatment choices. This scoping review aimed to explore and summarize what matters most to breast cancer patients when deciding on their treatment options. We found five main themes that were important to patients:Effectiveness: Patients highly value treatments that are effective in fighting cancer, prolonging survival, and preventing recurrence.Treatment-related process: The length of treatment and availability of different therapies influenced patients’ choices. Patients trust their doctors’ expertise but also value being involved in the decision-making process to have their preferences considered.Side Effects and Safety: Concerns about treatment-related side effects and the risk of secondary cancer were critical factors in decision-making.Quality of Life: Maintaining a good quality of life during treatment is crucial for patients.Financial Burden: The additional direct and indirect out-of-pocket costs of treatment were important considerations for patients.Understanding patients’ preferences is vital in developing personalized treatments that align with their values. Healthcare professionals need to communicate effectively with patients and involve them in the decision-making process. Patient decision aids and tailored financial assistance programs could also be helpful. Further research is needed to identify effective strategies to tailor treatments to meet patients’ preferences. Overall, this review sheds light on what matters most to breast cancer patients, empowering them to be more active participants in their treatment decisions and potentially improving treatment outcomes and overall well-being.Keywords: breast cancer, patient preference, treatment decision making, narrative scoping review

(1) Background: Obesity, a poor diet, and inactivity are major health issues among Saudi youth. However, satisfaction with unhealthy lifestyles could impede change. This study assessed lifestyle factors and related satisfaction among Saudi university students. (2) Methods: In this cross-sectional study, 1957 students at Jazan University completed surveys on demographics, physical activity, dietary habits, and 10-point satisfaction scales for weight, activity, and diet. Chi-squared tests and logistic regression were used to analyze the associations between behaviors and satisfaction. (3) Results: Overweight/obesity prevalence was 25.45%, and only 26.67% of the subjects met activity guidelines. Many of them exhibited poor dietary habits. Despite unhealthy behaviors, some expressed high satisfaction, especially regarding their diets. Subjects with a normal BMI had the highest weight satisfaction. Activity satisfaction increased with higher activity levels. Dietary satisfaction was minimally impacted by healthfulness. Males and higher incomes were correlated with greater satisfaction. (4) Conclusions: A concerning paradox exists between unhealthy lifestyles and satisfaction among Saudi university students, particularly regarding their diets. Multicomponent interventions informed by behavior change theories and employing motivational techniques are urgently needed to address this disconnect and facilitate positive behavior change.

Imposter syndrome (IS) and low self-esteem (SE) are common issues affecting medical students that can impact their well-being and development. This study aimed to assess the prevalence and factors associated with IS and SE among medical students at Jazan University, Saudi Arabia. In this cross-sectional study, 523 medical students in years 2-6 at Jazan University, Saudi Arabia, completed validated questionnaires on IS (Young Imposter Scale) and SE (Rosenberg Self-Esteem Scale). Sociodemographic factors were also collected. Descriptive statistics and logistic regression analyses were used to analyze IS and SE prevalence and correlates. Five hundred twenty-three students with a mean age of 22.09 ± 1.933 participated. The prevalence of low SE and positive IS was 17.6% and 24.3%, respectively. IS and SE had a significant negative correlation (p

Epithelial cancer cells rely on the extracellular matrix (ECM) attachment in order to spread to other organs. Detachment from the ECM is necessary for these cells to seed in other locations. When the attachment to the ECM is lost, cellular metabolism undergoes a significant shift from oxidative metabolism to glycolysis. Additionally, the cancer cells become more dependent on glutaminolysis to avoid a specific type of cell death known as anoikis, which is associated with ECM detachment.In our recent study, we observed increased expression of H3K27me3 demethylases, specifically KDM6A/B, in cancer cells that were resistant to anoikis. Since KDM6A/B is known to regulate cellular metabolism, we investigated the effects of suppressing KDM6A/B with GSK-J4 on the metabolic processes in these anoikis-resistant cancer cells.Our results from untargeted metabolomics revealed a profound impact of KDM6A/B inhibition on various metabolic pathways, including glycolysis, methyl histidine, spermine, and glutamate metabolism. Inhibition of KDM6A/B led to elevated reactive oxygen species (ROS) levels and depolarization of mitochondria, while reducing the levels of glutathione, an important antioxidant, by diminishing the intermediates of the glutamate pathway. Glutamate is crucial for maintaining a pool of reduced glutathione.Furthermore, we discovered that KDM6A/B regulates the key glycolytic genes expression like hexokinase, lactate dehydrogenase, and GLUT-1, which are essential for sustaining glycolysis in anoikis-resistant cancer cells.Overall, our findings demonstrated the critical role of KDM6A/B in maintaining glycolysis, glutamate metabolism, and glutathione levels. Inhibition of KDM6A/B disrupts these metabolic processes, leading to increased ROS levels and triggering cell death in anoikis-resistant cancer cells.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.

BackgroundAdaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood.MethodsTonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs.ResultsStrong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies.ConclusionOur results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.

High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and Toscana virus (TOSV) are two of these viruses commonly transmitted by Phlebotomus sandflies. While SFSV can cause rapidly resolving mild febrile illness, TOSV could involve the central nervous system (CNS), causing diseases ranging from aseptic meningitis to meningoencephalitis. Sandfly-associated phleboviruses have not been investigated before in Saudi Arabia and are potential causes of infection given the prevalence of sandflies in the country. Here, we investigated the seroprevalence of SFSV and TOSV in the western region of Saudi Arabia in samples collected from blood donors, livestock animals, and animal handlers. An overall seroprevalence of 9.4% and 0.8% was found in humans for SFSV and TOSV, respectively. Seropositivity was significantly higher in non-Saudis compared to Saudis and increased significantly with age especially for SFSV. The highest seropositivity rate was among samples collected from animal handlers. Specifically, in blood donors, 6.4% and 0.7% tested positive for SFSV and TOSV nAbs, respectively. Animal handlers showed higher seroprevalence rates of 16% and 1% for anti-SFSV and anti-TOSV nAbs, respectively, suggesting that contact with livestock animals could be a risk factor. Indeed, sera from livestock animals showed seropositivity of 53.3% and 4.4% in cows, 27.5% and 7.8% in sheep, 2.2% and 0.0% in goats, and 10.0% and 2.3% in camels for SFSV and TOSV, respectively. Together, these results suggest that both SFSV and TOSV are circulating in the western region of Saudi Arabia in humans and livestock animals, albeit at different rates, and that age and contact with livestock animals could represent risk factors for infection with these viruses.

ABSTRACTInfluenza and Respiratory Syncytial virus (RSV) infections together contribute significantly to the burden of acute lower respiratory tract infections. Despite the disease burden, no approved RSV vaccine is available. While approved vaccines are available for influenza, seasonal vaccination is required to maintain protection. In addition to both being respiratory viruses, they follow a common seasonality, which warrants the necessity for a concerted vaccination approach. Here, we designed bivalent vaccines by utilizing highly conserved sequences, targeting both influenza A and RSV, as either a chimeric antigen or individual antigens separated by a ribosome skipping sequence. These vaccines were found to be effective in protecting the animals from challenge by either virus, with mechanisms of protection being substantially interrogated in this communication.

Abstract Background The excessive inflammatory responses provoked by SARS-CoV-2 infection are critical factors affecting the severity and mortality of COVID-19. Previous work found that two adjacent co-occurring mutations R203K and G204R (KR) on the nucleocapsid (N) protein correlate with increased disease severity in COVID-19 patients. However, links with the host immune response remain unclear. Methods Here, we grouped nasopharyngeal swab samples of COVID-19 patients into two cohorts based on the presence and absence of SARS-CoV-2 nucleocapsid KR mutations. We performed nasopharyngeal transcriptome analysis of age, gender, and ethnicity-matched COVID-19 patients infected with either SARS-CoV-2 with KR mutations in the N protein (KR patients n = 39) or with the wild-type N protein (RG patients n = 39) and compared to healthy controls (n = 34). The impact of KR mutation on immune response was further characterized experimentally by transcriptomic and proteomic profiling of virus-like-particle (VLP) incubated cells. Results We observed markedly elevated expression of proinflammatory cytokines, chemokines, and interferon-stimulated (ISGs) genes in the KR patients compared to RG patients. Using nasopharyngeal transcriptome data, we found significantly higher levels of neutrophils and neutrophil-to-lymphocyte (NLR) ratio in KR patients than in the RG patients. Furthermore, transcriptomic and proteomic profiling of VLP incubated cells confirmed a similar hyper-inflammatory response mediated by the KR variant. Conclusions Our data demonstrate an unforeseen connection between nucleocapsid KR mutations and augmented inflammatory immune response in severe COVID-19 patients. These findings provide insights into how mutations in SARS-CoV-2 modulate host immune output and pathogenesis and may contribute to more efficient therapeutics and vaccine development.