Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials.

Background: Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear. Objectives: This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations. Design: A posthoc analysis of individual-participant level data (IPD). Methods: IPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark. Results: Among 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26-0.77), p = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations. Conclusion: This study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM. Trial registration: MAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).

Blood clot prevention drugs in multiple myeloma: usage and impact on patient outcomes Aims and Purpose of the Research This study aimed to understand how blood-thinning medications are used by patients with multiple myeloma, a type of blood cancer. Specifically, we wanted to find out how often these medications are used, what side effects they might cause, and whether they are linked with how long the patients live. Background of the Research This study is important because patients with multiple myeloma often have a higher risk of blood clots, especially when they are taking certain anticancer treatments. Blood-thinning drugs are usually recommended to prevent these clots, but it's not always clear how well these drugs work or what side effects they might cause. Methods and Research Design This study looked at data from three clinical trials involving a multiple myeloma drug called daratumumab. We looked at how often side effects occurred and how often blood-thinning drugs were used. Two groups of blood thinning drugs were investigated: antiplatelets and anticoagulants. We used two types of statistical methods, called logistic and Cox regression, to see if there was a connection between the use of these blood-thinning drugs and the occurrence of side effects or survival rates at the start of the study and after six months. Results and Importance The study found that the use of blood-thinning drugs increased over time and that using anticoagulants within the first six months was linked to a lower risk of blood clots. However, blood-thinning drugs were not linked with how long the patients lived. These results are important because they can help doctors better manage the use of blood-thinning drugs in patients with multiple myeloma. The key message is that more research is needed to improve guidelines for preventing blood clots and to better understand the safety and effectiveness of blood-thinning drugs in these patients.

High sulphur oil of Type II kerogen of the oil shales from Western Central Jordan based on molecular structure and kinetics.

Organic rich sedimentary rocks of the Late Cretaceous Muwaqqar Formation from the Lajjun outcrop in the Lajjun Sub-basin, Western Central Jordan were geochemically analyzed. This study integrates kerogen microscopy of the isolated kerogen from 10 oil shale samples with a new finding from unconventional geochemical methods [i.e., ultimate elemental (CHNS), fourier transform infrared spectroscopy and pyrolysis-gas chromatography (Py-GC)] to decipher the molecular structure of the analyzed isolated kerogen fraction and evaluate the kerogen composition and characteristics. The optical kerogen microscopy shows that the isolated kerogen from the studied oil shales is originated from marine assemblages [i.e., algae, bituminite and fluorescence amorphous organic matter] with minor amounts of plant origin organic matter (i.e., spores). This finding suggests that the studied kerogen is hydrogen-rich kerogen, and has the potential to generate high paraffinic oil with low wax content. The dominance of such hydrogen-rich kerogen (mainly Type II) was confirmed from the multi-geochemical ratios, including high hydrogen/carbon atomic of more than 1.30 and high A-factor of more than 0.60. This claim agrees with the molecular structure of the kerogen derived from Py-GC results, which suggest that the studied kerogen is mainly Type II-S kerogen exhibiting the possibility of producing high sulphur oils during earlier stages of diagenesis, according to bulk kinetic modeling. The kinetic models of the isolated kerogen fraction suggest that the kerogen conversion, in coincidence with a vitrinite reflectance range of 0.55-0.60%, commenced at considerably lower temperature value ranges between 100 and 106 °C, which have produced oils during the early stage of oil generation. The kinetic models also suggest that the commercial amounts of oil can generate by kerogen conversion of up to 50% during the peak stage of oil window (0.71-0.83%) at relatively low geological temperature values in the range of 122-138 °C. Therefore, further development of the Muwaqqar oil shale successions is highly approved in the shallowly buried stratigraphic succession in the Lajjun Sub-basin, Western Central Jordan.

A non-targeted metabolomics comparative study on plasma of pfizer and sinopharm COVID-19 vaccinated individuals, assessed by (TIMS-QTOF) mass spectrometry.

COVID-19 is a highly contagious infectious disease that has posed a global threat, leading to a widespread pandemic characterized by multi-organ complications and failures. AIMS: The present study was conducted to evaluate the impact of Pfizer and Sinopharm vaccines on metabolomic changes and their correlations with immune pathways. MAIN METHODS: The study used a cross-sectional design and implemented an untargeted metabolomics-based approach. Plasma samples were obtained from three groups: non-vaccinated participants, Sinopharm-vaccinated participants, and Pfizer-vaccinated participants. Comparative metabolomic analysis was conducted using TIMS-QTOF, and multiple t-tests with a 5 % false discovery rate (FDR) were performed using MetaboAnalyst software. KEY FINDINGS: Out of the 105 metabolites detected, 72 showed statistically significant changes (p-value < 0.05) across the different groups. Notably, several metabolites such as neopterin, pyridoxal, and syringic acid were markedly altered in individuals vaccinated with Pfizer. Conversely, in the Sinopharm-vaccinated group, significant alterations were observed in sphinganine, neopterin, and sphingosine. These metabolites hold potential as biomarkers for evaluating vaccine efficacy. Additionally, both Pfizer and Sinopharm vaccinations were found to influence sphingolipid and histidine metabolisms compared to the control group. The Sinopharm group also displayed changes in lysine degradation relative to the control group. When comparing the enriched pathways between the Pfizer and Sinopharm-vaccinated groups, differences were observed in purine metabolism. Furthermore, alterations in tryptophan and vitamin B6 metabolism were noted when comparing the Pfizer-vaccinated group with both the control and Sinopharm-vaccinated groups. SIGNIFICANCE: These findings highlight the importance of metabolomics in assessing vaccine effectiveness and identifying potential biomarkers for monitoring the efficacy of newly developed vaccines in a shorter timeframe.

Geochemical and Organic Petrological Characteristics of the Bituminous Carbonate Succession (Upper Cretaceous Shu'ayb Formation) in Northern Jordan: Implications for Organic Matter Input and Paleosalinity, Paleoredox, and Paleoclimatic Conditions.

Bituminous carbonate rocks of the Upper Cretaceous Shu'ayb Formation from the Ajloun outcrop in Northern Jordan were geochemically and petrologically analyzed in this study. This study integrates kerogen microscopy results with geochemical results (i.e., biomarker, stable carbon isotope, and major elemental compositions) to understand the organic matter (OM) inputs and to reveal the dispositional setting and its effect on the occurrence of OM. The Shu'ayb bituminous carbonate rocks have high total organic carbon (TOC) and sulfur (S) contents, with average values of 12.3 and 4.59 wt %, respectively, indicating redox conditions during their precipitation. The high abundance of alginite (i.e., lamalginite) in the Shu'ayb bituminous carbonate sediments is a further evidence for redox conditions. The finding of mainly marine-derived OM was also demonstrated by the biomarker distribution and carbon isotope composition. The biomarkers are represented by a narrow Pr/Ph ratio of up to 0.97, abundance of tricyclic terpanes, and high C27 regular sterane, indicating that the OM was primarily derived from phytoplankton algae, along with small amounts of land plant-derived materials, and were accumulated under reducing conditions. The studied Shu'ayb bituminous carbonate facies is composed of mainly calcium (CaO; average, 45.10 wt %), with significant amounts of silicon (Si2O3; avg., 9.35 wt %), aluminum (Al2O3; avg., 6.91 wt %), and phosphorus (P2O3; avg., 1.47 wt %) and low amounts of iron (Fe2O3) and titanium (TiO2) of less than 1 wt %, indicating that the detrital influx was low in an open water depth system with higher primary bioproductivity. The geochemical proxy suggests that the Shu'ayb bituminous carbonate facies was established in a saline water environment, with Ca/Ca + Fe and S/TOC values of more than 0.9 and 0.50, respectively, which could be attributed to the increase in reducing conditions of the water column. The chemical index of alteration values of more than 0.8 also indicate that the Shu'ayb bituminous carbonate facies formed during warm and humid climatic conditions, thereby resulting in intense subaerial weathering.

Scopoletin mitigates maternal separation-induced anxiety-like and depression-like behaviors in male mice through modulation of the Sirt1/NF-κB pathway.

RATIONALE: Early-life maternal separation can lead to anxiety-like and depression-like behaviors in mice reared under maternal separation conditions. Scopoletin, a compound with anti-inflammatory and antidepressant properties, may offer therapeutic benefits, but its effectiveness against behaviors induced by maternal separation during adulthood remains unexplored. OBJECTIVES: This study investigates scopoletin's efficacy in alleviating anxiety-like and depression-like phenotypes in male mice subjected to early-life maternal separation. METHODS: Male C57BL/6J mice experienced daily maternal separation for 4 h from postnatal day (PND) 2 to 21. From postnatal day 61(PND 61), scopoletin was administered intraperitoneally at 20 mg/kg/day for four weeks. Behavioral and biochemical assessments were conducted at postnatal day 95 (PND 95). RESULTS: Maternally separated mice displayed marked anxiety-like and depression-like behaviors, evident in behavioral tests like the open field and elevated plus maze. These mice also showed increased immobility in the forced swimming and tail suspension tests. Biochemically, there were elevated levels of IL-1ß, IL-6, and TNF-α in the hippocampus, with a decrease in Sirt1 and upregulation in NF-κB p65 expression. Scopoletin treatment significantly mitigated these behavioral abnormalities, normalizing both anxiety-like and depression-like behaviors. Correspondingly, it reduced the levels of pro-inflammatory cytokines and reinstated the expression of Sirt1 and NF-κB p65. CONCLUSIONS: Scopoletin effectively reverses the adverse behavioral and biochemical effects induced by early-life maternal separation in male mice, suggesting its potential as a therapeutic agent for treating anxiety-like and depression-like behaviors. Modulation of neuroinflammatory pathways and the Sirt1/NF-κB signaling axis is one possible mechanism.

Exploring Scopoletin's Therapeutic Efficacy in DSS-Induced Ulcerative Colitis: Insights into Inflammatory Pathways, Immune Modulation, and Microbial Dynamics.

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1ß, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

Lessons learnt from an aggressive tumour masquerading as a neuropathic heel ulcer: a case report.

Cutaneous malignant melanoma (cMM) can develop at any site, but one-third of cases primarily affect the lower extremities, with ankle and foot lesions representing 3-15% of all cases. However, cMM may become a clinical conundrum when it presents as chronic ulceration that is clinically indiscernible from other lower extremity ulcers in patients with diabetes. We present the case of a 71-year-old female patient with a longstanding history of diabetes, hypertension, obesity, chronic kidney disease and heart failure who presented to our hospital with a fungating heel ulcer. The lesion was initially managed in another hospital as a neuropathic diabetic foot ulcer (DFU), treated by multiple local wound debridement. However, the ulcer progressed into a fungating heel lesion that interfered with the patient's mobility and quality of life. Consequently, the patient was referred to our specialist diabetic foot service for further management. Excisional biopsy of the lesion disclosed a cMM. Positron emission tomography/computed-tomography scanning revealed hypermetabolic ipsilateral inguinal lymphadenopathy, and a right cerebral metastasis for which palliative chemotherapy was initiated. Immunotherapy was considered, but the patient died before it was started. Atypical foot ulcers in patients with diabetes warrant a careful diagnostic approach, especially for recalcitrant cutaneous lesions not responding to standard therapies. Conscientious management, without undue delay in obtaining a histopathological diagnosis, might lead to early diagnosis of melanoma and potentially more favourable outcomes. This case highlights the importance of consideration of atypical foot lesions, in general practice in addition to referral centres, to try to identify alarming features and act accordingly.

Role of pharmacists in the care of adult asthma patients: A scoping review.

BACKGROUND: Asthma is a common long-term condition that affects people of all ages. Evidence suggests that a significant proportion of asthma patients in the Gulf Cooperation Council (GCC) do not receive appropriate diagnosis, monitoring and/or treatment. When inadequately treated, asthma can negatively affect quality of life and may lead to hospitalisation and death. Although pharmacists play a role in asthma care globally, there appears to be no defined role for pharmacists in providing care to patients with asthma in the GCC countries. AIM: This scoping review aims to review and summarise studies conducted in the GCC countries involving pharmacists in the management of adults with asthma or evaluating pharmacists' asthma care knowledge and/or skills. METHOD: A systematic scoping review was undertaken. Seven databases were searched using relevant search terms for articles published up to May 2023. Studies that evaluated pharmacists roles, knowledge and skills in providing asthma care to adults in the United Arab Emirates (UAE), Qatar, Kuwait, Oman, Saudi Arabia, and Bahrain were considered eligible for inclusion. Extracted data were collated using tables and used to produce narrative descriptive summaries. RESULTS: Out of the 1588 search results, only seven studies met the inclusion criteria. Of those, only one developed and tested a pharmacist-led inhaler technique educational intervention in the UAE within community pharmacy setting for asthma patients. The remaining six studies assessed community pharmacists knowledge in providing asthma management and patient education in UAE, Saudi Arabia and Qatar. The quality of the included studies varied with four relying on simulated patients to assess pharmacists knowledge. The study that tested the intervention suggested improvement in inhaler technique and asthma symptoms control after receiving the intervention. The findings suggest a need to improve pharmacists knowledge of inhaler technique demonstration (mainly Metered Dose Inhalers), asthma management advice and assessment of asthma control and medication use. CONCLUSION: This review highlights a lack of research on pharmacist-led asthma interventions and identifies training needs to enable pharmacists to be involved in asthma care in the GCC countries. Future research could develop approaches involving pharmacists to improve asthma care and outcomes in the region.

Sildenafil prevents chronic psychosocial stress-induced working memory impairment: Role of brain-derived neurotrophic factor.

Background: Psychosocial stress, a common feature in modern societies, impairs cognitive functions. It is suggested that stress hormones and elevated excitatory amino acids during stress are responsible for stress-induced cognitive deficits. Reduced brain-derived neurotrophic factor (BDNF) levels, increased oxidative stress, and alteration of synaptic plasticity biomarkers are also possible contributors to the negative impact of stress on learning and memory. Sildenafil citrate is a selective phosphodiesterase type 5 (PDE5) inhibitor and the first oral therapy for the treatment of erectile dysfunction. It has been shown that sildenafil improves learning and memory and possesses antioxidant properties. We hypothesized that administering sildenafil to stressed rats prevents the cognitive deficit induced by chronic psychosocial stress. Methods: Psychosocial stress was generated using the intruder model. Sildenafil 3 mg/kg/day was administered intraperitoneally to animals. Behavioral studies were conducted to test spatial learning and memory using the radial arm water maze. Then, the hippocampal BDNF level and several antioxidant markers were assessed. Results: This study revealed that chronic psychosocial stress impaired short-term but not long-term memory. The administration of sildenafil prevented this short-term memory impairment. Chronic psychosocial stress markedly reduced the level of hippocampal BDNF (P˂0.05), and this reduction in BDNF was normalized by sildenafil treatment. In addition, neither chronic psychosocial stress nor sildenafil significantly altered the activity of measured oxidative parameters (P > 0.05). Conclusion: Chronic psychosocial stress induces short-term memory impairment. The administration of sildenafil citrate prevented this impairment, possibly by normalizing the level of BDNF.

The expression of salivary EGF, VEGF, endothelin, and transferrin in waterpipe and cigarette smokers.

The aim of this study was to evaluate the effects of two forms of tobacco smoking, cigarettes and water pipe smoking (WPS), on the expression of a panel of salivary proteins in healthy adults. Three groups of age and gender-matched participants were enrolled in the study: never-smokers, cigarette smokers and WPS (N = 55 per group). Expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), endothelin and transferrin in unstimulated whole saliva was estimated using enzyme-linked immunosorbent assays. Statistical analysis consisted of one-way ANOVA and Tukey's post hoc tests, in addition to bioinformatics analysis. VEGF expression was the least in WPS (51.1 ± 14.5 pg/ml) compared to both controls (150.1 ± 13.8 pg/ml) and cigarette smokers (93 ± 9.9 pg/ml), with a significant difference in WPS (p < 0.001) and cigarette smokers (p < 0.01) compared to controls. Furthermore, transferrin showed the weakest expression in the WPS group (1238 ± 261.4 pg/ml) compared to controls (2205.6 ± 298.6 pg/ml) (p = 0.05) and cigarette smokers (1805.4 ± 244 pg/ml). Neither EGF nor endothelin expression showed any statistical difference between the groups (p > 0.05). Gene-gene interaction network demonstrated that FLT1, TFRC, KDR, VEGFB and PGF genes had the highest potential for interaction with the studied proteins. Further functional annotations on the identified markers in the interaction network were performed to identify HIF-1 pathways among the most relevant pathways. In conclusion, smoking habits alter the expression of salivary VEGF and transferrin, which may correspond to early sub-clinical changes in the oral mucosa. The clinical relevance of these salivary changes requires further research.

Metabolomics and Proteomics in Prostate Cancer Research: Overview, Analytical Techniques, Data Analysis, and Recent Clinical Applications.

Prostate cancer (PCa) is a significant global contributor to mortality, predominantly affecting males aged 65 and above. The field of omics has recently gained traction due to its capacity to provide profound insights into the biochemical mechanisms underlying conditions like prostate cancer. This involves the identification and quantification of low-molecular-weight metabolites and proteins acting as crucial biochemical signals for early detection, therapy assessment, and target identification. A spectrum of analytical methods is employed to discern and measure these molecules, revealing their altered biological pathways within diseased contexts. Metabolomics and proteomics generate refined data subjected to detailed statistical analysis through sophisticated software, yielding substantive insights. This review aims to underscore the major contributions of multi-omics to PCa research, covering its core principles, its role in tumor biology characterization, biomarker discovery, prognostic studies, various analytical technologies such as mass spectrometry and Nuclear Magnetic Resonance, data processing, and recent clinical applications made possible by an integrative "omics" approach. This approach seeks to address the challenges associated with current PCa treatments. Hence, our research endeavors to demonstrate the valuable applications of these potent tools in investigations, offering significant potential for understanding the complex biochemical environment of prostate cancer and advancing tailored therapeutic approaches for further development.

Neutrosophic robust ratio type estimator for estimating finite population mean.

Various authors have put their sincere efforts into proposing ratio estimators for estimating the population's mean and variance under different situations and sampling methods. But the problem arises when data is unstable, imprecise, ambiguous, incomplete and vague. In such situations, classical methods of estimation do not yield precise results, as these methods are not meant for such problems. Given this difficulty, Neutrosophic statistics are the only alternative as it deals with indeterminacy. So in this study, we have proposed a generalized Neutrosophic robust ratio type estimator which can be used to provide good results in such situations, as well as in the case of the presence of outliers. For the evaluation point of view, we have made use of real data set and simulation study to check the efficacy of our suggested estimators over the mentioned existed estimators.

Human Papillomavirus Is Rare and Does Not Correlate with p16INK4A Expression in Non-Small-Cell Lung Cancer in a Jordanian Subpopulation.

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Cirsimaritin Alleviates Dextran Sodium Sulfate-Induced Acute Colitis in Experimental Animals: A Therapeutic Approach for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic disease that affects the entire digestive tract. IBD can be classified as ulcerative colitis or Crohn's disease. The key symptoms of IBD include the emergence of abscesses or pustules, pronounced abdominal discomfort, diarrhea, fistulas, and intestinal narrowing, all of which can greatly affect a patient's daily well-being. Several factors, including bacterial infections, immune response irregularities, and changes in the intestinal milieu, can contribute to the onset of IBD. The aim of this study was investigating the role of cirsimaritin in reducing the severity of colitis in animal model. To induce colitis in laboratory Swiss albino mice, a 4% dextran sulfate sodium (DSS) concoction was provided in their hydration source for a duration of six days. Before the onset of colitis, mice were treated with cirsimaritin (10 mg/kg) once daily to evaluate its potential treatment effects against DSS-induced inflammation. The results showed that 10 mg/kg of cirsimaritin decreased colitis severity (P<0.05). Moreover, cirsimaritin successfully reversed the detrimental effects induced by DSS, including weight reduction, colon truncation, tissue-related damage, increased levels of inflammatory cells in the affected region, and secretion of proinflammatory cytokines. Our findings suggest that cirsimaritin can effectively alleviate acute colitis triggered by DSS.

Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials.

Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08-1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03-1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97-1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.

Giant Armadillo Optimization: A New Bio-Inspired Metaheuristic Algorithm for Solving Optimization Problems.

In this paper, a new bio-inspired metaheuristic algorithm called Giant Armadillo Optimization (GAO) is introduced, which imitates the natural behavior of giant armadillo in the wild. The fundamental inspiration in the design of GAO is derived from the hunting strategy of giant armadillos in moving towards prey positions and digging termite mounds. The theory of GAO is expressed and mathematically modeled in two phases: (i) exploration based on simulating the movement of giant armadillos towards termite mounds, and (ii) exploitation based on simulating giant armadillos' digging skills in order to prey on and rip open termite mounds. The performance of GAO in handling optimization tasks is evaluated in order to solve the CEC 2017 test suite for problem dimensions equal to 10, 30, 50, and 100. The optimization results show that GAO is able to achieve effective solutions for optimization problems by benefiting from its high abilities in exploration, exploitation, and balancing them during the search process. The quality of the results obtained from GAO is compared with the performance of twelve well-known metaheuristic algorithms. The simulation results show that GAO presents superior performance compared to competitor algorithms by providing better results for most of the benchmark functions. The statistical analysis of the Wilcoxon rank sum test confirms that GAO has a significant statistical superiority over competitor algorithms. The implementation of GAO on the CEC 2011 test suite and four engineering design problems show that the proposed approach has effective performance in dealing with real-world applications.

Exploring the Use of YouTube as a Pathology Learning Tool and Its Relationship With Pathology Scores Among Medical Students: Cross-Sectional Study.

BACKGROUND: YouTube is considered one of the most popular sources of information among college students. OBJECTIVE: This study aimed to explore the use of YouTube as a pathology learning tool and its relationship with pathology scores among medical students at Jordanian public universities. METHODS: This cross-sectional, questionnaire-based study included second-year to sixth-year medical students from 6 schools of medicine in Jordan. The questionnaire was distributed among the students using social platforms over a period of 2 months extending from August 2022 to October 2022. The questionnaire included 6 attributes. The first section collected demographic data, and the second section investigated the general use of YouTube and recorded material. The remaining 4 sections targeted the participants who used YouTube to learn pathology including using YouTube for pathology-related content. RESULTS: As of October 2022, 699 students were enrolled in the study. More than 60% (422/699, 60.4%) of the participants were women, and approximately 50% (354/699, 50.6%) were second-year students. The results showed that 96.5% (675/699) of medical students in Jordan were using YouTube in general and 89.1% (623/699) were using it as a source of general information. YouTube use was associated with good and very good scores among the users. In addition, 82.3% (575/699) of medical students in Jordan used YouTube as a learning tool for pathology in particular. These students achieved high scores, with 428 of 699 (61.2%) students scoring above 70%. Most participants (484/699, 69.2%) reported that lectures on YouTube were more interesting than classic teaching and the lectures could enhance the quality of learning (533/699, 76.3%). Studying via YouTube videos was associated with higher odds (odds ratio [OR] 3.86, 95% CI 1.33-11.18) and lower odds (OR 0.27, 95% CI 0.09-0.8) of achieving higher scores in the central nervous system and peripheral nervous system courses, respectively. Watching pathology lectures on YouTube was related to a better chance of attaining higher scores (OR 1.96, 95% CI 1.08-3.57). Surprisingly, spending more time watching pathology videos on YouTube while studying for examinations corresponded with lower performance, with an OR of 0.46 (95% CI 0.26-0.82). CONCLUSIONS: YouTube may play a role in enhancing pathology learning, and aiding in understanding, memorization, recalling information, and obtaining higher scores. Many medical students in Jordan have positive attitudes toward using YouTube as a supplementary pathology learning tool. Based on this, it is recommended that pathology instructors should explore the use of YouTube and other emerging educational tools as potential supplementary learning resources.

Impact of Thermal Maturation of the Upper Cretaceous Bituminous Limestone of Attarat Um Ghudran Central Jordan on Calcareous Nannofossil Preservation.

Oil shale deposits of the Late Cretaceous from three boreholes in central Jordan were examined to assess the impact of thermal maturation on the content of nannofossils. Thermal activity has been shown to have a strong effect on organic matter content and composition but its effect on calcareous nannofossil assemblages remains inconclusive. This study aims to determine the impact of thermal maturation on nannofossil assemblages and to compare this to an estimated maturity level based on bulk geochemical analysis. Micropaleontological and geochemical analyses were conducted on 31 samples from three oil shale wells drilled in Attarat Um Ghudran central Jordan. Several types of nannofossil preservation have been recorded, including dissolution, overgrowth, and breakage. In the Jordan oil shale sections, nannofossils exhibit a variety of preservation types, with intense dissolution in the middle part of the study sections. The vast majority of the samples had high TOC enrichment, with 29 samples exceeding values of >10%. Kerogen recovery and quality from the oil shale are very good, with a predominance of fluorescent amorphous organic matter (AOM) and minor algal components. The low fluorescence preservation index (FPI), which is 1 in most of the samples, indicates that alteration occurred due to intense thermal activities in the study interval. The palynomorph and AOM fluorescence, ranging from a spore coloration index (SCI) of 3 to 5, suggest that the studied samples were approaching the oil window. A correlation between the nannofossil preservation and geochemical parameters shows a predominance of poorly preserved nannofossils along with high total organic carbon contents and an elevated hydrogen index (HI). We show that low FPI values and a higher level of maturity are associated with poor nannofossil preservation, suggesting that nannofossils, in conjunction with petrographic analysis of kerogen, could be used as a rapid screening technique for estimating levels of oil-shale maturity. The nature of the tectonism in the study area, including faulting and a metamorphosed zone, enhanced the maturity, which might explain why the nannofossils were so significantly affected.

Human dispersals out of Africa via the Levant.

Homo sapiens dispersed from Africa into Eurasia multiple times in the Middle and Late Pleistocene. The route, across northeastern Africa into the Levant, is a viable terrestrial corridor, as the present harsh southern Levant would probably have been savannahs and grasslands during the last interglaciation. Here, we document wetland sediments with luminescence ages falling in the last interglaciation in the southern Levant, showing protracted phases of moisture availability. Wetland sediments in Wadi Gharandal containing Levallois artifacts yielded an age of 84 ka. Our findings support the growing consensus for a well-watered Jordan Rift Valley that funneled migrants into western Asia and northern Arabia.

GRP78 is Overexpressed in Non-small Cell Lung Cancer Tissues and is Associated with High VEGF Expression in Squamous Cell Carcinoma: A Pilot Study.

BACKGROUND: Neovascularization is essential for the growth and progression of tumor tissues. GRP78 is frequently overexpressed in various cancers and has been suggested as a proangiogenic factor. PURPOSE: This study aimed to investigate the expression levels of GRP78 and to test for significant relationships with the angiogenic markers, VEGF, and CD31. METHODS: In this study, paraffin-embedded NSCLC tissue samples (71 adenocarcinomas and 23 squamous cell carcinoma) were retrospectively collected from 94 patients with NSCLC. The expressions of VEGF, CD31, and GRP78 were determined by immunohistochemistry. RESULTS: High expression levels of VEGF and GRP78 were observed in 65 and 74 cases, respectively. Thirty-six patients expressed high CD31 levels. Adenocarcinomas expressed higher levels of the three proteins than squamous cell carcinomas (p-value < 0.05). Moreover, a statistically significant association was found between the expression levels of VEGF and CD31 (p-value = 0.001) and VEGF and GRP78 (p-value=0.028). CONCLUSION: GRP78 overexpression was revealed in most of the investigated samples. The positive association between VEGF and GRP78 may indicate the proangiogenic role of GRP78 in lung cancer. Moreover, the positive association between VEGF and CD31 expression levels suggests that VEGF may cooperate with CD31 to promote angiogenesis in NSCLC.