Barriers Preventing Medical Trainees from Active Participation in Research Activities.

Background: Research has increasingly become important to career progression and a compulsory component in most medical programs. While medical trainees are consistently urged to undertake research endeavors, they frequently encounter obstacles at both personal and organizational levels that impede the pursuit of high-quality research. This study aims to identify the barriers and recommend successful interventions to increase research productivity amongst medical trainees. Methods: A descriptive cross-sectional survey was carried out among interns, residents, and fellows within a single hospital located in the emirate of Abu Dhabi, UAE. The survey included inquiries regarding perceived obstacles hindering engagement in research activities, factors driving motivation for research involvement, and the assessment of how research participation relates to their job in terms of relevance. Results: Fifty-seven medical trainees participated in the survey, reflecting a response rate of 53%. The survey highlighted common obstacles, notably including time constraints, insufficient statistical and methodology training, the weight of other educational commitments, as well as inadequate incentives and rewards. While a majority of participants expressed interest in engaging in research activities, the consensus was that more incentives and increased funding opportunities would significantly encourage their involvement. Conclusion: Implementing successful interventions such as allocating dedicated time for research, facilitating access to research mentors, and organizing training sessions have the potential to be effective strategies in fostering a thriving research culture and subsequently elevating research productivity of medical trainees.

Effect of fenugreek and flaxseed polysaccharide-based edible coatings on the quality attributes and shelf life of apple fruit during storage.

The present study was designed to explore the potential of fenugreek and flaxseed polysaccharide-based edible coatings to enhance the postharvest storage life of apple fruit. The experimental plan involved the preparation of five different coating formulations, which were subsequently applied to the fruit. The coated fruit was then stored at a temperature of 25 ± 2°C for a duration of 35 days. The effects of these coatings on physicochemical and biochemical attributes (weight loss, firmness, acidity, pH, sugar content, antioxidant activity, microbial growth, and sensory properties) of coated and uncoated samples were evaluated at regular intervals: 0, 7, 14, 21, 28, and 35 days of storage. The experimental results revealed a significant difference (p ≤ .05) in the physicochemical parameters of uncoated and coated apple at different storage times. The coated apple fruits showed significantly (p ≤ .05) lower weight loss, pH, total sugars, total soluble solids, and maximum retention of ascorbic acid, firmness, acidity, and antioxidant contents, leading to enhanced organoleptic properties. The application of edible coatings extended the shelf-life of the apples by inhibiting microbiological spoilage without substantial impact on sensory and nutritional properties. Based on these results, it is concluded that the edible coating formulation labeled T 1 (containing 2.5 g fenugreek polysaccharide and 1.5 g flax polysaccharide) effectively preserved the valuable physicochemical and organoleptic characteristics of the apple fruit throughout the storage period.

A discovery of potent kaempferol derivatives as multi-target medicines against diabetes as well as bacterial infections: an in silico approach.

Flavonoids demonstrate beneficial effects on human health because flavonoids contain important biological properties. Kaempferol is a flavonol, type of flavonoid found in eatable plants and in plants usually employed in ancient drugs (Moringa oleifera, Tilia spp., fern genus spp. and gingko etc.). Some medicinal studies have shown that the use of foods full of kaempferol decreases the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol derivatives were collected from PubChem database. Through Schrödinger software, 3D-QSAR study was performed for 50 compounds by using method of field base. Conformer of kaempferol derivatives was docked against anti-diabetic, anti-microbial co-crystal structures and protein. To monitor the best anti-diabetic and antibacterial agent, particular kaempferol derivatives were downloaded from PubChem database. Virtual screening by molecular docking provided four lead compounds with four different proteins. These hit compounds were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV and had the potential to suppress DNA gyrase and dihydrofolate reductase synthesis. Molecular dynamic simulation of docked complexes evaluates the value of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside (42) compound used as anti-diabetic and kaempferol 3-O-gentiobioside (3) as antibacterial with good results can be used for drug discovery.Communicated by Ramaswamy H. Sarma.

Evaluation of point-of-care ultrasound training among healthcare providers: a pilot study.

BACKGROUND: The use of Point-of-Care Ultrasound (POCUS) has become prevalent across a variety of clinical settings. Many healthcare professionals have started getting hands-on training. To evaluate the effectiveness of such training programs, this study aimed to assess a 4 day POCUS training course on healthcare providers' skills and knowledge acquisition. A secondary objective of this study is to gain valuable insights into the degree of perception, attitude, interest levels and perceived barriers of medical providers performing POCUS. METHODS: This is a prospective cohort study performed on healthcare providers in an integrated healthcare facility in Abu Dhabi undergoing the POCUS training course in February 2022. Course participants took a pre-course survey to evaluate their baseline knowledge, skills, confidence, perception, and interest in POCUS. The same survey was repeated immediately post-course. In total, seven healthcare professionals responded to the survey with a response rate of 53.8%. All data and information gathered were used to understand the effectiveness of POCUS training and gain insights into the degree of perception, interest and preparedness of POCUS among healthcare professionals in practice. RESULTS: Our results demonstrated that the brief POCUS course was effective in improving POCUS skills, knowledge and confidence amongst in-practice healthcare providers from varying medical specialties. The median skill score increased from 25% pre-course to 50% post-course. There is a notable increase in all skills scores after the POCUS training course with the greatest change in scores seen for adjusting 'gain and depth of image (54.84%), assessing VeXUS score (52.38%) and evaluating lung congestion (50%). The study also provided valuable insights into the perception, attitude, interest and potential barriers of POCUS implementation. Although significant barriers to POCUS are present including the lack of POCUS curriculum, what is challenging is lack of expertise and skills to perform POCUS. Therefore, medical providers must acquire prespecified skills to fully utilize POCUS effectively. CONCLUSION: The study confirmed the effectiveness of short POCUS training in improving the skills, knowledge and confidence of medical providers in practice. Healthcare professionals can master POCUS skills and techniques and gain confidence through brief training courses.

Nutritional Assessment of Lactarius drassinus and L. controversus from the Cold Desert Region of the Northwest Himalayas for Their Potential as Food Supplements.

Kargil is a cold desert with hostile ecological conditions such as low temperature and precipitation, as well as difficult terrains. However, several wild mushrooms thrive well under such an extreme environment. Despite their abundance, the chemical composition of indigenous mushrooms has not been explored. This study aimed to assess the potential of two wild edible mushrooms from Kargil, Lactarius drassinus and Lactarius controversus, as food supplements by evaluating their nutritional and nutraceutical properties. Nutritional attributes such as total protein, available carbohydrates, soluble sugars, and vitamins were found to be high in the mushroom species. Furthermore, high mineral accumulation and relatively lower antinutrient concentrations resulted in higher bioavailabilities of Zn, Fe, Ca, and Mg. Gas-chromatography-mass-spectrometry-based metabolite profiling revealed that although the two mushroom species showed similar metabolite compositions, their relative concentrations differed. Sugars were the predominant compounds identified in both the species, with sugar alcohols being the major contributor. The second most abundant class of compound in L. drassinus was amino acids, with 5-oxoproline as the major contributor. On the other hand, fatty acids were the second most abundant compounds in L. controversus, with high oleic and linoleic acid concentrations. In the ultra-performance-liquid-chromatography-based quantification of phenolic compounds, chlorogenic acid was found to be highest in in terms of its concentration in both the mushrooms studied, followed by quercetin dihydrate and gallic acid in L. drassinus and L. controversus, respectively. Moreover, high antioxidant activities attributable to their high phenol, flavonoid, and carotenoid concentrations were observed. Overall, the two mushrooms offer well-balanced sources of nutritional and nutraceutical compounds, making them healthy foods.

Phenolics Extracted from Jasminum sambac Mitigates Diabetic Cardiomyopathy by Modulating Oxidative Stress, Apoptotic Mediators and the Nfr-2/HO-1 Pathway in Alloxan-Induced Diabetic Rats.

Diabetes mellitus is a chronic metabolic disorder defined as hyperglycemia and pancreatic ß-cell deterioration, leading to other complications such as cardiomyopathy. The current study assessed the therapeutic effects of phenolic acids extracted from Jasminum sambac phenols of leaves (JSP) against diabetes-induced cardiomyopathy in rats. The rats were divided into four groups, with each group consisting of 20 rats. The rats were given intraperitoneal injections of alloxan monohydrate (150 mg/kg) to induce diabetes. The diabetes-induced groups (III and IV) received treatment for six weeks that included 250 and 500 mg/kg of JSP extract, respectively. In the treated rats, the results demonstrated that JSP extract restored fasting glucose, serum glucose, and hyperlipidemia. Alloxan induced cardiomyopathy, promoted oxidative stress, and altered cardiac function biomarkers, including cardiac troponin I, proBNP, CK-MB, LDH, and IMA. The JSP extract-treated rats showed improved cardiac function indicators, apoptosis, and oxidative stress. In diabetic rats, the mRNA expression of caspase-3, BAX, and Bcl-2 was significantly higher, while Bcl-2, Nrf-2, and HO-,1 was significantly lower. In the treated groups, the expression levels of the BAX, Nrf-2, HO-1, Caspase-3, and Bcl-2 genes were dramatically returned to normal level. According to our findings, the JSP extract prevented cardiomyopathy and heart failure in the hyperglycemic rats by improving cardiac biomarkers and lowering the levels of hyperlipidemia, oxidative stress, apoptosis, hyperglycemia, and hyperlipidemia.

Prescription drug dependence with and without concurrent illicit drug use: a multicenter cross-sectional survey among an addiction treatment seeking population.

Background: Dependence on prescription drugs and illicit drugs imposes a global health and social burden. Despite accumulating evidence of prescription drugs and illicit drugs dependence, none of the systematized studies has explored the magnitude of this problem in Pakistan. The aim is to investigate the extent and associated factors of prescription drug dependence (PDD), as opposed to concomitant prescription drug dependence and illicit drug use (PIDU), within a sample of individuals seeking addiction treatment. Methods: The cross sectional study was conducted on the sample recruited from three drug treatment centers in Pakistan. Face-to-face interviews were conducted with participants who met ICD-10 criteria for prescription drug dependence. Several aspects like substance use histories, negative health outcomes, patient attitude, pharmacy and physician practices also collected to predict the determinants of (PDD). Binomial logistic regression models examined the factors associated with PDD and PIDU. Results: Of the 537 treatment seeking individuals interviewed at baseline, close to one third (178, 33.3%) met criteria for dependence on prescription drugs. The majority of the participants were male (93.3%), average age of 31 years, having urban residence (67.4%). Among participants who met criteria for dependence on prescription drugs (71.9%), reported benzodiazepines as the most frequently used drug, followed by narcotic analgesics (56.8%), cannabis/marijuana (45.5%), and heroin (41.5%). The patients reported alprazolam, buprenorphine, nalbuphine, and pentazocin use as alternatives to illicit drugs. PDD was significantly negatively associated with injectable route (OR = 0.281, 95% CI, 0.079-0.993) and psychotic symptoms (OR = 0.315, 95% CI, 0.100, 0.986). This implies that PDD is less likely to be associated with an injectable route and psychotic symptoms in contrast to PIDU. Pain, depression and sleep disorder were primary reasons for PDD. PDD was associated with the attitude that prescription drugs are safer than illicit drugs (OR = 4.057, 95%CI, 1.254-13.122) and PDD was associated with being on professional terms (i.e., having an established relationship) with pharmaceutical drugs retailers for acquisition of prescription drugs. Discussion and conclusion: The study found benzodiazepine and opioid dependence in sub sample of addiction treatment seekers. The results have implications for drug policy and intervention strategies for preventing and treating drug use disorders.

Valorization of Using Agro-Wastes for Levan through Submerged Fermentation and Statistical Optimization of the Process Variables Applying Response Surface Methodology (RSM) Design.

Levan is a homopolysaccharide of fructose units that repeat as its structural core. As an exopolysaccharide (EPS), it is produced by a great variety of microorganisms and a small number of plant species. The principal substrate used for levan production in industries, i.e., sucrose, is expensive and, hence, the manufacturing process requires an inexpensive substrate. As a result, the current research was designed to evaluate the potential of sucrose-rich fruit peels, i.e., mango peels, banana peels, apple peels, and sugarcane bagasse, to produce levan using Bacillus subtilis via submerged fermentation. After screening, the highest levan-producing substrate, mango peel, was used to optimize several process parameters (temperature, incubation time, pH, inoculum volume, and agitation speed) employing the central composite design (CCD) of response surface methodology (RSM), and their impact on levan production was assessed. After incubation for 64 h at 35 °C and pH 7.5, the addition of 2 mL of inoculum, and agitation at 180 rpm, the highest production of levan was 0.717 g/L of mango peel hydrolysate (obtained from 50 g of mango peels/liter of distilled water). The F-value of 50.53 and p-value 0.001 were calculated using the RSM statistical tool to verify that the planned model was highly significant. The selected model's accuracy was proven by a high value (98.92%) of the coefficient of determination (R2). The results obtained from ANOVA made it clear that the influence of agitation speed alone on levan biosynthesis was statistically significant (p-value = 0.0001). The functional groups of levan produced were identified using FTIR (Fourier-transform ionization radiation). The sugars present in the levan were measured using HPLC and the levan was found to contain only fructose. The average molecular weight of the levan was 7.6 × 106 KDa. The findings revealed that levan can be efficiently produced by submerged fermentation using inexpensive substrate, i.e., fruit peels. Furthermore, these optimized cultural conditions can be applied on a commercial scale for industrial production and commercialization of levan.

Correction: Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors.

[This corrects the article DOI: 10.1039/D2RA07051K.].

Chitosan Oligosaccharide Promotes Junction Barrier through Modulation of PI3K/AKT and ERK Signaling Intricate Interplay in T84 Cells.

Chitosan oligosaccharide (COS) is a breakdown product of chitin, a polymer of N-acetyl-D-glucosamine. COS promotes barrier function in intestinal epithelial cells. However, the exact mechanism of COS-induced barrier function remains unknown. This study was aimed to explore the intricate signaling cascades in the junction barrier induced by COS (100 µg/mL) in human intestinal epithelial cells (T84 cells). COS (100 µg/mL) promoted tight junction assembly and increased transepithelial electrical resistance (TEER). COS inhibited FITC-dextran flux in T84 cell monolayers at 2 h, 4 h, 6 h and 24 h post treatment. In addition, the effect of COS on TEER and FITC-dextran flux was abrogated by pre-incubation of wortmannin (2 µM), an AKT (protein kinase B) inhibitor, at 2 h and 4 h post treatment, indicating that COS-induced tight junction integrity was mediated at least in part by AKT activation. COS-induced TEER was amplified at 24 h and 48 h post treatment by pre-incubation with SC79 (2.5 µM), an AKT activator. Moreover, COS induced inhibition of extracellular signal-regulated kinase (ERK) in T84 cells. Wortmannin and SC79 pre-incubation promoted ERK activation and ERK inhibition, respectively, suggesting that COS-induced ERK inhibition was mediated by AKT. Collectively, this study reveals that COS promotes junction barrier integrity via regulating PI3K/AKT and ERK signaling intricate interplay in T84 cell monolayers. COS may be beneficial in promoting junction barrier in intestinal disorders.

Impact of COVID-19 pandemic on older cancer patients: Proposed solution by the International Geriatric Radiotherapy Group.

Older cancer patients are disproportionally affected by the Coronavirus 19 (COVID-19) pandemic. A higher rate of death among the elderly and the potential for long-term disability have led to fear of contracting the virus in these patients. This fear can, paradoxically, cause delay in diagnosis and treatment that may lead to a poor outcome that could have been prevented. Thus, physicians should devise a policy that both supports the needs of older patients during cancer treatment, and serves to help them overcome their fear so they seek out to cancer diagnosis and treatment early. A combination of telemedicine and a holistic approach, involving prayers for older cancer patients with a high level of spirituality, may improve vaccination rates as well as quality of life during treatment. Collaboration between health care workers, social workers, faith-based leaders, and cancer survivors may be crucial to achieve this goal. Social media may be an important component, providing a means of sending the positive message to older cancer patients that chronological age is not an impediment to treatment.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

Quantitative Profiling of Alpha-Subunit of IL-3 Receptor on Single Acute Myeloid Leukemia Cells by Super-Resolution Imaging.

BACKGROUND: Quantitative profiling of specific cell surface markers is a new approach in characterization of tumor heterogeneity and single cell biology. The current tools have dearth in detection and quantification of receptor proteins on single cells. METHODS: we focused on our newly developed protocol to determine the distribution pattern and density of cell surface markers on single acute myeloid leukemia cells. Cell surface proteins were labeled with quantum dots (Qdots) followed by super resolution Structured Illumination Microscopy (SIM) imaging to imprisonment the optical signals emitted by Qdots which were further analyzed by software imaris to do three dimensional (3D) structure reconstruction and digital simulation. Furthermore, MTT assays and flow cytometry was performed to establish association between expression of cell surface markers and drug response. RESULTS: In the present study, we found that the Molm13 and cytarabine-enriched Molm13 cells exhibit different densities of CD123, an alpha-subunit of interleukin-3 receptor, i.e. 0.92 and 1.73 per µm2 of cell surface respectively. Sub-populations of Molm13 cells expressing higher densities of CD123 on cells membranes showed resistance against cytarabine. Further study revealed that romidepsin sensitized and augmented the cytotoxicity of cytarabine in Molm13 and cytarabine-enriched Molm13 cells. Romidepsin increased the percentage of cell death-induced by cytarabine from 21.6 % to 28.6 % and 37.1 % to 57.2 % in Molm13 and cytarabine-enriched Molm13 cells respectively. CONCLUSION: Altogether, the study suggests that Molm13 cells have sub-populations with differential expression of CD123+ phenotype. Romidepsin sensitizes and augments the effect of cytarabine in Molm13 and cytarabine-enriched Molm13 cells.

Evaluation of loci to predict ear morphology using two SNaPshot assays.

Human ear morphology prediction with SNP-based genotypes is growing in forensic DNA phenotyping and is scarcely explored in Pakistan as a part of EVCs (externally visible characteristics). The ear morphology prediction assays with 21 SNPs were assessed for their potential utility in forensic identification of population. The SNaPshot™ multiplex chemistries, capillary electrophoresis methods and GeneMapper™ software were used for obtaining genotypic data. A total of 33 ear phenotypes were categorized with digital photographs of 300 volunteers. SHEsis software was applied to make LD plot. Ordinal and multinomial logistic regression was implemented for association testing. Multinomial logistic regression was executed to construct the prediction model in 90% training and 10% testing subjects. Several influential SNPs for ear phenotypic variation were found in association testing. The model based on genetic markers predicted ear phenotypes with moderate to good predictive accuracies demonstrated with the area under curve (AUC), sensitivity and specificity of predicted phenotypes. As an additional EVC, the estimated ear phenotypic profiles have the possibility of determining the human ear morphology differences in unknown biological samples found in crimes that do not result in a criminal database hit. Furthermore, this can help in facial reconstruction and act as an investigational lead.

Impacts of the Wild Boar (Sus scrofa) on the Livelihood of Rural Communities in Pakistan and Understanding Public Attitudes towards Wild Boars.

Conservation goals can only be best achieved when there is firm support and cooperation from locals, especially in emerging economies where poor communities often bear most of the cost of human-wildlife conflicts (HWCs). In this study, we explored the economic losses caused by wild boars in two districts, i.e., the Peshawar district and the Nowshera district, in north-western Pakistan. Between May and June 2022, 589 respondents from 53 villages were interviewed. The results revealed that the wild boar was chiefly involved in crop raiding, causing an annual economic loss of USD 12,030 (USD 20.42/household). The highly raided crops included maize (40.24%), followed by wheat (24.95%), vegetables (22.65%), and sugarcane (6.29%). Wild boars were also held accountable for orchard damages. Most people consider the wild boar a common species in the area and want it completely eliminated. We believe that the increasing wild boar population is alarming and should be noticed. The government should collaborate with the local communities to use innovative methods to deter wild boars. Compensation schemes for crop damages should be launched. Moreover, the regular investigation of the wild boar population size and their carrying capacities should be enlisted as integral parts of wildlife management in the area.

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3-4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

Genetic diversity and forensic application of Y-filer STRs in four major ethnic groups of Pakistan.

17 Y-chromosomal STRs which are part of the Yfiler Amplification Kit were investigated in 493 unrelated Pakistani individuals belonging to the Punjabi, Sindhi, Baloch, and Pathan ethnic groups. We have assessed the forensic parameters and population genetic structure for each group. Among the 493 unrelated individuals from four ethnic groups (128 Baloch, 122 Pathan, 108 Punjabi, and 135 Sindhi), 82 haplotypes were observed with haplotype diversity (HD) of 0.9906 in Baloch, 102 haplotypes with HD value of 0.9957 in Pathans, 80 haplotypes with HD value of 0.9924 in Punjabi, and 105 haplotypes with HD value of 0.9945 in the Sindhi population. The overall gene diversity for Baloch, Pathan, Punjabi, and Sindhi populations was 0.6367, 0.6479, 0.6657, and 0.6112, respectively. The results had shown us that Pakistani populations do not have a unique set of genes but share the genetic affinity with regional (Central Asia and Northern India) populations. The observed low gene diversity (heterozygosity) values may be because of endogamy trends and this observation is equally supported by the results of forensic parameters which are mostly static across 4 combinations (minimal STRs, extended 11 Y-STRs, Powerplex 12 Y System, and Yfiler 17 Y-STRs) of STRs in these four populations.

Characterization and anticancer potential of Withania somnifera fruit bioactives (a native species to Pakistan) using gas chromatography-mass spectrometer, nuclear magnetic resonance and liquid chromatography-mass spectrometry-electrospray ionization.

INTRODUCTION: Withania somnifera (W. somnifera) is a plant with remarkable pharmacological properties. The plant has an impressive profile of medicinal uses in the folk medicine system of several civilizations. AIM: This comprehensive study is aimed to characterize phytochemicals in fruit of W. somnifera and tested for anticancer potential to find out active candidate in disease prevention and treatment. METHODS: The bioactive components from W. somn-ifera fruit were extracted with polar and non-polar solvents. Anticancer potential of the isolated bioactive was assessed against different cancer cell lines through MTT assay and Incucytes imaging analysis. The extracts were characterized for secondary metabolites using GC-MS (gas chromatography-mass spectrometer), LCMS (liquid chromatography-mass spectrometry)-ESI (electrospray Ionization) and 1H-NMR (electrospray Ionization) techniques. RESULTS: Both freeze-dried and rotary evaporator con-densed extracts exhibited anticancer potential against MDA-MB-231, MCF7- SKOV3 and SKBR3 cell lines. The tested extracts have cell growth inhibition potential ag-ainst mammalian cancer cell line. Hexacosanedioic acid purified from -hexane extract through HPLC was inves-tigated for its cytotoxicity against breast cancer cell line SKBR3 by using Incucytes imaging analysis. CONCLUSION: We found that a variety of bioactive compounds existed in this plant. One identified compound that was not investigated for cytotoxicity in previous studies was purified and its application showed cytotoxicity on breast cancer cell lines. A number of bioactive identified from fruit may have an effective potential for development into chemotherapy drugs.

Chitosan Oligosaccharide Prevents Afatinib-Induced Barrier Disruption and Chloride Secretion through Modulation of AMPK, PI3K/AKT, and ERK Signaling in T84 Cells.

Diarrhea is an important adverse effect of epidermal growth factor receptor-tyrosine kinase inhibitors, especially afatinib. Novel antidiarrheal agents are needed to reduce epidermal growth factor receptor-tyrosine kinase inhibitor-associated diarrhea to improve the quality of life and treatment outcome in cancer patients. This study aimed to investigate the anti-diarrheal activity of chitosan oligosaccharide against afatinib-induced barrier disruption and chloride secretion in human intestinal epithelial cells (T84 cells). Chitosan oligosaccharide (100 µg/mL) prevented afatinib-induced barrier disruption determined by changes in transepithelial electrical resistance and FITC-dextran flux in the T84 cell monolayers. In addition, chitosan oligosaccharide prevented afatinib-induced potentiation of cAMP-induced chloride secretion measured by short-circuit current analyses in the T84 cell monolayers. Chitosan oligosaccharide induced the activation of AMPK, a positive regulator of epithelial tight junction and a negative regulator of cAMP-induced chloride secretion. Moreover, chitosan oligosaccharide partially reversed afatinib-induced AKT inhibition without affecting afatinib-induced ERK inhibition via AMPK-independent mechanisms. Collectively, this study reveals that chitosan oligosaccharide prevents the afatinib-induced diarrheal activities in T84 cells via both AMPK-dependent and AMPK-independent mechanisms. Chitosan oligosaccharide represents a promising natural polymer-derived compound for further development of treatment for afatinib-associated diarrheas.

Prediction and Classification of COVID-19 Admissions to Intensive Care Units (ICU) Using Weighted Radial Kernel SVM Coupled with Recursive Feature Elimination (RFE).

Healthcare systems have been under immense pressure since the beginning of the COVID-19 pandemic; hence, studies on using machine learning (ML) methods for classifying ICU admissions and resource allocation are urgently needed. We investigated whether ML can propose a useful classification model for predicting the ICU admissions of COVID-19 patients. In this retrospective study, the clinical characteristics and laboratory findings of 100 patients with laboratory-confirmed COVID-19 tests were retrieved between May 2020 and January 2021. Based on patients' demographic and clinical data, we analyzed the capability of the proposed weighted radial kernel support vector machine (SVM), coupled with (RFE). The proposed method is compared with other reference methods such as linear discriminant analysis (LDA) and kernel-based SVM variants including the linear, polynomial, and radial kernels coupled with REF for predicting ICU admissions of COVID-19 patients. An initial performance assessment indicated that the SVM with weighted radial kernels coupled with REF outperformed the other classification methods in discriminating between ICU and non-ICU admissions in COVID-19 patients. Furthermore, applying the Recursive Feature Elimination (RFE) with weighted radial kernel SVM identified a significant set of variables that can predict and statistically distinguish ICU from non-ICU COVID-19 patients. The patients' weight, PCR Ct Value, CCL19, INF-ß, BLC, INR, PT, PTT, CKMB, HB, platelets, RBC, urea, creatinine and albumin results were found to be the significant predicting features. We believe that weighted radial kernel SVM can be used as an assisting ML approach to guide hospital decision makers in resource allocation and mobilization between intensive care and isolation units. We model the data retrospectively on a selected subset of patient-derived variables based on previous knowledge of ICU admission and this needs to be trained in order to forecast prospectively.