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Background: The leukemic microenvironment has become an area of interest for researchers in recent times. Nonmalignant T and B lymphocytes form a significant part of leukemic microenvironment and are postulated to have an effect on its progression and behavior. These lymphocytes are constantly interacting with blasts and are actively involved in innate and acquired immune responses against these blasts. We decided to look at the role of T-regulatory lymphocytes in tumor surveillance and treatment outcome. Aim and Objectives: The aims and objectives of the study are to evaluate the role of T-regulatory lymphocytes in acute leukemia cases and its correlation with treatment outcome. Materials and Methods: We evaluated consecutive 55 acute leukemia cases to investigate the prognostic effect of T-regulatory cells (T-regs) in acute leukemia. The study period was between January 2021 and December 2021. All patients whose complete records were available till the completion of induction were included in the study. The immunophenotype used to characterize and evaluate T-regs was CD4+CD25+ T lymphocytes. For comparison, a total of 10 healthy controls were included in the study. Clinicohematological parameters including fever, lymphadenopathy, hepatosplenomegaly, extramedullary involvement, day 1 total leukocyte count, and blast percentage in peripheral blood and bone marrow were studied and documented to establish any possible correlation with T-regs percentage and treatment outcome. The treatment outcome evaluated in the study was complete remission postfirst induction. Results: As compared to those of healthy participants, the frequencies of CD4+CD25+ T-regs in the peripheral blood of acute leukemia patients were significantly increased (1.5% [range: 0.50%–4.3%] vs. 0.58% [range: 0.40%–1.05%], P = 0.0001). Furthermore, the frequencies of CD4+CD25+ T-regs in the peripheral blood of acute leukemia patients who did not achieve remission were significantly increased as compared to those who achieved remission (2.9% [range: 0.20%–4.3%] vs. 1.3% [range: 0.30%–2.9%], P = 0.002). No significant correlation was noted in the T-reg cells and parameters such as fever, lymphadenopathy, hepatosplenomegaly, extramedullary involvement, day 1 total leukocyte count, and blast percentage. Conclusion: This study suggests the possibility of using T-regs percentages as a prognostic indicator of acute leukemia and possible role of anti-T-regulatory immunomodulators in improving the outcome of disease.

Abstract Cancer cells with BRCA1/2 deficiencies are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We evaluated the efficacy of talazoparib in DNA-Damage Repair (DDR)-altered patients. In this phase II trial, patients were enrolled onto one of four cohorts based on molecular alterations: (1) somatic BRCA1/2, (2) other homologous recombination repair pathway, (3) PTEN and (4) germline BRCA1/2. The primary endpoint was a clinical benefit rate (CBR): complete response, partial response or stable disease ≥24 weeks. 79 patients with a median of 4 lines of therapy were enrolled. CBR for cohorts 1–4 were: 32.5%, 19.7%, 9.4% and 30.6%, respectively. PTEN mutations correlated with reduced survival and a trend towards shorter time to progression.Talazoparib demonstrated clinical benefit in selected DDR-altered patients. PTEN mutations/loss patients derived limited clinical benefit. Further study is needed to determine whether PTEN is prognostic or predictive of response to PARP inhibitors.

Abstract The context of education has changed due to revolutionary developments in the information communication technology (ICT) industry in the post-COVID era. Innovative learning methods were introduced in the education sector to promote quality education. The students find it more convenient to use ICT tools to integrate their knowledge-seeking. China has recently paid more attention to developing and adopting electronic infrastructure. The study assesses the effect of technology self-efficacy (TSE) on ICT acceptance and implementation in China’s education sector. It also analyzed the role of perceived trust, perceived security, and electronic word of mouth (eWOM) in integrating digital information sharing and interaction tools. Data is collected from 382 business students at Chinese universities. The results revealed that perceived trust mediates the relationship between TSE and the actual use of ICT tools, intention to use ICT tools for information, and intention to use ICT tools for interaction. Further, perceived security and eWOM significantly moderate the relationship between TSE and perceived trust. The findings indicate that it is essential to offer assistance and instruction to students in the educational sector so they can use ICT technology more frequently. It is also crucial for organizations to establish a supportive culture and provide the necessary technological resources to facilitate the use of ICT.

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics. Methods Using mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model. Results Here we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes. Conclusions Taken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.

Purpose: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). Design: Prospective, placebo-controlled, double-blind, cross-over study. Methods: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. Results: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture) . A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. Conclusions: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

In this study, the polar root extract of Cyperus scariosus R.Br. was used for the biogenic synthesis of ZnO NPs. The results of this study show that ZnO NPs have a spherical structure with an average size of 85.4 nm. The synthesized catalysts were tested for their photocatalytic activity by degrading methyl orange and methylene blue under sunlight. Improved degradation efficiencies of 79.44% and 84.92% were achieved within 120 min. ZnO NPs exhibited strong antibacterial activity against both Gram-positive Listeria monocytogenes (18 mm) and Staphylococcus epidermidis (20 mm) and Gram-negative strains of Escherichia coli (16 mm) and Bordetella bronchiseptica (14 mm), as shown by the inhibition zones, which were comparable to the positive control (ceftriaxone) but larger than the plant root extract. ZnO NPs showed high antioxidant activity, as a ferric-reducing antioxidant power assay value of 66.29 µg (AAE µg·mL−1) and a DPPH value of 57.44 µg (AAE µg·mL−1) were obtained at a concentration of 500 µL, which was higher than those of the C. scariosus root extract. Quantification of the total phenolic and flavonoid content yielded values of 57.63 µg (GAE µg·mL−1) and 70.59 µg (QCE µg·mL−1), respectively. At a concentration of 500 μL (1 mg·mL−1), the tested nanoparticles (NPs) showed a greater anti-inflammatory effect (84.12%) compared to the root extract of C. scariosus (34.39%). Overall, our findings highlight the versatile properties of green synthesized ZnO NPs and demonstrate their potential for environmental remediation and antimicrobial formulations, as well as promising candidates for further investigation in biomedical fields such as drug delivery and therapy.

Samiah Shahid,1,2 Ayesha Khan,1 Wajeehah Shahid,3 Mehvesh Rehan,2 Roha Asif,1 Haseeb Nisar,4 Qudsia Kanwal,5 Jeong Ryeol Choi6 1Research Centre for Health Sciences (RCHS), The University of Lahore, Lahore, Pakistan; 2Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan; 3Department of Physics, The University of Lahore, Lahore, Pakistan; 4School of Life Sciences, University of Management and Technology, Lahore, Pakistan; 5Department of Chemistry, The University of Lahore, Lahore, Pakistan; 6School of Electronic Engineering, Kyonggi University, Suwon, Kyeonggi-do, 16227, Republic of KoreaCorrespondence: Samiah Shahid, Research Centre for Health Sciences (RCHS), Associate Professor, Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, 54590, Pakistan, Email samiah.shahid@yahoo.com Jeong Ryeol Choi, School of Electronic Engineering, Kyonggi University, Suwon, Kyeonggi-do, 16227, Republic of Korea, Email choiardor@hanmail.netAbstract: Breast and ovarian cancers, despite having chemotherapy and surgical treatment, still have the lowest survival rate. Experimental stages using nanoenzymes/nanozymes for ovarian cancer diagnosis and treatment are being carried out, and correspondingly the current treatment approaches to treat breast cancer have a lot of adverse side effects, which is the reason why researchers and scientists are looking for new strategies with less side effects. Nanoenzymes have intrinsic enzyme-like activities and can reduce the shortcomings of naturally occurring enzymes due to the ease of storage, high stability, less expensive, and enhanced efficiency. In this review, we have discussed various ways in which nanoenzymes are being used to diagnose and treat breast and ovarian cancer. For breast cancer, nanoenzymes and their multi-enzymatic properties can control the level of reactive oxygen species (ROS) in cells or tissues, for example, oxidase (OXD) and peroxidase (POD) activity can be used to generate ROS, while catalase (CAT) or superoxide dismutase (SOD) activity can scavenge ROS. In the case of ovarian cancer, most commonly nanoceria is being investigated, and also when folic acid is combined with nanoceria there are additional advantages like inhibition of beta galactosidase. Nanocarriers are also used to deliver small interfering RNA that are effective in cancer treatment. Studies have shown that iron oxide nanoparticles are actively being used for drug delivery, similarly ferritin carriers are used for the delivery of nanozymes. Hypoxia is a major factor in ovarian cancer, therefore MnO2-based nanozymes are being used as a therapy. For cancer diagnosis and screening, nanozymes are being used in sonodynamic cancer therapy for cancer diagnosis and screening, whereas biomedical imaging and folic acid gold particles are also being used for image guided treatments. Nanozyme biosensors have been developed to detect ovarian cancer. This review article summarizes a detailed insight into breast and ovarian cancers in light of nanozymes-based diagnostic and therapeutic approaches. Keywords: breast cancer, ovarian cancer, nanoenzymes, diagnosis, treatment

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) prevalence has doubled in the last 20 years and is becoming a vital health concern due to its increasing prevalence. Lean patients having normal-weight central obesity with NAFLD may have increased morbidity and all-cause mortality and thus form an important target for lifestyle modifications and preventive strategies. Objective: To determine frequencies of NAFLD and Metabolic Syndrome in lean individuals. Methods: The present cross-sectional study was undertaken at the Medicine Department, Pakistan Ordinance Factories Hospital, Wah Cantonment Pakistan from July 2018 to June 2020 enrolling 230 patients aged 20 to 70 years, of both sex. Demographic information, co-morbid conditions, BMI, and waist circumference were recorded. An abdominal ultrasound was performed to determine hepatic fatty infiltration. Blood samples were collected for serum HDL-cholesterol (HDL-C) and serum triglyceride estimation. SPSS 22.0 was used for data entry and analysis. Results: Mean age was 45.7+12.5 years with male predominance at 130 (56.5%). Diabetes mellitus was present in 104 (45.2%) and 102 (44.3%) were hypertensive. The mean BMI was 23.4+3.6 kg/m2. The mean serum triglyceride level was 209+10.1 mg/dl and elevated at 141 (61.3%). The mean serum HDL-C level was 23.1+4.2 mg/dl and was reduced by 142 (61.8%). NAFLD was seen in 38 (16.5%) patients and 24 (10.4%) had Metabolic Syndrome. Among the 38 lean NAFLD patients, 21 (55.3%) had Metabolic Syndrome. Conclusion: NAFLD was seen in almost one-fifth of lean patients enrolled. Metabolic syndrome was reported in more than one-half of these lean NAFLD patients

Abstract ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13, regulates the length of Von Willebrand factor (VWF) multimers and their platelet-binding activity. ADAMTS13 is constitutively secreted as an active protease and is not inhibited by circulating protease inhibitors. Therefore, the mechanisms that regulate ADAMTS13 protease activity are unknown. We performed an unbiased proteomics screen to identify ligands of ADAMTS13 by optimizing the application of BioID to plasma. Plasma BioID identified 5 plasma proteins significantly labeled by the ADAMTS13-birA* fusion, including VWF and plasminogen. Glu-plasminogen, Lys-plasminogen, mini-plasminogen, and apo(a) bound ADAMTS13 with high affinity, whereas micro-plasminogen did not. None of the plasminogen variants or apo(a) bound to a C-terminal truncation variant of ADAMTS13 (MDTCS). The binding of plasminogen to ADAMTS13 was attenuated by tranexamic acid or ε-aminocaproic acid, and tranexamic acid protected ADAMTS13 from plasmin degradation. These data demonstrate that plasminogen is an important ligand of ADAMTS13 in plasma by binding to the C-terminus of ADAMTS13. Plasmin proteolytically degrades ADAMTS13 in a lysine-dependent manner, which may contribute to its regulation. Adapting BioID to identify protein-interaction networks in plasma provides a powerful new tool to study protease regulation in the cardiovascular system.

Although batteries are a highly popular energy source in biosensors, batteries can be an economic limitation for low‐cost sensing applications and pose significant challenges in miniaturization, biocompatibility, and disposal. To surmount such issues, “self‐powered sensors” gain the spotlight thanks to their energy harvesting from the environment through embedded miniaturized systems. In this review, the recent developments in self‐powered devices are summarized with a specific focus on the integration of supercapacitors with sensors and biosensors. The working principles of microsupercapacitors, fabrication methods, their integration with biosensors, and their ultimate applications (i.e., biomedical monitoring and analytical biomarker detection) are described. Different energy harvesting systems are summarized and their integration with self‐powered sensors or biosensors is highlighted. The limitations and challenges of the existing approaches and the future of supercapacitor‐integrated sensing systems are also critically discussed.

IntroductionInconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting.MethodsRandom-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach.ResultsMeta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel.DiscussionCAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

This investigation portrays the phytochemical screening, green synthesis, characterization of Fe and Zn nanoparticles, their antibacterial, anti-inflammation, cytotoxicity, and anti-thrombolytic activities. Four dissimilar solvents such as, n-hexane, chloroform, ethyl acetate and n-butanol were used to prepare the extracts of Phlomis cashmeriana Royle ex Benth. This is valued medicinal plant (Family Lamiaceae), native to mountains of Afghanistan and Kashmir. In the GC-MS study of its extract, the identified phytoconstituents have different nature such as terpenoids, alcohol and esters. The synthesized nanoparticles were characterized by SEM, UV, XRD, and FT-IR. The phytochemical analysis showed that the plant contains TPC (total phenolic content) 297.51 mg GAE/g and TFC (total flavonoid content) 467.24 mg CE/g. The cytotoxicity values have shown that the chloroform, n-butanol and aqueous extracts were more toxic than other extracts. The anti-inflammatory potential of n-butanol and aqueous extracts was found higher than all other extracts. Chloroform and n-hexane extracts have low MIC values against both E. coli and S. aureus bacterial strains. Chloroform and aqueous extracts have great anti-thrombolytic potential than all other extracts. Overall, this study successfully synthesized the nanoparticles and provides evidence that P. cashmeriana have promising bioactive compounds that could serve as potential source in the drug formulation.

Objectives The study aimed to compare the risk of gastrointestinal infections among patients with and without metabolic dysfunction-associated fatty liver disease (MAFLD).Methods This was a population-based, retrospective, observational study using data from the National Inpatient Sample (NIS), the largest all-payer US inpatient care database.Setting Hospitalisation of adults aged ≥18 years old admitted in 2020 was identified using the NIS. Patients were stratified by the presence and absence of MAFLD.Participants 26.4 million adults aged ≥18 years old were included in the study. Patients younger than 18 and those with missing demographic or mortality data were excluded.Primary and secondary outcomes Primary outcome was to assess the overall risk of gastrointestinal infections in patients with and without MAFLD. Secondary outcomes were demographics and comorbidities stratified by the presence or absence of gastrointestinal infection, and the risk of specific gastrointestinal pathogens.Results Of 26.4 million patients admitted in 2020, 755 910 (2.85%) had the presence of MAFLD. There was a higher prevalence of bacterial gastrointestinal infections in patients with MAFLD than those without (1.6% vs 0.9%, p

Aims Patients with opioid dependence seek treatment for the discomforting withdrawal symptoms. Accurate clinical assessment is essential as medications are optimized based on these withdrawal symptoms. However, subjective reporting can present challenges. Heart rate variability (HRV) can enhance clinical assessment and has taxonomic and therapeutic implications. This study aimed to explore the correlation between HRV and subjective withdrawal in patients with opioid dependence and to compare the HRV parameters in patients undergoing detoxification to those maintained on opioid agonist treatment and healthy controls. Methods 3 groups of adult male participants were included. Group 1 included 40 patients with opioid dependence undergoing inpatient detoxification. Group 2 included 40 patients with opioid dependence receiving stable doses of buprenorphine on outpatient basis. Group 3 included 49 healthy controls. The Subjective Opiate Withdrawal Scale (SOWS) was used for withdrawal symptoms. For Group 1 and Group 2, HRV was assessed twice – before administration of morning dose of buprenorphine, and then 2 hours post administration. For Group 3 HRV was assessed once. Results At baseline, resting heart rate differed significantly between the 3 groups (p < 0.001), it was highest for Group 2 (92.4) and lowest for Group 3 (79.4). In time domain parameters of HRV, the beat-to-beat variability was highest for Group 1 with standard deviation of all normal RR intervals (SDNN) = 134.8, root mean square of successive differences between normal heartbeats (RMSSD) = 181.7 and RR tri index = 8.9 (p < 0.005). In frequency domain parameters of HRV, total power was highest for Group 1 (98334.1, p < 0.001) while relative power did not differ significantly among the groups. The SOWS had a weak negative correlation with RMSSD in Group 2 (r = -0.312, p < 0.05) but did not have any correlation with HRV parameters in Group 1. Post administration of morning buprenorphine, the HRV parameters did not show a significant change in either of the groups (except reduction in very low frequency percentage in Group 1 from 12.013 to 7.196, p < 0.05). Conclusion A higher degree of subjective withdrawal is associated with lower beat-to-beat variability in patients on stable doses of buprenorphine. However, this exploratory study did not find a robust relationship between HRV and subjective withdrawal symptoms. Higher RMSSD (representative of higher vagal tone) in patients undergoing detoxification may suggest greater physiological adaptation to withdrawal symptoms. This study provides additional insights into HRV in patients with opioid dependence.

In crops like wheat, terminal drought is one of the principal stress factors limiting productivity in rain-fed systems. However, little is known about root development after heading, when water uptake can be critical to wheat crops. The impact of water-stress on root growth was investigated in two wheat cultivars, Scout and Mace, under well-watered and post-anthesis water stress in three experiments. Plants were grown outside in 1.5-m long pots at a density similar to local recommended farming practice. Differences in root development were observed between genotypes, especially for water stress conditions under which Scout developed and maintained a larger root system than Mace. While under well-watered conditions both genotypes had shallow roots that appeared to senesce after heading, a moderate water stress stimulated shallow-root growth in Scout but accelerated senescence in Mace. For deep roots, post-heading biomass growth was observed for both genotypes in well-watered conditions, while under moderate water stress, only Scout maintained net growth as Mace deep roots senesced. Water stress of severe intensity affected both genotypes similarly, with root senescence at all depths. Senescence was also observed above ground. Under well-watered conditions, Scout retained leaf greenness (i.e. stay-green phenotype) for slightly longer than Mace. The difference between genotypes accentuated under moderate water stress, with rapid post-anthesis leaf senescence in Mace while Scout leaf greenness was affected little if at all by the stress. As an overall result, grain biomass per plant (‘yield’) was similar in the two genotypes under well-watered conditions, but more affected by a moderate stress in Mace than Scout. The findings from this study will assist improvement in modelling root systems of crop models, development of relevant phenotyping methods and selection of cultivars with better adaptation to drought.

Omar W Althomali,1,&ast; Junaid Amin,1,&ast; Daria Hussain Shaik,1 Wael Alghamdi,2 Ahmed Abdelmoniem Ibrahim,1,3 Hisham M Hussein,1,4 Raheela Kanwal1 1Department of Physical Therapy, College of Applied Medical Sciences, University of Ha’il, Ha’il, 2440, Saudi Arabia; 2Department of Nursing, College of Applied Medical Sciences, AlBaha University, AlBaha, 1988, Saudi Arabia; 3Department of Physical Therapy, Cairo University Hospitals, Giza, Egypt; 4Department of Basic Sciences for Physical Therapy, Faculty of Physical Therapy, Cairo University, Giza, Egypt&ast;These authors contributed equally to this workCorrespondence: Junaid Amin, Department of Physical Therapy, College of Applied Medical Sciences, University of Ha’il, Ha’il, 2440, Saudi Arabia, Tel +966-580931017, Email Junaid768@hotmail.comBackground: Prior research has revealed notable declines in health-related quality of life (HRQoL) and substantial psychological impacts among individuals infected with COVID-19. However, there is a noticeable gap in studies addressing the enduring long-term effects of COVID-19 on HRQoL and psychological well-being.Objective: The current study investigated and compared short and long-term effects of COVID-19 on HRQoL and psychological outcomes among the Saudi population.Methods: The Arabic version of the SF-36 questionnaire was used to assess HRQoL while Anxiety and depression were evaluated by the Hamilton Anxiety (HAM-A) and Depression Scales (HDRS). Participants (n=292) were categorized into three groups: the “never-been-infected” group (n=134), the “one-year infected group” (n=43), and the “more than one year infected” group (n=115). Descriptive statistics were presented using numerical values and frequencies. To compare the groups, a one-way analysis of variance (ANOVA) test was used.Results: Most SF-36 domains exhibited lower values while HAM-A and HDRS values were higher in individuals infected during last year compared to those who never infected. Social functioning subscale of the SF-36 showed a significant difference between the groups (F (2.289) = 6.094, p = 0.01) and the effect size was d = 0.95. Pairwise comparison showed a significant reduction in the social functioning component of SF-36 in “one-year group” compared to both groups “never-been-infected” group (mean difference − 13.58 (4.40– 22.76) p < 0.01) and “more than one year infected” group (mean difference − 10.80 (1.44– 20.16) p = 0.02). HAM-A and HDRS scores showed mild levels of anxiety (< 17 score) and depression (8 to 16 score) in all groups.Conclusion: The influence of COVID-19 on psychological well-being and HRQoL is significant regardless of whether individuals infected with the virus. Overall, the consistent presence of mild anxiety and depression across all groups highlights the need for a holistic approach to mental health.Plain Language Summary: In this study, we looked at how COVID-19 infection affected the quality of life and mental well-being of people in Saudi Arabia in both the short and long term. We used surveys to measure quality of life, anxiety, and depression among 292 participants, categorizing them based on whether they had never been infected, were infected within the last year, or were infected more than one year ago. The results showed that individuals who were infected in the last year had lower scores in various aspects of quality of life and higher levels of anxiety and depression compared to those who had never been infected.Although mild levels of anxiety and depression were found in all groups. The study suggests that there is an impact on mental health in individuals even one year post-infection compared to never infected individuals. This highlights the importance of ongoing mental health support for individuals who have experienced the virus. Overall, the study emphasizes the need for a comprehensive approach to mental health care that considers both those who have been infected and those who have not.Keywords: anxiety, COVID-19, depression, quality of life, SF-36

Introduction: Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species. However, CDT is limited by the lower amount of catalyst ions that can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome. Objectives: To overcome these limitations, a tailored approach, which utilizes dual metals cations (Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kill cancer cells by taking advantage of tumor acidic environment without used of any external stimuli. Methods: A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism. Results: AgNP have an effective ability to decompose endogenous H2O2 in cells. The decomposed endogenous H2O2 generates several different types of reactive species (•OH, O2•−) including peroxynitrite (ONOO−) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO). Conclusion: This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis.

This study investigates the role of transactional leadership as a pivotal antecedent to employee knowledge hiding, specifically focusing on tacit and explicit forms. Drawing on social learning theory, the study proposes and examines the indirect effect of transactional leadership on both tacit and explicit knowledge hiding through the mediation of perceived competition. Additionally, the study introduces leader knowledge hiding as a potential boundary condition to these relationships. Data were collected from university employees in Pakistan using a time-lagged design. The study employed structural equation modeling, utilizing AMOS 23, to rigorously test the proposed hypotheses. The results reveal that transactional leadership significantly encourages tacit and explicit knowledge hiding, with perceived competition as the underlying mechanism. However, the hypothesized moderating effect of leader knowledge hiding is not supported. This study is a pioneering effort to understand the nuanced relationship between transactional leadership, perceived competition, and the distinct forms of knowledge hiding—tacit and explicit. Incorporating leader knowledge hiding as a potential boundary condition adds a unique dimension to the existing literature, contributing novel insights. Our findings hold implications for knowledge management and transactional leadership literature. Practitioners can glean valuable insights from the study's results to inform strategies to mitigate knowledge hiding behaviors within organizational settings.

Abstract Rheumatoid arthritis (RA) is a systemic self-inflicted inflammatory disease that primarily affects middle-aged women. Globally, 1% of people live with RA. This review aims to provide updated information on the different aspects of RA, including its epidemiology, pathophysiology, diagnosis, treatment, and management. A web-based literature search was conducted through various databases, including PubMed, Google Scholar, and Science Direct, to identify the most relevant studies. Epidemiological studies have suggested that the prevalence and occurrence of RA have remained inconsistent across geographical areas in different periods. Many factors such as age, gender, inheritances, and environmental exposure can contribute to the severity of the disease. The acute form of RA usually presents with pain, and if left untreated, it can result in joint deformities and influence a patient's quality of life (QoL). RA diagnosis is usually based on the manifestation of pain with inflammation. Currently, many therapeutic strategies are available for the cure of RA. The management of daily routine activities is required with treatment to curtail the damage, avoid future deformities, and ultimately minimize the aching trouble of the patient.

Sustainable and water-wise cities maintain an eco-friendly urban hydrological cycle (UHC). Regrettably, the UHC of Pakistani cities is not consistently eco-friendly. Pakistan is situated within the influential area of the world's largest monsoon weather system. Cities like Lahore face simultaneous vulnerabilities to urban flooding and water scarcity due to extreme climate change events. Therefore, Pakistan's urban areas necessitate Urban Water Infrastructural Transformation (UWIT), achievable only after identifying suitable Rainwater and Stormwater Harvesting Potential Sites (RSWHPS) in Lahore. Hence, we conducted spatial analysis to pinpoint these RSWHPS within Lahore city for 2020, utilizing the World View Water Index (WV-WI). The results indicate 85.54 km2 of available areas for rain and stormwater harvesting potential during monsoon rains in Lahore. The area with the highest potential in Lahore is Wagha town, featuring 19.96 km2 of stagnant water. Additionally, RSWHPS is classified into four categories based on potential: high, medium, low, and water bodies in Lahore. Urgent transformation is required for the identified storm and rainwater harvesting sites. Consequently, this study will serve as a snapshot for policymakers to systematically address water shortage and urban flooding, making Lahore's hydrological cycle eco-friendly and sustainable. HIGHLIGHTS The study addresses the importance of sustainable and water-wise cities in maintaining an eco-friendly urban hydrological cycle.; Recognizing the pressing need for change, the research emphasizes the requirement for urban water infrastructural transformation in Pakistan's urban areas.; The study is a valuable resource for policymakers, providing insights to systematically address water shortages and urban flooding.;

Background: Hepatitis C, caused by the Hepatitis C Virus (HCV), is the second most common form of viral hepatitis. The geographical distribution of HCV genotypes can be quite complex, making it challenging to ascertain the most prevalent genotype in a specific area. Methods: To address this, a review was conducted to determine the prevalence of HCV genotypes across various provinces and as a whole in Pakistan. The scientific literature regarding the prevalence, distribution, genotyping, and epidemiology of HCV was gathered from published articles spanning the years 1996–2020. Results: Genotype 1 accounted for 5.1% of the patients, with its predominant subtype being 1a at 4.38%. The frequencies of its other subtypes, 1b and 1c, were observed to be 1.0% and 0.31% respectively. Genotype 2 had a frequency of 2.66%, with the most widely distributed subtype being 2a at 2.11% of the patients. Its other subtypes, 2b and 2c, had frequencies of 0.17% and 0.36% respectively. The most prevalent genotype among all isolates was 3 (65.35%), with the most frequent subtype being 3a (55.15%), followed by 3b (7.18%). The prevalence of genotypes 4, 5, and 6 were scarce in Pakistan, with frequencies of 0.97%, 0.08%, and 0.32% respectively. The prevalence of untypeable and mixed genotypes was 21.34% and 3.53% respectively. Estimating genotypes proves to be a productive method in assisting with the duration and selection of antiviral treatment. Different HCV genotypes can exhibit variations in their response to specific antiviral treatments. Different genotypes may have distinct natural histories, including variations in disease progression and severity. Some genotypes may lead to more rapid liver damage, while others progress more slowly. Conclusions: This information can guide screening and testing strategies, helping to identify individuals at higher risk of developing severe complications. Studying the distribution of HCV genotypes in a population can provide valuable insights into the transmission dynamics of the virus.

Abstract 5G technology continues to evolve, and its potential to revolutionize various aspects of society is becoming increasingly evident. However, the successful adoption and utilization of 5G technology depends on various factors, particularly among consumers expected to be early adopters and critical drivers of technological advancements. This study investigates the effect of social influence, environmental awareness, and safety affordance on Chinese university students' actual use of 5G (AU5G) technologies. It also analyzed the mediating role of trustworthiness and intention to use 5G (ITU5G) between them and the moderating role of facilitation conditions between trustworthiness and ITU5G. Data was collected from university students (n = 364) in Beijing and was examined employing the structural equation modelling (SEM) approach. The outcomes confirm that trustworthiness and ITU5G significantly mediate the relationship between social influence, environmental awareness, and safety affordance on AU5G technologies among Chinese students. Further, the supportive facilitation conditions strengthen the relationship between trustworthiness and ITU5G. These findings are backed by UTAUT2 models that support the technology acceptance and adoption among the users. The study outcomes can help policymakers design strategies to address potential barriers and encourage greater uptake of 5G services among university students.

Abstract Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease’s origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript. Graphical abstract

Background and aims: Prediabetes is defined as a state of impaired glucose metabolism with hemoglobin A1c (HbA1c) levels that precede those of a diabetic state. There is increasing evidence that suggests that hyperglycemic derangement in prediabetes leads to microvascular and macrovascular complications even before progression to overt diabetes mellitus. We aim to identify the association of prediabetes with acute cardiovascular events. Methods: We utilized the National inpatient sample 2018-2020 to identify adult hospitalizations with prediabetes after excluding all hospitalizations with diabetes. Demographics and prevalence of other cardiovascular risk factors were compared in hospitalizations with and without prediabetes using the chi-square test for categorical variables and the t-test for continuous variables. Multivariate regression analysis was further performed to study the impact of prediabetes on acute coronary syndrome, acute ischemic stroke, intracranial hemorrhage, and acute heart failure. Results: Hospitalizations with prediabetes had a higher prevalence of cardiovascular risk factors like hypertension, hyperlipidemia, obesity, and tobacco abuse. In addition, the adjusted analysis revealed that hospitalizations with prediabetes were associated with higher odds of developing acute coronary syndrome (OR-2.01; C.I:1.94-2.08; P

Background: Oral Submucous Fibrosis (OSMF) is defined as severe submucosal fibrosis and decreased vascularity, resulting in a compromised blood supply leading to hypoxia of tissues. The key biomarker involved is Hypoxia Inducible Factor-1α (HIF-1α). The objective of this research was to analyze the expression of HIF-1α in saliva samples of individuals across the clinical stages of OSMF and healthy controls. Methods: This case-control study consisted of 120 participants, 60 patients had different clinical stages of OSMF and 60 healthy controls. Samples of saliva were collected and quantification of salivary samples was done using ELISA. Kolmogorov-Smirnov test assessed data normality. Kruskal Wallis test was applied to assess the association between salivary HIF-1α levels and clinical stages of OSMF. The Kendall Tau correlation test was used to assess the relationship between different stages of OSMF and salivary HIF-1α levels. Results: The comparison of HIF-1α expression in different stages of OSMF and healthy controls was done. In comparison, it was found that HIF-1α expression increased significantly (p=0.00) in patients than controls. The expression was increased with stages, stage I (16.84 ± 9.74), stage II (19.51 ± 7.99), stage III (24.43 ± 7.49), and stage IV (28.92 ± 5.12), respectively. The odd ratio indicates for every progressive stage, the odds for high salivary HIF-1α levels increase by 1.63 times. Conclusion: Levels of salivary HIF-1α showed increased expression with the progressive stages of OSMF. This variation in the levels of salivary HIF-1α suggests its possible role as an early non-invasive detective marker in the assessment of disease progression.

Background: Gout is the most prevailing type of inflammatory arthropathy and its incidence has risen in recent decades. As previously no such research was found through an extensive literature survey, the current study aimed to evaluate gout patients residing in Lahore, Pakistan. Methods: To conduct this cross-sectional study, n=203 responses were obtained by a simple and objective-oriented questionnaire devised for the collection of data. Dependent variables association was measured by the Pearson Chi-square. A p-value

Oral submucous fibrosis (OSMF) is a premalignant condition, which involves the oral cavity as well as pharynx and upper third of the esophagus. It is a predominant disease of South and South-East Asian population. OSMF has the highest rate of malignant transformation among the other oral premalignant disorders (OPMD) that is 7-30% with a prevalence of about 0.03% to 6.42%. OSMF is described by extensive fibrosis of submucosa and reduced vascularity, which results in compromised blood supply guiding to hypoxia of tissue. This tissue hypoxia brings about the transcription of a set of genes associated with angiogenesis, breakdown of iron/glucose, cell division and cell stability. Hypoxia Inducible Factor-1α (HIF-1α) is the main biomarker intervening in this reaction. The alteration of cells to hypoxia emerges to be mediated through hypoxia inducible factor, which is said to be linked with malignant transformation of epithelium. Research-based studies covered on the probable mechanism of HIF-1α were explored using PubMed and Google Scholar. In this review, we analyzed over 40 articles from the years 2004-2021, which were published regarding the structure and function of HIF-1α, and its association with OSMF. Research articles in which HIF-1α is used separately or in combination with other biomarkers in oral submucous fibrosis have been selected. Keywords: Biomarker; Oral Submucous Fibrosis; Esophagus; Hypoxia.

Background: Oral submucous fibrosis (OSMF), a chronic debilitating condition distinguished by juxtaepithelial fibrosis or extensive fibrosis of submucosa and reduced vascularity, results in compromised blood supply causing tissue hypoxia. This brings about the transcription of a set of genes associated with angiogenesis, breakdown of iron/glucose, cell division and cell stability. Hypoxia Inducible Factor-1α (HIF-1α) is the main biomarker intervening in this reaction. The aim of research was to measure the salivary levels of HIF-1α in OSMF patients and healthy controls. Methods: This study included 60 participants (30 Oral submucous fibrosis cases and 30 healthy controls). The consecutive sampling technique was used for the recruitment of the study participants. The enzyme-linked immunosorbent assay (ELISA) was used to evaluate HIF-1α levels in saliva. In order to determine data normality, the Kolmogorov-Smirnov test was used. Independent t test was applied to compare salivary levels of HIF-1α between cases and controls and p-value of less than 0.05 was considered statistically significant. Results: The mean salivary HIF-1α value for the oral submucous fibrosis group was 20.18±7.78, compared to healthy controls 13.62±8.86. A statistically significant difference was seen between levels of HIF-1α in the OSMF and control group (p=0.003). The mean mouth opening for cases was 22.94±9.51 mm and for controls 42.00±5.19 mm. There was no correlation among salivary levels of HIF-1α in both the case and control groups (-0.059, -0.030) respectively. Conclusion: Higher levels of HIF-1α were seen in the OSMF group in comparison to healthy individuals suggesting that HIF-1α may play a role in malignant transformation of OSMF. Keywords: Oral Submucous Fibrosis; Saliva; Hypoxia Inducible Factor-1α.

Background: Regenerative medicine is a collaborative field that applies combined concepts of tissue engineering and cell biology to promote regeneration. Tissue regeneration initiate the emergence of remedies that can replace and revive tissues and loss of organs through illness and injury and reduce dependency on organ transplantation. The objective was to isolate a homogenous population of human amniotic epithelial stem cells (hAECs) and to determine their phenotype under a live-cell imaging microscope at 1st, 3rd and 8th-day intervals. Methods: This was an experimental in-vitro study conducted on human placenta (amniotic epithelial stem cells) at Ziauddin Hospital and University. The 22 human placenta were collected from patients with age 20-30 years having healthy full-term pregnancies, with a preference for elective cesarean sections. In vitro isolation of human amniotic epithelial stem cells was used after manual removal of the amniotic membrane from the chorionic membrane of human term placenta via single-step enzymatic digestion. The morphology of the attached cells was analyzed at different magnifications i.e., 10X, 20X and 40X. Results: The isolated human amniotic epithelial stem cells on day 3 started forming colonies and attained a characteristic cuboid epithelial shape and exhibited a confluent single layer on day 8. Morphologically resembled cobblestones with a characteristic of fully vacuolated cytoplasm were found uncontaminated with spindle-shaped human amniotic mesenchymal stem cells (MSCs). Conclusion: The isolated population of hAESCs were highly proliferative and not contaminated with MSCs. Therefore, this optimized protocol may be used for the isolation and the biobanking of hAESCs for future cellular transplantation. Keywords: Human Amniotic Epithelial Stem Cells (hAESCs); Regenerative Medicine; Perinatal Stem Cells; Placental Membrane; Amniotic Membrane.

Skin cancer is a pervasive and potentially life-threatening disease. Early detection plays a crucial role in improving patient outcomes. Machine learning (ML) techniques, particularly when combined with pre-trained deep learning models, have shown promise in enhancing the accuracy of skin cancer detection. In this paper, we enhanced the VGG19 pre-trained model with max pooling and dense layer for the prediction of skin cancer. Moreover, we also explored the pre-trained models such as Visual Geometry Group 19 (VGG19), Residual Network 152 version 2 (ResNet152v2), Inception-Residual Network version 2 (InceptionResNetV2), Dense Convolutional Network 201 (DenseNet201), Residual Network 50 (ResNet50), Inception version 3 (InceptionV3), For training, skin lesions dataset is used with malignant and benign cases. The models extract features and divide skin lesions into two categories: malignant and benign. The features are then fed into machine learning methods, including Linear Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Decision Tree (DT), Logistic Regression (LR) and Support Vector Machine (SVM), our results demonstrate that combining E-VGG19 model with traditional classifiers significantly improves the overall classification accuracy for skin cancer detection and classification. Moreover, we have also compared the performance of baseline classifiers and pre-trained models with metrics (recall, F1 score, precision, sensitivity, and accuracy). The experiment results provide valuable insights into the effectiveness of various models and classifiers for accurate and efficient skin cancer detection. This research contributes to the ongoing efforts to create automated technologies for detecting skin cancer that can help healthcare professionals and individuals identify potential skin cancer cases at an early stage, ultimately leading to more timely and effective treatments.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by disrupted blood cell production and function. Recent investigations have highlighted the potential of targeting glutamine metabolism as a promising therapeutic approach for AML. Asparaginases, enzymes that deplete circulating glutamine and asparagine, are approved for the treatment of acute lymphoblastic leukemia, but are also under investigation in AML, with promising results. We previously reported an elevation in plasma serine levels following treatment with Erwinia-derived asparaginase (also called crisantaspase). This led us to hypothesize that AML cells initiate the de novo serine biosynthesis pathway in response to crisantaspase treatment and that inhibiting this pathway in combination with crisantaspase would enhance AML cell death. Here we report that in AML cell lines, treatment with the clinically available crisantaspase, Rylaze, upregulates the serine biosynthesis enzymes phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) through activation of the Amino Acid Response (AAR) pathway, a cellular stress response mechanism that regulates amino acid metabolism and protein synthesis under conditions of nutrient limitation. Inhibition of serine biosynthesis through CRISPR-Cas9-mediated knockout of PHGDH resulted in a ~250-fold reduction in the half-maximal inhibitory concentration (IC50) for Rylaze, indicating heightened sensitivity to crisantaspase therapy. Treatment of AML cells with a combination of Rylaze and a small molecule inhibitor of PHGDH (BI4916) revealed synergistic anti-proliferative effects in both cell lines and primary AML patient samples. Rylaze-BI4916 treatment in AML cell lines led to the inhibition of cap-dependent mRNA translation and protein synthesis, as well as a marked decrease in intracellular glutathione levels, a critical cellular antioxidant. Collectively, our results highlight the clinical potential of targeting serine biosynthesis in combination with crisantaspase as a novel therapeutic strategy for AML.

The plant Conocarpus lancifolius from Combertaceae family, has been documented to have strong medicinal potential. The objective of this research was to determine antioxidant, anti-inflammatory, and cytotoxic potential of C. lancifolius by in vitro, in vivo as well as computational studies. A forecast was made that a novel compound “lancifolian” can significantly improve inflammation, radical scavenging ability as well as cytotoxicity. For antioxidant study ABTS, DPPH, FRAP and β-carotene bleaching assays were performed. Anti-inflammatory activity was determined by carrageenan induced paw edema. Cytotoxic effects against four cancer cell lines: MCF-7, A549, COR-L23 and MDA-MB-231, were observed. Molecular docking was also performed to predict anti-inflammatory and cytotoxic properties by observing the binding affinity of lancifolian with respective receptors and validation of molecular docking was performed. Dichloromethane (DCM) and methanolic extract of C. lancifolius show strong radical scavenging ability. Different extracts showed a significant reduction in inflammation in the paw edema method. C. lancifolius extract and lancifolian showed significant cytotoxic effects against four cancer cell lines: MCF-7, A549, COR-L23 and MDA-MB-231. Subsequently, molecular docking highlighted the strong binding affinity of lancifolian with respective receptors.

OBJECTIVES/GOALS: This study aimed to characterize urinary exosomal miRNA content in African American adults with diabetic kidney disease. METHODS/STUDY POPULATION: Male and female participants between the ages of 18 and 65 were recruited from the Diabetes Treatment Center and the Nephrology Clinic at the Howard University Hospital. Exosomes were isolated from cleared urine of healthy controls (n=3), type 2 diabetics (n=3), and participants with chronic kidney disease (n=3). The purity and size of isolated microparticles was evaluated using NanoSight technology (30nm to 120nm size range) and western blot analysis for exosome-specific markers (TSG101 and CD81) RESULTS/ANTICIPATED RESULTS: Expression of 5 selected microRNAs, miR-4534, miR-320c, miR-451, miR-362-3p and miR-877-3p were evaluated by qRT-PCR. miR-4534 and miR-451 was increased between healthy controls and the type diabetic group. MiR-320c was increased in the CKD group, in comparison to healthy controls. Conversely, there was no difference in miR-877-5p between the three groups. DISCUSSION/SIGNIFICANCE: These findings will provide insight into the use of circulating miRNAs as early markers of DKD, ultimately creating more effective treatments and preventive measures.

Objective: To determine the frequency of infections in cardiac implantable Electronic device patients, identify risk factors, and look for optimization in reducing Cardiac Implantable Electronic Device infections, with a resultant decrease in mortality and morbidity, decrease in hospital stay, and total expenditure. Study Design: Cross-sectional study. Place and Duration of Study: Electrophysiology Department of National Institute of Cardiovascular Diseases, Karachi Pakistan, from Jul 2019 to Jun 2020. Methodology: The study was conducted on the patients with cardiac implantable devices. Adult patients of either gender with cardiac implantable Electronic device and infection were included. Epicardial leads and surgical site infections within six weeks were excluded. Results: One thousand and forty-six (1046) patients were enrolled in the study. There were 596(57%) male patients. 385(36.8%) patients were implanted with single chamber pacemakers, 390(37.3%) with dual chamber pacemakers, 146(14%) single chamber ICD (implantable cardiac defibrillator), 67(6.4%) dual-chamber cardiac implantable Electronic device, 46(4.4%) CRT-D, 12(1.1%) TPM, 134(12.8%) Re-do, 114(10.9%), 114(10.9%) generator change, 20(1.9%) leads revision, 26(2.5%) patients had extraction. The rate of CIED infection was 34(2.1%). The association of the study parameters with infection rate revealed that type of device (p=0.002), extraction, suture type, and post-procedure hematoma (p

Objective: To explore a novel and dynamic role for neurogenin-2 in promoting cortical neurogenesis in cells produced from co-culturing neonatal cortical neural progenitor cells with bone marrow stromal cells. Method: The experimental study was conducted from June 2016 to January 2019 at the neuropharmacology laboratory of the Hussein Ebrahim Jamal Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, Karachi. The growth of cells at different stages in harvested cells was determined by 3-(4, 5- dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. Immunocytochemistry was used to evaluate the protein expressions of neuronal markers and transcription factors. Data was analysed using SPSS 20. Results: Data showed significant generation of neuronal cells and this was also verified by increased expression of nesting in cortical co-cultures with bone marrow stromal cells. Immunoreactive outcomes showed over expressions in co-cultured chlorotoxin cells. Subsequently, neurogenin-2 was found intermixed with induced expressions of transcriptional factor NeuroD1 and reduced glial fibrillary acidic protein-labelled cells. Conclusion: Better understanding of the mechanisms underlying transcriptional modulation of neurogenic events hold the key for emerging treatment approaches towards neurodegeneration. Key Words: Coculture, Glial Fibrillary, Bromides, Immunohistochemistry, Chlorotoxin, diphenyl, Neuropharmacology, Mesenchymal, Neurogenesis, Stem Cells.

Objective: To isolate a homogenous population of human amniotic epithelial cells (hAECs) from the amniotic membrane of the human placenta and differentiate them into hepatic-like cells with the help of small molecules. Method: hAECs were isolated by using the enzymatic digestion method and characterized for the presence of specific stem cell markers. In-vitro, hepatic differentiation of hAECs was carried out by using a combination of small molecules. Differentiated cells were observed under a live cell imaging microscope for morphological changes followed by gene and protein expression analysis by qPCR and immunocytochemistry respectively. Results: The isolated hAECs attained characteristic cuboid epithelial shape and express stem cells marker. The hepatic differentiation method was optimized based on soluble chemical compounds supplied in the culture medium. The differentiated hAECs phenotypically acquire hepatic-like cell features and expressed hepatic markers as well as hepatic protein albumin at immature levels. Conclusion: The isolated population of hAECs is highly proliferative. Moreover, hepatic markers expression in the isolated hAECs makes them an exclusive source for the treatment of chronic liver diseases. Keywords: Amnion, Immunohistochemistry, Epithelial, Albumins, Liver, Digestion, Placenta

Hybrid nanofluids (HNFs) of metallic oxide-based nanoparticles (NPs) have been prepared in different basefluids (BFs) employing the thermal plasma technique. NPs of ZnO–MgO were directly dispersed into pristine coolant, engine oil, distilled water (DW), and coconut oil. Plasma was generated between two identical electrodes applying 8.0 kV at the ambient conditions and proved economically viable in preparing stable HNFs. X-ray Diffractometry (XRD) showed ZnO and MgO NPs possessed hexagonal and cubic crystal structures, respectively. The band gap is calculated through UV-visible spectroscopy. The thermal conductivity (TC) of the HNFs has been measured using a thermal conductivity analyzer based on the transient hot wire method. The band gaps of pristine coolant and its HNFs were obtained to be 3.35 eV and 3.33 eV, respectively. In engine oil and its HNFs, band gaps of 3.16 eV and 3.02 eV have been extracted. There appears to be a slight reduction in band gap for coolant and engine oil-based HNFs. The band gap value of coconut oil-based HNFs was 4.05 eV, which showed a higher value than the pristine coconut oil-based HNFs (3.95 eV). The band gap calculated in the case of DW-based HNFs was 3.79 eV. TC of HNFs with volume concentration of 0.019 % for DW, 0.020 % for coolant, 0.016 % for engine oil, and 0.017 % for coconut oil were tested between 20 and 60 °C. An increase in TC was observed with the rise in temperature of the HNFs. Maximum increment in TC was observed at 60 °C for coolant-based HNFs, which was 19 %, followed by DW (18%), coconut oil (18%), and engine oil (16%), respectively. DW-based HNFs can be used as a coolant and optical filter for optoelectronics devices like photovoltaic cells for better performance. The study underscores precise control of NPs size as pivotal for band gap influence. HNFs hold promise as the next-gen heat transfer fluids (HTFs), revolutionizing thermal conductivity across industries. This research lays a firm foundation for plasma-synthesized HNFs' application in enhanced heat transfer and optoelectronic devices. Coolant-based HNFs excel in thermal conductivity, addressing heat transfer challenges.

The clinical application of nanomaterials for chemodynamic therapy (CDT), which generate multiple reactive oxygen species (ROS), presents significant challenges. These challenges arise due to insufficient levels of endogenous hydrogen peroxide and catalytic ions necessary to initiate Fenton reactions. As a result, sophisticated additional delivery systems are required. In this study, a novel bimetallic copper (II) pentacyanonitrosylferrate (Cu(II)NP, Cu[Fe(CN) 5 NO]) material was developed to address these limitations. This material functions as a multiple ROS generator at tumoral sites by self-inducing hydrogen peroxide and producing peroxynitrite (ONOO-) species. The research findings demonstrate that this material exhibits low toxicity towards normal liver organoids, yet shows potent antitumoral effects on High Grade Serous Ovarian Cancer (HGSOC) organoid patients, regardless of platinum resistance. Significantly, this research introduces a promising therapeutic opportunity by proposing a single system capable of replacing the need for H2O2, additional catalysts, and NO-based delivery systems. This innovative system exhibits remarkable multiple therapeutic mechanisms, paving the way for potential advancements in clinical treatments.

There are numerous studies where data on population units’ auxiliary variables and attributes are simultaneously available. Therefore, due to cost-effectiveness and ease of recording, the study variable and several linearly related auxiliary variables are recorded. These auxiliary variables are commonly observed as quantitative and qualitative (attributes) variables and are jointly used to estimate the study variable’s population mean using a mixture estimator. In order to achieve this, a family of generalized mixture estimators was proposed under simple random sampling with the aim of improving performance under symmetrical and asymmetrical distributions. In addition, the estimator’s behavior for various sample sizes was examined with regard to its convergence to the normal distribution. The suggested generalized mixture estimator’s mean square error is deduced up to the first order of approximation. It is discovered that for the normal, uniform, Weibull, and gamma distributions, the suggested estimator estimates the population mean of the study variable with greater accuracy than the competing estimators. It is also revealed that when the proposed estimator converges to normality, the sample size is at least taken as 110, 1000, and 120. Furthermore, the implementation of three real-life datasets related to the finance and health sectors is also presented to support the proposed estimator’s significance.

Abstract Objective: We investigated the missed treatment opportunities affecting programmes using mid-upper arm circumference (MUAC) as the sole anthropometric criterion for identification and monitoring of children suffering from severe acute malnutrition (SAM). Design: Alongside MUAC, we assessed weight-for-height Z-score (WHZ) in children screened and treated according to the national MUAC only protocol in Pakistan. Besides, we collected parents’ perceptions regarding the treatment received by their children through qualitative interviews. Setting: Data were collected from October to December 2021 in Tando Allah Yar District, Sindh. Subjects: All children screened in the health facilities (n 8818) and all those discharged as recovered (n 686), throughout the district, contributed to the study. All children screened in the community in the catchment areas of five selected health facilities also contributed (n 8459). Parents of forty-one children randomly selected from these same facilities participated in the interviews. Results: Overall, 80·3 % of the SAM cases identified during community screening and 64·1 % of those identified in the health facilities presented a ‘WHZ-only’ diagnosis. These figures reached 93·9 % and 84·5 %, respectively, in children aged over 24 months. Among children treated for SAM and discharged as recovered, 25·3 % were still severely wasted according to WHZ. While parents positively appraised the treatment received by their children, they also recommended to extend eligibility to other malnourished children in their neighbourhood. Conclusion: In this context, using MUAC as the sole anthropometric criterion for treatment decisions (referral, admission and discharge) resulted in a large number of missed opportunities for children in need of timely and adequate care.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Bis(dimethylamino)benzophenone derivatives 1–27 were synthesized from bis(dimethylamino)benzophenone via two-step reaction. Different spectroscopic techniques, including EI-MS and 1H NMR, were employed to characterize all synthetic derivatives. The elemental composition of synthetic compounds was confirmed by elemental analysis and results were found in agreement with the calculated values. The synthetic compounds 1–27 were evaluated for α-glucosidase inhibitory activity, except five compounds all derivatives showed good to moderate inhibitory potential in the range of IC50 = 0.28 ± 2.65 - 0.94 ± 2.20 μM. Among them, the most active compounds were 5, 8, 9, and 12 with IC50 values of 0.29 ± 4.63, 0.29 ± 0.93, 0.28 ± 3.65, and 0.28 ± 2.65, respectively. Furthermore, all these compounds were found to be non-toxic on human fibroblast cell lines (BJ cell lines). Kinetics study of compounds 8 and 9 revealed competitive type of inhibition with Ki values 2.79 ± 0.011 and 3.64 ± 0.012 μM, respectively. The binding interactions of synthetic compounds were also confirmed through molecular docking studies that indicated that compounds fit well in the active site of enzyme. Furthermore, a total of 30ns MD simulation was carried out for the most potent complexes of the series. The molecular dynamics study revealed that compound-8 and compound-12 were stable during the MD simulation.