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Background: Nanomedicine, as the combination of radiopharmaceutical and nanocarrier (QDs), is developed for treating cancer. Gallic acid is antimutagenic, anti-inflammatory, and anti-carcinogenic. Typical retention time of gallic acid is approximately 4 to 8 h. To increase the retention time gallic acid is converted to prodrug by adding lipophilic moieties, encapsulating in lipophilic nanoparticles, or liposome formation. Similarly, thymoquinone is powerful antioxidant, anti-apoptotic, and anti-inflammatory effect, with reduced DNA damage., Methods: In this study, a hydrophilic drug (gallic acid) is chemically linked to the hydrophobic drug (thymohydroquinone) to overcome the limitations of co-delivery of drugs. Thymohydroquinone (THQG) as the combination of gallic acid (GA) and thymoquinone (THQ) is loaded onto the PEI functionalized antimonene quantum dots (AM-QDs) and characterized by FTIR, UV-visible spectroscopy, X-ray powder diffraction, Zeta sizer, SEM and AFM, in-vitro and in-vivo assay, and hemolysis., Results: The calculated drug loading efficiency is 90 %. Drug release study suggests the drug combination is pH sensitive and it can encounters acidic pH, releasing the drug from the nanocarrier. The drug and drug-loaded nanocarrier possesses low cytotoxicity and cell viability on MCF-7 and Cal-27 cell lines. The proposed drug delivery system is radiolabeled with Iodine-131 ( 131 I) and Technetium ( 99m Tc) and its deposition in various organs of rats' bodies is examined by SPECT-CT and gamma camera. Hemolytic activity of 2, 4, 6, and 8 μg/mL is 1.78, 4.16, 9.77, and 15.79 %, respectively, reflecting low levels of hemolysis. The system also sustains oxidative stress in cells and environment, decreasing ROS production to shield cells and keep them healthy., Conclusions: The results of this study suggest that the proposed drug carrier system can be used as a multi-modal theragnostic agent in cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Central line-associated bloodstream infections (CLABSIs) pose a significant risk to critically ill patients, particularly in intensive care units (ICU), and are a significant cause of hospital-acquired infections. We investigated whether implementation of a multifaceted intervention was associated with reduced incidence of CLABSIs., Methods: This was a prospective cohort study over nine years. We implemented a bundled intervention approach to prevent CLABSIs, consisting of a comprehensive unit-based safety program (CUSP). The program was implemented in the Neonatal ICU, Medical ICU, and Surgical ICU departments at the Aga Khan University Hospital in Pakistan., Results: The three intervention ICUs combined were associated with an overall 36% reduction in CLABSI rates and a sustained reduction in CLABSI rates for > a year (5 quarters). The Neonatal ICU experienced a decrease of 77% in CLABSI rates lasting ∼1 year (4 quarters). An attendance rate above 88% across all stakeholder groups in each CUSP meeting correlated with a better and more sustained infection reduction., Conclusions: Our multifaceted approach using the CUSP model was associated with reduced CLABSI-associated morbidity and mortality in resource-limited settings. Our findings suggest that a higher attendance rate (>85%) at meetings may be necessary to achieve sustained effects post-intervention., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study addresses membrane biofouling in membrane bioreactors (MBRs) by exploring fungal-to-bacterial quorum quenching (QQ) strategies. While most research has been focused on bacterial-to-bacterial QQ tactics, this study identified fungal strain Vanrija sp. MS1, which is capable of degrading N-acyl-homoserine lactones (signaling molecules of Gram-negative bacteria). To determine the benefits of fungal over bacterial strains, after immobilization on fluidizing spherical beads in an MBR, MS1 significantly reduced the fouling rate by 1.8-fold compared to control MBR, decreased extracellular polymeric substance levels in the biofilm during MBR operation, and favorably changed microbial community and bacterial network, resulting in biofouling mitigation. It is noteworthy that, unlike Rhodococcus sp. BH4, MS1 enhanced QQ activity when switching from neutral to acidic conditions. These results suggest that MS1 has the potential for the effective treatment of acidic industrial wastewater sources such as semiconductor and secondary battery wastewater using MBRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oxidative stress is a trigger for many diseases and occurs with the unstable hypochlorite (ClO - ), known as one of the reactive oxygen species (ROS) in organisms. Then, HOCI is acknowledged as an oxidizing species that eliminates a variety of environmental pollutants. Hence, the development of novel methodologies for the selective and precise identification of HOCl/ ClO - is considered to be of utmost importance. In this study, the design, characterization, and applications of a fluorene-based fluorescent probe (FHBP) dependent on the ESIPT mechanism with a "turn-on" response for the sensitive/selective determination of ClO - against other competing samples were reported. The experimental results indicated that the detection limit for ClO - could be quantitatively determined by the probe to be 8.2 × 10 -7  M. The binding constant of the probe FHBP with ClO - was computed as 9.75 × 10 3  M -1 . In addition, the response time of FHBP was appointed to be 30 s, indicating a rapid reaction with ClO - . It has also been demonstrated that this probe can be successfully used for the detection of ClO - on filter papers, TLC sheets, cotton swabs, and real samples., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neoadjuvant treatment is the standard treatment in locally advanced ESCC. However, the optimal chemotherapy regimen is not known., Method: This is a retrospective observational cohort study conducted with propensity score matching. Patients with resectable ESCC from 13 tertiary centers from Türkiye were screened between January 2011 and December 2021. We compared the efficacy and safety of neoadjuvant chemoradiotherapy with the CF and the CROSS regimens in patients with ESCC., Results: Three hundred and sixty-two patients were screened. Patients who received induction chemotherapy (n = 72) and CROSS-ineligible (n = 31) were excluded. Two hundred and fifty nine patients received neoadjuvant chemoradiotherapy. After propensity score matching (n = 97 in both groups), the mPFS was 18.4 months (95% CI, 9.3-27.4) and 25.7 months (95% CI, 15.6-35.7; p = 0.974), and the mOS was 35.2 months (95% CI, 18.9-51.5) and 39.6 months (95% CI 20.1-59.2; p = 0.534), in the CF and the CROSS groups, respectively. There was no difference between subgroups regarding PFS and OS. Compared with the CF group, the CROSS group had a higher incidence of neutropenia (34.0% vs. 62.9%, p < 0.001) and anemia (54.6% vs. 75.3%, p = 0.003) in all grades. On the other hand, there was no significant difference in grade 3-4 anemia, grade 3-4 neutropenia, and febrile neutropenia between groups. There were more dose reductions and dose delays in the CROSS group than in the CF group (11.3% vs. 3.1%, p = 0.026 and 34.0% vs. 17.5%, p = 0.009, respectively). The resection rate was 52.6% in the CF-RT and 35.1% in the CROSS groups (p = 0.014)., Conclusion: Favorable PFS and pCR rates and a comparable OS were obtained with the CROSS regimen over the CF regimen as neoadjuvant chemoradiotherapy in patients with ESCC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

In this work, pure and S-N/WO3 (1%-7%) nanoparticles (NPs) have been developed for the degradation of MB dye. Optical properties, vibrational analysis, morphology, structural analysis, and photocatalytic activity of the samples have been evaluated using a variety of characterization techniques, including UV-vis, PL, FTIR, SEM, and x-ray diffraction (XRD). The XRD patterns showed that the stability of the orthorhombic phase of WO3 was affected by the concentrations of S and N. In SEM, nanospheres with an average size of 80 nm of NPs have been observed. The PL results showed that the e-, h+ recombination rate for the S-N7%/WO3 sample was the lowest. The degradation of MB dye has also been investigated in order to investigate the photocatalytic performance. Remarkably, S-N7%/WO3 shows the best results, with a maximum degradation of 90% in 120 min. The stability of the improved catalyst was tested using recycling and trapping studies. S-N7%/WO3 catalyst's exceptional photocatalytic activity highlights its potential use in wastewater treatment. This study will be helpful for manufacturing innovation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Dynamic changes in sarcopenia status following stressor events are defined as acute sarcopenia; it is currently unknown how to stratify risk. Prospective observational study involving elective colorectal surgery, emergency abdominal surgery, and medical patients with infections aged ≥70 years-old. Handgrip strength, muscle quantity (ultrasound Bilateral Anterior Thigh Thickness, BATT, and Bioelectrical Impedance Analysis), and muscle quality (rectus femoris echogenicity) were measured preoperatively in the elective group, and within 48hours, 7days after, and 13weeks after admission/surgery. Serum/plasma samples were collected preoperatively (elective group) and within 48hours of admission/surgery (all groups). LASSO models adjusting for baseline sarcopenia status were performed. Seventy-nine participants were included (mean age 79.1, 39.2% female). Chronic Obstructive Pulmonary Disease (COPD) (48hours β 0.67, CI 0.59-0.75), and prescription of steroids during admission (48hours β 1.11, CI 0.98-1.24) were positively associated with sarcopenia at 7days. Delirium was negatively associated with change in BATT to 7days (7days β -0.47, CI -0.5- -0.44). COPD (Preoperative β 0.35, CI 0.12-0.58) and delirium (48hours β 0.13, CI 0.06-0.2) were positively associated with change in echogenicity to 7days in analysis including systemic biomarkers. Participants with sarcopenia at baseline had higher IL-7 concentrations during acute phase of illness (median 8.78pg/mL vs 6.52pg/mL; p=0.014). IL-1b within 48hours of admission/surgery was positively associated with sarcopenia status at 7days (β 0.24, CI 0.06-0.42). Patients most at risk of acute sarcopenia or reductions in muscle quantity and quality included those prescribed steroids, with COPD or delirium, or with heightened systemic inflammation.

Prolonged Grief Disorder (PGD) manifests as a long-lasting and incapacitating response to bereavement. The goal of this qualitative study is to understand the intricate interplay of risk and protective factors that underlie PGD by exploring into the perspectives of expert clinicians in Pakistan. Our investigation encompassed in-depth interviews with eight clinical experts comprising clinical psychologists ( N  = 4, possessing Higher Education Commission-recognized degrees) and psychiatrists ( N  = 4, certified by Pakistan Medical Commission). Collectively, these professionals possessed a wealth of knowledge exceeding five years in the specialized management of PGD. Thematic analysis of the transcribed interviews, conducted using NVIVO, revealed a comprehensive taxonomy of risk factors contributing to PGD. These encompassed maladaptive thought patterns, psychological distress, attachment styles, and environmental factors. We identified a host of protective factors that may mitigate the development of PGD. These encompassed cultural, social, and familial support systems, individual coping mechanisms, and various treatment modalities.

The COVID-19 pandemic has great effects for economies internationally. This study studies the interconnection between COVID-19 metrics and Pakistan's premier stock exchange, the Karachi Stock Exchange (KSE) with the object of identifying the most effective machine learning (ML) model for predicting KSE developments in the pandemic. Our investigation periods the peak COVID-19 period from March 1, 2020, to November 26, 2021, applying data from both the KSE 100 index and COVID-19 associated variables. Five various ML methods were applied involving Linear Regression (LR), K-Nearest Neighbors (KNN), Random Forest (RF), Regression Tree (Rtree), and Support Vector Machine (SVM) and measured their performance employing critical accuracy metrics such as Mean Absolute Percentage Error (MAPE), Mean Squared Error (MSE), Mean Absolute Error (MAE), and R-squared (R 2 ). The outcomes discover that the RF model outperformed its equivalents realizing an R 2 of 0.91 with k = 5. These results conflict with a previous study that supported a negative impact of COVID-19 on improved stock markets. The visions from this study can assist investors in managing strategic investment decisions and assist policymakers in making measures to reduce the pandemic's effects on the stock market., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Carcinogenesis often involves significant alterations in the cancer genome architecture, marked by large structural and copy number variations (SVs and CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping and nanopore sequencing are attractive technologies that bridge this resolution gap and offer enhanced performance for cytogenetic applications. These methods profile native, individual DNA molecules, thus capturing epigenetic information. We applied both techniques to characterize a clear cell renal cell carcinoma (ccRCC) tumor's structural and copy number landscape, highlighting the relative strengths of each method in the context of variant size and average read length. Additionally, we assessed their utility for methylome and hydroxymethylome profiling, emphasizing differences in epigenetic analysis applicability., Competing Interests: The authors declare no competing interests.

Muscle fascicles are shorter and stiffer than normal in spastic Cerebral Palsy (CP). Increasing fascicle length (FL) has been attempted in CP, the outcomes of which have been unsatisfactory. In healthy muscles, FL can be increased using eccentric exercise at high velocities (ECC). Three conditions are possibly met during such ECC: muscle micro-damage, positive fascicle strain, and momentary muscle deactivation during lengthening. Participants with and without CP underwent a single bout of passive stretching at (appropriately) high velocities using isokinetic dynamometry, during which we examined muscle and fascicle behaviour. Vastus lateralis (VL) FL change was measured using ultrasonography and showed positive fascicle strain. Measures of muscle creatine kinase were used to establish whether micro-damage occurred in response to stretching, but the results did not confirm damage in either group. Vastus medialis (VM) and biceps femoris muscle activity were measured using electromyography in those with CP. Results supported momentary spastic muscle deactivation during lengthening: all participants experienced at least one epoch (60 ms) of increased activation followed by activation inhibition/deactivation of the VM during knee flexion. We argue that high-velocity passive stretching in CP provides a movement context which mimics ECC and could be used to increase spastic FL with training.

In various practical situations, the information about the process distribution is sometimes partially or completely unavailable. In these instances, practitioners prefer to use nonparametric charts as they don't restrict the assumption of normality or specific distribution. In this current article, a nonparametric double homogeneously weighted moving average control chart based on the Wilcoxon signed-rank statistic is developed for monitoring the location parameter of the process. The run-length profiles of the newly developed chart are obtained by using Monte Carlo simulations. Comparisons are made based on various performance metrics of run-length distribution among proposed and existing nonparametric counterparts charts. The extra quadratic loss is used to evaluate the overall performance of the proposed and existing charts. The newly developed scheme showed comparatively better results than its existing counterparts. For practical implementation of the suggested scheme, the real-world dataset related to the inside diameter of the automobile piston rings is also used., (© 2024. The Author(s).)

Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to counter iron deficiency anemia and neural tube anomalies. Although Iron Folic Acid supplementation is integral to Ethiopian antenatal care, one in four women in Ethiopia experiences anemia during pregnancy suggesting poor compliance. This study aimed to investigate compliance level and associated factors of Iron Folic Acid supplementation among pregnant women attending antenatal care in Wuchale Woreda of North Shoa Zone, Ethiopia. An institutional-based cross-sectional study was conducted among 302 pregnant women from March 20 to April 5, 2021, who were selected using a systematic random sampling technique. Data were collected through face-to-face interview, entered epi-data, and exported to Statistical Package for the Social Sciences for analysis. A multivariable logistic regression was used to identify factors associated with compliance level. All the results were presented with 95% confidence intervals. The compliance with Iron Folic Acid supplementation was 47.0%. Residing nearest to the health facility (AOR = 2.46; 95% CI 1.32, 4.57), initiating antenatal care at health center (AOR = 2.23; 95% CI 1.17, 4.51), having a family size of 4 and above (AOR = 4.99; 95% CI 2.43, 10.24), and receiving information from health extension workers (AOR = 5.52; 95% CI 1.30, 23.54) increased compliance with Iron Folic Acid supplementation. Less than half of the pregnant women were compliant with Iron Folic Acid utilization. There is a need to prioritize promoting the importance of Iron Folic Acid supplementation through health education particularly by targeting pregnant women with identified factors., (© 2024. The Author(s).)

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus. In this study, we investigated 17 affected individuals (8 males, 9 females) from 10 unrelated consanguineous families, 10 diagnosed with DMC and seven with SMC type 2. The mean age at diagnosis was 9.61 ± 9.72 years, ranging from 20 months to 34 years, and the average height at diagnosis was 92.85 ± 15.50 cm. All patients exhibited variable degrees of short trunk with a barrel chest, protruding abdomen, hyperlordosis, and decreased joint mobility. A total of nine different biallelic variants were identified, with six being located in the DYM gene and the remaining three detected in RAB33B. Notably, five variants were classified as novel, four in the DYM gene and one in the RAB33B gene. This study aims to comprehensively assess clinical, radiological, and molecular findings along with the long-term follow-up findings in 17 patients with DMC and SMC type 2. Our results suggest that clinical symptoms of the disorder typically appear from infancy to early childhood. The central notches of the vertebral bodies were identified as early as 20 months and tended to become rectangular, particularly around 15 years of age. Pseudoepiphysis was observed in five patients; we believe this finding should be taken into consideration when evaluating hand radiographs in clinical assessments. Furthermore, our research contributes to an enhanced understanding of clinical and molecular aspects in these rare "skeletal golgipathies," expanding the mutational spectrum and offering insights into long-term disease outcomes., (© 2024 Wiley Periodicals LLC.)

Phenolic compounds present in wastewater were utilized for first-principle calculations based on DFT to observe adsorption effects. Results indicate that bismuthene exhibits different adsorption characteristics for different compounds. Following the adsorption process, the aromatic ring remains in the same plane, while CH 3 and OH groups move upward, causing slight changes in the molecules' overall position. The calculated results show that bisphenol A has the least atomic distance (4.00 Å) from the bismuthene surface and the highest adsorption energy value (12.8509 eV), indicating the stability and smoothness of the adsorption process. The electronic properties results reveal that phenolic compounds exhibit overlapping peaks at a distance from the Fermi level, describing the stability of the adsorption system. Additionally, the charge transfer results mirror the adsorption energy calculation results, showing that the bisphenol A adsorption system accepts a greater amount of (-0.116 e ) charge from the bismuthene surface, demonstrating a strong adsorption effect., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.

In recent years, a cancer research trend has shifted towards identifying novel therapeutic compounds from natural assets for the management of cancer. In this study, we aimed to assess the cytotoxic activity of Kigelia Africana (KA) extracts on breast cancer (MDA-MB-231 and MCF-7) and noncancerous kidney cells (HEK-293T) to develop an efficient anticancer medication. We used gas chromatography mass spectrometry (GC-MS to analyze the constituents of EKA and HKA extracts meanwhile the crystal violet and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used to examine the possible cytotoxic effects of plant extracts on our cancer cell lines along with non-cancerous control. The quantitative real-time PCR (RT-PCR) was run on cell samples to evaluate the differential expression of cell proliferative markers of cancer (BCL-2 and TP53). These phytochemicals have been reported to have binding affinity for some other growth factors and receptors as well which was evaluated by the in-silico molecular docking against Bcl2, EGFR, HER2, and TP53. Our Morphological observation showed a significant difference in the cell morphology and proliferation potential which was decreased under the effect of plant extracts treatment as compared to the control samples. The ethanol extract exhibited a marked antiproliferative activity towards MDA-MB-231 and MCF-7 cell lines with IC50 = 20 and 32 μg/mL, respectively. Quantitative RT-PCR gene expression investigation revealed that the IC50 concentration of ethanolic extract regulated the levels of mRNA expression of apoptotic genes. With the target and active binding site amino acids discovered in the molecular docking investigation, TP53/Propanoic acid, 3-(2, 3, 6-trimethyl-1, 4-dioxaspiro [4.4] non-7-yl)-, methyl ester (-7.1 kcal/mol) is the best-docked ligand. The use of this plant in folk remedies justifies its high in vitro anti-cancer capabilities. This work highlights the role of phytochemicals in the inhibition of cancer proliferation. Based on all these findings, it can be concluded that EKA extract has promising anti-proliferative effect on cancerous cells but more study is required in future to further narrow down the active ingredients of total crude extract with specific targets in cancer cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kalsoom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bone infections caused by Staphylococcus aureus may lead to an inflammatory condition called osteomyelitis, which results in progressive bone loss. Biofilm formation, intracellular survival, and the ability of S. aureus to evade the immune response result in recurrent and persistent infections that present significant challenges in treating osteomyelitis. Moreover, people with diabetes are prone to osteomyelitis due to their compromised immune system, and in life-threatening cases, this may lead to amputation of the affected limbs. In most cases, bone infections are localized; thus, early detection and targeted therapy may prove fruitful in treating S. aureus-related bone infections and preventing the spread of the infection. Specific S. aureus components or overexpressed tissue biomarkers in bone infections could be targeted to deliver active therapeutics, thereby reducing drug dosage and systemic toxicity. Compounds like peptides and antibodies can specifically bind to S. aureus or overexpressed disease markers and combining these with therapeutics or imaging agents can facilitate targeted delivery to the site of infection. The effectiveness of photodynamic therapy and hyperthermia therapy can be increased by the addition of targeting molecules to these therapies enabling site-specific therapy delivery. Strategies like host-directed therapy focus on modulating the host immune mechanisms or signaling pathways utilized by S. aureus for therapeutic efficacy. Targeted therapeutic strategies in conjunction with standard surgical care could be potential treatment strategies for S. aureus-associated osteomyelitis to overcome antibiotic resistance and disease recurrence. This review paper presents information about the targeting strategies and agents for the therapy and diagnostic imaging of S. aureus bone infections., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The facilegreen synthesis techniqueis becoming more and more important, and it has been proposed as a potential substitute for chemical techniques. The current study describes a low-cost, environmentally friendly method for producing tungsten trioxide (WO 3 ) and tantalum (Ta) doped WO 3 nanoparticles that uses 15 % (w/v) Azadirachta indica (Neem) leaf extract and different concentrations of Ta dopant (1 to 5 %) due to its well-matched ionic radius with WO 3 . Various techniques FESEM, TEM, EDX, BET, UV-Vis and PL, XRD, and FTIR were used to illustrate the morphological, elemental, optical, structural, and vibrational analysis of the synthesized nanoparticles respectively. Interestingly, the band gap was significantly reduced to 1.88 eV by the addition of a dopant element. For 3 % Ta/WO 3 , the average particle size was also reduced to 31.6 nm. The synthesized WO 3 nanoparticles employed in the current study have been used for photocatalytic activitypurposes. Methylene blue (MB), one of the principal water pollutants, was degraded more quickly by the synthesized Ta/WO 3 nanoparticles when exposed to UV radiation. Among them, 3 % Ta/WO 3 gives significantly higher photodegradation 89 % attributed to the Burstein-Moss effect. The significant output of optimized nano-photocatalyst has been observed from the trapping experiment and reusability test. Furthermore, Zeta potential and TOC analysis have been taken to check the stability and mineralization performance. Additionally, the results of the simulation that was carried out using the finite element analysis approach in the RF module of COMSOL Multiphysics 5.3a are quite similar to the experimental findings. This simulation method made it easier for readers to understand the numerous aspects of the photocatalytic process that has been discussed here., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients with targeted next-generation sequencing (NGS)., Method: In patients with OI, a targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform., Results: Fifty-six patients (female/male: 25/31) from 46 different families were enrolled in the study. Consanguinity between parents was noted in 15 (32.6%) families. Clinically according to Sillence classification; 18(33.1%) patients were considered to type I, 1(1.7%) type II, 26(46.4%) type III and 11(19.6%) type IV. Median body weight was -1.1 (-6.8, - 2.5) SDS, and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity was detected in 30 (53.5%) of the patients, while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) patients had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 genes were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes (FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected in all investigated genes were not previously reported in the literature and were classified to be pathogenic according to ACMG guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in a total of 13 OI genes included in the panel., Conclusion: Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. In addition, 9 new variants were assessed in known OI genes which is a significant contribution to the literature.

The subject matter of surfaces in computer aided geometric design (CAGD) is the depiction and design of surfaces in the computer graphics arena. Due to their geometric features, modeling of Bézier curves and surfaces with their shape parameters is the most well-liked topic of research in CAGD/computer-aided manufacturing (CAM). The primary challenges in industries such as automotive, shipbuilding, and aerospace are the design of complex surfaces. In order to address this issue, the continuity constraints between surfaces are utilized to generate complex surfaces. The parametric and geometric continuities are the two metrics commonly used for establishing connections among surfaces. This paper proposes continuity constraints between two generalized Bézier-like surfaces (gBS) with different shape parameters to address the issue of modeling and designing surfaces. Initially, the generalized form of C3 and G3 of generalized Bézier-like curves (gBC) are developed. To check the validity of these constraints, some numerical examples are also analyzed with graphical representations. Furthermore, for a continuous connection among these gBS, the necessary and sufficient G1 and G2 continuity constraints are also developed. It is shown through the use of several geometric designs of gBS that the recommended basis can resolve the shape and position adjustment problems associated with Bézier surfaces more effectively than any other basis. As a result, the proposed scheme not only incorporates all of the geometric features of curve design schemes but also improves upon their faults, which are typically encountered in engineering. Mainly, by changing the values of shape parameters, we can alter the shape of the curve by our choice which is not present in the standard Bézier model. This is the main drawback of traditional Bézier model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ameer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Metformin protects against age-related muscle decline, termed sarcopenia. However, the effects on sarcopenia quality-of-life (SarQoL) are unknown. We investigated the effects of metformin on SarQoL and associated mechanisms in older adults., Method: This double-blind randomized, placebo-controlled trial included geriatric adult men, divided into non-sarcopenic controls (age = 72.2 ± 4.3 years, n = 52) and two groups of patients with sarcopenia randomized into placebo (age at baseline = 74.4 ± 5.7 years, n = 54) and metformin (age at baseline = 71.2 ± 3.9 years, n = 47) groups. Patients in the metformin group received 1.7 grams twice daily for four months. We evaluated SarQoL, handgrip strength (HGS), plasma zonulin, c-reactive protein (CRP), and 8-isoprostanes., Results: Patients with sarcopenia had lower HGS and SarQoL than controls (both p <0.05). Metformin improved the HGS and the SarQoL domains related to physical and mental health, locomotion, and leisure activities, as well as cumulative SarQoL scores (all p <0.05). Metformin also prevented the decline in the SarQoL domains for functionality and fear. Among plasma biomarkers, metformin reduced the levels of zonulin, CRP, 8-isoprostanes, and creatine kinase. We also found a significant correlation of plasma zonulin with cumulative SarQoL in patients with sarcopenia taking metformin, suggesting a role for intestinal repair in improving SarQoL. Finally, metformin did not affect body composition and gait speed., Conclusion: Overall, metformin improved HGS and SarQoL by repairing intestinal leakage. Our data have clinical relevance for improving the quality of life in older adults with sarcopenia., (Copyright © 2024. Published by Elsevier Inc.)

Brassicaceae sprouts are promising candidates for functional food because of their unique phytochemistry and high nutrient density compared to their seeds and matured vegetables. Despite being admired for their health-promoting properties, white cabbage sprouts have been least explored for their nutritional significance and behavior to lactic acid fermentation. This study aimed to investigate the role of lactic acid fermentation, i.e., inoculum vs. spontaneous, in reducing intrinsic toxicants load and improving nutrients delivering potential of the white cabbage sprouts. White cabbage sprouts with a 5-7 cm average size were processed as raw, blanched, Lactiplantibacillus plantarum-inoculated fermentation, and spontaneous fermentation. Plant material was dehydrated at 40 °C and evaluated for microbiological quality, macronutrients, minerals, and anti-nutrient contents. The results indicate L. plantarum inoculum fermentation of blanched cabbage sprouts (IF-BCS) to increase lactic acid bacteria count of the sprouts from 0.97 to 8.47 log CFU/g. Compared with the raw cabbage sprouts (RCS), inoculum fermented-raw cabbage sprouts (IF-RCS), and spontaneous fermented-raw cabbage sprouts (SF-RCS), the highest content of Ca (447 mg/100 g d.w.), Mg (204 mg/100 g d.w.), Fe (9.3 mg/100 g d.w.), Zn (5 mg/100 g d.w.), and Cu (0.5 mg/100 g d.w.) were recorded in IF-BCS. L. plantarum-led fermentation of BCS demonstrated a reduction in phytates, tannins, and oxalates contents at a rate of 42%, 66%, and 53%, respectively, while standalone lactic acid fermentation of the raw sprouts reduced the burden of anti-nutrients in a range between 32 and 56%. The results suggest L. plantarum-led lactic acid fermentation coupled with sprout blanching is the most promising way to improve the nutritional quality and safety of the white cabbage sprouts., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A novel family of multifunctional nanomaterials called MXenes is quickly evolving, and it has potential applications that are comparable to those of graphene. This article provides a current explanation of the design and performance assessment of MXene-based membranes. The production of MXenes nanosheets are first described, with an emphasis on exfoliation, dispersion stability, and processability, which are essential elements for membrane construction. Further, critical discussion is also given to MXenes potential applications in Vacuum assisted filtration, casting method, Hot press method, electrospinning and electrochemical deposition and layer-by-layer assembly for the creation of MXene and MXene derived nanocomposite membranes. Additionally, the discussion is carried forward to give an insight to the modification methods for the construction of MXene-based membrane are described in the literature, including pure or intercalated nanomaterials, surface modifiers and miscellaneous two-dimensional nanomaterials. Furthermore, the review article highlights the potential utilization of MXene and MXene based membranes in separation and purification processes including removal of small organic molecules, heavy metals, oil-water separation and desalination. Finally, the perspective use of MXenes strong catalytic activity and electrical conductivity for specialized applications that are difficult for other nanomaterials to accomplish are discussed in conclusion and future prospectus section of the manuscript. Overall, important information is given to help the communities of materials science and membranes to better understand the potential of MXenes for creating cutting-edge separation and purification membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To assess if limiting elective surgeries during specific pandemic phases significantly affected COVID-19 incidence among operating room (OR) staff., Study Design: Retrospective cohort study. Place and Duration of the Study: Operation Theatre (OT), The Aga Khan University Hospital, Karachi, Pakistan, from May 2020 to 2021., Methodology: This retrospective study compared two pandemic waves: Wave 1, during which elective surgeries were restricted (REL), and Wave 2, during which elective surgeries were continued routinely (EL). Exposure levels were measured based on OR activity. Incidence rates were calculated per 100 OR staff, per 100 ORs, and per 100 surgeries for both Groups., Results: No statistically significant difference emerged in COVID-19 incidence among OR staff between REL (13.8 per 100 staff) and EL (14.4 per 100 staff) Groups (p = 0.825). However, the EL Group exhibited a significantly lower incidence risk per running OR (5.6 per 100 ORs vs. REL's 12 per 100 ORs, p <0.001). Additionally, the EL Group showed a lower incidence per 100 surgeries (1.5 vs. REL's 2.9, p <0.002)., Conclusion: Restricting elective surgeries during the early pandemic phase did not significantly reduce COVID-19 incidence among OR staff. Infections were primarily linked to interactions with colleagues and the community, emphasising the need for a balanced pandemic response considering patient care and the consequences of surgery restrictions., Key Words: COVID-19 infection, Operating room staff, COVID-19 waves, COVID-19 transmission, Hospital epidemiology, Pandemic response.

Hearing loss (HL) is a heterogenous trait with pathogenic variants in more than 200 genes that have been discovered in studies involving small and large HL families. Over one-third of families with hereditary HL remain etiologically undiagnosed after screening for mutations in the recognized genes. Genetic heterogeneity complicates the analysis in multiplex families where variants in more than one gene can be causal in different individuals even in the same sibship. We employed exome or genome sequencing in at least two affected individuals with congenital or prelingual-onset, severe to profound, non-syndromic, bilateral sensorineural HL from four multiplex families. Bioinformatic analysis was performed to identify variants in known and candidate deafness genes. Our results show that in these four families, variants in a single HL gene do not explain HL in all affected family members, and variants in another known or candidate HL gene were detected to clarify HL in the entire family. We also present a variant in TOGARAM2 as a potential cause underlying autosomal recessive non-syndromic HL by showing its presence in a family with HL, its expression in the cochlea and the localization of the protein to cochlear hair cells. Conclusively, analyzing all affected family members separately can serve as a good source for the identification of variants in known and novel candidate genes for HL., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Left ventricular assist device (LVAD) systems are preferred as a bridging to transplantation or as a destination therapy in the treatment of end-stage heart failure. LVAD-related complications are seen in different clinical variations with the widespread use of LVADs. Some of these complications are seen as related to outflow graft, such as graft stenosis, graft kinking and graft thrombosis. Outflow graft complications have a direct impact on LVAD flow rate and acutely impair the clinical condition of patients. Treatment modalities include surgical approach, endovascular approach, and medical approach. In this case report, we aim to share a 57-year-old male patient, who had outflow graft stenosis near the anastomosis line between ascending aorta and the left ventricular assist device outflow graft, and the endovascular treatment., (© 2023. The Japanese Society for Artificial Organs.)

The dairy industry is reshaping itself and becoming commercialized in Pakistan due to the increased demand for milk to overcome the shortage. Exotic breeds such as Holstein Friesian, a high milk producing breed have started being reared more on farms in Pakistan. Along with other issues, mastitis does affects the milk production of this breed. The objective of this study was to evaluate the milk composition in terms of bacterial communities in Holstein Friesian reared in Punjab, Pakistan and alteration in microbial composition with healthy and mastitic udder. Milk samples (n = 36) from farms rearing Holstein Friesian were collected. Among these samples, 05 samples from each three groups, HHF(healthy), CHF (clinical mastitis) and SHF (subclinical mastitis), based on their udder health condition, were processed using the 16 S r=RNA gene based technique. Diversity assessment as carried out by alpha diversity indices showed that milk samples from the udder infected with clinical mastitis were the least diverse and those from the healthy udder were more diverse. Beta diversity across samples showed a scattered pattern suggesting overlap amongst bacterial communities across different groups samples as depicted by PCA plots of beta diversity indices. The taxonomic profile revealed that Proteobacteria Firmicutes, Bacteroidota and Actinobacteriota were the major phyla detected across all groups. Proteobacteria dominated the HHF and SHF group while abundance of Firmicutes was higher in CHF group. Differences at other levels including order, genus and species were also recorded. The overall picture concludes that diverse microbiota is associated with different udder health conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Obstructive sleep apnea (OSA) is an increasingly relevant cause of cardiovascular morbidity worldwide. Although the association between OSA and the cardiovascular system is well-known, the extent of its effects is still a topic of interest, including pathophysiologic mechanisms, cardiovascular sequelae, and OSA therapies and their effects. Commonly described mechanisms of cardiovascular etiologies revolve around sympathetic activation, inflammation, and intermittent hypoxia resulting from OSA. Ultimately, these effects lead to manifestations in the cardiovascular system, such as arrhythmias, hypertension, and heart failure, among others. The resulting sequelae of OSA may also have differential effects based on gender and age; several studies suggest female gender to have more susceptibility to cardiovascular mortality, as well as an increase in age. Furthermore, several therapies for OSA, both established and emerging, show a reduction in cardiovascular morbidity and may even reduce cardiovascular burden. Namely, the establishment of CPAP has led to improvement in hypertension and cardiac function in patients with heart failure and even reduced the progression of early stages of atherosclerosis. Effective management of OSA decreases abnormal neural sympathetic activity, which results in better rhythm control and blood pressure control, both in waking and sleep cycles. With newer therapies for OSA, its effects on the cardiovascular system may be significantly reduced or even reversed after long-term management. The vast extent of OSA on the cardiovascular system, as well as current and future therapeutic strategies, will be described in detail in this review.

In recent days researchers have tried to handle the maximum information and use those techniques and methods in which there is no chance of data loss or loss of information is minimum. The structure like fuzzy set and complex fussy set cannot discuss the upper and lower approximations. Moreover, we can observe that a fuzzy rough set cannot discuss the second dimension and in this case, there is a chance of data loss. To cover all these issues in previous ideas, the notion of a complex fuzzy rough set in Cartesian form is the demand of the day because this structure can discuss the second dimension as well as upper and lower approximations. For this purpose, in this manuscript, we have developed the theory of complex fuzzy relation and complex fuzzy rough set in Cartesian form. Moreover, we have initiated the fundamental laws for complex fuzzy rough numbers based on Frank t-norm and t-conorm. The fundamental tools that can convert the overall input into a single output are called aggregation operators (AOs). So based on the characteristics of AOs, we have defined the notion of complex fuzzy rough Frank average and complex fuzzy rough Frank geometric AOs. The utilization of the developed theory is necessary to show the importance and validity of the delivered approach. So based on developed notions, we have defined an algorithm for this purpose along with an illustrative example. We have utilized the introduced structure for the classification of AI tools for civil engineering. Moreover, the comparative analysis of the delivered approach shows the advancement of the introduced structure as compared to existing notions., (© 2024. The Author(s).)

In this manuscript we demonstrate interval-valued bipolar complex fuzzy set (IVBCFS) and then interval-valued bipolar complex fuzzy soft set (IVBCFSS), as a generalization of fuzzy set, interval-valued fuzzy set, bipolar fuzzy set, complex fuzzy set and soft set. We also initiate operational laws and basic results and properties for IVBCFS and IVBCFSS. Further explanation is given for the basic algebraic operations like complement, extended union, extended intersection, restricted union, and restricted intersection, AND product and OR product for IVBCFSS. Moreover, we demonstrate some fundamental aggregation operators like IVBCFS average aggregation, IVBCFS geometric and as well as their properties. To emphasize the usefulness and application of the system, we also develop the decision-making method and joint instances of the IVBCFSS (set-ups 1 and 2). In order to describe the effectiveness and influence of the approaching novel work, this study uses a comparative analysis of the new creating concept with prevailing ideas., (© 2024. The Author(s).)

Supplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines., Competing Interests: A.F.S. is listed as co-inventor on a patent application covering the AP205 cVLP vaccine platform technology (WO2016112921 A1) and is an employee, founder, and shareholder of AdaptVac, a company commercializing cVLP technology.

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings., (© 2024. The Author(s).)

The time fractional Schrödinger equation contributes to our understanding of complex quantum systems, anomalous diffusion processes, and the application of fractional calculus in physics and cubic B-spline is a versatile tool in numerical analysis and computer graphics. This paper introduces a numerical method for solving the time fractional Schrödinger equation using B-spline functions and the Atangana-Baleanu fractional derivative. The proposed method employs a finite difference scheme to discretize the fractional derivative in time, while a θ-weighted scheme is used to discretize the space directions. The efficiency of the method is demonstrated through numerical results, and error norms are examined at various values of the non-integer parameter, temporal directions, and spatial directions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mubashir Hayat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bovine mastitis is a widespread and costly disease that affects dairy farming globally, characterized by mammary gland inflammation. Bovine intramammary gland infection has been associated with more than 135 different pathogens of which Staphylococcus aureus is the main etiology of sub-clinical mastitis (SCM). The current study was designed to investigate the prevalence, antibiotic resistance pattern, and the presence of antibiotic resistance genes (mecA, tetK, aacA-aphD and blaZ) in S. aureus isolated from the raw milk of cows with subclinical mastitis. A total of 543 milk samples were collected from lactating cows such as Holstein Friesian (n = 79), Sahiwal (n = 175), Cholistani (n = 107), and Red Sindhi (n = 182) from different dairy farms in Pakistan. From the milk samples microscopic slides were prepared and the somatic cell count was assessed to find SCM. To isolate and identify S. aureus, milk was streaked on mannitol salt agar (MSA) plates. Further confirmation was done based on biochemical assays, including gram staining (+ coccus), catalase test (+), and coagulase test (+). All the biochemically confirmed S. aureus isolates were molecularly identified using the thermonuclease (nuc) gene. The antibiotic resistance pattern of all the S. aureus isolates was evaluated through the disc diffusion method. Out of 543 milk samples, 310 (57.09%) were positive for SCM. Among the SCM-positive samples, S. aureus was detected in 30.32% (94/310) samples. Out of 94 isolates, 47 (50%) were determined to be multidrug resistant (MDR). Among these MDR isolates, 11 exhibited resistance to Cefoxitin, and hence were classified as methicillin-resistant Staphylococcus aureus (MRSA). The S. aureus isolates showed the highest resistance to Lincomycin (84.04%) followed by Ampicillin (45.74%), while the least resistance was shown to Sulfamethoxazole/Trimethoprim (3.19%) and Gentamycin (6.38%). Polymerase chain reaction (PCR) analysis revealed that 55.31% of the isolates carried blaZ gene, 46.80% carried tetK gene, 17.02% harbored the mecA gene, whereas, aacA-aphD gene was found in 13.82% samples. Our findings revealed a significant level of contamination of milk with S. aureus and half (50%) of the isolates were MDR. The isolated S. aureus harbored various antibiotic resistance genes responsible for the absorbed phenotypic resistance. The alarmingly high prevalence of MDR S. aureus isolates and MRSA strains in these cases possess a serious risk to public health, emphasizes the urgent need to address this issue to protect both human and animal health in Pakistan., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Temporomandibular joint disorder (TMD) is a common condition affecting the masticatory muscles and joint mobility., Objectives: The primary objective was to compare the effects of massage therapy alone and massage therapy combined with post-isometric relaxation exercises in patients with TMD for pain and maximal mouth opening., Design: Assessor-blinded randomized controlled trial., Setting: Sir Ganga Ram Hospital, Chaudhry Muhammad Akram Dental Hospital, Lahore Medical and Dental Hospital., Subjects: Temporomandibular joint disorder patients., Intervention: Group A (n = 23) received conventional treatment including massage and therapeutic exercises consecutively for 2 weeks. Group B (n = 23) received post-isometric relaxation technique along with conventional treatment for consecutive 2 weeks., Main Measures: The main outcome measures were pain and maximal mouth opening. Pain was measured using the Visual Analogue Scale (VAS) and maximal mouth opening (MMO) was measured using the TheraBite Scale., Results: Both groups demonstrated significant improvements in pain and MMO scores post-treatment. However, Group B (massage with post-isometric relaxation exercises) showed significantly better outcomes compared to Group A (massage alone). There was a statistically significant difference in post-treatment pain scores (P = 0.000) and MMO scores (P = 0.000) between the two groups., Conclusion: The results suggest that massage therapy combined with post-isometric relaxation is more effective than massage therapy alone in managing pain and improving mouth opening in TMD patients. The study provides evidence supporting the use of these therapies in TMD management., Trial Registry Number: NCT05810831. Date of registration/First submission: 15 March 2023., (© 2024. The Author(s).)

Precise insertion of fluorescent proteins into lineage-specific genes in human pluripotent stem cells (hPSCs) presents challenges due to low knockin efficiency and difficulties in isolating targeted cells. To overcome these hurdles, we present the modified mRNA (ModRNA)-based Activation for Gene Insertion and Knockin (MAGIK) method. MAGIK operates in two steps: first, it uses a Cas9-2A-p53DD modRNA with a mini-donor plasmid (without a drug selection cassette) to significantly enhance efficiency. Second, a deactivated Cas9 activator modRNA and a 'dead' guide RNA are used to temporarily activate the targeted gene, allowing for live cell sorting of targeted cells. Consequently, MAGIK eliminates the need for drug selection cassettes or labor-intensive single-cell colony screening, expediting precise gene editing. We showed MAGIK can be utilized to insert fluorescent proteins into various genes, including SOX17, NKX6.1, NKX2.5, and PDX1, across multiple hPSC lines. This underscores its robust performance and offers a promising solution for achieving knockin in hPSCs within a significantly shortened time frame., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome., Methods: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed., Findings: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups., Interpretation: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone., Funding: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GWS reports speaker fees from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott, Amgen, and Boehringer Ingelheim; has served as a consultant to Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, and Oxitope; has equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave paid directly to institution; and his daughter is an employee at IQVIA. S-LC reports speaker fees from Microport, Pulnovo, Boston International Scientific, Medtronic, Sanofi, and BioMed; and grants from the National Scientific Foundation of China. GSM received honorarium from Boston Scientific. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The link between neuroinflammation and depression is a subject of growing interest in neuroscience and psychiatry; meanwhile, the precise mechanisms are still being unrevealed. However, glial cell activation, together with cytokine level elevation, suggests a connection between neuroinflammation and the development or exacerbation of depression. Glial cells (astrocytes) communicate with neurons via their extracellular neurotransmitter receptors, including glutamate receptors NMDARs. However, these receptor roles are controversial and enigmatic in neurological disorders, including depression. Therefore, we hypothesized whether NMDAR subnit NR2C deletion in the astrocytes exhibited anti-depressive effects concurrent with neuroinflammation prevention. To assess, we prepared astrocytic-NR2C knockout mice (G-2C: GFAP Cre+ Grin2C flox/flox ), followed by LPS administration, behavior tests, and biochemical analysis. Stimulatingly, astrocytic-NR2C knockout mice (G-2C) did not display depressive-like behaviors, neuroinflammation, and synaptic deficits upon LPS treatment. PI3K was impaired upon LPS administration in control mice (Grin2C flox/flox ); however, they were intact in the hippocampus of LPS-treated G-2C mice. Further, PI3K activation (via PTEN inhibition by BPV) restored neuroinflammation and depressive-like behavior, accompanied by altered synaptic protein and spine numbers in G-2C mice in the presence of LPS. In addition, NF-κB and JNK inhibitor (BAY, SP600125) treatments reversed the effects of BPV. Moreover, these results were further validated with an NR2C antagonist DQP-1105. Collectively, these observations support the astrocytic-NR2C contribution to LPS-induced neuroinflammation, depression, and synaptic deficits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of rural clean energy is the key to cope with the shortage of traditional energy supply in the rural revitalization strategy and improve the sustainability of rural energy supply. Under the background of digital age, the development and utilization of rural clean energy Internet has become the focus of rural economic development. The government partners of the Rural clean Energy Internet PPP project (RCEIPPPP) are the key to promoting the green and intelligent development of rural energy. In this paper, the index system of project partner selection is constructed, and the problem of government partner selection for RCEIPPPP is studied by AHP and fuzzy comprehensive evaluation. The results of this study are as follows: 1) Partners' financial ability, technical ability, management ability, performance experience, corporate reputation, cooperation ability and risk management are the influencing factors for government partner selection of rural clean energy Internet PPP projects (RCEIPPPPs); 2) Compared with other factors, financial ability, technical ability, management ability and performance experience are the four key factors that are more important in choosing partners; 3) The empirical research shows that AHP, fuzzy comprehensive evaluation and the index system constructed by this research can be applied to the practice of government partner selection for RCEIPPPPs. This study puts forward the evaluation system of government cooperation selection of energy Internet PPP projects from the theoretical level, improves the existing research methods, and makes the theoretical system in this field more complete. From the practical level, it provides scientific basis and suggestions for the government to make decisions on energy Internet PPP projects, and improves the engineering efficiency and quality of rural clean energy Internet construction. This study demonstrates the complexity of clean energy projects, the need for an integrated approach to decision-making, and the need for project managers to actively manage communication and collaboration with partners to ensure successful project implementation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Bayesian Control charts are emerging as the most efficient statistical tools for monitoring manufacturing processes and providing effective control over process variability. The Bayesian approach is particularly suitable for addressing parametric uncertainty in the manufacturing industry. In this study, we determine the monitoring threshold for the shape parameter of the Inverse Gaussian distribution (IGD) and design different exponentially-weighted-moving-average (EWMA) control charts based on different loss functions (LFs). The impact of hyperparameters is investigated on Bayes estimates (BEs) and posterior risks (PRs). The performance measures such as average run length (ARL), standard deviation of run length (SDRL), and median of run length (MRL) are employed to evaluate the suggested approach. The designed Bayesian charts are evaluated for different settings of smoothing constant of the EWMA chart, different sample sizes, and pre-specified false alarm rates. The simulative study demonstrates the effectiveness of the suggested Bayesian method-based EWMA charts as compared to the conventional classical setup-based EWMA charts. The proposed techniques of EWMA charts are highly efficient in detecting shifts in the shape parameter and outperform their classical counterpart in detecting faults quickly. The proposed technique is also applied to real-data case studies from the aerospace manufacturing industry. The quality characteristic of interest was selected as the monthly industrial production index of aircraft from January 1980 to December 2022. The real-data-based findings also validate the conclusions based on the simulative results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Javed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The classification of locally rotationally symmetric Bianchi type V spacetime based on its killing vector fields is presented in this paper using an algebraic method. In this approach, a Maple algorithm is employed to transform the Killing's equations into a reduced evolutive form. Subsequently, the integration of the Killing's equations is carried out subject to the constraints provided by the algorithm. The algorithm demonstrates that there exist fifteen distinct metrics that could potentially possess Killing vector fields. Upon solving the Killing equations for all fifteen metrics, it is observed that seven out of the fifteen metrics exclusively exhibit the minimum number of Killing vector fields. The remaining eight metrics admit a varying number of Killing vector fields, specifically 6, 7, or 10. The Kretschmann scalar has been computed for each of the obtained metrics, revealing that all of them possess a finite Kretschmann scalar and thus exhibit regular behavior., (© 2024. The Author(s).)

Objective: To determine trend of following medical advice and safety of high-risk diabetic patients during Ramadan practicing updated IDF DAR guidelines., Methods: The cross-sectional study was conducted at Outpatient Department of Diabetes, Endocrinology and Metabolic Disorders Hayatabad Medical Complex Peshawar, Pakistan from April to June 2022, and comprised of high-risk diabetic patients (>6.0) based on updated IDF-DAR guidelines 2022 intending to fast. A questionnaire was designed to document patient risk factors score, type and duration of diabetes, HbA1c, comorbidities and complications developed during Ramadan. Data was analyzed using SPSS 20., Results: Among all 130 participants, 78(60%) followed medical advice and did not fast and 52(40%) patients fasted against medical advice during month of Ramadan. Out of 130 participants, 89.2% were having type-2 diabetes Mellitus, 55.4% were female and mean age of participants was 52+14.6.40%. In fasting group, 57.7% were in the age range of 16 to 50 years while in non-fasting group 69.2% participants were more than 50 years old (P-value 0.031). There were 80.8% female participants in fasting group versus 38.5% in non-fasting group (P-value 0.001). Hypoglycemia occurred in 58.3% patients in fasting group and 29.3% non-fasting group. (P-value 0.021). On the other hand, 27.8% patients in fasting group and 55.2% of non-fasting group had hyperglycemia (P-value 0.025)., Conclusion: Despite advised against fasting in these high-risk patients as per IDF DAR guidelines, almost half of patients fasted considering fasting a religious obligation. Those who fasted had significant hypoglycemia despite adjustment of medications as in guidelines. There is need of more intensive education before fasting, especially in high-risk diabetic patients., Competing Interests: Conflict of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Healthcare workers increasingly use Electronic Health Information Resources (EHIRs) to make evidence-based decisions. Our study was intended to assess the perception, attitude, and practice of healthcare professionals in medicine, pharmacy, and nursing regarding their perceived value and use of EHIRs., Methods: We conducted an observational cross-sectional study using a pre-validated questionnaire among healthcare professionals in Jazan province from September 2022 to February 2023. We included healthcare professionals and interns with medical, pharmacy, or nursing degrees and excluded those who refused informed consent., Results: We included fully completed data from 294 participants, with an actual response rate of just 80.1 %. Almost 87.41 % utilized the health information resources at their workplace, with UpToDate [39.45 %] and Medscape [67.01 %] being the most frequently used medical databases. The health facilities' access to electronic health resources significantly impacted healthcare professionals' [p = 0.04] and medical interns' [p = 0.02] roles. Faculty members felt the need to access electronic health information at their workplace [p = 0.00]. Lack of time to access electronic health information due to a busy schedule was a significant reason that impacted the attitude of medical professionals [p = 0.008] and nursing staff [p = 0.025]. An excessive amount of clinically unrelated data was the primary obstacle (181/294, p < 0.0001) in using electronic health information resources., Conclusion: Our study showed the pattern of healthcare professionals using EHIRs in the Jazan province, Saudi Arabia. We believe the study's outcome can help increase the calibre of electronic health information services available to healthcare professionals and raise awareness of different EHIRs in improving clinical care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Purpose/background: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown., Methods/procedures: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone., Findings/results: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores., Implications/conclusions: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Statins medications negatively affect age-associated loss of muscle mass and strength, termed sarcopenia, and neuromuscular junction (NMJ) integrity. However, their association with the sarcopenia-related-quality-of-life (SarQoL) is unknown., Methods: In this cross-sectional, case control study, we recruited male nonusers (n = 75 and age 75.2 ± 5.9 years) and users (n = 77 and age 77.1 ± 6.2 years) of statins to evaluate SarQoL and handgrip strength (HGS). We also measured plasma C-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation., Results: Statin users had higher CAF22, and lower HGS, and cumulative SarQoL scores than non-users (all p < 0.05). Plasma CAF22 exhibited negative correlations with SarQoL scores for physical and mental health, locomotion, functionality, activities-of-daily-living, and cumulative SarQoL in statins users and non-users (all p < 0.05). Lastly, the cumulative SarQoL scores exhibited positive associations with HGS and gait speed in the study participants (all p < 0.05)., Conclusions: Collectively, statin usage was associated with NMJ degradation and reduced SarQoL. Statins should be cautiously prescribed in patients with sarcopenia with reduced QoL., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A 78-year-old male patient with a history of coronary artery disease (he had undergone coronary artery bypass surgery 4 years ago), heart failure with mildly reduced ejection fraction, diabetes mellitus, and transient ischemic attack presented to the emergency department with complaints of dyspnea (New York Heart Association Class 4) despite the optimal medical therapy.