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Qudsia Tabassam,1 Tahir Mehmood,1,2 Abdul Rauf Raza,1 Azmat Ullah,3 Farhan Saeed,4 Faqir Muhammad Anjum5 1Department of Chemistry, University of Sargodha, Sargodha, Pakistan; 2Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences-UVAS, Lahore, Pakistan; 3Department of Food Science and Human Nutrition, University of Veterinary and Animal Sciences-UVAS, Lahore, Pakistan; 4Institute of Home & Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 5Vice Chancellor Secretariat, University of the Gambia, Banjul, The GambiaCorrespondence: Tahir Mehmood; Faqir Muhammad Anjum Email tahir.mehmoodbiochem@uvas.edu.pk; dranjum@utg.edu.gmBackground: Nanotechnology is gaining emerging interest in advanced drug discovery therapeutics due to their tremendous properties including enhanced delivery of therapeutic payload, extensive surface to volume ratio, high permeability, retention behaviors, etc. The gold nanoparticles (AuNPs) are favored due to their advanced features, such as biogenic, tunable physiochemical response, ease in synthesis, and wide range of biomedical applications. The phytochemicals have been focused to design Au nano-carrier-based conjugation for active-targeting drug delivery due to their nano conjugation ability.Aim: The present study describes the facile synthesis of 20nm spherical AuNPs and their conjugation with reported anti-cancer phytocompound Withanolide-A (1).Methods: The 20nm sAuNPs were synthesized chemically and characterized their phytochemical gold nanoconjugates through UV-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging techniques. The anti-cancer therapeutic potentials were tested with both nanoconjugates and pure WithanolideA (1) by using SKBR3 breast cancer cells line.Results: The synthesized sAuNPs showed significant conjugation with Withanolide-A and showed stability. Furthermore, these Au nanoconjugates with Withanolide-A (1) significantly induce blockage of SKBR3 cell growth at half maximal active concentration that compared to pure Withanolide-A (1).Conclusion: Our findings provide a foundation to further progress how they can overcome cancer drug resistance by conjugating active drugs in combination with AuNPs through optimizing the effective drug concentration and removing the surface barrier.Keywords: Withania somnifera, Withanolide-A, gold nanoparticle; AuNP, breast cancer, anti-cancer and incucyte

Fused deposition modeling (FDM) is a widely employed additive manufacturing (AM) technique owing to its affordability and availability of equipment and materials. Polylactic Acid (PLA) is one of the most widely used materials due to its low cost, good mechanical properties, and biocompatibility. Mechanical performance is significantly influenced by FDM printing parameters. One of the most critical parameters that affect mechanical properties is infill density. In this study, standardized tests are used to ensure rigorous evaluations of the effects of different infill densities on PLA mechanical properties. Tensile strength, hardness, and impact strength are all considered in a comprehensive analysis. Results are then systematically compared with those of other commonly used FDM filaments, such as Acrylonitrile Butadiene Styrene (ABS) and High-density Polyethylene (HDPE). Through a rigorous experimental trial, we can analyze the effect of infill density on mechanical performance in FDM printing using PLA, ABS, and HDPE.

Since the collapse of Saddam Hussein’s regime in Iraq in 2003, the Kurdistan Region of Iraq has shown a dramatic change. To some extent, regional and international journalists have brought the change into the international spotlight. As an Autonomous region, Iraqi Kurdistan, which possesses its government, parliament and constitution, is formally recognized in the Iraqi Federal constitution, and the KRG was granted 17% of the Iraqi budget. In a very short time, the region attracted many national and international companies for business and trade. Trade and investment increased rapidly, and the private sectors improved. This, in turn, created various job opportunities. Consequently, the region became a suitable place for foreign skilled professionals. Iraqi Kurdistan did not have the skilled workers to meet or fulfil the requirement that the market needed. This immense economic growth required highly skilled and qualified human capital, which the higher education system of Kurdistan had failed to provide. Therefore, to satisfy the market's needs, the KRG, through the ministry of Higher Education and Scientific Research, has invested millions of US dollars in higher education to produce human capital. The ministry has adopted the Human Capacity Development Program (HCDP) that has sent two-three thousands of students to western countries to study at best-known universities. The aim was to satisfy the needs of the region’s market and develop the region's production system. This study explores to what extent investment in higher education has led to development. In other words, it investigates to what extent the HCDP program of human capital, which is achieved through formal training and education, has led to human skills capabilities, growth and mobility in the Kurdistan region.

The escalating threat of heavy metal and metalloid stress on plant ecosystems requires innovative strategies to strengthen plant resilience and ensure agricultural sustainability. This review provides important insights into the advanced epigenetic pathways to improve plant tolerance to toxic heavy metals and metalloid stress. Epigenetic modifications, including deoxyribonucleic acid (DNA) methylation, histone modifications, and small ribonucleic acid (RNA) engineering, offer innovative avenues for tailoring plant responses to mitigate the impact of heavy metal and metalloid stress. Technological advancements in high-throughput genome sequencing and functional genomics have unraveled the complexities of epigenetic regulation in response to heavy metal and metalloid contamination. Recent strides in this field encompass identifying specific epigenetic markers associated with stress resilience, developing tools for editing the epigenome, and integrating epigenetic data into breeding programs for stress-resistant crops. Understanding the dynamic interaction between epigenetics and stress responses holds immense potential to engineer resilient crops that thrive in environments contaminated with heavy metals and metalloids. Eventually, harnessing epigenetic strategies presents a promising trajectory toward sustainable agriculture in the face of escalating environmental challenges. Plant epigenomics expands, the potential for sustainable agriculture by implementing advanced epigenetic approaches becomes increasingly evident. These developments lay the foundation for understanding the growing significance of epigenetics in plant stress biology and its potential to mitigate the detrimental effects of heavy metal and metalloid pollution on global agriculture., Competing Interests: Declaration of Competing Interest The authors declare that they have no 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.)

Alpha-chymotrypsin is a serine protease. Its overexpression is responsible for several ailments, such as chronic obstructive pulmonary disease, autoimmune diseases, pancreatitis, and colon cancers. Therefore, the discovery of potent α-chymotrypsin inhibitors is essential for the treatment of the aforementioned ailments. In this study, we identified new α-chymotrypsin inhibitors through a systematic approach, utilizing the in silico and in vivo studies to predict and confirm the inhibitory potential of isoniazid derivatives. During this study, six compounds 2, 3, 4, 7, 9, and 10 were shortlisted from ten isoniazid derivatives through in silico screening. After that, MD simulations were performed for these compounds. The shortlisted compounds were evaluated through an in vitro α-chymotrypsin inhibitory assay. Compounds 9 and 10 showed a potent inhibition against α-chymotrypsin. The identified compounds or their derivatives can be further investigated as drug leads against the ailments caused by α-chymotrypsin and related serine proteases., 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 Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs are commonly administered orally to manage pain and inflammation, but they can have negative gastrointestinal side effects. Topical delivery is an alternative, and microemulsions (μEs) have been shown to be effective in facilitating, but they suffer from a liquid nature and low long-term retention on the skin. Hence, microemulsified gels (μEGs) have been developed, and in this study, we explored certain μEGs with diclofenac sodium (DF-Na) and naproxen sodium (NP-Na) with the hypothesis to ensure a slower and more sustained delivery of NSAIDs through the skin. The μEGs comprised castor oil (∼8%), water (∼12%), Tween-20 (∼72%), Span-20 (∼8%), poloxamer 407, and DF-Na or NP-Na. Optical microscopy was used to study the microstructures in the μEs and μEGs, and phase transitions from water-in-oil (w/o) to oil-in-water (o/w) with continuous networks were observed. Based on studies with dynamic light scattering and analyses of electron micrographs, it was observed that the μEs and μEGs loaded with DF-Na and NP-Na comprised monomodal nanodroplets. The average sizes of the droplets were (∼35 nm) and (∼60 nm) for the μEGs, without and with drugs. Fluorescence spectroscopy was used to ensure that the drugs were more likely to be present in the hydrophobic microenvironment of the formulations. Moreover, ex vivo permeation studies were conducted at pH values of 5.5 and 7.4 across rabbit skin. The release rates of DF-Na (>99 ± 1.5%, P < 0.07) and NP-Na (>89 ± 1.1%, P < 0.01) were slower for the μEGs within 8-10 h than for the μEs at the low pH, which is of relevance to the optimal pH of the skin. It was observed that μEGs with high viscosities are effective and may have potential for use in topical drug delivery applications.

With the swift advancement of technology and growing popularity of internet in business and communication, cybersecurity posed a global threat. This research focuses new Deep Learning (DL) model referred as FinSafeNet to secure loose cash transactions over the digital banking channels. FinSafeNet is based on a Bi-Directional Long Short-Term Memory (Bi-LSTM), a Convolutional Neural Network (CNN) and an additional dual attention mechanism to study the transaction data and influence the observation of various security threats. One such aspect is, relying these databases in most of the cases imposes a great technical challenge towards effective real time transaction security. FinSafeNet draws attention to the attack and reproductive phases of Hierarchical Particle Swarm Optimization (HPSO) feature selection technique simulating it in a battle for extreme time performance called the Improved Snow-Lion optimization Algorithm (I-SLOA). Upon that, the model then applies the Multi-Kernel Principal Component Analysis (MKPCA) accompanied by Nyström Approximation for handling the MKPCA features. MKPCA seeks to analyze and understand a non-linear structure of data whereas, Nyström Approximation reduces the burden on computational power hence allows the model to work in situations where large sizes of datasets are available but with no loss of efficiency of the model. This causes FinSafeNet to work easily and still be able to make accurate forecasts. Besides tackling feature selection and dimensionality reduction, the model presents advanced correlation measures as well as Joint Mutual Information Maximization to enhance variable correlation analysis. These improvements further help the model to detect the relevant features in transaction data that may present a threat to the security of the system. When tested on commonly used database for testing banks performance, for instance the Paysim database, FinSafeNet significantly improves upon the previous and fundamental approaches, achieving accuracy of 97.8%., (© 2024. The Author(s).)

Dengue, a mosquito-borne viral infection caused by the dengue virus (DENV), is a global health challenge. Annually, approximately 400 million cases are reported worldwide, signaling a persistent upward trend from previous years and projected a manifold increase in the future. There is a growing need for innovative and integrated approaches aimed at effective disease management. In this regard, scientific efforts are underway to find a new antiviral inhibitor that is desperately needed due to the growing prevalence of dengue, along with inadequate vector control and few vaccinations. The NS2B-NS3 protease complex within the DENV genome holds significant importance, making it an attractive target for potential interventions. Many competitive inhibitors are not clinically relevant even after extensive study, and these early hits are often not followed up to viable leads. The current focus is on exploring alternative target sites for developing effective anti-dengue compounds, resulting in the identification of various allosteric sites in recent years. While previous reviews have extensively covered active site inhibitors, this is to the best of our knowledge the first comprehensive review discussing the allosteric sites and allosteric inhibitors in greater detail. The present survey may assist researchers in understanding the key aspects and identifying new antagonists targeting the allosteric site of DENV protease., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Standardized welfare assessment protocols are crucial to enhance animal welfare; up to date, there is no data on the level of welfare of camels kept under pastoralism. A tailored protocol for measuring welfare in dromedary camels kept under nomadic pastoralist conditions was recently developed, drawing from the currently available welfare protocol for dromedary camels kept in intensive systems. This study, therefore, aimed to apply the newly developed tailored protocol and assess the welfare of dromedary camels kept under pastoralism in the Southern Punjab Province of Pakistan. A total of 44 welfare indicators (animal-, resource, and management-based measures) aligning with animal welfare principles ("Good Feeding", "Good Housing", "Good Health", and "Appropriate Behavior") were gathered into two assessment levels: "Caretaker-Herd level" and "Animal level". Data were collected in 2023 in the Cholistan desert in the southern Punjab province. Fifty-four herds were evaluated for a total population of 1,186 camels, of which 510 (495 females and 15 males; average age: 5-6 years old) were assessed at the animal level. The indicators were scored and aggregated to obtain Principle Aggregated Indexes (PAIs) and a total Welfare Index (TWI). Using the PAIs classification, 4 herds were categorized as excellent, 42 satisfactory, and 8 unsatisfactory. Total Welfare Index (TWI) varied from 55.7 to 82.2, and the thresholds for classification into tertiles were 65.4 and 70.6. Good feeding and Good housing were the most problematic PAIs, with Good feeding as the most influential variable for classification into welfare categories. As expected, camels kept under pastoralism had a higher level of welfare than those reported in the literature for intensive systems, especially concerning the Appropriate Behavior principle. Our findings are a first step in proposing welfare standards for dromedary in Pakistan and worldwide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Padalino, Faraz, Masebo, Waheed, Ishaq, Tauqir, Abbasi and Menchetti.)

Anticancer chemotherapies damage normal tissues, and various drug carriers are under consideration to address this issue. Metal-organic frameworks (MOFs) are promising due to their drug-carrying capacity and tunable properties. Target-inspired surface functionalization may further magnify their potential. In this study, we aim to investigate the anticancer activity of reduced iron-based MOFs (RMOFs) functionalized with ferritin and folic acid and loaded with doxorubicin. Successful synthesis and functionalization are confirmed by electron microscopes, Fourier transform infrared spectroscopy and X-ray diffraction. Anticancer activity is evaluated in different tumor cell lines at various doses. Results indicate that the folic acid functionalized and Dox loaded MOF (FADMOF) showed maximum anticancer potential, leaving only 6 % of 4 T1 cells alive at the highest dose. Ferritin and combo MOFs followed closely, while the plain RMOF lagged behind. Furthermore, in HeLa cells, the RMOF showed the best cytotoxicity, reducing cell viability to a mere 30 % at the highest dose. Similarly, in MCF7 cells, theRMOF) showed the best cytotoxicity, reducing cell viability in a dose-dependent manner and to a mere 25 % at the highest dose. Taken together, this study shows that functionalized MOFs have promising anticancer potential across various cancer cell lines. However, loading with doxorubicin reduces their cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Muhammad Imran Khan, Fenfen Li, Yi Hu and Bensheng Qiu has a patent pending to University of Science and Technology of China. If there are other authors, they 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.)

Heterogeneity of a probe image is one of the most complex challenges faced by researchers and implementers of current surveillance systems. This is due to existence of multiple cameras working in different spectral ranges in a single surveillance setup. This paper proposes two different approaches including spatial sparse representations (SSR) and frequency sparse representation (FSR) to recognize on-the-move heterogeneous face images with database of single sample per person (SSPP). SCface database, with five visual and two Infrared (IR) cameras, is taken as a benchmark for experiments, which is further confirmed using CASIA NIR-VIS 2.0 face database with 17580 visual and IR images. Similarity, comparison is performed for different scenarios such as, variation of distances from a camera and variation in sizes of face images and various visual and infrared (IR) modalities. Least square minimization based approach for finding the solution is used to match face images as it makes the recognition process simpler. A side by side comparison of both the proposed approaches with the state-of-the-art, classical, principal component analysis (PCA), kernel fisher analysis (KFA) and coupled kernel embedding (CKE) methods, along with modern low-rank preserving projection via graph regularized reconstruction (LRPP-GRR) method, is also presented. Experimental results suggest that the proposed approaches achieve superior performance., Competing Interests: “The authors show no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Butt 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 size of the initial primordial follicle pool in the ovary depends on primordial follicle formation, which determines the female reproductive lifespan. However, the molecular regulation of primordial follicle formation in chickens remains unclear. In this study, the left ovaries of chickens were collected at 2 d posthatch (dph), 5.5 dph, and 10.5 dph to examine the formation of primordial follicles. Single-cell mRNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to explore the ovarian microenvironment and identify regulatory pathways involved in the formation of primordial follicles in chickens. Histomorphological analysis of chicken ovary tissues revealed the presence of germ cell cysts at 1 dph, which began to disintegrate at 2 dph. Primordial follicles appeared at 5.5 dph and continued to develop into larger-diameter follicles. scRNA-seq and spatial transcriptomic analysis revealed 24 cellular clusters involved in chicken primordial follicle formation. The metabolic pathway of steroid hormone synthesis was found in pregranulosa and pretheca cells. Histological analysis showed that chicken ovaries did not form primordial follicles after the inhibition of the steroid hormone synthesis pathway by simvastatin or tamoxifen. In addition, mRNA transcriptomic and bioinformatics analyses revealed that GREB1 was a downstream gene of the steroid hormone synthesis pathway during the formation of chicken primordial follicles. This study provides a valuable foundation for investigating primordial follicle formation in avian species and optimizing their reproductive performance., Competing Interests: DISCLOSURES The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The emergence of antimicrobial resistance within bacterial communities poses formidable challenges to existing therapeutic strategies aimed at mitigating biofilm-mediated infections. Recent advancements in this domain have spurred the development of targeted antimicrobial agents, designed to selectively eradicate the primary etiological agents while preserving the beneficial microbial diversity of the oral cavity. Targeting glucosyltransferases (GTFs), which play crucial roles in dental biofilm formation, offers a precise strategy to inhibit extracellular polysaccharide synthesis without compromising oral microbiota. This review article delves into the intricate mechanisms underlying dental caries, with a specific focus on the role of GTFs, enzymes produced by S. mutans. It further provides an overview of current research on GTF inhibitors, exploring their mechanisms of action, efficacy, and potential applications in clinical practice. Furthermore, it discusses the challenges and opportunities in the development of novel GTF inhibitors, emphasizing the need for innovative approaches to combat biofilm-mediated oral diseases effectively., 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.)

Background and Objectives: Acute appendicitis is one of the most commonly encountered surgical emergencies on a global level. Due to the requirement of an immediate clinical diagnosis and the presence of limited resources, clinicians and diagnosticians refer to scoring systems to diagnose this condition, among which Alvarado and Tzanakis scoring systems are widely used. This meta-analysis aims to compare the diagnostic accuracy of these two systems., Methods: We searched PubMed, Google Scholar, and SCOPUS databases. All studies that reported diagnostic parameters of Alvarado and Tzanakis scores in patients with suspected acute appendicitis were selected. Diagnostic values such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were extracted from the selected studies and statistical analysis was performed with Meta Disc 1.4 software. Quality assessment of the selected studies was performed using the QUADAS-2 and QUADAS-C tools. Fourteen studies were included in our meta-analysis which enrolled 2235 patients., Results: The overall sensitivity of the Tzanakis score was calculated as 0.86 (95% CI; 0.84-00.87) while the specificity was 0.73 (95% CI; 0.69-0.78). In addition, the area under the curve (AUC) was 0.9261 (SE; 0.0169) and the diagnostic Odds Ratio (OR) was 22.52 (95% CI; 9.47-53.56). The pooled sensitivity of Alvarado score was 0.67 (95% CI; 0.65-0.69) and the specificity was 0.74 (95% CI; 0.69-0.79). Moreover, the area under the curve (AUC) of the Alvarado score was 0.7389 (SE; 0.0489) and the diagnostic Odds Ratio was 4.92 (95% CI; 2.48-9.75)., Interpretation and Conclusion: The Tzanakis scoring system has a higher sensitivity, area under the curve, and diagnostic odds ratio when compared to the Alvarado score. However, the Alvarado score has a marginally better specificity making it more reliable in excluding acute appendicitis., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

The highly adaptable optoelectronic and morphological properties of non-fullerene acceptors (NFAs) have made them a prominent research topic in the organic solar cell (OSC) field. This work describes the design of new molecules and investigates the potential optoelectronic aspects of remodified Y-series NFAs endowing with five new semi-circular shaped derivatives (BTPB1-BTPB5) based on the DFT-based quantum simulations. The designed molecules possess higher-lying LUMO energy levels with narrowed bandgaps and excellent coherence between the acceptor and core via inserted bridges. The molecules demonstrate a significant red shift and a wide-ranging absorption spectrum extending from 400 nm to 1500 nm, with the most extensive absorption occurring in the near-infrared (NIR) region. Effective π-π stacking and drastically lower binding energy certify facile charge dissociation and transmission rate. Thiophene-based bridge modification decreased reorganization energy by 47 % which results in facile charge transmission and high current density. Theoretically, simulated PCE is achieved as high as 31.49 % owing to the higher-lying LUMOs. The results demonstrate the value of designing systems and exploring new possibilities for developing effective Y-series NFAs-based high-performance organic solar cells., 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.)

Neuropathic pain (NeP) arises from pathologies of the nervous system, significantly impacting patient functionality and quality of life. Pregabalin is a first-line treatment for NeP, but there has been limited focus on patient-reported outcomes (PROs). This systematic review synthesizes PROs from clinical studies assessing pregabalin's efficacy in treating NeP, with a focus on sleep disturbance, mental health, and health-related quality of life (HRQOL). Following Cochrane Collaboration guidelines, we conducted a systematic search of randomized controlled trials and epidemiological studies reporting PROs associated with pregabalin treatment for NeP. Sixteen studies met the inclusion criteria and were narratively synthesized. The findings indicate that pregabalin significantly improved sleep interference and HRQOL across multiple studies, particularly at doses of 300 mg/day or higher. However, improvements in mental health outcomes, such as anxiety and depression, were inconsistent across studies. No meta-analysis was conducted due to the heterogeneity of outcomes. In conclusion, while pregabalin shows robust efficacy in reducing NeP-related sleep disturbances, its effects on mental health and HRQOL are less consistent. These findings highlight the need for a more holistic approach to NeP treatment, incorporating both clinical outcomes and PROs., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wang et al.)

Background: The del Nido cardioplegia solution is a widely used method for myocardial protection in various settings. However, there is limited evidence of its effectiveness in adult cardiac surgery, and the baseline solution, Plasma Lyte A, is not readily available, leading to the use of alternative baseline solutions. This study aims to investigate the effectiveness of routine del Nido cardioplegia in adult cardiac surgery and the impact of different baseline solutions on myocardial protection and other perioperative outcomes., Methods: This study was a prospective, double-blind randomized parallel group clinical trial conducted at a single tertiary care hospital in Iran. A total of 187 adult patients were evaluated for eligibility, of which 120 met the inclusion criteria for elective isolated CABG surgery. The patients were randomly assigned to three groups, with each group consisting of 40 patients. The control group received a normal saline-based routine del Nido cardioplegia, Intervention Group A received Ringer lactate-based del Nido cardioplegia, and Intervention Group B received plain Ringer-based del Nido cardioplegia. The levels of Creatine Kinase-MB (CK-MB), Troponin T, Troponin I, and lactate were primarily assessed at four different times: after anesthesia induction (Baseline), 2 h, 12 h, and 24 h., Results: Preoperative demographic and clinical characteristics were the same among groups with insignificant differences (p > 0.05). There was no significant difference among groups based on CK-MB, Troponin T, Troponin I, and lactate levels (p = 0.078, 0.143, 0.311, and 0.129 respectively). However, there was a significant difference in the time effect of Troponin T and Lactate (p = 0.034, p = <0.001)., Conclusion: Normal saline, Ringer lactate, and plain Ringer provide comparable myocardial protection in adult-isolated CABG surgery with modified del Nido cardioplegia. Larger studies are needed to identify the best alternative to Plasma Lyte A while maintaining del Nido cardioplegia as the control., (© The Author(s), published by EDP Sciences, 2024.)

Background: Malignant distal biliary obstruction (MDBO) is a challenging clinical condition commonly managed with endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative, especially in complex cases where ERCP fails or is deemed risky. This study aimed to compare the efficacy, safety and cost-effectiveness of EUS-BD vs. ERCP in the palliation of MDBO., Methods: We conducted a systematic review and meta-analysis, following PRISMA guidelines. Three databases were searched up to December 2023, including MEDLINE/PubMed, OVID and the Cochrane Central Register of Controlled Trials, for studies comparing EUS-BD with ERCP. Primary outcomes were technical and clinical success rates, while secondary outcomes included procedural times, hospital stay duration, 30-day mortality, reintervention rates, and adverse events such as pancreatitis., Results: Seven studies involving 1245 patients met the inclusion criteria. The meta-analysis revealed that EUS-BD had a technical success rate of 92%, compared to 85% for ERCP. Clinical success rates were similar for both EUS-BD and ERCP, at approximately 89%. EUS-BD was associated with a significantly lower incidence of pancreatitis (2% vs. 10% for ERCP)., Conclusions: EUS-BD offers a viable and potentially superior alternative to ERCP for the primary palliation of MDBO, particularly in terms of technical success and a lower risk of pancreatitis. These findings support the adoption of EUS-BD in clinical settings equipped to perform this technique, though future research should focus on long-term outcomes and further economic analysis to solidify these recommendations., Competing Interests: Conflict of Interest: None, (Copyright: © 2024 Hellenic Society of Gastroenterology.)

In the current quantum chemical study, indacenodithiophene donor core-based the end-capped alterations of the reference chromophore BTR drafted eight A2-A1-D-A1-A2 type small non-fullerene acceptors. All the computational simulations were executed under MPW1PW91/6-31G (d, p) level of DFT. The UV-Vis absorption, open circuit voltage, electron affinity, ionization potential, the density of states, reorganization energy, orbital analysis, and non-covalent interactions were studied and compared with BTR. Several molecules of our modeled series BT1-BT8 have shown distinctive features that are better than those of the BTR. The open circuit voltage (V OC ) of BT5 has a favorable impact, allowing it to replace BTR in the field of organic solar cells. The charge carrier motilities for proposed molecules generated extraordinary findings when matched to the reference one (BTR). Further charge transmission was confirmed by creating the complex with a PM6 donor molecule. The remarkable dipole moment contributes to the formation of non-covalent bond interactions with chloroform, resulting in superior charge mobility. Based on these findings, it can be said that every tailored molecule has the potential to surpass chromophore molecule (BTR) in OSCs. So, all tailored molecules may enhance the efficiency of photovoltaic cells due to the involvement of potent terminal electron-capturing acceptor2 moieties. Considering these obtained results, these newly presented molecules can be regarded for developing efficient solar devices in the future., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Burnout, characterized by emotional exhaustion (EX), depersonalization (DP), and a reduced sense of personal efficacy (PF) among medical and nursing students can lead to suicidal ideation, lack of empathy, and dropouts. Previous studies have used over-simplified definitions of burnout that fail to capture its complexity. We describe the prevalence of burnout profiles and its risk factors among medical and nursing students., Methods: A cross sectional study was conducted at a tertiary care University Hospital in Pakistan. The Maslach Burnout Inventory (MBI) survey was disseminated via SurveyMonkey over a period of 4 months (November 2019 to February 2020) to 482 Medical and 441 nursing students. The MBI tool measures the dimensions of EX, DP, and PF to describe seven burnout profiles. Multivariable regression was used to identify predictors of burnout., Results: The response rate was 92% in nursing and 87.3% in medical students. The prevalence of burnout in medical and nursing students was 16.9% and 6.7% respectively (p<0.001), with 55.7% (n = 427) suffering from at least one burnout profile. Only 32.5% (n = 250) students felt engaged, (42.3% medical, 22.7% nursing students, p<0.001). The most common profile was ineffective (32.5%, n = 250), characterized by a reduced sense of personal efficacy (35.6% medical, 29.4% nursing students; p = 0.065). Medical students were at higher risk of burnout compared to nursing students (OR = 2.49 [1.42, 4.38]; p<0.001) with highest risk observed in year 4 (OR = 2.47 [1.02, 5.99]; p = 0.046). Other risk factors for burnout included occasional drug use (OR = 1.83 [1.21, 8.49]; p = 0.017) and living in a hostel (OR = 1.64 [1.01,2.67]; p = 0.233)., Conclusion and Relevance: Two-thirds of our participants experienced at least one dimension of burnout with the highest prevalence of a reduced sense of PF. Drivers of burnout unique to a lower-middle-income country need to be understood for effective interventions. Faculty training on principles of student evaluation and feedback may be beneficial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mufarrih 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.)

Purpose: To evaluate four decontamination strategies utilizing enzymatic agents available in most clinical settings to determine (1) the amount of biomaterial that can be removed in a group of previously used healing abutments (uHAs) and (2) the degree to which the decontaminated HAs are capable of inducing an inflammatory response in vitro compared to new HAs., Materials and Methods: In total, 50 HAs were collected following 2 to 4 weeks of intraoral use and distributed randomly into five test groups (groups A-E; n &#61; 10 per group). Group A used enzymatic cleaner foam and an autoclave. Group B used an ultrasonic bath with enzymatic cleaner and an autoclave. Group C used a prophy jet, enzymatic cleaner foam, and an autoclave. Group D used a prophy jet, an ultrasonic bath with enzymatic cleaner, and an autoclave. Lastly, group E used a prophy jet and an autoclave. The control group consisted of 10 new and sterile HAs. Residual protein concentration was determined by a Micro BCA protein assay (Thermo Fisher Scientific), while HAs from each group were stained with Phloxine B and macroscopically examined for the presence of debris. To examine the inflammatory potential, human primary macrophages were exposed to HAs, and supernatant levels of nine cytokine and chemokine profiles were analyzed using a multiplex bead assay., Results: All test groups showed differences in the degree of visual decontamination compared to controls. Groups D and E displayed the most effective surface debris removal and reduced protein concentration, while group A was the least effective. However, compared to controls, all test groups showed high levels of inflammatory cytokine secretion via multiplex assay for up to 5 days., Conclusions: Our study found that decontamination of uHAs utilizing enzymatic cleaners failed to reestablish inert HA surfaces and prevent an inflammatory immune response in vitro. Clinicians should not reuse HAs even after attempts to decontaminate and sterilize HA surfaces.

Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms "PFK-1", "PFKP-1", "PFKL-1", "PFKM-1", "PFKM-1 and cancer", "PFKP-1 and cancer", "PFKL-1 and cancer", and "inhibitors of PFK-1" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and β-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI., Methods: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable., Results: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months)., Conclusions: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the era of global energy crises and the pressing concern of fossil fuel depletion, the quest for sustainable alternatives has become paramount. The current study aims to optimize biodiesel extraction from a combination of waste cooking oil (WCO) and sesame seed oil (SSO) through response surface methodology (RSM) and artificial neural network (ANN). The cold flow properties of biodiesel produced from WCO are a major obstacle to the commercial use of biodiesel. On the other hand, SSO possesses better oxidation stability and cold flow properties. A mixture of waste cooking oil (i.e. 70 % by volume) and sesame seed oil (i.e. 30 % by volume) has been prepared for biodiesel production via a microwave-assisted transesterification process. For biodiesel yield optimization, the interaction among the operating parameters is developed by RSM, whereas biodiesel yield is predicted by ANN. The operating parameters include reaction speed, RPM (100-600 rpm), reaction time (1-5 min), methanol to oil ratio (8:1-12:1 v/v), and catalyst concentration (0.1-2 % w/w). The highest biodiesel yield of 94 % is found at a reaction speed of 350 rpm, reaction time of 3 min, catalyst concentration of 1.05 w/w, and methanol to oil ratio of 10:1. Furthermore, it is discovered that when estimating biodiesel production rate depending on reaction constraints, ANN shows lower comparative error compared to RSM. The results show that ANN outperforms RSM in terms of percentage improvement when it comes to biodiesel production prediction., 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 Ltd.)

Purpose: Lutetium-177 [ 177 Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [ 177 Lu]Lu-PSMA-617., Methods: In this retrospective study, 68 men with progressive mCRPC treated with [ 177 Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [ 177 Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [ 177 Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [ 177 Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUV max and SUV mean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates., Results: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [ 177 Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUV max or SUV mean did not correlate with PSA-PFS or OS., Conclusion: We successfully implemented same-day post-therapy SPECT/CT after [ 177 Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of ecofriendly fabrication phenomenon is essential requirement for commercialization of non-fullerene acceptors. Recently, end-capped modeling is employed for computational design of five non-fullerene acceptors to elevate various photovoltaic properties. All new molecules are formulated by altering the peripheral acceptors of CH 3 -2F and DFT methodology is employed to explore the opto-electronic, morphological and charge transfer analysis. From the computational investigation, all reported molecules manifested red shifted absorption with remarkable reduced band gap. Among investigated molecules, FA1-FA3 evinced effectively decreased value of band gaps and designed molecules have low excitation energy justifying proficient charge transference. The lower values of binding energy of FA1 and FA2 suggest their facile exciton dissociation leading to improved charge mobility. By blending with J61 donor, FA4 have sufficiently enhanced value of V OC (1.72 eV) and fill factor (0.9228). Energy loss of the model (R) is 0.57 eV and statistical calculation demonstrate that all our modified molecules except FA3 has profoundly reduced energy loss compelling in its pivotal utilization. From accessible supportive outcomes of recent investigation, it is recommended that our modified chromophore exhibit remarkable noteworthy applications in solar cells for forthcoming innovations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures., Methods: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26., Results: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030)., Conclusions: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.

Introduction: The Macrophage Migration Inhibitory Factor (MIF), a key pro-inflammatory mediator, is responsible for modulating immune responses. An array of inflammatory and autoimmune diseases has been linked to the dysregulated activity of MIF. The significance in physiological as well as pathophysiological phenomena underscores the potential of MIF as an attractive target with pharmacological relevance. Extensive research in past has uncovered a number of inhibitors, while the ISO-1, or (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester being recognized as a benchmark standard so far. Recent work by Yang and coworkers identified five promising dietary flavonoids, with superior activity compared to the standard ISO-1. Nevertheless, the exact atomic-level inhibitory mechanism is still elusive. Methods: To improve the dynamic research, and rigorously characterize, and compare molecular signatures of MIF complexes with ISO-1 and flavonoids, principal component analysis (PCA) was linked with molecular dynamics (MD) simulations and binding free energy calculations. Results: The results suggest that by blocking the tautomerase site these small molecule inhibitors could modify the MIF activity by disrupting the intrinsic dynamics in particular functional areas. The stability matrices revealed the average deviation values ranging from 0.27-0.32 nm while the residue level fluctuations indicated that binding of the selected flavonoids confer enhanced stability relative to the ISO-1. Furthermore, the gyration values extracted from the simulated trajectories were found in the range of 1.80-1.83 nm. Discussion: Although all the tested flavonoids demonstrated remarkable results, the one obtained for the potent inhibitors, particularly Morin and Amentoflavone exhibited a good correlation with biological activity. The PCA results featured relatively less variance and constricted conformational landscape than others. The stable ensembles and reduced variation in turns might be the possible reasons for their outstanding performance documented previously. The results from the present exploration provide a comprehensive understanding of the molecular complexes formed by flavonoids and MIF, shedding light on their potential roles and impacts. Future studies on MIF inhibitors may benefit from the knowledge gathered from this investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Siddiqui, Mushtaq, Sardar, Atta, Nur-e-Alam, Ahmad and Ul-Haq.)

Breast tumor detection and classification on the Internet of Medical Things (IoMT) can be automated with the potential of Artificial Intelligence (AI). Deep learning models rely on large datasets, however, challenges arise when dealing with sensitive medical data. Restrictions on sharing these medical data result in limited publicly available datasets thereby impacting the performance of the deep learning models. To address this issue, we propose an approach that combines different magnification factors of histopathological images using a residual network and information fusion in Federated Learning (FL). FL is employed to preserve the privacy of patient data, while enabling the creation of a global model. Using the BreakHis dataset, we compare the performance of FL with centralized learning (CL). We also performed visualizations for explainable AI. The final models obtained become available for deployment on internal IoMT systems in healthcare institutions for timely diagnosis and treatment. Our results demonstrate that the proposed approach outperforms existing works in the literature on multiple metrics.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) serves as a nuclear receptor with a pivotal function in governing diverse facets of metabolic processes. In diabetes, the prime physiological role of PPAR-γ is to enhance insulin sensitivity and regulate glucose metabolism. Although PPAR-γ agonists such as Thiazolidinediones are effective in addressing diabetes complications, it is vital to be mindful that they are associated with substantial side effects that could potentially give rise to health challenges. The recent surge in the discovery of selective modulators of PPAR-γ inspired us to formulate an integrated computational strategy by leveraging the promising capabilities of both machine learning and in silico drug design approaches. In pursuit of our objectives, the initial stage of our work involved constructing an advanced machine learning classification model, which was trained utilizing chemical information and physicochemical descriptors obtained from known PPAR-γ modulators. The subsequent application of machine learning-based virtual screening, using a library of 31,750 compounds, allowed us to identify 68 compounds having suitable characteristics for further investigation. A total of four compounds were identified and the most favorable configurations were complemented with docking scores ranging from -8.0 to -9.1 kcal/mol. Additionally, the compounds engaged in hydrogen bond interactions with essential conserved residues including His323, Leu330, Phe363, His449 and Tyr473 that describe the ligand binding site. The stability indices investigated herein for instance root-mean-square fluctuations in the backbone atoms indicated higher mobility in the region of orthosteric site in the presence of agonist with the deviation peaks in the range of 0.07-0.69 nm, signifying moderate conformational changes. The deviations at global level revealed that the average values lie in the range of 0.25-0.32 nm. In conclusion, our identified hits particularly, CHEMBL-3185642 and CHEMBL-3554847 presented outstanding results and highlighted the stable conformation within the orthosteric site of PPAR-γ to positively modulate the activity., 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 Inc. All rights reserved.)

Background: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi., Methods: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed., Results: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination., Conclusion: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations., Competing Interests: Declaration of Competing Interest The authors declare that they have no Conflict of Interest to Declare., (Copyright © 2024. Published by Elsevier Ltd.)

Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA., Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers., Results: OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort., Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

The improved wear and corrosion resistance of gray cast iron (GCI) with enhanced mechanical properties is a proven stepping stone towards the longevity of its versatile industrial applications. In this article, we have tailored the microstructural properties of GCI by alloying it with titanium (Ti) and tungsten (W) additives, which resulted in improved mechanical, wear, and corrosion resistance. The results also show the nucleation of the B-, D-, and E-type graphite flakes with the A-type graphite flake in the alloyed GCI microstructure. Additionally, the alloyed microstructure demonstrated that the ratio of the pearlite volume percentage to the ferrite volume percentage was improved from 67/33 to 87/13, whereas a reduction in the maximum graphite length and average grain size from 356 ± 31 µm to 297 ± 16 µm and 378 ± 18 µm to 349 ± 19 µm was detected. Consequently, it improved the mechanical properties and wear and corrosion resistance of alloyed GCI. A significant improvement in Brinell hardness, yield strength, and tensile strength of the modified microstructure from 213 ± 7 BHN to 272 ± 8 BHN, 260 ± 3 MPa to 310 ± 2 MPa, and 346 ± 12 MPa to 375 ± 7 MPa was achieved, respectively. The substantial reduction in the wear rate of alloyed GCI from 8.49 × 10 -3 mm 3 /N.m to 1.59 × 10 -3 mm 3 /N.m resulted in the upgradation of the surface roughness quality from 297.625 nm to 192.553 nm. Due to the increase in the corrosion potential from -0.5832 V to -0.4813 V, the impedance of the alloyed GCI was increased from 1545 Ohm·cm 2 to 2290 Ohm·cm 2 . On the basis of the achieved experimental results, it is suggested that the reliability of alloyed GCI based on experimentally validated microstructural compositions can be ensured during the operation of plants and components in a severe wear and corrosive environment. It can be predicted that the proposed alloyed GCI components are capable of preventing the premature failure of high-tech components susceptible to a wear and corrosion environment.

Background: We conducted this study to assess the compliance with secondary rheumatic prophylaxis among preoperative patients with rheumatic mitral valve disease undergoing valvular heart surgery at a tertiary care cardiac hospital in a developing country., Methods: This is a descriptive cross-sectional study conducted at a tertiary care cardiac hospital in Karachi, Pakistan. The inclusion criteria encompassed patients of any sex, aged between 18 and 80 years, who had been diagnosed with rheumatic mitral valve disease through transthoracic echocardiography and had undergone valvular heart surgery. The level of compliance with secondary rheumatic prophylaxis and barriers toward noncompliance was assessed during routine preoperative interview session. This preventive measure plays a crucial role in reducing the progression of the disease and improving patient outcomes., Results: Out of the 239 patients included in the study, 125 (52.3%) were females, with a mean age of 38.8 ± 11.8 years. The majority of patients (88.7%) came from rural areas. Among the patients, 79 (33.1%) received rheumatic prophylaxis, while 160 (66.9%) did not adhere to it regularly. The common barriers for receiving rheumatic prophylaxis were non availability (41.0%) and nonaffordability (40.6%). Additionally, 28.0% of patients had lacked awareness of the importance of rheumatic prophylaxis, and 2.5% expressed fear of injection site pain and subsequent symptoms., Conclusions: A concerning level of noncompliance with secondary rheumatic prophylaxis was observed. The barriers identified in patients who did not receive rheumatic prophylaxis were primarily related to affordability, availability, lack of awareness, and fear of injection site pain and subsequent symptoms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols were further validated by Molecular Docking and via ADME and Toxicity predictions. The shortlisted compounds were then subjected to MD Simulations of the membrane-bound FFAR4-ligand complexes for 100 ns each. Molecular analyses, encompassing binding interactions, RMSD, RMSF, RoG, PCA, and FEL, were conducted to scrutinize the protein-ligand complexes at the inter-atomic level. The analyses revealed significant interactions of the shortlisted compounds with the crucial residues of FFAR4 previously documented. FFAR4 as part of the complexes demonstrated consistent RMSDs, ranging from 3.57 to 3.64, with minimal residue fluctuations 5.27 to 6.03 nm, suggesting stable complexes. The gyration values fluctuated between 22.8 to 23.5 nm, indicating structural compactness and orderliness across the studied systems. Additionally, distinct conformational motions were observed in each complex, with energy contours shifting to broader energy basins throughout the simulation, suggesting thermodynamically stable protein-ligand complexes. The two compounds CHEMBL2012662 and CHEMBL64616 are presented as potential FFAR4 agonists, based on these insights and in-depth analyses. Collectively, these findings advance our comprehension of FFAR4's functions and mechanisms, highlighting these compounds as potential FFAR4 agonists worthy of further exploration as innovative treatments for metabolic and immune-related conditions., (© 2024. The Author(s).)

We demonstrate how using two qubits can drastically improve the estimation of environment parameters compared to using only a single qubit. The two qubits are coupled to a common harmonic oscillator environment, and the properties of the environment are imprinted upon the dynamics of the two qubits. The reduced density matrix of only one of these qubits contains a decoherence factor and an additional factor taking into account the indirect interaction induced between the qubits due to the interaction with their common environment. This additional factor can drastically improve the estimation of the environment parameters, as quantified by the quantum Fisher information. In particular, we investigate the estimation of the cutoff frequency, the coupling strength, and the temperature using our two-qubit scheme compared to simply using a single qubit. We find that the precision of the estimates can be improved by orders of magnitude., (© 2024. The Author(s).)

Objectives: To determine the levels of angiogenic biomarkers: vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 1 (sVEGFR1 or sFlt-1), platelet count, and the VEGF/platelet ratio in preeclampsia., Methods: Forty-four cases of preeclampsia and 44 controls were recruited., Results: The serum VEGF, sVEGFR1, and VEGF/platelet ratio were significantly higher and platelet counts lower in preeclampsia in comparison to controls (VEGF: median = 178 vs. 97 pg/mL, p  < 0.0001, sVEGFR1: 1634 vs. 627 pg/mL, p  < 0.0001, VEGF/platelet ratio: 1.148 vs. 0.417, and platelet count: 178 × 10 3 /µL vs. 232 × 10 3 /µL, p  = 0.0006). The VEGF and VEGF/platelet ratio showed better diagnostic accuracy for differentiating preeclampsia, with an area under the curve of 97.47% (95% CI: 0.95-1.00) and 89.46% (95% CI: 0.82-0.96), respectively. VEGFA : c.-2055A>C (rs699947) AA genotype exhibited higher serum VEGF levels associated with preeclampsia., Conclusion: The higher levels of angiogenic biomarkers in preeclampsia, suggest a role in the pathogenesis and potential diagnosis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Addressing aging related functional declines in older adults has become a top priority for countries around the world. The aim of this study was to investigate the effectiveness of a blended happy age education program in promoting active aging among community-based pre-disable older adults., Methods: We conducted a two-arm trial study in Khyber Pakhtunkhwa, Pakistan. Participants were randomly assigned into two groups using a computer-generated random sequence of 150 participants., Results: Blended Happy Age Education Program (BHAEP) reduced time for 3 m walk (Estimated mean 19.5 ± 3.4 to 13.7 ± 1.3, effect size ηp² = 0.98, (P < 0.001). The current level of happiness improved in B-HAEP group from 4.7 ± 1.05 scores to 7.8 ± 1.6, P < 0.001, effect size (ηp² = 0.540). Healthy lifestyle significantly improved (P < 0.001, ηp² = 0.4)., Conclusions: B-HAEP can be an effective intervention strategy to promote active aging in older adults with risk for immobility., Competing Interests: Declaration of competing interest We, Dr Rashida Bibi, and Dr Zhang Yan, hereby declare that we have no financial, professional, or personal interests that could be construed as a potential conflict of interest or that might have influenced the research presented in this manuscript titled “Effectiveness of Blended Happy Age Education Program (B-HAEP) on Active Aging Determinants among Pre-Disable Community Based Older Adults of Pakistan: A Randomized Control Trail”. I confirm that neither I nor any of my co-authors have any affiliations with organizations or entities that might have a direct or indirect interest in the research outcomes or the publication of this work. Additionally, we have received no financial support or sponsorship from any organization that could bias the research or its conclusions. Furthermore, we affirm that there are no personal relationships or situations that could present a conflict of interest in the research or its interpretation. We acknowledge that full transparency regarding potential conflicts of interest is essential for maintaining the integrity and credibility of scholarly research, and we are committed to upholding these principles., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peripheral blood smear examination is one of the basic steps in the evaluation of different blood cells. It is a confirmatory step after an automated complete blood count analysis. Manual microscopy is time-consuming and requires professional laboratory expertise. Therefore, the turn-around time for peripheral smear in a health care center is approximately 3-4 hours. To avoid the traditional method of manual counting under the microscope a computerized automation of peripheral blood smear examination has been adopted, which is a challenging task in medical diagnostics. In recent times, deep learning techniques have overcome the challenges associated with human microscopic evaluation of peripheral smears and this has led to reduced cost and precise diagnosis. However, their application can be significantly improved by the availability of annotated datasets. This study presents a large customized annotated blood cell dataset (named the Bio-Net dataset from healthy individuals) and blood cell detection and counting in the peripheral blood smear images. A mini-version of the dataset for specialized WBC-based image processing tasks is also equipped to classify the healthy and mature WBCs in their respective classes. An object detection algorithm called You Only Look Once (YOLO) with a refashion disposition has been trained on the novel dataset to automatically detect and classify blood cells into RBCs, WBCs, and platelets and compare the results with other publicly available datasets to highlight the versatility. In short the introduction of the Bio-Net dataset and AI-powered detection and counting offers a significant potential for advancement in biomedical research for analyzing and understanding biological data., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Twisted van der Waals (vdW) quantum materials have emerged as a rapidly developing field of two-dimensional (2D) semiconductors. These materials establish a new central research area and provide a promising platform for studying quantum phenomena and investigating the engineering of novel optoelectronic properties such as single photon emission, nonlinear optical response, magnon physics, and topological superconductivity. These captivating electronic and optical properties result from, and can be tailored by, the interlayer coupling using moiré patterns formed by vertically stacking atomic layers with controlled angle misorientation or lattice mismatch. Their outstanding properties and the high degree of tunability position them as compelling building blocks for both compact quantum-enabled devices and classical optoelectronics. This paper offers a comprehensive review of recent advancements in the understanding and manipulation of twisted van der Waals structures and presents a survey of the state-of-the-art research on moiré superlattices, encompassing interdisciplinary interests. It delves into fundamental theories, synthesis and fabrication, and visualization techniques, and the wide range of novel physical phenomena exhibited by these structures, with a focus on their potential for practical device integration in applications ranging from quantum information to biosensors, and including classical optoelectronics such as modulators, light emitting diodes, lasers, and photodetectors. It highlights the unique ability of moiré superlattices to connect multiple disciplines, covering chemistry, electronics, optics, photonics, magnetism, topological and quantum physics. This comprehensive review provides a valuable resource for researchers interested in moiré superlattices, shedding light on their fundamental characteristics and their potential for transformative applications in various fields.

Background: Breast cancer is a highly prevalent and life-threatening ailment that is commonly detected among the females. The downregulation of PTEN in breast cancer is associated with a poor prognosis, aggressive tumor type, and metastasis to lymph nodes, as it activates the pro-survival pathway PI3K/AKT, which is considered the ultimate proliferative pathway., Material and Methods: The mRNA expression of PTEN and AKT genes was investigated using RT-qPCR and TaqMan primer probe chemistry. Moreover DNA was also isolated from the same tissue samples and exonic regions of both genes were amplified for mutational analysis. The proteins expression of PTEN and AKT from seven human breast cancer cell lines was checked through western blot experiments., Result: The study revealed a decrease in PTEN expression in 73.3% of the samples, whereas an increase in AKT expression in 40% of samples was observed when compared to the distant normal breast tissue. Conversely, the remaining 60% of samples exhibited a decrease in AKT mRNA expression. There was no observed alteration in the genetic sequence of AKT and PTEN within the targeted amplified regions of breast cancer samples. The high levels of PTEN protein in T-47D and MDA-MB-453 resulted in a lower p-AKT. Two cell lines ZR-75-1 and MDA-MB-468 appeared to be PTEN negative on western blot but mRNA was detected on RT-qPCR., Conclusion: In breast cancer the status/expression of PTEN & AKT at mRNA and protein level might be obliging in forecasting the path of disease progression, treatment and prognosis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Microplastic/nanoplastics (MPs/NPs) contamination is not only emerging threat to the agricultural system but also constitute global hazard to the environment worldwide. Recent review articles have addressed the environmental distribution of MPs/NPs and their single-exposure phytotoxicity in various plant species. However, the mechanisms of MPs/NPs-induced phytotoxicity in conjunction with that of other contaminants remain unknown, and there is a need for strategies to ameliorate such phytotoxicity. To address this, we comprehensively review the sources of MPs/NPs, their uptake by and effects on various plant species, and their phytotoxicity in conjunction with antibiotics, heavy metals, polycyclic aromatic hydrocarbons (PAHs), and other toxicants. We examine mechanisms to ameliorate MP/NP-induced phytotoxicity, including the use of phytohormones, biochar, and other plant-growth regulators. We discuss the effects of MPs/NPs -induced phytotoxicity in terms of its ability to inhibit plant growth and photosynthesis, disrupt nutrient metabolism, inhibit seed germination, promote oxidative stress, alter the antioxidant defense system, and induce genotoxicity. This review summarizes the novel strategies for mitigating MPs/NPs phytotoxicity, presents recent advances, and highlights research gaps, providing a foundation for future studies aimed at overcoming the emerging problem of MPs/NPs phytotoxicity in edible crops., 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 © 2023 Elsevier B.V. All rights reserved.)

Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study evaluated the influence of traumatic occlusion in the dentin-pulp complex a molar teeth submitted to subluxation., Material and Methods: Ninety Wistar rats were divided into groups Naïve (N), Subluxation (S) and Subluxation with traumatic occlusion (STO) and submitted to histological analysis after 7 and 21 days. A quantitative analysis was submitted to one-way ANOVA and Tukey's post-hoc test, and Chi-square and Bonferronís post-hoc test., Results: S and STO showed a significant increase in blood vessels area (p < 0.0005), amorphous fundamental substance (p < 0.0005) and reactionary dentin formation (p < 0.0005), as well as a decrease in the nuclear profile (p < 0.0005), odontoblast layer (p = 0.013 and p < 0.0005) by day 7 when compared with N. These changes normalized by day 21, except for the reactionary dentin (p < 0.0005) in both S and STO groups. Interestingly, the STO group exhibited significant changes in the increase of pulp calcification (p < 0.0005), presence of tubules with nuclei (p < 0.0005), and inflammatory infiltrate (p < 0.0005), as well reduction of nuclear profile (p < 0.0005), odontoblast layer (p < 0.0005) compared with N and S at day 21., Conclusions: STO impaired the defence response and decreased pulp regeneration capacity by increasing the inflammatory infiltrate and pulp calcification, and decreasing the nucleated cell number in the odontoblast layer and central pulp., 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., (© 2023 THE AUTHORS. Published by Elsevier B.V. on behalf of King Saud University.)