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Thapsigargin, a sesquiterpene lactone derived from Thapsia garganica L., has demonstrated mixed potential as an anticancer agent due to its potent ability to disrupt calcium signaling and induce apoptosis. This review evaluates the chemopreventive and chemotherapeutic potential of thapsigargin, focusing on its molecular mechanisms and toxicity. An extensive literature review of studies published since 2015 was conducted using databases such as PubMed/MedLine and Science Direct. Findings indicate that thapsigargin's primary mechanism is the inhibition of sarco/endoplasmic reticulum calcium ATPase, leading to endoplasmic reticulum stress and cell death in various cancer types. Despite these effects, thapsigargin's non-specific cytotoxicity results in significant side effects, including organ damage and histamine-related reactions. Recent advances in targeted delivery, especially with the prodrug mipsagargin, initially suggested promise in minimizing these toxicities by selectively activating in cancer cells expressing prostate-specific membrane antigen (PSMA). However, the completion of clinical trials with no ongoing studies suggests that the viability of mipsagargin and other prodrugs remains uncertain, especially in light of the toxicities observed. While thapsigargin and its derivatives present a potential pathway in cancer treatment, their future role in oncology requires careful re-evaluation., Competing Interests: Declarations Competing interests Authors wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. Ethical approval Not Applicable. Consent for publication Not Applicable. Consent to participate Not Applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammatory bowel disease (IBD) encompasses complex gastrointestinal (GI) conditions, primarily Crohn's disease (CD) and ulcerative colitis (UC), requiring precise imaging for effective diagnosis and management of complications. This systematic review aimed to evaluate the current role of imaging modalities in diagnosing IBD and detecting related complications. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search using text words and controlled vocabulary applying Boolean operators "AND," "OR," with various combinations on databases such as PubMed, Embase, and Cochrane Library. The search targeted open-access articles involving humans, with full-text available, and published in the English Language from 2005 to 2024. The quality of the included studies was assessed using the Cochrane Risk-of-Bias (RoB) checklist. Our search process identified 127 records from Cochrane (39), Embase (29), and PubMed (59). After removing 98 irrelevant records, 29 underwent further screening. Five were excluded as they involved irrelevant problems or outcomes, leaving us with 24 reports with full text, all of which were accessible. Following the eligibility assessment, two more reports were excluded due to inaccessibility, and 22 studies were included in the final analysis. The risk of bias and methodological quality assessment revealed that out of 22 studies analyzed, five (23%) had a high risk of bias, while 13 (59%) were classified as moderate risk, and four (18%) showed low risk. This distribution highlights a predominance of moderate-risk studies in research on imaging in IBD, emphasizing the need for enhanced study designs in future investigations. Our findings revealed the varying effectiveness of imaging modalities in diagnosing complications of CD and UC. Magnetic resonance enterography (MRE) stands out as the preferred method for CD due to its high sensitivity and noninvasive nature. In contrast, colonoscopy remains the gold standard for UC, providing direct visualization of mucosal lesions. While techniques like ultrasound and capsule endoscopy offer valuable insights, they have limitations that may affect their utility in certain cases., 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, Younis et al.)

Energy harvesting from ambient sources present in the environment is essential to replace traditional energy sources. These strategies can diversify the energy sources, reduce maintenance, lower costs, and provide near-perpetual operation of the devices. In this work, a triboelectric nanogenerator (TENG) based on silane-coupled Linde type A/polydimethylsiloxane (LTA/PDMS) is developed for harsh environmental conditions. The silane-coupled LTA/PDMS-based TENG can produce a high output power density of 42.6 µW/cm 2 at a load resistance of 10 MΩ and operates at an open-circuit voltage of 120 V and a short-circuit current of 15 µA under a damping frequency of 14 Hz. Furthermore, the device shows ultra-robust and stable cyclic repeatability for more than 30 k cycles. The fabricated TENG is used for the physiological monitoring and charging of commercial capacitors to drive low-power electronic devices. Hence, these results suggest that the silane-coupled LTA/PDMS approach can be used to fabricate ultra-robust TENGs for harsh environmental conditions and also provides an effective path toward wearable self-powered microelectronic devices., (© 2024. The Author(s).)

The adoption of transformer networks has experienced a notable surge in various AI applications. However, the increased computational complexity, stemming primarily from the self-attention mechanism, parallels the manner in which convolution operations constrain the capabilities and speed of convolutional neural networks (CNNs). The self-attention algorithm, specifically the matrix-matrix multiplication (MatMul) operations, demands a substantial amount of memory and computational complexity, thereby restricting the overall performance of the transformer. This paper introduces an efficient hardware accelerator for the transformer network, leveraging memristor-based in-memory computing. The design targets the memory bottleneck associated with MatMul operations in the self-attention process, utilizing approximate analog computation and the highly parallel computations facilitated by the memristor crossbar architecture. Remarkably, this approach resulted in a reduction of approximately 10 times in the number of multiply-accumulate (MAC) operations in transformer networks, while maintaining 95.47% accuracy for the MNIST dataset, as validated by a comprehensive circuit simulator employing NeuroSim 3.0. Simulation outcomes indicate an area utilization of 6895.7 μ m 2 , a latency of 15.52 seconds, an energy consumption of 3 mJ, and a leakage power of 59.55 μ W . The methodology outlined in this paper represents a substantial stride towards a hardware-friendly transformer architecture for edge devices, poised to achieve real-time performance., (© 2024. The Author(s).)

Modern technological breakthroughs depend on nonlinear optical (NLO) and photovoltaic (PV) materials, essential for creating advanced photonic devices and efficient solar cells. Herein, the NLO, PV, electrical, and photophysical characteristics of proposed chromophores (WLK-1-WLK-6) designed from pyridoquinazolindone-containing triphenylamine have been systematically altered by the addition of different spacers categorized as K1, K2, K3, K4, K5, and K6 (named as i-series). This fine-tuning was accomplished using TD-DFT, DFT computations, and the Scharber model. The impact of spectrum of medium polarity, ranging from the least polar to the most polar, including water ( ε = 78.36), methanol ( ε = 32.61), DMSO ( ε = 46.83), tetrahydrofuran ( ε = 7.43), benzene ( ε = 2.27) and chloroform ( ε = 4.71), is explored in detail utilizing the IEFPCM model on NLO and PV properties. Moreover, the response of different analyses like DOS, NCI, NBO, FMO, dipole moments ( µ ), and hyperpolarizability ( β ) in both gas, polar and non-polar solvents was analyzed. Our structure-property relationship studies revealed that adding extra spacer groups, particularly those containing thiophene spacers, considerably impacted the lowering of the energy gap (3.853-4.190 eV). The simulated UV-Vis spectra illustrate significant π → π* transitions and lower n → π* transitions, primarily in the near-infrared (IR) range of 558.613 to 429.844 nm. Push-pull chromophores showed extraordinary frequency-dependent NLO properties, SHG β (-2 ω , ω , ω ), and EOPE β (- ω , ω , 0) effect computed at laser frequencies of 1064 and 532 nm. Among the proposed compounds, WLK-6 with the K6 spacer demonstrated a smaller energy gap (3.853 eV), resulting in a maximum optical absorption peak at λ max = 558.613 nm and the maximum hyperpolarizability in benzene (9.00 × 10 4 a.u.), methanol (1.22 × 10 5 a.u.), THF (1.12 × 10 5 a.u.), DMSO (1.23 × 10 5 a.u.), and water (1.23 × 10 5 a.u.). Our study found that WLK-6, WLK-5, and WLK-1 compounds also had good photovoltaic (PV) capabilities, reaching a power conversion efficiency (PCE) of around 5% and an injection efficiency (Δ G inject ) of 0.191. In addition to these analyses, we performed topologic studies, such as TDM, ELF, NCI, MEP, LOL, and electron-hole overlap plots to better understand both intra and intermolecular interactions. Based on these results, it is clear that modifying longer π-linker groups in A-D-π-A conjugated systems benefits the optoelectronic characteristics and NLO responses for organic PV devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Schizophrenia (SZ) is a severe mental disorder characterised by disruptions in cognition, behaviour, and perception, significantly impacting an individual's life. Traditional SZ diagnosis methods are labour-intensive and prone to errors. This study presents an innovative automated approach for detecting SZ acquired through electroencephalogram (EEG) sensor signals, aiming to improve diagnostic efficiency and accuracy. We utilised Fast Independent Component Analysis to remove artefacts from raw EEG sensor data. A novel Automated Log Energy-based Empirical Wavelet Reconstruction (ALEEWR) technique was introduced to reconstruct decomposed modes based on their variability, ensuring effective extraction of meaningful EEG signatures. Cepstral-based features-cepstral activity, cepstral mobility, and cepstral complexity-were used to capture the power, rate of change, and irregularity of the cepstrum of preprocessed EEG signals. ANOVA-based feature selection was applied to refine these features before classification using the K-Nearest Neighbour (KNN) algorithm. Our approach achieved an exceptional accuracy of 99.4%, significantly surpassing previous methods. The proposed ALEEWR and cepstral analysis demonstrated high precision, sensitivity, and specificity in the automated diagnosis of schizophrenia. This study introduces a highly accurate and efficient method for SZ detection using EEG technology. The proposed techniques offer significant improvements in diagnostic accuracy, with potential implications for enhancing SZ diagnosis and patient care through automated systems.

This report details the genome sequence of Escherichia coli strain Hakim RU_GHWS, isolated from sewage water. The assembled genome comprises 5.022 Mb with 77.675× coverage, depicting an average GC content of 50.50%. This genome contains 10 CRISPR arrays, 14 prophages, 65 antibiotic resistance genes, and 28 virulence factor genes., Competing Interests: The authors declare no conflict of interest.

Microplastic (MP) pollution is a critical environmental challenge worldwide, however limited research is reported in remote lakes of Pakistan. This study assessed MPs (>5 mm) prevalence, distribution and risk perspective in water and sediment of eight remote and high-altitude lakes (>1500 m above sea level) of Gilgit Baltistan, Pakistan. The lakes exhibited an average abundance of 152.6 ± 104.6 to 12.1 ± 7 MP/kg of dry sediments and 2 ± 0.9 to 17.1 ± 17.2 MP/L of surface water. MPs <200 μm dominated in both matrices. Surface water predominantly contained polyester and polypropylene, while polypropylene and polyethylene dominated in sediments. The gradient of elevation did not show any pronounced impact on the fiber loading or MP count in both matrices. Backward air mass trajectory revealed that air masses vastly travelled from western-Asia, Arabian sea and Bay of Bengal with an average transmission distance of 2500-3500 km (500 m a.s.l) that can be a potential deposition MP source in the area. Pollution Load Index of the lakes were >1 exhibiting pollution. All other lakes except Batura and Borith manifested a moderate hazard index. Naltar lake along with aforementioned two lakes also manifested high polymer toxicity. Further research should emphasize understanding the mechanisms and biotic interactions in high-mountain ecosystems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maryem Mehboob reports financial support was provided by Campus France. 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 Ltd. All rights reserved.)

Cold agglutinin-induced hemolytic anemia presents diagnostic and management challenges, particularly in resource-limited settings like Pakistan. A 92-year-old male presented with altered consciousness, fever, weakness, and severe asthenia. Laboratory findings revealed severe anemia, elevated mean corpuscular volume, and deranged renal function tests. The diagnosis was confirmed via a positive Direct Coombs test and elevated cold agglutinin titers. Multidisciplinary management led to symptom resolution, including blood transfusions and immunosuppressive therapy. This case report and literature review emphasize the complexities of diagnosing and managing cold agglutinin-induced hemolytic anemia in Pakistan. By enhancing awareness and understanding of this condition, clinicians can optimize patient outcomes through timely intervention and multidisciplinary care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Laparoscopic sleeve gastrectomy (LSG) is a widely performed bariatric surgery that involves the removal of a portion of the stomach. Routinely, the resected gastric tissue is sent for histopathological examination to screen for malignancies or other significant pathological findings. However, the necessity of this routine practice remains uncertain. This study aims to evaluate the histopathological outcomes of LSG specimens over a five-year period at our institution., Methods: We conducted a retrospective analysis of 203 patients who underwent LSG between January 2017 and December 2022 at Heartlands Hospital, University Hospitals Birmingham. Data collected included patient demographics, body mass index (BMI), use of preoperative oesophagogastroduodenoscopy (OGD), and histopathological findings. Patients with incomplete records or those who underwent Roux-en-Y gastric bypass were excluded from the study., Results: Data were extracted for 310 patients, of whom 107 were excluded. The majority of the 203 patients analyzed were female (83%), with a mean age of 45.7 years and a mean BMI of 45.4 ± 7.3. Preoperative OGD was performed in only 0.5% of cases. Histopathological examination revealed that 81.3% (n=165) of patients had normal gastric mucosa, while 14.3% (n=29) had chronic gastritis. Clinically significant findings were rare, with only 1% (n=2) of patients showing gastrointestinal stromal tumors (GISTs) or focal intestinal metaplasia. None of the patients required additional treatment or follow-up based on these histopathological findings., Conclusion: Most LSG specimens in our study showed normal or non-significant histopathological findings, raising questions about the routine use of histopathological examination in LSG procedures. It remains unclear whether histopathology is necessary following sleeve gastrectomy. While no patients in our cohort required further treatment or surveillance, there are reports in the literature where surveillance or further treatment was necessary, though the incidence remains low. Given the low incidence of clinically significant pathology, further studies with larger sample sizes and multi-center data are needed to establish clear guidelines on this issue., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Khattak et al.)

Context: Dye-sensitized solar cells (DSSCs) present a convincing substitute for conventional silicon-based solar cells because of their possible lower manufacturing costs and versatile uses. Electron injection and dye regeneration processes are important in meeting the need for photosensitizers with improved efficiency and stability. Aimed at enhancing the performance and efficiency of DSSCs, this study focuses on the structural engineering to performance metrics of novel indoline-benzo[d][1,2,3]thiadiazole based push-pull sensitizers (LHZ1 to LHZ9) with D-D-A-π-A framework. The current study provides insights into the photovoltaic and optoelectronic properties of the investigated dyes, which are significantly influenced by the modification of auxiliary donors (D), internal acceptors with thiophene as a spacer, and cyanoacrylic acid (A) as the terminal acceptor. These modifications enhance rapid charge transfer among the dyes, highlighting the critical role of dye-semiconductor interactions., Methods: The suitability of developed sensitizers for DSSCs applications is confirmed by executing quantum methods like NBO, TDM, FMO, DOS, E b , ΔG reg , ΔG inject , VRP, and ICT parameters q CT (e - ), D CT ( A ∘ ), H index ( A ∘ ), ∆( A ∘ ), t index ( A ∘ ), and μ CT (D). All of the investigated dyes have HOMO levels lower than the electrode I-/I 3 -'s redox potential (-4.8 eV) and LUMO values that are appropriately higher than the conduction band of TiO 2 (-4.0 eV). The novel dyes showed a closing of the energy gap (2.38-1.84 eV). The LHZ7 and LHZ8 molecules with the lowest E g (1.97 eV and 1.84 eV) demonstrated the highest absorption (up to 746 nm > 402 nm for LHZ), which was caused by the insertion effect of varied donors and internal acceptors. Almost all photosensitizers appeared with remarkable properties, i.e., red-shifted absorption maxima (746 nm), lowest E x (1.66 eV), E b (0.02 eV), and highest values of LHE (0.958). The TDM analysis revealed high charge density on HOMO of donor and LUMO of acceptors in designed dyes. DOS analysis revealed that the donor parts of the molecules delocalized the highest occupied molecular orbitals of dye particles. The electronic properties predicted by the NBO analysis showed that donor groups donate high and faster transfer of charge, and internal acceptor groups rapidly accept them. The electron injection (ΔG inject ) and dye regeneration (ΔG reg ) analysis of photosensitizers attached with TiO 2 proved efficient charge transfer properties from the donor of newly designed dyes onto the conduction band of TiO 2 . This study, also supported by the thermodynamic stability of dyes with negative values of Gibbs free energy, revealed that the performance of the designed dyes is augmented by modifying the donor and internal acceptors of the reference photosensitizer for effective application in the experimental community. All of the dyes are suitable for DSSCs based on the calculated parameters. Still, the LHZ9 dye proved proficient in applying dye-sensitized solar cells due to its remarkable properties, i.e., lowest gap and red-shifted absorption maxima., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fish protein hydrolysates (FPH) are inherently unstable in their liquid form, necessitating either freezing or dewatering for stabilization. Gentle methods such as freeze concentration can be used to remove water, this can be achieved by freezing water in solution by decreasing the bulk temperature below freezing point and separating pure ice crystals from concentrated solution. This approach serves as an alternative to techniques like evaporation and reverse osmosis for concentrating solutions that have high water content, significant nutritional value, and thermolabile compounds. This is crucial as many bioactive compounds degrade when exposed to elevated temperatures. Another notable advantage of this technology is its potential to reduce energy consumption by up to 40% when integrated into the FPH drying process. Although this technology is currently industrialized primarily for juices, it can achieve concentrations of up to 60°Brix and manage viscosities up to 400 mPa.s. Numerous studies have been dedicated to enhancing design and processes, leading to a 35% reduction in the system's capital cost and a 20% reduction in energy consumption. Moreover, freeze concentration can synergize with other concentration techniques, creating more efficient hybrid processes. This review aims to introduce freeze concentration as a superior option for preserving fish protein hydrolysates, enhancing their stability, and maintaining their nutritional and bioactive qualities., Competing Interests: Declaration of competing interest The authors declare no competing interests or relationships that could influence this work., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Potassium nitrate poisoning is a rare but potentially serious condition that can result in methemoglobinemia and subsequent cyanosis. This case report presents a unique instance of rapid-onset methemoglobinemia resulting from the ingestion of a traditional medicine preparation containing potassium nitrate, known as "kalmi shora.", Case Presentation: A 14-year-old Pakistani boy reported to the emergency department with a history of sudden-onset headache, drowsiness agitation, irritability, and generalized cyanosis. Pulse oximetry showed a concerning oxygen saturation level of 58%, whereas arterial blood gas analysis revealed a normal partial pressure of oxygen (90 mmHg). The profile of abrupt onset of symptoms, generalized cyanosis, and the discrepancy between the partial pressure of oxygen and oxygen saturation readings necessitated a comprehensive assessment including inquiries into potential toxins. The peculiar appearance of the blood, resembling chocolate in color, further indicated the possibility of methemoglobinemia. The patient was successfully treated with methylene blue, leading to a prompt resolution of symptoms., Conclusion: This case highlights the significance of considering toxin exposures, such as traditional-medicine-induced poisoning, in emergency settings. The report contributes to the medical literature by highlighting the potential risks associated with traditional remedies and emphasizes the critical role of prompt diagnosis and intervention in optimizing patient outcomes. Recognition of the specific etiology of methemoglobinemia, in this case, traditional medicine ingestion, is essential for effective management in emergency medicine., (© 2024. The Author(s).)

Autoimmune encephalitis (AE) is a rare yet critical neurological disorder characterized by inflammation of the brain, typically triggered by an abnormal immune response. The early detection and diagnosis of AE are crucial for effective treatment and improved patient outcomes. However, the diagnostic process is often complicated by the diverse clinical presentations of AE, which can mimic other neurological and psychiatric conditions. Currently, diagnosis relies on a combination of clinical evaluation, neuroimaging, cerebrospinal fluid analysis, and the detection of specific autoantibodies. Despite advances in these areas, challenges remain, particularly in cases where patients are seronegative or present with nonspecific symptoms. This narrative review provides a comprehensive overview of emerging biomarkers for the early detection of AE, highlighting their potential to enhance diagnostic accuracy and speed. We explore a variety of biomarkers, including novel autoantibodies, inflammatory markers, cytokines, and neuronal damage indicators, and discuss their clinical implications. This review emphasizes the need for biomarkers that are not only sensitive and specific but also accessible and rapid to facilitate earlier diagnosis and treatment. By synthesizing current research, this review aims to contribute to the ongoing efforts to refine the diagnostic approach to AE, ultimately improving outcomes for patients affected by this challenging condition., 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, Bokhari et al.)

Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of -6.4, -5.1, -6.6, -5.1, and - 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function., (© 2024. The Author(s).)

Microsporidia, a group of unicellular eukaryotic parasites, rely intensely on secretory effectors for successful invasion and proliferation within host cells. This review focuses on the identification, characterization, and functional roles of effectors, including secretory proteins and microRNAs. The adhesion proteins like the Ricin-B-lectin facilitate initial invasion, which binds to the host cell surface. Once inside, microsporidia deploy a range of effectors to modulate host immune responses, such as serpin proteins, and redirect host cell metabolism to meet the parasite's nutritional needs through hexokinase. Some effectors such as microRNAs, alter the host gene expression to create a more favorable intracellular parasitic environment. In conclusion, the secretory effectors of microsporidia play a pivotal role spanning from host cell invasion to intracellular establishment. In the future, more effectors secreted by microsporidia will be studied, which will not only help to elucidate the molecular mechanism of pathogenic manipulation of the host but also help to provide the potential targets for anti-parasitic treatments., (© 2024 International Society of Protistologists.)

Background: Leadless pacemakers have emerged as a promising alternative to transvenous pacemakers in patients with kidney disease. However, studies investigating leadless pacemaker outcomes and complications based on kidney dysfunction are limited., Objective: The objective of this study was to evaluate the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with inpatient complications and outcomes of leadless pacemaker implantations., Methods: National Inpatient Sample and International Classification of Diseases, Tenth Revision codes were used to identify patients with CKD and ESRD who underwent leadless pacemaker implantations in the United States from 2016 to 2020. Study end points assessed included inpatient complications, outcomes, and resource utilization of leadless pacemaker implantations., Results: A total of 29,005 leadless pacemaker placements were identified. Patients with CKD (n = 5245 [18.1%]) and ESRD (n = 3790 [13.1%]) were younger than patients without CKD and had higher prevalence of important comorbidities. In crude analysis, ESRD was associated with higher prevalence of major complications, peripheral vascular complications, and inpatient mortality. After multivariable adjustment, CKD and ESRD were associated with inpatient mortality (CKD: adjusted odds ratio [aOR], 1.62 [95% CI, 1.40-1.86]; ESRD: aOR, 1.38 [95% CI, 1.18-1.63]) and prolonged length of stay (CKD: aOR, 1.55 [95% CI, 1.46-1.66]; ESRD: aOR, 1.81 [95% CI 1.67-1.96]). ESRD was also associated with higher hospitalization costs (aOR, 1.63; 95% CI, 1.50-1.77) and major complications (aOR, 1.33; 95% CI, 1.13-1.57) after leadless pacemaker implantation., Conclusion: Approximately one-third of patients undergoing leadless pacemaker implantation had CKD or ESRD. CKD and ESRD were associated with greater length and cost of stay and inpatient mortality., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

In view of their exceptional approach, excellent inherent biocompatibility and biodegradability properties, and interaction with the local extracellular matrix, protein-based polymers have received attention in bone tissue engineering, which is a multidisciplinary field that repairs and regenerates fractured bones. Bone is a multihierarchical complex structure, and it performs several essential biofunctions, including maintaining mineral balance and structural support and protecting soft organs. Protein-based polymers have gained interest in developing ideal scaffolds as emerging biomaterials for bone fractured healing and regeneration, and it is challenging to design ideal bone substitutes as perfect biomaterials. Several protein-based polymers, including collagen, keratin, gelatin, serum albumin, etc., are potential materials due to their inherent cytocompatibility, controlled biodegradability, high biofunctionalization, and tunable mechanical characteristics. While numerous studies have indicated the encouraging possibilities of proteins in BTE, there are still major challenges concerning their biodegradability, stability in physiological conditions, and continuous release of growth factors and bioactive molecules. Robust scaffolds derived from proteins can be used to replace broken or diseased bone with a biocompatible substitute; proteins, being biopolymers, provide excellent scaffolds for bone tissue engineering. Herein, recent developments in protein polymers for cutting-edge bone tissue engineering are addressed in this review within 3-5 years, with a focus on the significant challenges and future perspectives. The first section discusses the structural fundamentals of bone anatomy and ideal scaffolds, and the second section describes the fabrication techniques of scaffolds. The third section highlights the importance of proteins and their applications in BTE. Hence, the recent development of protein polymers for state-of-the-art bone tissue engineering has been discussed, highlighting the significant challenges and future perspectives.

We have sequenced the genome of Kurthia gibsonii strain Hakim RU&#95;BHWE, isolated from sewage water. The assembled genome consists of 2.891 Mb with 58.6883× coverage, presenting an average GC content of 36.60%. This genome includes 8 CRISPR arrays, 3 prophages, 3 antibiotic resistance genes, and 12 virulence factor genes., Competing Interests: The authors declare no conflicts of interest.

The objective of this study was to investigate the effectiveness of Simulated Equestrian Therapy and Neuro-Motor Therapy in improving Motor Proficiency among Down syndrome children using a double-blinded Randomized Controlled Trial. This study was conducted at Dar-ul-Sukun Institute and Dr. Ziauddin Hospital from April to September 2023 by enrolling a total of 56 participants with Down syndrome (DS) after obtaining informed, voluntary assent from the guardians of the participants. Each participant was allocated randomly to the treatment group ( n = 28) that received Simulated Equestrian Therapy (SET) and the control group ( n = 28) that received Neuro-motor Therapy (NMT) using the envelop method of simple random sampling. The participants and their guardians were blind to the allocations. Participants' blood pressure and heart rate were recorded before and after each session to ensure safety. Each participant was assessed at baseline and after 6 th and 12 th week of intervention using Bruinink's test of motor proficiency (BOT-2). The data was analyzed using Medcalc software. The results reveal significant findings for improving motor proficiency after 12 th week of intervention of SET and NMT. No protocol was found to be superior to another in improvement of the tested parameters. Hence, our study concludes that SET and NMT effectively improve motor proficiency among DS children. However, studies with a follow-up period should be conducted to further evaluate these therapies' long-term benefits.

In recent years, innovative technologies have gained prominence in stroke patient rehabilitation worldwide, with virtual reality-based mirror therapy (VRBMT) emerging as a notable example. Hence, the present study aims to determine the efficacy of VRBMT on upper extremity motor function, manual performance, and gross manual dexterity among stroke patients. The systematic search utilized Population, Intervention, Comparison, Outcome, and Design (PICOD) paradigm, and the study searched was based on 2012-2023, utilizing different databases. The meta-analysis data was evaluated using MedCalc version 18.11.3. The Pooled effect size mean was statistically examined using a fixed and random effect model. Among the 6 studies selected, 4 studies involving upper-limb stroke patients were identified between the VRBMT. Pooled analysis of VRBMT revealed no significant effect on motor function [standardized mean difference (SMD) 0.815; 95% CI 0.00 to 81.37; P = 0.5562]. The remaining 2 of 6 studies participated in the study of the manual performance stroke patients (SMD 0.869; 95% CI 0.00 to 93.22; P = 0.0684). The pooled analysis of VRBMT revealed no significant effect. The last 2 of 6 included studies on gross manual dexterity in stroke. The pooled analysis also showed no significant effects on VRBMT (SMD 0.198; 95% CI 0.00 to 0.00; P = 0.6951). The present study concluded although VRBMT exhibits potential as a novel method for stroke rehabilitation, its effects on gross manual dexterity, manual performance, and upper extremity motor function are not statistically significant may be due to a limited number of studies on VRBMT in stroke patients.

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a major candidate for the blood-stage malaria vaccine. Genetic polymorphisms of global pfama-1suggest that the genetic diversity of the gene can disturb effective vaccine development targeting this antigen. This study was conducted to explore the genetic diversity and gene structure of pfama-1 among P. falciparum isolates collected in the Khyber Pakhtunkhwa (KP) province of Pakistan. A total of 19 full-length pfama-1 sequences were obtained from KP-Pakistan P. falciparum isolates, and genetic polymorphism and natural selection were investigated. KP-Pakistan pfama-1 exhibited genetic diversity, wherein 58 amino acid changes were identified, most of which were located in ectodomains, and domains I, II, and III. The amino acid changes commonly found in the ectodomain of global pfama-1 were also detected in KP-Pakistan pfama-1. Interestingly, 13 novel amino acid changes not reported in the global population were identified in KP-Pakistan pfama-1. KP-Pakistan pfama-1 shared similar levels of genetic diversity with global pfama-1. Evidence of natural selection and recombination events were also detected in KP-Pakistan pfama-1.

One of the significant challenges in tone mapping is to preserve the perceptual quality of the tone-mapped images. Traditional tone mapping operators (TMOs) compress the luminance of high dynamic range (HDR) images with little to no consideration of image color information resulting into suboptimal colors. Existing color management algorithms require either manual parameter tuning or introducing lightness and hue shifts. The current study aimed to develop a color correction model in plausible agreement with the psychophysical phenomenon of color appearance perception for optimal color reproduction of tone mapped images. The proposed model leverages CIECAM16 perceptual correlates i.e., lightness, chroma, and hue. It is adaptive and entirely automatic while preserving the lightness of the tone-mapped image and maintaining the hue from the HDR image. Moreover, it does not require any gamut mapping correction algorithm in natural color reproduction. The effectiveness of the model was validated using objective and subjective methods. The experiments revealed that the model achieved optimal color reproduction in terms of the naturalness of the colors.

Background: Patients' compliance and receptivity to nonimmersive virtual reality (NIVR) can enhance their long-term exercise therapy compliance for neurological illnesses. Patients with Parkinson disease (PD) have age-standardized rates of disability, death, and prevalence that are rising the fastest; several researches have revealed that there is no known cure for PD at this time. Thus, the current study investigates how NIVR affects patients with PD using Wii-Fit exercises. Therefore, the present study investigates the effects of NIVR using Wii-Fit exercises among patients with PD., Materials and Methods: The population, intervention, comparison, outcome approach was used to select the research studies. Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, PubMed, Physiotherapy Evidence Database, and ProQuest were checked for citations from 2012 to 2022. RevMan was used to analyze data. A fixed and random effects model was used to analyze the pooled effect size in terms of mean and standard deviation. The heterogeneity was calculated using the I2 statistic. Cochrane examined for bias in randomized controlled trials., Results: This review comprised 12 trials in total. Using the Berg Balance Scale, the pooled analysis showed statistically significant effects on the NIVR group (pooled standardized mean difference = 0.61 [95% confidence interval, 0.28-0.95]; I2 = 53%; P = .0003). The pooled effects of cognition showed nonsignificant effects of NIVR (pooled standardized mean difference = 0.15 [95% confidence interval, -0.21 to 0.51]; I2 = 0%; P = .41)., Conclusions: The review suggests that NIVR is effective for balance rehabilitation but ineffective for cognitive improvement in patients with PD aged >18 to 85 years., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens., (© 2024. The Author(s).)

We have revealed the genomic sequence of Acinetobacter baumannii strain Hakim RU&#95;CBWP isolated from pond surface water. Our assembled genome covers 3.787 Mb with 45.5629× coverage, showcasing an average GC content of 38.60%. This genome contains two CRISPR arrays, 17 prophages, 22 antibiotic resistance genes, and 20 virulence factor genes., Competing Interests: The authors declare no conflict of interest.

The issue of antibiotic resistance in pathogenic microbes is a global concern. This study was aimed to explore in silico and in vitro analysis of the antibacterial efficacy of different natural ligands against bacterial activity. The ligands included in the study were Propolis Neoflavanoide 1, Carvacrol, Cinnamaldehyde, Thymol, p-benzoquinone, and Ciprofloxacin (standard drug S*). The outcomes of molecular docking revealed that Propolis Neoflavaniode-1 showed a highly significant binding energy of - 7.1 and - 7.2 kcal/mol for the two gram-positive bacteria, as compared to the gram-negative bacteria. All ligands demonstrated acute toxicity (oral, dermal), except for Propolis Neoflavanoide 1 and S* drugs, with a confidence score range of 50-60%. Using a molecular dynamic simulation approach, we investigated Propolis Neoflavaniode-1's potential for therapeutic use in more detail. An MD simulation lasting 100 ns was performed using the Desmond Simulation software to examine the conformational stability and steady state of Propolis Neoflavaniode-1 in protein molecule complexes. Additionally, in vitro studies confirmed the antimicrobial activity of Propolis Neoflavaniode 1 by increasing the zone of inhibition against Gram-positive bacteria, p < 0.005 as compared to gram-negative bacteria. This study revealed the promising antibacterial efficacy of Propolis Neoflavaniode 1, demonstrated through robust in silico analyses, minimal toxicity, and confirmed in vitro antimicrobial activity, suggesting its potential as a viable alternative to combat antibiotic resistance., (© 2024. The Author(s).)

Objectives: This study was conducted to evaluate the effects of vitamin C on apoptotic and proliferative genes in injured HepG2 cells., Methods: In silico analysis was performed using molecular docking of chemical compounds with vascular endothelial growth factor (VEGF). The different computational tools used were AutoDock Vina, BIOVIA DISCOVERY studio, and PyMOL. Drug likeness and toxicity were analyzed by SWISS ADMET. Cells that were 60-70% confluent were treated with different concentrations of hydrogen peroxide (H 2 O 2 ) (100-2000 μM) and ascorbic acid (30, 60, 90 μg/mL). The MTT cell proliferation assay was performed to compare the proliferative potential of HepG2 cells treated with H 2 O 2 or ascorbic acid with untreated HepG2 cells using 96-well plates., Results: The lowest binding energy of VEGF with vitamin C -5.2 kcal/mol and L-ascorbic acid-2 glycoside -4.7 kcal/mol was observed by in silico analysis. Vitamin C was selected because it exhibited a high interaction with VEGF and fulfilled Lipinski's rule, and had better oral viability and pharmacokinetics compared to L-ascorbic acid-2 glycoside. Cell viability assays showed that vitamin C had significant apoptotic effects (P < 0.0001). After treating HepG2 cells with ascorbic acid, reduced VEGF (angiogenesis) was observed as determined by apoptotic and proliferative gene expression. Ascorbic acid treatment of HepG2 cells led to downregulation of the proliferation markers, proliferating cell nuclear antigen, Ki67, and DNA topoisomerase II alpha. Increased apoptosis after treatment with vitamin C was observed due to upregulation of p53 and annexin V., Conclusion: The results of this study showed that vitamin C inhibited the growth of cancer cells, thus protecting HepG2 cells from oxidative stress. Vitamin C exhibited antiproliferative activity as observed in silico and in vitro , as well as by the inhibited expression of genes involved in protein synthesis., (© 2024 The Authors.)

Context: For the first time, the use of monocyclic rings C 18 and B 9 N 9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C 18 and B 9 N 9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C 18 and B 9 N 9 rings of the complexes., Methods: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B 9 N 9 , MKN@B 9 N 9 , MRY@B 9 N 9, and THC@B 9 N 9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C 18 , MKN@C 18 , MRY@C 18 , and THC@C 18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B 9 N 9 and C 18 , the analyte recovery time for C 18 is much shorter (9.91 × 10 -11 for THC@C 18 ) than that for B 9 N 9 shorter recovery time value of 3.75 × 10 -9 for EPT@B 9 N 9 . These results suggest that our reported sensors B 9 N 9 and C 18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B 9 N 9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016., Methods: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model., Results: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84)., Conclusion: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

To maintain a green and sustainable environment for human beings, rapid detection of potentially toxic heavy metals like mercury (Hg(II)) has attracted great attention. Recently, sensors have been designed which can selectively detect Hg(II) over other common available cations and give a naked eye or fluorometric response. In the last two decades, the trend is shifting from bulky organic chemosensors toward nanoparticles due to their rapid response, low cost, eco-friendly and easy synthesis. In this review, promising nanoparticles-based sensors for Hg(II) detection are discussed. The nano-sensors are functionalized with nucleotide or other suitable materials which coordinate with Hg(II) ions and give clear color or fluorescence change. The operational mechanisms are discussed focusing on its four basic types. The nanoparticles-based sensors are even able to detect Hg in three different oxidation states (Hg(II), Hg(I) and Hg(0)). Recently, the trend has been shifted from ordinary nanoparticles to magnetic nanoparticles to simultaneously detect and remove Hg(II) ions from environmental samples. Furthermore, the nano-sensors for Hg(II) are compared with each other and with the reported organic chemosensors.

Introduction: This systematic review and meta-analysis assessed the characteristics, types, and impact of interventions to improve adherence to attention-deficit hyperactivity disorder (ADHD) medications within the context of the three phases of adherence, namely, initiation, implementation, and discontinuation., Methods: PubMed, Psychological Information Database, Embase, International Pharmaceutical Abstracts, and Google Scholar were systematically searched for relevant trials using appropriate search terms. Interventions were classified as educational, behavioural, affective, and multifaceted. Data was pooled using odds ratios and proportions., Results: Seventeen studies were included in this review. In a pooled analysis of four RCTs, interventions did not significantly improve medication adherence (OR = 2.32; 95%-Confidence Interval=CI = 0.91-5.90; p  = 0.08). In seven non-randomized trials, a pooled proportion of people who adhered to ADHD medication was considerably higher in the intervention group (85%, 95%CI = 78%-91%) than in the control group (47%, 95%CI = 33%-61%). Interventions varied in terms of study design, methods and their impact on different phases of adherence., Conclusions: Despite some promising results, the lack of consideration of phase-specific adherence factors may limit the effectiveness and sustainability of interventions to improve adherence in clinical practice. Future interventions should be phase-specific, guided by factors which are pertinent to each phase. Meanwhile, clinicians should choose or tailor interventions based on individual needs and preferences.

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

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%-85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20 years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy., 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 Murshed, Alnoud, Ahmad, Khan, Alissa, Alsuwat, Ahmed and Khan.)

We report a case of a cannulated nasopharyngeal airway (NPA) in a patient having a neurological deficit, absent gag reflex, and no clinically obvious signs of respiratory distress. The patient had two episodes of vomiting before admission and was admitted with the initial working diagnosis of aspiration pneumonia; however, a preliminary chest X-ray (CXR) revealed an NPA, sitting vertically in the airway. It is our emphasis that thorough clinical history and radiological imaging are of paramount importance in prompt management of such airway complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Khan et al.)

Background: The present study aimed to investigate the in-vitro anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of Ficus benghalensis , including leaves, stem, and roots, as well as isolated column fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C)., Methods: The extracts and subsequent fractions were evaluated for their inhibitory activity against key enzymes involved in diabetes [α-glucosidase and α-amylase], neurodegenerative diseases [acetylcholinesterase and butyrylcholinesterase], and inflammation (cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX))., Results: The results showed that F. benghalensis leaf extract exhibited the highest α-glucosidase inhibitory activity (73.84%) and α-amylase inhibitory activity (76.29%) at 1000 µg/mL. The stem extract (65.50%) and F-B-2 C fraction (69.67%) also demonstrated significant α-glucosidase inhibitory activity. In terms of anti-cholinesterase activity, the extracts of roots, leaves, and stem showed promising inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with half maximal inhibitory concentration (IC50) values ranging from 50.50 to 474.83 µg/mL. The derived fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C) also exhibited notable inhibition of AChE and BChE, with IC50 values from 91.85 to 337.94 µg/mL. Moreover, the F-B-3 C fraction demonstrated the highest COX-2 inhibitory potential (85.72%), followed by F-B-1 C (83.13%), the stem extract (80.85%), and the leaves extract (79.00%). The F-B-1 C fraction showed the highest 5-LOX inhibitory activity (87.63%), while the root extract exhibited the lowest inhibition (73.39%)., Conclusions: The results demonstrated promising bioactivity, suggesting the potential of F. benghalensis as a source of natural compounds with therapeutic applications. Further studies are required to identify and isolate the active components responsible for these effects and to evaluate their in-vivo efficacy and safety., Competing Interests: The authors declare no conflict of interest. Given his role as Guest Editor and Editorial Board Member of Frontiers in Bioscience-Landmark, Marcello Iriti had no involvement in the peer-review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jen-Tsung Chen., (© 2024 The Author(s). Published by IMR Press.)

We unveil the genomic sequence of the Klebsiella pneumoniae Hakim-RU strain isolated from a patient with urinary tract infections. Our assembled genome spans 4.3 Mb with 73.0× coverage, an average GC content of 57.41%, 4 plasmids, 2 CRISPR arrays, 10 prophages, 41 antibiotic resistance genes, and 6 virulence factor genes., Competing Interests: The authors declare no conflict of interest.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Quality sleep plays a vital role in living beings as it contributes extensively to the healing process and the removal of waste products from the body. Poor sleep may lead to depression, memory deficits, heart, and metabolic problems, etc . Sleep usually works in cycles and repeats itself by transitioning into different stages of sleep. This study is unique in that it uses wearable devices to collect multiple parameters from subjects and uses this information to predict sleep stages and sleep patterns. For the multivariate multiclass sleep stage prediction problem, we have experimented with both memoryless (ML) and memory-based models on seven database instances, that is, five from the collected dataset and two from the existing datasets. The Random Forest classifier outclassed the ML models that are LR, MLP, kNN, and SVM with accuracy (ACC) of 0.96 and Cohen Kappa 0.96, and the memory-based model long short-term memory (LSTM) performed well on all the datasets with the maximum attained accuracy of 0.88 and Kappa 0.82. The proposed methodology was also validated on a longitudinal dataset, the Multiethnic Study of Atherosclerosis (MESA), with ACC and Kappa of 0.75 and 0.64 for ML models and 0.86 and 0.78 for memory-based models, respectively, and from another benchmarked Apple Watch dataset available on Physio-Net with ACC and Kappa of 0.93 and 0.93 for ML and 0.92 and 0.87 for memory-based models, respectively. The given methodology showed better results than the original work and indicates that the memory-based method works better to capture the sleep pattern., Competing Interests: The authors declare that they have no competing interests., (© 2024 Waqar and Ghani Khan.)

Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, poses a significant healthcare challenge worldwide. The accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein drives neuronal degeneration and neuroinflammation, perpetuating disease progression. Despite advancements in understanding the cellular and molecular mechanisms, treatment hurdles persist, emphasizing the need for innovative intervention strategies. Quantum dots (QDs) emerge as promising nanotechnological tools with unique photo-physical properties, offering advantages over conventional imaging modalities. This systematic review endeavors to elucidate the theranostic potential of QDs in AD by synthesizing preclinical and clinical evidence. A comprehensive search across electronic databases yielded 20 eligible studies investigating the diagnostic, therapeutic, or combined theranostic applications of various QDs in AD. The findings unveil the diverse roles of QDs, including inhibiting Aβ and tau aggregation, modulating amyloidogenesis pathways, restoring membrane fluidity, and enabling simultaneous detection of AD biomarkers. The review highlights the potential of QDs in targeting multiple pathological hallmarks, delivering therapeutic payloads across the blood-brain barrier, and facilitating real-time imaging and high-throughput screening. While promising, challenges such as biocompatibility, surface modifications, and clinical translation warrant further investigation. This systematic review provides a comprehensive synthesis of the theranostic potential of QDs in AD, paving the way for translational research and clinical implementation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sinha et al.)

Benzimidazole-based pyrrole/piperidine analogs ( 1 - 26 ) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds ( 1 - 13 ) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC 50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC 50 = 16.11 ± 0.33 µM) and galantamine (IC 50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC 50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC 50 = 18.14 ± 0.05 µM) and galantamine (IC 50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds ( 14 - 26 ) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC 50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC 50 = 20.01 ± 0.12 µM) and galantamine (IC 50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC 50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC 50 = 18.14 ± 0.05 µM) and galantamine (IC 50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2 , 4 , 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively., Competing Interests: The authors declare no conflicts of interest.

Long non-coding RNAs (lncRNAs) are RNA molecules that regulate gene expression at several levels, including transcriptional, post-transcriptional, and translational. They have a length of more than 200 nucleotides and cannot code. Many human diseases have been linked to aberrant lncRNA expression, highlighting the need for a better knowledge of disease etiology to drive improvements in diagnostic, prognostic, and therapeutic methods. Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. LncRNAs play an essential role in the complex process of heart formation, and their abnormalities have been associated with several CVDs. This Review article looks at the roles and relationships of long non-coding RNAs (lncRNAs) in a wide range of CVDs, such as heart failure, myocardial infarction, atherosclerosis, and cardiac hypertrophy. In addition, the review delves into the possible uses of lncRNAs in diagnostics, prognosis, and clinical treatments of cardiovascular diseases. Additionally, it considers the field's future prospects while examining how lncRNAs might be altered and its clinical applications., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Background: Stress is a pervasive issue in modern life, affecting both physical and mental health. Identifying biomarkers like cell-free DNA (cfDNA) could provide insights into stress response and help detect individuals at risk for stress-related disorders., Objective: The aim of this study is to investigate the potential use of cfDNA as a diagnostic biomarker in individuals experiencing stress., Methodology: A case-control analysis was conducted using convenient sampling on university participants (N = 285 cases, N = 500 controls) aged 18-24. The study assessed haematological and lipid profile parameters using the Sysmex XP-300TM automated analyzer and an automated biochemistry analyzer, and cfDNA was extracted using a standardized in house developed Phenol-Chloroform protocol and estimated using Agarose Gel Electrophoresis and Nanodrop. Statistical analysis was performed using SPSS ver. 21.0., Results: The results indicated a significant difference between stressed individuals and healthy controls in demographic, haematological and biochemical parameters. Specifically, stressed cases had significantly higher levels of cholesterol, LDL cholesterol, triglycerides, glucose, VLDL cholesterol, and lower levels of HDL compared to healthy controls. Stressed cases also showed significantly elevated levels of circulating cfDNA relative to healthy controls., Conclusion: These findings suggest that cfDNA may have potential as a diagnostic biomarker for stress., 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).)

Cardiovascular disease, particularly coronary heart disease, is becoming more common among those living with HIV. Individuals with HIV face an increased susceptibility to myocardial infarction, also known as a heart attack, as compared to the general population in developed countries. This heightened risk can be attributed mainly to the presence of effective antiretroviral drugs and the resulting longer lifespan. Some cardiac issues linked to non-antiretroviral medications, including myocarditis, endocarditis, cardiomyopathy with dilation, pulmonary hypertension, and oedema of the heart, may affect those not undergoing highly active antiretroviral therapy (ART). Impaired immune function and systemic inflammation are significant contributors to this phenomenon after initiating highly aggressive antiretroviral treatment ART. It is becoming more challenging to determine the best course of treatment for HIV-associated cardiomyopathy due to new research suggesting that protease inhibitors might have a negative impact on the development of HF. Currently, the primary focus of research on ART medications is centered on the cardiovascular adverse effects of nucleoside reverse transcriptase inhibitors and protease inhibitors. This review paper thoroughly evaluates the advancements achieved in cardiovascular disease research and explores the potential implications for prospects. Additionally, it considers the field's future prospects while examining how ART might be altered and its clinical applications., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests among them., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiovascular diseases (CVDs) are still leading to a significant number of deaths worldwide despite the remarkable advancements in medical technology and pharmacology. Managing patients with established CVDs is a challenge for healthcare providers as it requires reducing the chances of recurring cardiovascular events. On the other hand, changing one's way of life can also significantly impact this area, reducing the likelihood of cardiovascular disease and death through their unique advantages. Consequently, it is advisable for healthcare providers to regularly advise their patients with coronary issues to participate in organized physical exercise and improve their overall physical activity. Additionally, patients should adhere to a diet that promotes heart health, cease smoking, avoid exposure to secondhand smoke, and address any psychosocial stressors that may heighten the risk of cardiovascular problems. These lifestyle therapies, whether used alongside drug therapy or on their own in patients who may have difficulty tolerating medications, face financial barriers, or experience ineffectiveness, can substantially reduce cardiovascular mortality and the likelihood of recurring cardiac events. Despite the considerable advancements in creating interventions, it is still necessary to determine the optimal intensity, duration, and delivery method for these interventions. Furthermore, it is crucial to carry out further investigations incorporating extended monitoring and assessment of clinical outcomes to get a more comprehensive comprehension of the efficacy of these therapies. Presenting the findings within the framework of "lifestyle medicine," this review seeks to offer a thorough synopsis of the most recent scientific investigations into the potential of behavioral modifications to lower cardiovascular disease risk., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) are a unique family of endogenous RNAs devoid of 3' poly-A tails and 5' end caps. These single-stranded circRNAs, found in the cytoplasm, are synthesized via back-splicing mechanisms, merging introns, exons, or both, resulting in covalently closed circular loops. They are profusely expressed across the eukaryotic transcriptome and offer heightened stability against exonuclease RNase R compared to linear RNA counterparts. This review endeavors to provide a comprehensive overview of circRNAs' characteristics, biogenesis, and mechanisms of action. Furthermore, aimed to shed light on the potential of circRNAs as significant biomarkers in various cancer types. It has been performed an exhaustive literature review, drawing on recent studies and findings related to circRNA characteristics, synthesis, function, evaluation techniques, and their associations with oncogenesis. CircRNAs are intricately associated with tumor progression and development. Their multifaceted roles encompass gene regulation through the sponging of proteins and microRNAs, controlling transcription and splicing, interacting with RNA binding proteins (RBPs), and facilitating gene translation. Due to these varied roles, circRNAs have become a focal point in tumor pathology investigations, given their promising potential as both biomarkers and therapeutic agents. CircRNAs, due to their unique biogenesis and multifunctionality, hold immense promise in the realm of oncology. Their stability, widespread expression, and intricate involvement in gene regulation underscore their prospective utility as reliable biomarkers and therapeutic targets in cancer. As our understanding of circRNAs deepens, advanced techniques for their detection, evaluation, and manipulation will likely emerge. These advancements might catalyze the translation of circRNA-based diagnostics and therapeutics into clinical practice, potentially revolutionizing cancer care and prognosis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes. One of the primary reasons for mortality in individuals with diabetes is the presence of cardiac structural damage and functional abnormalities, which are the primary pathological features of DC. The aetiology of dilated cardiomyopathy is multifaceted and encompasses a range of processes, including metabolic abnormalities, impaired mitochondrial function, dysregulation of calcium ion homeostasis, excessive cardiomyocyte death, and fibrosis. In recent years, many empirical investigations have demonstrated that exercise training substantially impacts the prevention and management of diabetes. Exercise has been found to positively impact the recovery of diabetes and improve several metabolic problem characteristics associated with DC. One potential benefit of exercise is its ability to increase systolic activity, which can enhance cardiometabolic and facilitate the repair of structural damage to the heart caused by DC, leading to a direct improvement in cardiac health. In contrast, exercise has the potential to indirectly mitigate the pathological progression of DC through its ability to decrease circulating levels of sugar and fat while concurrently enhancing insulin sensitivity. A more comprehensive understanding of the molecular mechanism via exercise facilitates the restoration of DC disease must be understood. Our goal in this review was to provide helpful information and clues for developing new therapeutic techniques for motion alleviation DC by examining the molecular mechanisms involved., Competing Interests: Declaration of Competing Interest 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 © 2023 Elsevier Inc. All rights reserved.)

Tissue engineering is currently one of the fastest-growing areas of engineering, requiring the fabrication of advanced and multifunctional materials that can be used as scaffolds or dressings for tissue regeneration. In this work, we report a bilayer material prepared by electrospinning a hybrid material of poly(vinyl alcohol) (PVA) and bacterial cellulose (BC NFs) (top layer) over a highly interconnected porous 3D gelatin-PVA hydrogel obtained by a freeze-drying process (bottom layer). The techniques were combined to produce an advanced material with synergistic effects on the physical and biological properties of the two materials. The bilayer material was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a water contact measurement system (WCMS). Studies on swelling, degradability, porosity, drug release, cellular and antibacterial activities were performed using standardized procedures and assays. FTIR confirmed cross-linking of both the top and bottom layers, and SEM showed porous structure for the bottom layer, random deposition of NFs on the surface, and aligned NFs in the cross section. The water contact angle (WCA) showed a hydrophilic surface for the bilayer material. Swelling analysis showed high swelling, and degradation analysis showed good stability. The bilayer material released Ag-sulfadiazine in a sustained and controlled manner and showed good antibacterial activities against severe disease-causing gram + ive and -ive ( Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa ) bacterial strains. In vitro biological studies were performed on fibroblasts (3T3) and human embryonic kidneys (HEK-293), which showed desirable cell viability, proliferation, and adhesion to the bilayer. Thus, the synergistic effect of NFs and the hydrogel resulted in a potential wound dressing material for wound healing and soft tissue engineering., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)