Novel carbamodithioate regulates cellular hypoxia through chemical activation of prolyl hydroxylase-2 for breast cancer chemoprevention.

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.

Investigating the role of rotenone on human blood platelets: Molecular insights into abnormal platelet functions in Parkinson's disease.

Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin-induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca2+ mobilization from inositol 1,4,5-trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase-mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT-induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients.

Platelets and inter-cellular communication in immune responses: Dialogue with both professional and non-professional immune cells.

Platelets, derived from bone marrow megakaryocytes, are essential for vascular integrity and play multifaceted roles in both physiological and pathological processes within the vasculature. Despite their small size and absence of a nucleus, platelets are increasingly recognized for their diverse immune functions. Recent research highlights their pivotal role in interactions with various immune cells, including professional cells like macrophages, dendritic cells, natural killer cells, T cells, and B cells, influencing host immune responses. Platelets also engage with non-professional immune cells, contributing to immune responses and structural maintenance, particularly in conditions like inflammation and atherosclerosis. This review underscores the emerging significance of platelets as potent immune cells, elucidating their interactions with the immune system. We explore the mechanisms of platelet activation, leading to diverse functions, such as aggregation, immunity, activation of other immune cells, and pathogen clearance. Platelets have become the predominant immune cells in circulation, involved in chronic inflammation, responses to infections, and autoimmune disorders. Their immunological attributes, including bioactive granule molecules and immune receptors, contribute to their role in immune responses. Unlike professional antigen-presenting cells, platelets process and present antigens through an MHC-I-dependent pathway, initiating T-cell immune responses. This review illuminates the unique features of platelets and their central role in modulating host immune responses in health and disease.

Guarding Our Guardians: Navigating Adverse Reactions in Healthcare Workers Amid Personal Protective Equipment (PPE) Usage During COVID-19.

The widespread utilization of personal protective equipment (PPE) during the COVID-19 pandemic has been crucial for reducing transmission risk among healthcare workers (HCWs) and the public. However, the extensive use of PPE has brought about potential adverse reactions, particularly among HCWs. This study aims to investigate the prevalence and characteristics of adverse skin reactions associated with PPE use among different categories of HCWs, including faculty, residents, and nursing officers (NOs), in a dedicated tertiary care COVID-19 hospital. The study design was a hospital-based cross-sectional analytical study conducted over one month, involving a total of 240 participants. The participants were required to complete a pre-tested semi-structured questionnaire that covered demographic information, PPE-related data, preventive measures, observed reactions, and self-management strategies. Results indicated that adverse skin reactions were common among HCWs, with reactions reported by all participants. The most commonly used PPE included N95 masks, goggles, gloves, face shields, isolation gowns, and medical protective clothing. Excessive sweating (60% residents, 21.1% NOs, and 16.25% faculties), facial rash, dry palms (>70% of HCWs), and itching were among the most prevalent adverse reactions. Urticarial lesions (28.5% among NOs), pressure marks and pain (100% on the cheek among all HCWs), fungal infections (18.5% among residents at the web space of fingers), and skin breakdown were also reported. Factors such as age, gender, pre-existing skin problems, and oily/acne-prone skin history were found to be significantly associated with adverse skin reactions. In conclusion, the findings highlight the common adverse reactions reported by HCWs during the use of different PPEs. Certain steps taken by HCWs for the prevention of adverse reactions due to PPE emphasize the importance of tailored preventive measures and strategies to mitigate these adverse reactions, such as proper PPE selection, well-fitting equipment, regular breaks, and appropriate skincare practices. These insights contribute to the development of guidelines for optimal PPE usage and support the well-being of HCWs in their essential roles.

Natural product inspired diastereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones and their in-silico studies.

Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.

Assessing Residents in the Department of Surgery at a Tertiary Care Centre Using Mini-Clinical Evaluation Exercise (Mini-CEX).

OBJECTIVE: This study aimed to introduce, sensitize, and train our postgraduate students and faculty of the department of general surgery with the use of mini-Clinical Evaluation Exercise (mini­CEX) and to assess the perception of students and faculty towards it. MATERIAL AND METHODS: A cross­sectional observational study was conducted over a period of four months. Ten surgery residents in the department were asked to volunteer to participate and five professors conducted the session. Five sessions of mini­CEX (nine points) were conducted for each resident in different settings of the out­patient department (OPD) and in­patient department (IPD). A total of five skills were tested. Feedback from faculty and residents regarding the perception of mini­CEX was also taken. RESULTS: A statistically significant difference in mean scores of all domains was observed comparing the first and last assessment (p<0.05). Hundred percent of the residents scored superior category (7-9) in the final assessment in all domains, whereas the maximum was in a satisfactory scoring grade in 1st assessment. The time taken for the assessment significantly reduced from 1st assessment to the last assessment in OPD and IPD settings (p=0.001). The mini-CEX assessment tool got 100% feedback from faculty in terms of skill improvement, method, attitude of residents, and ability to identify gaps in knowledge. However, one assessor thought that "time given for assessment" was inadequate and more effort was required than the usual traditional assessment methods. The most identified problem faced by residents was that the "time given during assessment" was less (50%); however, overall residents also found it valid, effective, and helpful in identifying knowledge gaps and improving clinical and communication skills. CONCLUSION: Mini­CEX improves the learning environment in residency and also leads to improvement in medical interviewing skills, physical examination skills, humanistic qualities/professionalism, and counseling skills. So, it can be used for residency training in clinical departments.

Nanoinformatics based insights into the interaction of blood plasma proteins with carbon based nanomaterials: Implications for biomedical applications.

In the past three decades, interest in using carbon-based nanomaterials (CBNs) in biomedical application has witnessed remarkable growth. Despite the rapid advancement, the translation of laboratory experimentation to clinical applications of nanomaterials is one of the major challenges. This might be attributed to poor understanding of bio-nano interface. Arguably, the most significant barrier is the complexity that arises by interplay of several factors like properties of nanomaterial (shape, size, surface chemistry), its interaction with suspending media (surface hydration and dehydration, surface reconstruction and release of free surface energy) and the interaction with biomolecules (conformational change in biomolecules, interaction with membrane and receptor). Tailoring a nanomaterial that minimally interacts with protein and lipids in the medium while effectively acts on target site in biological milieu has been very difficult. Computational methods and artificial intelligence techniques have displayed potential in effectively addressing this problem. Through predictive modelling and deep learning, computer-based methods have demonstrated the capability to create accurate models of interactions between nanoparticles and cell membranes, as well as the uptake of nanomaterials by cells. Computer-based simulations techniques enable these computational models to forecast how making particular alterations to a material's physical and chemical properties could enhance functional aspects, such as the retention of drugs, the process of cellular uptake and biocompatibility. We review the most recent progress regarding the bio-nano interface studies between the plasma proteins and CBNs with a special focus on computational simulations based on molecular dynamics and density functional theory.

Novel furan chalcone modulates PHD-2 induction to impart antineoplastic effect in mammary gland carcinoma.

Normoxic inactivation of prolyl hydroxylase-2 (PHD-2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF-1α and NF-κB. Henceforth, the present study is aimed to identify small molecule activators of PHD-2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD-2 activation potential of screened compound was determined using in vitro 2-oxoglutarate assay. The cytotoxic activity and apoptotic potential of screened compound was determined using various staining techniques, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 4',6-diamidino-2-phenylindole (DAPI), 1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), and acridine orange/ethidium bromide (AO/EB), against MCF-7 cells. 7,12-Dimethylbenz[a]anthracene (DMBA) model of mammary gland cancer was used to study the in vivo antineoplastic efficacy of screened compound. [(E)-1-(4-fluorophenyl)-3-(furan-2-yl) prop-2-en-1-one] (BBAP-7) was screened and validated as a PHD-2 activator by an in vitro 2-oxo-glutarate assay. The IC50 of BBAP-7 on MCF-7 cells is 18.84 µM. AO/EB and DAPI staining showed nuclear fragmentation, blebbing and condensation in MCF-7 cells following BBAP-7 treatment. The red-to-green intensity ratio of JC-1 stained MCF-7 cells decreased after BBAP-7 treatment, indicating mitochondrial-mediated apoptosis. DMBA caused mammary gland dysplasia, duct hyperplasia and ductal carcinoma in situ. Carmine staining, histopathology, and scanning electron microscopy demonstrated that BBAP-7, alone or with tirapazamine, restored mammary gland surface morphology and structural integrity. Additionally, BBAP-7 therapy significantly reduced oxidative stress and glycolysis. The findings reveal that BBAP-7 activates PHD-2, making it a promising anticancer drug.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

The Microbiome Modulates the Immune System to Influence Cancer Therapy.

The gut microbiota composition can affect the tumor microenvironment and its interaction with the immune system, thereby having implications for treatment predictions. This article reviews the studies available to better understand how the gut microbiome helps the immune system fight cancer. To describe this fact, different mechanisms and approaches utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only calorie intake but also the variety and quality of diet can influence cancer patients' immunotherapy treatment because dietary patterns can impair immunological activities either by stimulating or suppressing innate and adaptive immunity. Therefore, it is interesting and critical to understand gut microbiome composition as a biomarker to predict cancer immunotherapy outcomes and responses. Here, more emphasis will be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies, which is beneficial for cancer patients.

Oxidative stress in Alzheimer's disease: current knowledge of signaling pathways and therapeutics.

Alzheimer's disease's pathophysiology is still a conundrum. Growing number of evidences have elucidated the involvement of oxidative stress in the pathology of AD rendering it a major target for therapeutic development. Reactive oxygen species (ROS) generated by altered mitochondrial function, dysregulated electron transport chain and other sources elevate aggregated Aß and neurofibrillary tangles which further stimulating the production of ROS. Oxidative stress induced damage to lipids, proteins and DNA result in neuronal death which leads to AD. In addition, oxidative stress induces apoptosis that is triggered by the modulation of ERK1/2 and Nrf2 pathway followed by increased GSK-3ß expression and decreased PP2A activity. Oxidative stress exaggerates disease condition by interfering with various signaling pathways like RCAN1, CREB/ERK, Nrf2, PP2A, NFκB and PI3K/Akt. Studies have reported the role of TNF-α in oxidative stress stimulation that has been regulated by drugs like etanercept increasing the level of anti-oxidants. Other drugs like pramipexole, memantine, carvedilol, and melatonin have been reported to activate CREB/RCAN1 and Nrf2 pathways. In line with this, epigallocatechin gallate and genistein also target Nrf2 and CREB pathway leading to activation of downstream pathways like ARE and Keap1 which ameliorate oxidative stress condition. Donepezil and resveratrol reduce oxidative stress and activate AMPK pathway along with PP2A activation thus promoting tau dephosphorylation and neuronal survival. This study describes in detail the role of oxidative stress in AD, major signaling pathways involving oxidative stress induced AD and drugs under development targeting these pathways which may aid in therapeutic advances for AD.

Tackling municipal solid waste crisis in India: Insights into cutting-edge technologies and risk assessment.

Municipal Solid Waste (MSW) management is a pressing global concern, with increasing interest in Waste-to-Energy Technologies (WTE-T) to divert waste from landfills. However, WTE-T adoption is hindered by financial uncertainties. The economic benefits of MSW treatment and energy generation must be balanced against environmental impact. Integrating cutting-edge technologies like Artificial Intelligence (AI) can enhance MSW management strategies and facilitate WTE-T adoption. This review paper explores waste classification, generation, and disposal methods, emphasizing public awareness to reduce waste. It discusses AI's role in waste management, including route optimization, waste composition forecasting, and process parameter optimization for energy generation. Various energy production techniques from MSW, such as high-solids anaerobic digestion, torrefaction, plasma pyrolysis, incineration, gasification, biodegradation, and hydrothermal carbonization, are examined for their advantages and challenges. The paper emphasizes risk assessment in MSW management, covering chemical, mechanical, biological, and health-related risks, aiming to identify and mitigate potential adverse effects. Electronic waste (E-waste) impact on human health and the environment is thoroughly discussed, highlighting the release of hazardous substances and their contribution to air, soil, and water pollution. The paper advocates for circular economy (CE) principles and waste-to-energy solutions to achieve sustainable waste management. It also addresses complexities and constraints faced by developing nations and proposes strategies to overcome them. In conclusion, this comprehensive review underscores the importance of risk assessment, the potential of AI and waste-to-energy solutions, and the need for sustainable waste management to safeguard public health and the environment.

Harnessing two-dimensional nanomaterials for diagnosis and therapy in neurodegenerative diseases: Advances, challenges and prospects.

Neurodegenerative diseases (NDDs) are specific brain disorders characterized by the progressive deterioration of different motor activities as well as several cognitive functions. Current conventional therapeutic options for NDDs are limited in addressing underlying causes, delivering drugs to specific neuronal targets, and promoting tissue repair following brain injury. Due to the paucity of plausible theranostic options for NDDs, nanobiotechnology has emerged as a promising field, offering an interdisciplinary approach to create nanomaterials with high diagnostic and therapeutic efficacy for these diseases. Recently, two-dimensional nanomaterials (2D-NMs) have gained significant attention in biomedical and pharmaceutical applications due to their precise drug-loading capabilities, controlled release mechanisms, enhanced stability, improved biodegradability, and reduced cell toxicity. Although various studies have explored the diagnostic and therapeutic potential of different nanomaterials in NDDs, there is a lack of comprehensive review addressing the theranostic applications of 2D-NMs in these neuronal disorders. Therefore, this concise review aims to provide a state-of-the-art understanding of the need for these ultrathin 2D-NMs and their potential applications in biosensing and bioimaging, targeted drug delivery, tissue engineering, and regenerative medicine for NDDs.

Prospecting the Potential of Plant Growth-Promoting Microorganisms for Mitigating Drought Stress in Crop Plants.

Drought is a global phenomenon affecting plant growth and productivity, the severity of which has impacts around the whole world. A number of approaches, such as agronomic, conventional breeding, and genetic engineering, are followed to increase drought resilience; however, they are often time consuming and non-sustainable. Plant growth-promoting microorganisms are used worldwide to mitigate drought stress in crop plants. These microorganisms exhibit multifarious traits, which not only help in improving plant and soil health, but also demonstrate capabilities in ameliorating drought stress. The present review highlights various adaptive strategies shown by these microbes in improving drought resilience, such as modulation of various growth hormones and osmoprotectant levels, modification of root morphology, exopolysaccharide production, and prevention of oxidative damage. Gene expression patterns providing an adaptive edge for further amelioration of drought stress have also been studied in detail. Furthermore, the practical applications of these microorganisms in soil are highlighted, emphasizing their potential to increase crop productivity without compromising long-term soil health. This review provides a comprehensive coverage of plant growth-promoting microorganisms-mediated drought mitigation strategies, insights into gene expression patterns, and practical applications, while also guiding future research directions.

Recent advances in the synthesis and utility of thiazoline and its derivatives.

Thiazolines and their derivatives hold significant importance in the field of medicinal chemistry due to their promising potential as pharmaceutical agents. These molecular entities serve as critical scaffolds within numerous natural products, including curacin A, thiangazole, and mirabazole, and play a vital role in a wide array of physiological reactions. Their pharmacological versatility encompasses anti-HIV, neurological, anti-cancer, and antibiotic activities. Over the course of recent decades, researchers have extensively explored and developed analogs of these compounds, uncovering compelling therapeutic properties such as antioxidant, anti-tumor, anti-microbial, and anti-inflammatory effects. Consequently, thiazoline-based compounds have emerged as noteworthy targets for synthetic endeavors. In this review, we provide a comprehensive summary of recent advancements in the synthesis of thiazolines and thiazoline-based derivatives, along with an exploration of their diverse potential applications across various scientific domains.

Two-year results from Onyx ONE clear in patients with high bleeding risk on one-month DAPT with and without intracoronary imaging.

BACKGROUND: Patients with high bleeding risk (HBR) are often treated with abbreviated dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) to reduce bleeding risk, however this strategy is associated with an increase in ischemic events, especially if the acute PCI result is suboptimal. We compared clinical outcomes among patients with HBR treated with 1-month DAPT who underwent intravascular ultrasound (IVUS)- or optical coherence tomography (OCT)-guided PCI versus those who underwent angiography-guided PCI without intravascular imaging. METHODS: The Onyx ONE Clear study includes patients with HBR from the Onyx ONE US/Japan and Onyx ONE randomized studies who were treated with the Resolute Onyx zotarolimus-eluting stent. The primary endpoint was the composite of cardiac death (CD) or myocardial infarction (MI) between 1 month and 2 years after PCI. Propensity-score adjustments and matching were performed for differences in baseline and procedural characteristics between groups. RESULTS: Among the 1507 patients in Onyx ONE Clear, 271 (18.0 %) had IVUS or OCT used during PCI (Imaging-guided group) and 1236 (82.0 %) underwent Angiography-guided PCI (Angio-guided group). Imaging-guided patients were less likely to present with atrial fibrillation, acute coronary syndrome, and left ventricle ejection fraction ≤35 %. Conversely, Imaging-guided patients were more likely to have complex (ACC/AHA type B2/C), longer, and heavily calcified lesions. Between 1 month and 2 years, the composite rate of CD or MI was similar between Imaging-guided and Angio-guided patients (9.9 % vs. 12.4 %, P = 0.33). There was also no difference between groups after adjustment; (P = 0.56). However, CD was significantly lower among Imaging-guided patients (2.7 % vs. 6.1 %, P = 0.048). There were no between-group differences in MI or stent thrombosis. Propensity score matching results were similar. CONCLUSION: Despite higher lesion complexity, using intravascular imaging guidance for PCI between 1-month and 2-years follow-up had comparable outcomes with angiographic guidance alone in patients with HBR treated with 1-month DAPT. (ClinicalTrials.gov: Identifier: NCT03647475 and NCT03344653). NON-STANDARD ABBREVIATIONS AND ACRONYMS: BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; DES: drug-eluting stent; HBR: high bleeding risk; IVUS: intravascular ultrasound; OCT: optical coherence tomography; SAPT: single antiplatelet therapy.

HIV cure: Are we going to make history?

BACKGROUND: At present, combination antiretroviral therapy (cART) is the mainstay for the treatment of people living with HIV/AIDS. cART can suppress the viral load to a minimal level; however, the possibility of the emergence of full-blown AIDS is always there. In the latter part of the first decade of the 21st century, an HIV-positive person received stem cell transplantation (SCT) for treatment of his haematological malignancy. The patient was able to achieve remission of the haematological condition as well as of HIV following SCT. Thorough investigations of various samples including blood and biopsy could not detect the virus in the person's body. The person was declared to be the first cured case of HIV. LITERATURE SEARCH: Over the next decade, a few more similar cases were observed and have recently been declared cured of the infection. A comprehensive search was performed in PubMed, Cochrane library and Google Scholar. Four such additional cases were found in literature. DESCRIPTION & DISCUSSION: These cases all share a common proposed mechanism for the HIV cure, that is, transplantation of stem cells from donors carrying a homozygous mutation in a gene encoding for CCR5 (receptor utilized by HIV for entry into the host cell), denoted as CCR5△32. This mutation makes the host immune cells devoid of CCR5, causing the host to acquire resistance against HIV. To the best of our knowledge, this is the first review to look at relevant and updated information of all cured cases of HIV as well as the related landmarks in history and discusses the underlying mechanism(s).

A novel hybrid model integrating MFCC and acoustic parameters for voice disorder detection.

Voice is an essential component of human communication, serving as a fundamental medium for expressing thoughts, emotions, and ideas. Disruptions in vocal fold vibratory patterns can lead to voice disorders, which can have a profound impact on interpersonal interactions. Early detection of voice disorders is crucial for improving voice health and quality of life. This research proposes a novel methodology called VDDMFS [voice disorder detection using MFCC (Mel-frequency cepstral coefficients), fundamental frequency and spectral centroid] which combines an artificial neural network (ANN) trained on acoustic attributes and a long short-term memory (LSTM) model trained on MFCC attributes. Subsequently, the probabilities generated by both the ANN and LSTM models are stacked and used as input for XGBoost, which detects whether a voice is disordered or not, resulting in more accurate voice disorder detection. This approach achieved promising results, with an accuracy of 95.67%, sensitivity of 95.36%, specificity of 96.49% and f1 score of 96.9%, outperforming existing techniques.

Artificial Intelligence and Machine Learning in Pharmacological Research: Bridging the Gap Between Data and Drug Discovery.

Artificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.

Characteristic features of self-avoiding active Brownian polymers under linear shear flow.

We present Brownian dynamics simulation results of a flexible linear polymer with excluded-volume interactions under shear flow in the presence of active noise. The active noise strongly affects the polymer's conformational and dynamical properties, such as the stretching in the flow direction and compression in the gradient direction, shear-induced alignment, and shear viscosity. In the asymptotic limit of large activities and shear rates, the power-law scaling exponents of these quantities differ significantly from those of passive polymers. The chain's shear-induced stretching at a given shear rate is reduced by active noise, and it displays a non-monotonic behavior, where an initial polymer compression is followed by its stretching with increasing active force. The compression of the polymer in the gradient direction follows the relation ∼WiPe-3/4 as a function of the activity-dependent Weissenberg number WiPe, which differs from the scaling observed in passive systems ∼WiPe-1/2. The flow-induced alignment at large Péclet numbers Pe ≫ 1, where Pe is the Péclet number, and large shear rates WiPe ≫ 1 displays the scaling behavior WiPe-1/2, with an exponent differing from the passive value -1/3. Furthermore, the polymer's zero-shear viscosity displays a non-monotonic behavior, decreasing in an intermediate activity regime due to excluded-volume interactions and increasing again for large Pe. Shear thinning appears with increasing Weissenberg number with the power-laws WiPe-1/2 and WiPe-3/4 for passive and active polymers, respectively. In addition, our simulation results are compared with the results of an analytical approach, which predicts quantitatively similar behaviors for the various aforementioned physical quantities.