ABSTRACT
Developing effective strategies to predict areas susceptible to landslides and reducing risk is vital. This involves using ensemble methods to meet the precise prediction and addressing challenges like data limitation. Recent studies have highlighted the potential of using ensemble methods to enhance the prediction of landslide susceptibility maps (LSM). Ensemble methods present a sampling of landslides and non-landslide points from high and low susceptible areas, respectively. Extensive research has explored their application in machine learning processes, particularly in classification-related problems. This study delves into strategies of ensemble as a promising method in future landslide applications. The proposed method was tested considering Kangra district of Himachal Pradesh as study area where three datasets were prepared consisting of presence and absence points. Dataset 1 consisted of initial landslide and randomly generated non-landslide points. In dataset 2, additional landslide points obtained from the very high susceptibility of initial LSM were supplemented with initial landslide data, while the non-landslide points were generated randomly from the study area. Finally, dataset 3 was composed of the landslide points as in dataset 2, and the non-landslide points were obtained from the very low susceptible areas of initial LSM. These datasets are used with random forest (RF) and support vector machine (SVM), thereby preparing six landslide susceptibility maps. To analyze the applicability of the proposed method, we have used metrics such as AUC-ROC, precision, recall, F-score, accuracy and Mathew's correlation coefficient (MCC). The AUC for dataset 1 with SVM and RF is 0.89, which increased to 0.898 and 0.952 for datasets 2 and 3 with SVM and 0.937 and 0.954 with RF. Among all the methods, the precision and recall values were highest for dataset 3 with SVM as well as RF. Hence, based on several accuracy metrics, we conclude that when the landslides and non-landslides samples were sampled from very high and very low susceptible areas respectively, the LSM performed better than all the other methods. Sampling landslides from very high susceptible areas only (dataset 2) does not perform well thereby committing misclassification error. The study demonstrated that the landslide and non-landslide data were obtained from very high and very low susceptibility; the predictive capability of the LSM increased significantly. Thus, the results demonstrate the effectiveness of the proposed ensemble approach in providing precise delineation of landslide zones, facilitating informed decision-making for land and hazard management.
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Parkinson's disease (PD) results from the degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Adenosine A2AR acting through the striato-pallidal pathway has emerged as a non-dopaminergic target in the therapy of PD. In the present work, the anti-parkinsonian potential of (4E)-4-(4-bromobenzylideneamino)-3-phenyl-2,3-dihydro-2-thioxo- thiazole-5-carbonitrile (BBPT) was explored. BBPT exhibited significant antioxidant activity in situ. In the MTT assay, the BBPT treatment showed insignificant toxicity to the primary midbrain neuronal (PMDN) cells. 6-OHDA induced PMDN cells, 3h post-treated with BBPT showed 80-85% survival of the cells and restoration of dopamine and TNF-α levels. The acute and sub-acute toxicity test for BBPT was performed with Sprague Dawley (SD) rats. In toxicity assay, any significant physical, hematological, or biochemical changes in the rats were not observed. To evaluate the effect of BBPT in vivo, a 6-OHDA-induced unilaterally lesioned SD rat model of PD was established. We observed that the BBPT treatment improved the behavioral symptoms in 6-OHDA-induced unilaterally lesioned rats. The proteins of 6-OHDA-induced BBPT-treated rats were isolated from the brain tissue to assess the antioxidant effect (GSH, catalase, SOD, lipid-peroxidation, nitrite), dopamine levels, and the restoration in the apoptosis and inflammation. Our results demonstrated that BBPT increased the anti-oxidant enzyme levels, restored the caspase-3/Bcl-2 levels to arrest apoptosis, and attenuated the TNF-α/IL-6 levels, thus restoring the neuronal damage in unilaterally lesioned 6-OHDA-induced SD rats. Precisely, the findings suggested that BBPT possessed significant anti-parkinsonian activity and has the potential to prevent dopaminergic neurodegeneration.
ABSTRACT
PURPOSE: This study aims to identify and prioritize the reasons for social media use among medical practitioners to facilitate the selection of the most appropriate social media platforms for healthcare providers. The findings of this study will help address the challenges posed by the wide variety of available social media platforms and assist healthcare providers in choosing platforms that best meet their professional needs. DESIGN/METHODOLOGY/APPROACH: This cross-sectional study was conducted in the period of two months, i.e., August and September 2021. This study is based on the AHP (Analytic Hierarchy Process) method of the MCDM (Multi-Criteria Decision-Making) approach. In the first phase, a four-hour brainstorming session was held to identify the medical Practitioner's reasons for social media usage; in the second phase, the identified reasons were linked with the top five social media platforms to determine the prioritized order of preference. FINDINGS: The top three reasons driving medical practitioners' usage of social media platforms include "Getting an update on current affairs," "Network with industry professionals," and "Healthy Lifestyle and Wellness Promotion." In contrast, the bottom three causes include "Advocacy for causes," "Get Updates about friends and family members," and "Opinions and ideas sharing." The prioritized order of social media platforms is LinkedIn, followed by Instagram, WhatsApp, Facebook, and Twitter. PRACTICAL IMPLICATIONS: This study helps solve the medical Practitioner's dilemma of selecting suitable social media platforms that serve their intended functions. In the future, it is expected that the usage of SM platforms will increase for causes such as Institution Branding and Healthcare Issues related Advocacy as well. ORIGINALITY/VALUE: Previous research has not adequately identified the reasons driving social media usage by physicians. This study is one of the few studies that has attempted to prioritize reasons for social media usage by physicians and has provided a prioritized list of social media platforms.
ABSTRACT
This study examines the concept of health advocacy and explores related scholarly material to understand its evolution from 1977 to 2021. The bibliometric analysis investigates the publication trends, most relevant authors, keywords-based clusters, research trends, author productivity, and future research areas in health advocacy. The relevant articles were extracted from the Scopus database and analyzed to identify and explore the most active authors, author-wise contribution to the sources, sub-research topics, core sources, top authors' production over time, global cited documents, thematic maps, word cloud, country-wise collaboration network and map, author keywords-based network, historiograph, and spectroscope. The study finds that health advocacy as a concept is under-explored and thus warrants a need for future research work. Limited authors have contributed to this theme, and the continuity of publication needs to be improved. The study highlights that there needs to be a robust framework to assess, evaluate, and implement health advocacy. The researchers are limited to only a few authors who have published in limited journals. The current study brings out the need for research and publications on health advocacy to develop a framework for assessing and implementing health advocacy. Also, the study highlights emerging themes of Coronavirus pandemic and emergency and disaster preparation. The niche themes that emerged during the survey highlight keywords such as agenda-setting and maternal health.
ABSTRACT
Worldwide, colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related deaths. Thymidylate synthase (TS) is a crucial component of DNA biosynthesis and has drawn interest as an essential target for cancer treatment. In the current work, we have designed and synthesized twenty-eight new diaryl-based pyrido[2,3-d]pyrimidine/alkyl-substituted pyrido[2,3-d]pyrimidine derivatives and evaluated their anticancer activity against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines cell lines. Additionally, we have carried out TS inhibitory activity and in silico studies for compounds 1n and 2j. All the synthesized compounds exhibited good anticancer activity, but among them, compounds 1n and 2j showed excellent anticancer activity, having IC50 values of 1.98 ± 0.69, 2.18 ± 0.93, 4.04 ± 1.06, and 4.18 ± 1.87 µM; and 1.48 ± 0.86, 3.18 ± 0.79, 3.44 ± 1.51, and 5.18 ± 1.85 µM, against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines respectively with control raltitrexed (IC50 1.07 ± 1.08, 1.98 ± 0.72, 1.34 ± 1.0, and 3.09 ± 0.96 µM, respectively) and hTS inhibitory activity with IC50 values of 20.47 ± 1.09 and 13.48 ± 0.96 nM with control raltitrexed (IC50 14.95 ± 1.01 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 1n and 2j to the catalytic site of TS with docking scores of -10.6 and - 9.5 kcal/mol, respectively, with reference raltitrexed (-9.4 kcal/mol). Additionally, the assessment of physicochemical, biochemical, structural, and toxicological characteristics were also in the acceptable range for these compounds. Based on the anticancer activity of compounds, SAR was also performed for lead optimization.
ABSTRACT
Employee empowerment as a management intervention promotes employee engagement: Psychological empowerment is found to influence employee engagement and organizational commitment, but the effect of structural empowerment (SE) is not explored much. SE increases employees' self-esteem, which can encourage a dissatisfied employee to look for other better work options, thus influencing their continuance commitment (CC). Workplace bullying is associated with higher turnover intentions and reduced commitment. This study investigates the mediating effects of person-related bullying (PB) and work-related bullying (WB) on the relationship between SE and CC. The study findings highlight the partial mediation effect of PB and serial mediation of WB and PB on the relationship between SE and CC. This study establishes that in comparison to WB, PB causes more damage to employee relationships with the organization. Moreover, the serial mediation effect of WB and PB is also noticed on the relationship between SE and CC. Organizations should regularly measure their employees' CC, as SE negatively affects CC. Organizations should take adequate measures to curb PB to preserve employee morale and confidence. This study uniquely reports a negative relationship between SE and CC.
This study validates that person-related bullying (PB) causes more damage to employee morale and confidence in comparison to work-related bullying (WB).Establishes the inverse relationship between structural empowerment (SE) and workplace bullying.Establishes the existence of a positive association between workplace bullying and PB.This study provides evidence of the mediating effect of PB on the relationship between SE and continuance commitment (CC).This study establishes WB induces personal bullying, which is established by the serial mediation effects of WB and PB on the relationship between SE and CC.
ABSTRACT
Male breast cancer (MBC), one of the rare types of cancer among men where the global incidence rate is 1.8% of all breast cancers cases with a yearly increase in a pace of 1.1%. Since the last 10 years, the incidence has been increased from 7.2% to 10.3% and the mortality rate was decreased from 11% to 3.8%. Nevertheless, the rate of diagnoses has been expected to be around 2.6% in the near future, still there is a great lack in studies to characterize the MBC including the developed countries. Based on our search, it is evidenced from the literature that the number of risk factors for the cause of MBC are significant, which includes the increase in age, family genetic history, mutations in specific genes due to various environmental impacts, hormonal imbalance and unregulated expression receptors for specific hormones of high levels of estrogen or androgen receptors compared to females. MBCs are broadly classified into ductal and lobular carcinomas with further sub-types, with some of the symptoms including a lump or swelling in the breast, redness of flaky skin in the breast, irritation and nipple discharge that is similar to the female breast cancer (FBC). The most common diagnostic tools currently in use are the ultrasound guided sonography, mammography, and biopsies. Treatment modalities for MBC include surgery, radiotherapy, chemotherapy, hormonal therapy, and targeted therapies. However, the guidelines followed for the diagnosis and treatment modalities of MBC are mostly based on FBC that is due to the lack of prospective studies related to MBC. However, there are distinct clinical and molecular features of MBC, it is a need to develop different clinical methods with more multinational approaches to help oncologist to improve care for MBC patients.
Subject(s)
Breast Neoplasms, Male , Humans , Breast Neoplasms, Male/therapy , Breast Neoplasms, Male/epidemiology , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/etiology , Male , Risk Factors , Incidence , FemaleABSTRACT
The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.
Subject(s)
NF-kappa B , Phytochemicals , Signal Transduction , Wound Healing , Wound Healing/drug effects , Humans , NF-kappa B/metabolism , NF-kappa B/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Phytochemicals/pharmacology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Phytotherapy/methodsABSTRACT
Natural Products continue to be the purest source of physiologically active molecules employed in the identification of possible lead compounds in the drug discovery process. Acanthaceae is a big plant family with around 2500 species, found primarily in subtropical and tropical regions, as well as the Mediterranean, Australia, and the United States. Several species of the Acanthaceae family have been used traditionally to treat a variety of diseases, including gastrointestinal and cardiovascular ailments, etc. Ruellia tuberosa commonly known as "Mexican Bluebell" is a perennial herb that originated in Central America and has spread to some countries in the Southern tropics and Southeast Asia. It has been utilized as a traditional Rasayana plant from ancient times. R. tuberosa extracts and phytochemicals showed potent bioactivities, such as anticancer, anti-inflammatory, wound healing, antifungal, antimicrobial, anti-diabetic, hypoglycemic, hypolipidemic, gastro-protective, and anthelminthic activities. Chemical analyses have unveiled a range of bioactive constituents within the plant, including alkaloids, flavonoids, saponins, and phenolic compounds, suggestive of its therapeutic potential. Collectively, this review provides an overview of R. tuberosa, encompassing its traditional uses, ethnomedicinal importance, phytochemistry, pharmacological properties, and toxicity.
Subject(s)
Acanthaceae , Medicine, Traditional , Phytochemicals , Humans , Phytochemicals/pharmacology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Acanthaceae/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , AnimalsABSTRACT
BACKGROUND: There are eighteen members of the Poly (ADP-ribose) polymerases (PARPs) family, which oversee various cellular processes such as maintaining the integrity of the genome, regulating transcription, cell cycle progression, initiating the DNA damage response, and apoptosis. PARP1 is an essential member of the PARP family and plays a crucial role in repairing single-strand breaks in eukaryotic cells through a process called BER (base excision repair). It is the most extensively studied and commonly found member of this family. AREA COVERED: This article discusses the advancements in developing PARP inhibitors for human cancers. It covers the discovery of new PARP1 inhibitors with chemical classification that selectively target multiple areas using cancer models in vitro and in vivo and evaluates them critically. The focus is on patents that have been published from 2017 to 2023, except tankyrase inhibitors. EXPERT OPINION: PARP1 inhibitors were developed by various companies and academic groups from the 1990s to enhance the effectiveness of chemo and radiotherapy. However, their progress was hindered due to their severe toxicity when combined with these treatments. Therefore, on finding PARP1 inhibitors that can amplify the ability of chemotherapy agents to kill tumors while causing minimal toxicity, these substances can either be used alone as part of the synthetic lethality approach or in conjunction with radiotherapy or chemotherapy, resulting in a mutually beneficial outcome.
ABSTRACT
Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.
Subject(s)
Phytochemicals , Prunus , Humans , Phytochemicals/chemistry , Phytochemicals/pharmacology , Prunus/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Pharmacognosy , Asia, Southeastern , AnimalsABSTRACT
The role of noncoding RNA has made remarkable progress in understanding progression, metastasis, and metastatic castration-resistant prostate cancer (mCRPC). A better understanding of the miRNAs has enhanced our knowledge of their targeting mainly at the therapy level in solid tumors, such as prostate cancer (PCa). microRNAs (miRNAs) belong to a class of endogenous RNA that deficit encoded proteins. Therefore, the role of miRNAs has been well-coined in the progression and development of PCa. miR-21 has a dual nature in its work both as a tumor suppressor and oncogenic role, but most of the recent studies showed that miR-21 is a tumor promoter and also is involved in castration-resistant prostate cancer (CRPC). Upregulation of miR-21 suppresses programmed cell death and inducing metastasis and castration resistant in PCa. miR-21 is involved in the different stages, such as proliferation, angiogenesis, migration, and invasion, and plays an important role in the progression, metastasis, and advanced stages of PCa. Recently, various studies directly linked the role of high levels of miR-21 with a poor therapeutic response in the patient of PCa. In the present review, we have explained the molecular mechanisms/pathways of miR-21 in PCa progression, metastasis, and castration resistant and summarized the role of miR-21 in diagnosis and therapeutic levels in PCa. In addition, we have spotlighted the recent therapeutic strategies for targeting different stages of PCa.
Subject(s)
Disease Progression , MicroRNAs , Prostatic Neoplasms , Humans , MicroRNAs/genetics , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Neoplasm Metastasis , Gene Expression Regulation, Neoplastic , PrognosisABSTRACT
We develop a theory to calculate structural correlations and thermodynamic properties of a fluid confined in a random porous solid medium (matrix). We used density functional formalism to derive an annealed averaged expression for the density profile and excess free energy of fluid arising due to random fields of a particular realization of the matrix. After performing the second average over the quenched-disordered variables, the excess free energy is organized to give one- and two-body potentials for fluid particles. The average over disorder reduces the system to an effective one-component system of fluid in which particles feel one-body (external) potential and interact via effective pair potential. The effective pair potential is a sum of the bare (the one in the pure fluid) and the matrix-induced potential. The resulting partition function involves only fluid variables. Equations are derived for fluid-fluid and fluid-matrix correlation functions and for free energy, pressure, and chemical potential of the fluid. The theory is applied to a model system of hard spheres and results for the effective pair potential, correlation functions, and thermodynamic properties are reported. The effective pair potential is found to be attractive at the contact and develops a repulsive peak before decaying to zero. Results for pair correlation function and structure factor are compared with simulation results for several fluid densities at two matrix densities. In all the cases, a very good agreement has been found.
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In view of the increasing risk of neurodegenerative diseases, epigenetics plays a fundamental role in the field of neuroscience. Several modifications have been studied including DNA methylation, histone acetylation, histone phosphorylation, etc. Histone acetylation and deacetylation regulate gene expression, and the regular activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) provides regulatory stages for gene expression and cell cycle. Imbalanced homeostasis in these enzymes causes a detrimental effect on neurophysiological function. Intriguingly, epigenetic remodelling via histone acetylation in certain brain areas has been found to play a key role in the neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. It has been demonstrated that a number of HATs have a role in crucial brain processes such regulating neuronal plasticity and memory formation. The most recent therapeutic methods involve the use of small molecules known as histone deacetylase (HDAC) inhibitors that antagonize HDAC activity thereby increase acetylation levels in order to prevent the loss of HAT function in neurodegenerative disorders. The target specificity of the HDAC inhibitors now in use raises concerns about their applicability, despite the fact that this strategy has demonstrated promising therapeutic outcomes. The aim of this review is to summarize the cross-linking between histone modification and its regulation in the pathogenesis of neurological disorders. Furthermore, these findings also support the notion of new pharmacotherapies that target particular areas of the brain using histone deacetylase inhibitors.
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BACKGROUND: v-RAF murine sarcoma viral homolog B1 (BRAF) is one of the most frequently mutated kinases in human cancers. BRAF exhibits three classes of mutations: Class I monomeric mutants (BRAFV600), class II BRAF homodimer mutants (non-V600), and class III BRAF heterodimers (non-V600). METHOD: In this manuscript, the protein-ligand interaction site of all three mutants: BRAF monomer, BRAF homodimer BRAF2:14-3-32, and BRAF heterodimer BRAF:14-3-32:MEK (Mitogen extracellular Kinase) has been discussed. FDA-approved drugs still have limitations against all three classes of mutants, especially against the second and third classes. Using the DesPot grid model, 1114 new compounds were designed. Using virtual screening, the three PDB Ids 4XV2 for monomers, 7MFF for homodimers, and 4MNE for heterodimers were used for 1114 newly designed compounds. RESULT: Dabrafenib, encorafenib, sorafenib and vemurafenib were included as standard drugs. The top 10 hit molecules were identified for each protein. Additional binding studies were performed using molecular docking studies on the protein-ligand site of each PDB identifier. Absorption, distribution, metabolism, excretion (ADME) and toxicity studies were also performed. CONCLUSION: It was identified that top-hit molecules had better binding and interaction activity than standard in all three classes of mutants.
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Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient's experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-ß, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.
Subject(s)
Complementary Therapies , Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/drug therapy , Wound Healing , Cytokines/metabolism , InflammationABSTRACT
PURPOSE: The objective of our study is to understand the factors associated with non-adherence to the physician's follow-up advice by persons with glaucoma. METHODS: We use a four-year panel dataset containing demographic, clinical, and intervention details and doctor's advised follow-up date for a random sample of 2,622 glaucoma patients from an Indian tertiary eye care hospital. We model this unique "advised follow-up date" in multivariate logistic regressions to identify factors associated with patients' coming early or late as against on-time. An OLS regression also examines an association between delayed follow-up and declining visual acuity. RESULTS: Demographic variables such as age, gender, distance to hospital, IOP, and visual acuity were not associated with delayed adherence to follow-up. Patients advised to review within 2 months (p < .001), paying patients (p < .001), and those habituated to routine follow-up (diabetes patients) (p < .01) are less likely to delay care-seeking. Patients are more likely to come on-time in visits immediately after clinical interventions relative to later ones (p < .001). Our second analysis reveals the presence of cataract and the very first post-surgery visit as factors influencing patients to come early. Our third analysis reveals that a higher proportion of delayed visits had resulted in worsening of vision in the glaucoma-affected eye. CONCLUSION: Our results suggest that active counselling by doctors, especially for routine follow-up visits, can help in better follow-up adherence and prevention of glaucoma-related visual impairment.
Subject(s)
Cataract , Glaucoma , Humans , Intraocular Pressure , Follow-Up Studies , Glaucoma/complications , Visual Acuity , Cataract/complicationsABSTRACT
Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).
Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , HIV-1 , Humans , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Molecular Docking Simulation , HIV Infections/drug therapy , Acquired Immunodeficiency Syndrome/chemically induced , Acquired Immunodeficiency Syndrome/drug therapy , HIV Reverse Transcriptase/metabolismABSTRACT
Deoxyuridine-5'-triphosphate nucleotidohydrolase (dUTPase), a vital enzyme in pyrimidine metabolism, is a prime target for treating colorectal cancer. Uracil shares structural traits with DNA/RNA bases, prompting exploration by medicinal chemists for pharmacological modifications. Some existing drugs, including thymidylate synthase (TS) and dUTPase inhibitors, incorporate uracil moieties. These derivatives hinder crucial cell proliferation pathways encompassing TS, dUTPases, dihydropyrimidine dehydrogenase, and uracil-DNA glycosylase. This review compiles uracil derivatives that have served as dUTPase inhibitors across various organisms, forming a library for targeting human dUTPase. Insights into their structural requisites for human applications and comparative analyses of binding pockets are provided for analyzing the compounds against human dUTPase.
Subject(s)
Colorectal Neoplasms , Uracil , Humans , Uracil/pharmacology , Uracil/therapeutic use , Chemistry, Pharmaceutical , Pyrophosphatases/metabolism , Colorectal Neoplasms/drug therapyABSTRACT
The amalgamation of the Internet of Things (IoT) and federated learning (FL) is leading the next generation of data usage due to the possibility of deep learning with data privacy preservation. The FL architecture currently assumes labeled data samples from a client for supervised classification, which is unrealistic. Most research works in the literature focus on local training, update receiving, and global model updates. However, by principle, the labeling must be performed on the client side because the data samples cannot leave the source under the FL principle. In the literature, a few works have proposed methods for unlabeled data for FL using "class-prior probabilities" or "pseudo-labeling". However, these methods make either unrealistic or uncommon assumptions, such as knowing class-prior probabilities are impractical or unavailable for each classification task and even more challenging in the IoT ecosystem. Considering these limitations, we explored the possibility of performing federated learning with unlabeled data by providing a clustering-based method of labeling the sample before training or federation. The proposed work will be suitable for every type of classification task. We performed different experiments on the client by varying the labeled data ratio, the number of clusters, and the client participation ratio. We achieved accuracy rates of 87% and 90% by using 0.01 and 0.03 of the truth labels, respectively.