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Background: Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.Methods: In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3beta in IDCs of breast.Results: Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.Conclusion: The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3beta with beta-catenin in implementing EMT in these cells. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy., Methods: Human MSCs were derived from bone marrow (BM) and Wharton's Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined., Results: Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCs HYP+APO were superior to BM-MSCs HYP+APO for immune regulation. These induced the differentiation of CD4 + T-cell into Tregs, enhanced Th2 effector responses, and simultaneously mitigated Th1- and Th17 responses. Additionally, this approach led to the polarization of M1 macrophages toward an M2 phenotype., Conclusion: Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD., (© 2024. The Author(s).)

The WNT/β-catenin is among one of the most extensively studied cellular signaling pathways involved in the initiation and progression of several deadly cancers. It is now understood that the WNT/β-catenin signaling, during tumor progression operates in a very complex fashion beyond the earlier assumed simple WNT 'On' or 'Off' mode as it recruits numerous WNT ligands, receptors, transcriptional factors and also cross-talks with other signaling molecules including the noncanonical WNT regulators. WNT/β-catenin signaling molecules are often mutated in different cancers which makes them very challenging to inhibit and sometimes ranks them among the undruggable targets. Furthermore, due to the evolutionary conservation of this pathway, inhibiting WNT/β-catenin has caused significant toxicity in normal cells. These challenges are reflected in clinical trial data, where the use of WNT/β-catenin inhibitors as standalone treatments remains limited. In this review, we have highlighted the crucial functional associations of diverse WNT/β-catenin signaling regulators with cancer progression and the phenotypic switching of tumor cells. Next, we have shed light on the roles of WNT/β-catenin signaling in drug resistance, clonal evolution, tumor heterogeneity, and immune evasion. The present review also focuses on various classes of routine and novel WNT/β-catenin therapeutic regimes while addressing the challenges associated with targeting the regulators of this complex pathway. In the light of multiple case studies on WNT/β-catenin inhibitors, we also highlighted the challenges and opportunities for future clinical trial strategies involving these treatments. Additionally, we have proposed strategies for future WNT/β-catenin-based drug discovery trials, emphasizing the potential of combination therapies and AI/ML-driven prediction approaches. Overall, here we showcased the opportunities, possibilities, and potentialities of WNT/β-catenin signaling modulatory therapeutic regimes as promising precision cancer medicines for the future., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Purusottam Mohapatra reports financial support, equipment, drugs, or supplies, and travel were provided by DBT India. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A balanced equilibrium between carnivores and their prey is crucial for maintaining ecosystem sustainability. In this study, we applied the predator-prey power law equation to assess the balance between the biomass densities of carnivores and their wild prey within Nepal's lowland protected areas during 2013, 2018, and 2022. The estimated value of the power law exponent k for predator-prey biomass was 0.71 (95% CI = 0.39-1.05), indicating an approximate threefold increase in predator biomass density for every fivefold increase in prey biomass density. Consequently, this creates a systematically bottom-heavy predator-prey biomass pyramid. This finding, consistent with the k  = 3/4 trophic biomass scaling across ecosystems, suggests that predator biomass is proportionally sustained by prey biomass, indicating a balance between top predators and their wild prey in Nepal's lowland protected areas. We further demonstrated it is possible to retain the overall power law exponent while jointly measuring intraguild competition between two predators with canonical correlation analysis. This understanding opens avenues for future research directed toward unraveling the factors that drive these consistent growth patterns in ecological communities., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Canine distemper virus (CDV) is responsible for a highly contagious and often fatal neurological disease that affects various carnivores, including domestic dogs. In Nepal, recent reports of CDV exposure and illness in leopards (Panthera pardus) have raised concerns about the transmission of the virus among domestic dogs and wild carnivores. To investigate the genetic lineage and spread of CDV, our study utilized archived post-mortem samples from four leopards that exhibited clinical signs suggestive of canine distemper infection. These leopards were rescued in the Palpa, Dolakha, Kathmandu, and Parbat districts. Our phylogenetic analysis revealed that the CDV strains circulating among the leopards belong to the Asia-5 lineage, which is also prevalent among dogs and wild carnivores in Nepal and neighboring India. The genetic relatedness between the leopard CDV sequences and those from both dogs and other carnivores within the Asia-5 lineage suggests that leopards in Nepal may have acquired the virus from multiple sources, potentially facilitated by their generalist dietary habits preying on dogs and even mesocarnivores. Furthermore, we inspected specific amino acid substitution in the hemagglutinin gene of leopard CDV, which also suggests possible transmission from both domestic dogs and non-canid hosts, although further research is needed to draw definitive conclusions. Given the vulnerable state of the leopard population in Nepal, already threatened by poaching and retaliatory killing, the emergence of CDV as a potential novel threat is deeply concerning. Comprehensive surveillance studies are essential to understand the dynamics of CDV spillover and to develop informed interventions. Urgent measures, including vaccination programs and effective control of the dog population, are needed to mitigate the impact of this disease and safeguard the future of Nepal's leopards and other wild carnivores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Chimeric antigen receptor (CAR) T-cell therapy represents a significant advancement in cancer treatment, particularly for hematologic malignancies. Various cancer immunotherapy strategies are presently being explored, including cytokines, cancer vaccines, immune checkpoint inhibitors, immunomodulators monoclonal antibodies, etc. The therapy has shown impressive efficacy in treating conditions such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma, often leading to complete remission in refractory cases. However, the clinical application of CAR T-cell therapy is accompanied by challenges, notably severe side effects. Effective management of these adverse effects requires meticulous monitoring and prompt intervention, highlighting the critical role of nursing in this therapeutic process. Nurses play a crucial role in patient education, monitoring, symptom management, care coordination, and psychosocial support, ensuring safe and effective treatment. As research advances and new CAR T-cell therapies are developed, the role of nursing professionals remains pivotal in optimizing patient outcomes. The continued evolution of CAR T-cell therapy promises improved outcomes, with nursing professionals integral to its success., (© 2024 The Authors.)

Imazethapyr is the most common herbicide used for weed management in pulses. A field trial was carried out with imazethapyr 10% SL formulation at 100 and 150 g a.i./ha application rates, as pre-and post-emergence, to study dissipation of imazethapyr in soil, persistence in urdbean plant, terminal residues in urdbean grains and effect on soil microbes. An acetate buffered- quick, easy, cheap, effective, rugged, and safe (QuEChERS) method in combination with high-performance liquid chromatography (HPLC) was validated for imazethapyr residue analysis. The half-life of imazethapyr in soil ranged from 15.12 to 18.02 days. The residues of imazethapyr persist up to 60 days in soil and up to 7-15 days in urdbean plant. Residues were not detected in grains at the time of harvest. Persistence of imazethapyr residues in soil significantly impact soil microbial populations depending on herbicide application rates and timing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings., (© 2024 International Federation of Cell Biology.)

Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other's beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell's genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy., 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 Dagar, Gupta, Shankar, Chauhan, Macha, Bhat, Das, Goyal, Bhoriwal, Pandita, Prasad, Sarkar, Pandita and Singh.)

Despite many efforts, a comprehensive understanding and clarification of the intricate connections within cancer cell metabolism remain elusive. This might pertain to intracellular dynamics and the complex interplay between cancer cells, and cells with the tumor stroma. Almost a century ago, Otto Warburg found that cancer cells exhibit a glycolytic phenotype, which continues to be a subject of thorough investigation. Past and ongoing investigations have demonstrated intricate mechanisms by which tumors modulate their functionality by utilizing extracellular glucose as a substrate, thereby sustaining the essential proliferation of cancer cells. This concept of "aerobic glycolysis," where cancer cells (even in the presence of enough oxygen) metabolize glucose to produce lactate plays a critical role in cancer progression and is regulated by various signaling pathways. Recent research has revealed that the canonical wingless-related integrated site (WNT) pathway promotes aerobic glycolysis, directly and indirectly, thereby influencing cancer development and progression. The present review seeks to gather knowledge about how the WNT/β-catenin pathway influences aerobic glycolysis, referring to relevant studies in different types of cancer. Furthermore, we propose the concept of impeding the glycolytic phenotype of tumors by employing specific inhibitors that target WNT/β-catenin signaling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The purpose of the study was to compare the effectiveness of yoga as a form of Vestibular Rehabilitation (VR) to standard VR for managing patients with symptoms such as dizziness, disequilibrium and gait instability., Methods: 150 participants based on 18-point difference in the DHI score were randomly assigned to group 1- Yoga, group 2- VR and group 3- control group using block randomization. The intervention was provided for 12 weeks. The participants were assessed for Dizziness Handicap Inventory (DHI) at baseline, 4 th , 8 th and 12 th week., Results: The mean DHI for group 1(41.12±7.13) group 2 (42.96±10.54) group 3 (50.84±10.78), p<0.001 decreased significantly in group 1 and 2 when compared to baseline. There was no statistically significant difference in overall Dizziness Handicap Inventory (DHI) scores between the Yoga and Physiotherapy groups after one month; however, both groups resulted in a significant decrease in scores when compared to the control group. Similarly, by the end of the second and third months, there was no significant distinction between the Yoga and Physiotherapy groups, even though both had a considerable decrease in DHI scores when compared to the control group. Furthermore, an examination of the functional, emotional, and physical components of DHI demonstrated persistent trends of significant improvement in both the Yoga and Physiotherapy groups as compared to the control group over a three-month period., Conclusions: In addition to VR, Yoga and medications administered concurrently can provide effective therapeutic effects. Yoga has an advantage over VR since it offers a customized cure for giddiness in addition to symptom relief. Yoga might be a great alternative to the conventional VR because along with enhancing overall body relaxation, it is affordable and is easy to learn., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Vaishali K et al.)

Purpose: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS., Methods: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression., Results: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4)., Conclusion: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

The effect of the increase in the alkyl chain length of cation on the properties of deep eutectic solvents based on ethylene glycol has been investigated employing classical molecular dynamics simulations. The change in the structural and dynamic properties in both the bulk and liquid-vapor interface is explored through various analyses. The interaction between the anion and the ethylene glycol increases with an increase in the alkyl chain length of the cation, as observed in the increase of the lifetime of the hydrogen bond formed between the two. The terminal carbon atoms are found to be closer to each other when the cation changes from tetraethylammonium to tetrabutylammonium. The cations are located closer to the interface, and the association of the alkyl chains becomes more significant with increased alkyl chain length, decreasing the surface tension values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sheet metal forming is one of the key processes for the automotive sector to be considered. Sheet metal formability is being tested as received, joining them with different welding/joining processes (i.e., tailored blanks) and making them as sandwich forms to reduce the total weight of the body. These sandwich formations of sheets are an advanced method by incorporating PVC/polymer sheets in between metal sheets with a suitable binder. The present work has investigated the formability of AA5052-PVC-AA5052 (Al-PVC-Al) sandwich sheets by considering the sheet rolling direction as a parameter. The mechanical properties of base metal and sandwich sheets were evaluated by conducting the uniaxial tensile tests. For forming behaviour of Al-PVC-Al sandwich sheets, in-plane plane stretching tests were performed on the universal tensile testing machine. From the results, it has been observed that 0-degree and 90-degree rolling direction of AA5052 sheets provided almost similar forming behaviour where the 45-degree rolling direction showed less formability. The limit strains (by which the forming limit curve has been developed and the safe and failure zones are separated) are 0.043, 0.038, and 0.043 of 0°, 45°, and 90°, respectively. Considering 0°-P-90°, 90°-P-90, 0°-P-45°, 0°-P-90°, and 45°-P-45° sandwich sheets with their corresponding limit strains of 0.060, 0.058,0.057, 0.052, and 0.050, a better formability is seen in 0°-P-90° sandwich, followed by 90°-P-90, 0°-P-45°, 0°-P-90°, and 45°-P-45°. The improvement in the formability is calculated as 28.33%, 25.86%, and 24.0% in comparison with the base metal in 0-degree, 90-degree, and 45-degree rolling directions and 0°-P-90°, 90°-P-90, and 45°-P-45° sandwich sheets., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 P. Praveen Kumar Reddy et al.)

β-catenin is an evolutionary conserved, quintessential, multifaceted protein that plays vital roles in cellular homeostasis, embryonic development, organogenesis, stem cell maintenance, cell proliferation, migration, differentiation, apoptosis, and pathogenesis of various human diseases including cancer. β-catenin manifests both signaling and adhesive features. It acts as a pivotal player in intracellular signaling as a component of versatile WNT signaling cascade involved in embryonic development, homeostasis as well as in carcinogenesis. It is also involved in Ca 2+ dependent cell adhesion via interaction with E-cadherin at the adherens junctions. Aberrant β-catenin expression and its nuclear accumulation promote the transcription of various oncogenes including c-Myc and cyclinD1, thereby contributing to tumor initiation, development, and progression. β-catenin's expression is closely regulated at various levels including its stability, sub-cellular localization, as well as transcriptional activity. Understanding the molecular mechanisms of regulation of β-catenin and its atypical expression will provide researchers not only the novel insights into the pathogenesis and progression of cancer but also will help in deciphering new therapeutic avenues. In the present review, we have summarized the dual functions of β-catenin, its role in signaling, associated mutations as well as its role in carcinogenesis and tumor progression of various cancers. Additionally, we have discussed the challenges associated with targeting β-catenin molecule with the presently available drugs and suggested the possible way forward in designing new therapeutic alternatives against this oncogene.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions., Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs., Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records., Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma., Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Psychiatry.)

The soundscape study of an eastern Indian coastal city (Puri) has been investigated. Acoustic data were collected at 36 sampling locations during two time intervals in and around Puri. A number of noise indices, namely, Lmin, Lmax, and Leq, were calculated to demonstrate the noise level of this city. Noise maps are generated using ARC-GIS to investigate the impact of road traffic noise on the soundscape of the city. The response of the public was appraised by a questionnaire. Due to variable traffic features, the equivalent noise level (Leq) as well as peak (L 10 ) and background noise (L 90 ) levels varied with location and time of the day. It was found that socio-demographic characteristics have no bearing on the amount of annoyance. However, a link was observed between age, hearing condition, and noise perception, as well as between gender and impacts of noise., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Conventionally, the fattened beam is being used in radiotherapy for routine clinical cases even after introduction of intensity-modulated radiotherapy with incorporation of multi-leaf collimator system. With the removal of the flattening filter (FF) from the beam's path average energy of the photon gets reduced resulting in reduced scatter, reduction in treatment time, and reduced neutron contamination for high-energy beam and ultimately resulting in treatment plan quality deviations. This study aims to investigate the usefulness of the FF-free (FFF) beam for routine head-and-neck cancer (HNC) cases treated with volumetric arc therapy (VMAT) and dosimetrically compares the result with the FF beam., Materials and Methods: In this study, 20 patients treated on Halcyon TM (unmatched 6 megavoltage [6MV] FFF beam) medical linear accelerator with VMAT of different HNC selected and for comparison with 6MV FF beam, 20 equivalent treatment plans are created for Truebeam TM configuration and the plans have been evaluated for target coverage, doses to the organ at risk (OAR), and other dose quality indices., Results: Comparable target coverage, doses to OARs except for rest right parotid ( P = 0.02) between 6MV FFF beam and 6MV FF beam is observed. Insignificant differences in conformity index, homogeneity index, and gradient index have been observed. Higher monitor unit (MU) ( P ≤ 0.001) and lesser beam on time (BOT) ( P = 0.003) have been observed in 6MV FFF., Conclusion: 6MV FFF beam provides comparable target coverage and improved dose-sparing effect to most of the OARs. 6MV FFF beam has lesser BOT, but on the other hand number of MUs is higher as compared to 6MV-FF plans., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Physics.)

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients., (© 2023 Wiley Periodicals LLC.)

Purpose: This phase II trial is designed to test whether the performance status (PS) of metastatic non-small cell lung cancer (mNSCLC) patients (pts) can improve with chemotherapy if their poor PS (Eastern Cooperative Oncology Group (ECOG) PS of ≥ 2) is due to disease burden rather than comorbidities., Methods: Age18-65 years, Charlson's comorbidity index < 9, serum albumin ≥ 3.5 g/dl, adequate bone marrow and organ function, & ECOG PS ≥ 2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60 mg/m 2 /dose. The primary endpoint was an improvement in ECOG PS by 1 point at 4 weeks; others: toxicity (CTCAE v 5.0), quality of life (QoL) assessment at baseline and 4 weeks by EORTC QLQ-C30 and EORTC QLQ-LC13. Optimal Simon's 2-stage design was used., Results:  Forty-six patients were included with a median age of 56 years (interquartile range, IQR 54-59), 12 (26%) had comorbid conditions, and 87% with ECOG PS 3/4. PS improved in 11 pts at 4 weeks and in 7 beyond this time point. Grade 3/4 toxicities are seen in 20% (most common: anemia and diarrhea). At a median follow-up of 4.8 m (95% CI 3.27-14.9), the median progression-free survival and overall survival were 3.3 months (95% CI 2.36-5.6) and 6.8 months (95% CI 2.47-8.8), respectively. QoL improved for global QoL, role functioning, pain, dyspnea, insomnia, pain in the chest, pain in other parts, and worsened for alopecia and sore mouth., Conclusions:  Abbreviated chemotherapy is a useful, well-tolerated strategy in carefully selected poor PS mNSCLC patients that can improve PS and QoL., Clinical Trial: Clinical trial information: CTRI/2020/01/022617., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cancer cell lines play a crucial role as invaluable models in cancer research, facilitating the examination of cancer progression as well as the advancement of diagnostics and treatments. While they may not perfectly replicate the original tumor, they generally exhibit similar characteristics. Low-passage cancer cell lines are generally preferred due to their closer resemblance to the original tumor, as long-term culturing can alter the genetic and molecular profiles of a cell line thereby highlighting the importance of monitoring the passage number (PN). Variations in proliferation, migration, gene expression, and drug sensitivity can be linked to PN differences. PN can also influence DNA methylation levels, metabolic profiles, and the expression of genes/or proteins in cancer cell lines. When conducting research on cancer cell lines, it is crucial for researchers to carefully select the appropriate PN to maintain consistency and reliability of results. Moreover, to ensure dependability and replicability, scientists ought to actively track the growth, migration, and gene/or protein profiles of cancer cell lines at specific PNs. This approach enables the identification of the most suitable range of PNs for experiments, guaranteeing consistent and precise results. Additionally, such efforts serve to minimize disparities and uphold the integrity of research. In this review, we have laid out recommendations for laboratories to overcome these PN discrepancies when working with cancer cell lines., (© 2023 Wiley Periodicals LLC.)

In urban areas around the world, air pollution introduced by vehicular movement is a key concern. However, restricting vehicular traffic during the COVID-19 shutdown improved air quality to some extent. This study was conducted out in the smart city of Bhubaneswar, which is also the state capital of Odisha, India. The study has tried to map Bhubaneswar by collecting the air quality data before, during, and after the COVID lockdown of six air quality monitoring stations present in Bhubaneswar established under "National Ambient Air Monitoring Program" (NAMP). Furthermore, plants, which are the most vulnerable to air pollution, can show a variety of visible changes depending on their level of sensitivity. Moreover, leaves of Mangifera indica, Monoon longifolium, Azadirachta indica, Millettia pinnata, Aegle marmelos were collected from nearby of six air monitoring stations to assess the "Air Pollution Tolerance Index." M. indica was found to be intermediately tolerant, and all of the other species were found to be sensitive. The structural equation modeling results also revealed a significant relationship between total chlorophyll content, relative water content, ascorbic acid content, leaf extract pH, APTI with species, air quality index, and PM 10 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Human activities can influence behaviors of predators and prey, as well as predator-prey interactions. Using camera trap data, we investigated whether or to what extent human activities influenced behaviors of predators (tigers and leopards) and prey (sambar deer, spotted deer, wild boar, and barking deer), and predator-prey interactions in the Barandabhar Corridor Forest (BCF), Chitwan District, Nepal. A multispecies occupancy model revealed that the presence of humans altered the conditional occupancy of both prey and predator species. Specifically, the conditional occupancy probability of prey was substantially higher ( ψ  = 0.91, CI = 0.89-0.92) when humans were present than when humans were absent ( ψ  = 0.68, CI = 0.54-0.79). The diel activity pattern of most prey species overlapped strongly with humans, whereas predators were generally more active when humans were absent. Finally, the spatiotemporal overlap analysis revealed that human-prey interactions (i.e., the probability that both humans and prey species being present on the same grid at the same hourly period) was ~3 times higher (10.5%, CI = 10.4%-10.6%) compared to spatiotemporal overlap between humans and predators (3.1%, CI = 3.0%-3.2%). Our findings are consistent with the human shield hypothesis and suggest that ungulate prey species may reduce predation risk by using areas with high human activities., Competing Interests: There are no competing interests declared by any of the authors., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Frosted branched angiitis (FBA) is characteristic florid translucent retinal perivascular sheathing of both arterioles and venules in association with variable uveitis and vasculitis affecting the entire retina. The vascular sheathing is supposed to be an immune-mediated reaction, possibly due to immune complex deposition in vessel walls secondary to various underlying etiologies. The authors aim to report a case of FBA secondary to herpes simplex virus and Toxoplasma gondii infection causing the diagnostic dilemma. This is the first case report on FBA from Nepal., Case Report: An 18-year-old young boy hospitalized with the diagnosis of acute viral meningo-encephalitis presented with the complaint of diminution of vision and floaters in both eyes for a week. Herpetic infection was confirmed with the cerebro-spinal fluid analysis and was under antiviral drugs. His presenting visual acuity was 20/80 in both eyes and ocular features were suggestive of FBA. The vitreous sample analysis revealed raised toxoplasma titre so intravitreal clindamycin was administered twice. The ocular features resolved in the subsequent follow ups with intravenous antiviral treatment and intravitreal antitoxoplasma treatment., Conclusions: FBA is a very rare clinical syndrome secondary to many immunological or pathological causes. So, possible etiologies must be ruled out for timely management and good visual prognosis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article, (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Trachyspermum ammi (L.) Sprague (Apiaceae), commonly known as "Ajwain" is distributed throughout India. Ajwain fruits contain fiber, carbohydrates, phenolic acids, flavonoids, and tannins. The fruits also yield a small amount of essential oil, with Thymol as the principal constituent. Ajwain has various pharmacological activities like anti-leishmanial, antimicrobial, cytotoxic, antispasmodic, nematocidal, and anthelmintic. The fruits are of high therapeutic value; thus, it becomes quite essential to evaluate the quality of Trachyspermum ammi (L.) Sprague to authenticate and ensure its therapeutic and nutritional properties. The ethyl acetate fraction of Trachyspermum ammi (L.) Sprague fruits exhibited the highest total phenolic and flavonoid content values of 149.55 ± 1.19 mg rutin equivalent and 682.85 ± 3.68 mg gallic acid equivalent, respectively. Metabolite profiling of the ethyl acetate fraction using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry analysis resulted in identifying 19 phytomolecules. A validated high-performance thin-layer chromatography method was developed to quantify standard phytomolecules in the ethyl acetate fraction. The highest and lowest percentages of phytomarker were found to be caffeic acid (5.51% ± 0.16% w/w) and gallic acid (1.29% ± 0.09% w/w), respectively. This validated rapid, accurate, and precise method for standardization of Trachyspermum ammi (L.) Sprague will be beneficial for its quality evaluation as well as the derived products., (© 2023 Wiley-VCH GmbH.)

From wild dogs (Lycaon pictus) in the Serengeti to tigers (Panthera tigris altaica ) in the Russian Far East, canine distemper virus (CDV) has been repeatedly identified as a threat to wild carnivores. Between 2020 and 2022, six Indian leopards (P. pardus fusca ) presented to Nepali authorities with fatal neurological disease, consistent with CDV. Here, we report the findings of a serosurvey of wild felids from Nepal. A total of 48 serum samples were tested, comprising 28 Bengal tigers (P. t. tigris ) and 20 Indian leopards. Neutralizing antibodies were identified in three tigers and six leopards, equating to seroprevalences of 11% (CI: 2.8-29.3%, n = 28) and 30% (CI: 12.8-54.3%, n = 20), respectively. More than one-third of seropositive animals were symptomatic, and three died within a week of being sampled. The predation of domestic dogs (Canis lupus familiaris ) has been posited as a potential route of infection. A comparison of existing diet studies revealed that while leopards in Nepal frequently predate on dogs, tigers do not, potentially supporting this hypothesis. However, further work, including molecular analyses, would be needed to confirm this.

The impact of global warming on soil carbon (C) mineralization from bulk and aggregated soil in conservation agriculture (CA) is noteworthy to predict the future of C cycle. Therefore, sensitivity of soil C mineralization to temperature was studied from 18 years of a CA experiment under rice-wheat cropping system in the Indo-Gangetic Plains (IGP). The experiment comprised of three tillage systems: zero tillage (ZT), conventional tillage (CT), and strip tillage (ST), each with three levels of residue management: residue removal (NR), residue burning (RB), and residue retention (R). Cumulative carbon mineralization (C t ) in the 0-5 cm soil depth was significantly higher in CT with added residues (CT-R) and ZT with added residues (ZT-R) compared with the CT without residues (CT-NR). It resulted in higher CO 2 evolution in CT-R and ZT-R. The plots, having crop residue in both CT and ZT system, had higher ( p < 0.05) Van't-Hoff factor (Q 10 ) and activation energy (Ea) than the residue burning. Notably, micro-aggregates had significantly higher Ea than bulk soil (~14%) and macro-aggregates (~40%). Aggregate-associated C content was higher in ZT compared with CT ( p < 0.05). Conventional tillage with residue burning had a reduced glomalin content and β-D-glucosidase activity than that of ZT-R. The ZT-R improved the aggregate-associated C that could sustain the soil biological diversity in the long-run possibly due to higher physical, chemical, and matrix-mediated protection of SOC. Thus, it is advisable to maintain the crop residues on the soil surface in ZT condition (~CA) to cut back on valuable C from soils under IGP and similar agro-ecologies.

Background: Zoological gardens (Zoo) provide abode to various threatened animals or trafficked animals seized by the authorities, and injured and orphaned animals. Captive animals are more susceptible to infection as they are under significant stress due to diet and space which further dwindle their resistance to parasitic infections., Objectives: This study was conducted to determine the prevalence and burden of gastrointestinal parasites in captive mammals housed at Central Zoo., Methods: Fresh faecal samples from three orders of mammals including carnivora (n = 24), rodentia (n = 28) and artiodactyla (n = 35) were examined by direct smear, faecal floatation and sedimentation techniques, and the McMaster technique was applied to quantify parasite eggs per gram (EPG)/oocysts per gram (OPG) of a faecal sample., Results: One or more parasite taxa were detected in 19.54% of the examined samples and five types of GIPs including one protozoon (Eimeria spp.) and four helminths (Strongyloides spp., Haemonchus spp. and Trichostrongylus spp. and hookworm) were recorded. The protozoan prevalence (6.89 %) was lower than helminths (12.64%). The Eimeria spp. was the most prevalent parasite (6.89%) with the highest OPG (427.77 ± 25.45SD) in spotted deer (Axis axis), and the highest prevalence was noticed among artiodactyla (34.28%) followed by carnivora (12.5%) and rodentia (7.14%). Artiodactyla had both single infection (25.71%) and double (8.57%) infection. The percentage of single infection (16.09%) was found to be higher than double infection (3.44%) among the captive mammals. The wild boar (Sus scrofa) had the highest EPG of 383.33 ± 76.37SD (Strongyloides spp.), while the spotted deer had the lowest EPG of 216.66 ± 76.37SD (hookworm)., Conclusions: Despite careful management practices, the parasitic infection may be attributed to the narrow enclosure, group housing and environmental contamination. The present finding provides baseline information on the parasitic infection in captive mammals, and can be used by zoo managers for the better life of captive animals., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Epithelial-to-mesenchymal transition (EMT) confers the most lethal characteristics to cancer cells i.e., metastasis and resistance to chemo-and-radio-therapy, and therefore exhibit an appealing target in the field of oncology. Research in the past decade has demonstrated the crucial role of aerobic glycolysis in EMT, which is generally credited as the glucose metabolism for the creation of biomass such as fatty acids, amino acids, and nucleotides thereby providing building blocks for limitless proliferation. In the present review, apart from discussing EMT's evident role in the metastatic process and cancer stemness, we also talked about the vital role of glycolytic enzymes viz. GLUTs, HKs, PGI, PFK-1, aldolase, enolase, PK, LDHA, etc. in the induction of the EMT process in cancerous cells., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Marine plastic pollution is a global issue that has calamitous consequences for global economy, biodiversity, human health, and the climate. A few of the studies were carried out on the Gopalpur coast and the current baseline survey was conducted during Covid-19 pandemic lockdown (April-August 2021) and post lockdown (August-September 2021).The survey was covered about 1500 m along the coast, divided into 10 equal zones of each (20 × 150 m 2 ) to collect the plastic debris based on colour, density, and weight. Plastic debris was categorized into 33 types with an average 1.276 g/m 2 during lockdown and was categorized into 34 types with an average 3.34 g/m 2 in post lockdown. The results imply that tourism has a greater impact on the beach in terms of pollution when compared with the local sources, which will have a drastic effect on the aesthetics of the beach, neighbouring turtle nesting site and indirectly on human health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mugger crocodile is found in various locations of Nepal, ranging from Eastern to Western lowlands, and is also a resident crocodilian of the Koshi Tappu Wildlife Reserve (KTWR). Fewer studies have been carried out on the status and distribution of this crocodilian with limited information on its habitat characteristics. This study sets forth to highlight the population status, distribution and habitat use by mugger crocodile in and around KTWR. Detailed surveys were conducted in the rivers, natural and private ponds of the KTWR in December 2020. Every 500 m along the survey transects, habitat characteristics were recorded in each habitat station as part of the habitat survey. The dependent variables were presence or absence of mugger crocodile in each habitat station. Meanwhile, the independent variables included habitat predictors such as; water depth, slope, elevation, distance to roads, distance to settlements, bank substrate, and human disturbance. Generalized Linear Model under binary logistic regression was employed to test variables associated with presence and absence of muggers for statistical significance. The population survey of the muggers was assessed by day counts either using dugout canoe or walking along transects. During the research period, 35 individuals of muggers were recorded. The probability of mugger sighting augmented with increased slope and depth. 34 muggers (97.14 %) were basking, while 1 (2.85%) were seen swimming out of the total muggers detected. In private and public ponds, 22 muggers were sighted, while 13 were sighted in the main Koshi river, its branches, and the Moriya river. Sixteen muggers (45.71 %) were sighted within the reserve, while the remaining 19 muggers (54.28 %) were sighted in the buffer-zone areas. The probability of mugger sighting varied considerably with regard to slope and water depth among the seven habitat predictors examined. In lieu of prevailing fishing pressure in the river systems of the KTWR and easy availability of prey species for muggers in private fishponds; the muggers are likely use private fishponds more frequently. In order to subdue the muggers inside the KTWR, the reserve authority has a vital role for proper habitat management decisions and regulation of fishing activities., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Importance: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial., Methods: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes., Results: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I 2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I 2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I 2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm., Conclusion: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Colorectal cancer (CRC) is a predominant life-threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer-associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell-like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine- and chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine- and chemokine-mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review., (© 2022 Sidra Medicine. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat-Sen University Cancer Center.)

Background: The use of computers and other Visual Display Terminal (VDT) screens is increasing in Nepal. However, there is a paucity of evidence on the prevalence of Computer Vision Syndrome (CVS) and other occupational health concerns among employees working in front of VDT screens in the Nepalese population., Objectives: This study aims to estimate the prevalence of CVS, musculoskeletal and work-related stress among VDT screen users in the office, as well as their understanding and usage of preventive measures., Methods: The study was a cross-sectional descriptive study among 319 VDT users in office settings in Kathmandu Metropolitan City, Nepal, using a semi-structured self-administered questionnaire. Multivariate logistic regression analysis was conducted to identify the associated factors at 95% CI. P-value <0.05 was considered as statistically significant., Results: The prevalence of CVS was 89.4%. More than eight out of ten study participants reported at least one visual and musculoskeletal symptom. Work-related stress, which was moderate-difficult to handle, was present in 36.7% of the study population. The mean±SD computer usage per day was 7.9±1.9 hours. Tired eye (63.3%), feeling of dry eye (57.8%), headache (56.9%) were the common visual symptoms of CVS reported. Total computer use/day > = 8 hours OR 2.6, improper viewing distance OR 3.2, Not using an anti-glare screen OR 2.6, not using eye-drops, and not wearing protective goggles OR 3.1 were significantly associated with the presence of CVS. There was no statistically significant association between visual symptoms of CVS, musculoskeletal symptoms, and stress with gender., Conclusion: CVS was substantially related to not employing preventive measures, working longer hours, and having an incorrect viewing distance. With more hours per day spent in front of a VDT screen, work-related stress and musculoskeletal complaints were also found to be important correlates. Similarly, work-related stress was found more among those who had less than five years of job., Competing Interests: The authors have declared that no competing interests exist.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m 2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two-six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end-point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression-free survival (PFS), time to progression and overall survival (OS). An intent-to-treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow-up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide-refractory myeloma population., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Esophageal cancer is a complex gastrointestinal malignancy with an extremely poor outcome. Approximately 80% of cases of this malignancy in Asian countries including India are of squamous cell origin, termed Esophageal Squamous Cell Carcinoma (ESCC).The five-year survival rate in ESCC patients is less than 20%. Neo-adjuvant chemo-radiotherapy (NACRT) followed by surgical resection remains the major therapeutic strategy for patients with operable ESCC. However, resistance to NACRT and local recurrence after initial treatment are the leading cause of dismal outcomes in these patients. Therefore, an alternative strategy to promote response to the therapy and reduce the post-operative disease recurrence is highly needed. At the molecular level, wide variations have been observed in tumor characteristics among different populations, nevertheless, several common molecular features have been identified which orchestrate disease progression and clinical outcome in the malignancy. Therefore, determination of candidate molecular pathways for targeted therapy remains the mainstream idea of focus in ESCC research. In this review, we have discussed the key signaling pathways associated with ESCC, i.e., Notch, Wnt, and Nrf2 pathways, and their crosstalk during disease progression. We further discuss the recent developments of novel agents to target these pathways in the context of targeted cancer therapy. In-depth research of the signaling pathways, gene signatures, and a combinatorial approach may help in discovering targeted therapy for ESCC., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Introduction: Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS., Methods: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) DISCUSSION: The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention., Trial Registration: Clinical Trials Registry of India  CTRI/2021/01/030592 . Prospectively registered on January 19, 2021., (© 2022. The Author(s).)

In recent years, sunlight has been used in several fields such as photovoltaic cells, flat plate collectors, solar cookers, green buildings, and agricultural applications. Improved thermal performance has been seen which comes of three sides absorber plate with glass cover compared to the traditional one. This paper presents the Nusselt (Nu) number, collector efficiency factor (CEF), and collector heat removal factor (CHRF) for the optimal solution of three sides artificially roughened solar air heater. Five input variables such as Reynolds (Re) number, relative roughness pitch, relative roughness height, mass flow rate, and air temperature of the duct are taken into account for improved efficiency optimization of collector, collector heat removal factor, and Nu number. Technique for order of preference by similarity to ideal solution (TOPSIS) technique is used to identify the best alternative amongst a number of performance measures by converting them into an equivalent single variable. Moreover, the results revealed the high accuracy of the CEF, CHRF, and Nu number of 75-80%, 74-78%, and 63-71%, respectively. Meanwhile, it has been also observed that roughness Re number varies between 12,500 and 13,500, and height of relative roughness is 0.0245, including pitch of relative roughness 10 along with the rate of mass flow is 0.041 kg/s.

The most well-known and widely used non-traditional manufacturing method is electrical discharge machining (EDM). It is well-known for its ability to cut rigid materials and high-temperature alloys that are difficult to machine with traditional methods. The significant challenges encountered in EDM are high tool wear rate, low material removal rate, and high surface roughness caused by the continuous electric spark generated between the tool and the workpiece. Researchers have reported using a variety of approaches to overcome this challenge, such as combining the die-sinking EDM process with cryogenic treatment, cryogenic cooling, powder-mixed processing, ultrasonic assistance, and other methods. This paper examines the results of these association techniques on various performance measures, such as material removal rate (MRR), tool wear rate (TWR), surface roughness, surface integrity, and recast layer formed during machining, and identifies potential gap areas and proposes a solution. The manuscript is useful for improving performance and introducing new resolutions to the field of EDM machining.

Introduction: Stereopsis is defined as the ability to perceive object depth. It is measured in seconds of arc. Reduced stereoacuity impinges one's academic as well as a professional performance. Hence in this study, we aim to find out the mean stereoacuity among the undergraduate medical and nursing students using the Titmus fly test., Methods: A descriptive cross-sectional study was conducted among undergraduate students at a medical college of Nepal from April 2021 to July 2021. Ethical approval was obtained from the Institutional review committee (Registration number: 487 (6-11) E2 077/078). Simple random sampling method was used. Data were collected from undergraduate medical and nursing students while the post-graduate students were excluded from the study. Overall, 80 students were included in the study. Titmus fly test was used to assess the stereopsis. Statistical Package for Social Sciences version 21 and Microsoft Excel was used for data analysis. Point estimate at 95% confidence interval was calculated along with mean, standard deviation, frequency, and proportion., Results: The mean stereoacuity was 62.63±46.56 (range 40-800) sec of arc (52.77-72.49 at 90% Confidence Interval). A total of 80 participants in our study among which 50 (62.5%) were male and 30 (37.5%)were female. About 41 (51.2%) of the study participants had normal, borderline (>40 and ≤ 120) stereopsis was seen in 35 (43.8%) of the study participants while only 4 (5%) had reduced stereopsis (≥120 sec of arc)., Conclusions: This study showed that the mean stereoacuity among the undergraduate medical and nursing students was in subnormal range which was similar to other studies.

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients ( p  = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Background: Psychoactive substance use among adolescents has been identified as an important health issue in Nepal. Therefore, this study examined the psychoactive substance use and factors associated with its use among adolescent students in the Rupandehi district of Nepal., Methods: A school-based cross-sectional study was conducted from December 2017 to July 2018 with 460 school students aged between 15 to 19 years across sampled public and private schools in the Rupandehi district of Nepal. Structured interview schedule was used to collect information on psychoactive substance use. The generalized estimating equation was used to identify the factors associated with the use of psychoactive substances., Results: Over a quarter (27.4%) of school-going adolescents used at least one type of psychoactive substance. Commonly used psychoactive substance included tobacco products (59.3%) followed by cannabis (55.6%), marijuana (35.8%), hashish (23.5%), alcohol (22.2%), heroin (18.5%), nitrogen tablets (14.8%), sulfa (13.6%) and opium (13.6%), respectively. Being male (AOR=2.0, 95% CI: 1.19-3.36), having peers (AOR=1.8, 95% CI: 1.13-3.03) or family members (AOR=2.2, 95% CI: 1.40-3.54) that used psychoactive substances and father's education level (AOR=2.5, 95% CI: 1.05-5.78) were significantly associated with the psychoactive substance use., Conclusions: This study identified that over a quarter of school-going adolescents reported the use of at least one illegal psychoactive substance. This study provided details on the extent of behaviours, and can be used to develop a comprehensive prevention and control program. Such programs should address the socio-cultural factors that enable substance use and address gaps in knowledge to prevent and control of psychoactive substance use.