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Purpose: To evaluate the anatomic and visual outcomes and safety profile of initial Indian eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. Methods: This retrospective multicentric, real-world study enrolled consecutive eyes with nAMD that were treated with IVI brolucizumab after it was launched in India in October 2020. Data collected for each eye included best-corrected visual acuity (BCVA), central subfield thickness (CSFT), subretinal fluid (SRF), and intraretinal fluid (IRF) status at 6, 12, and 24 months follow-up. Also recorded were the lens status, treatment protocol, number of injections received before enrollment (in switch-over cases), total number of injections, and adverse effects noticed during the study period. Primary outcomes were change in BCVA, CSFT at follow-up visits, and incidence of intraocular inflammation (IOI). Secondary outcomes were profile of macular neovascularization, treatment protocols, mean number of injections, and maximum injection-free interval observed in eyes treated by pro-re-nata (PRN) protocol. Results: In total, 331 eyes received a mean of 3.55 ± 1.83 injections. Most frequent treatment protocol was PRN (53%). BCVA data was available for 100%, 96%, and 74% eyes at 6, 12, and 24 months follow-up. BCVA and CSFT improved significantly (P < 0.001) at all follow-ups. Two hundred and seventy-six (83.38%) out of 331 eyes received more than one injection; out of these, 241 (87.3%) eyes that were treated by PRN protocol could achieve mean “maximum injection-free interval” of 19.43 ± 8.82 weeks. IOI and retinal vasculitis were reported in 2.11% (7/331) and 0.60% (2/331) eyes, respectively. None of the eyes with IOI or vasculitis lost any vision at the final follow-up. Conclusion: This study demonstrated favorable visual and anatomic outcomes and safety profile for eyes with nAMD treated by IVI brolucizumab. Mean maximum injection-free interval in eyes treated with PRN was 19 weeks.

During the recent Coronavirus disease (COVID-19) pandemic, different parts of the globe faced indefinite lockdowns. To maintain the lockdown measures, government authorities deployed security forces and police. The primary role of the police is to monitor the movement of the people and advise/guide them to follow the lockdown. In the current work, we propose a nonlinear mathematical model to study the role of police and security personnel in controlling COVID-19. It is observed that the proposed model possesses two equilibria, namely, trivial and non-trivial. We performed the stability analysis of the non-trivial equilibrium point by using the compound matrix technique. Finally, we perform a detailed numerical simulation to investigate the feasibility of the theoretical results. The current study demonstrates that police forces played a significant role in controlling the pandemic.

Summary: Changes in taste have been perceived as a common side effect of different cancers and may lead to malnutrition. Hence, the importance of understanding cancer patients' sensory taste perceptions and its impact on nutritional status, quality of life (QoL), and oral nutrition supplements (ONS) compliance becomes crucial. This qualitative study involved semi-structured, in-depth interviews with 24 adults (15 with multiple myeloma and 9 with head & neck cancer). The interviews were transcribed and the data analysis was conducted using reflexive thematic analysis and template analysis. This guided the development of four themes: 1. Taste and smell changes, 2. Impact on nutritional status and quality of life, 3. Information and help available for people experiencing changes in their taste, and 4. ONS and its compliance. Our findings show significant negative impact of chemosensory changes on nutritional status, quality of life and ONS compliance. Patient's experience with the level of support received for the management of taste changes during cancer treatment varied widely. Providing adequate information and support in a timely manner about changes in taste during treatment can improve patients' coping strategies and maintain their nutritional status. Overall, the findings highlight the importance of addressing taste changes and ONS compliance for people with multiple myeloma and head and neck cancer undergoing treatment. Specifically, the taste changes and its impact experienced by people with head and neck cancer were found to be more severe than those experienced by multiple myeloma patients. This study provides an understanding of changes in sensory taste perception experienced by cancer patients and its impact on nutritional status and QoL. This understanding can provide insight into ways to improve ONS consumption and compliance for preventing malnutrition. It is crucial to further conduct ONS sensory evaluations that cater to the specific needs of this cohort to help prevent malnutrition among cancer patients.

Marjan Farid,1 Sheri L Rowen,2 Majid Moshirfar,3 Derek Cunningham,4 Ian B Gaddie,5 Gerard Smits,6 Teresa Ignacio,6 Preeya K Gupta7 1UCI Health, Irvine, CA, USA; 2NVISION Eye Centers, Newport Beach, CA, USA; 3Hoopes Vision Research Center, Hoopes Vision, Draper, UT, USA; 4Dell Laser Consultants, Austin, TX, USA; 5Gaddie Eye Centers, Louisville, KY, USA; 6Orasis Pharmaceuticals, Ponte Vedra, FL, USA; 7Triangle Eye Consultants, Raleigh, NC, USACorrespondence: Marjan Farid, UCI Health, 850 Health Sciences Road, Irvine, CA, 92617, USA, Tel +1-949-824-2020, Fax +1-855-376-5057, Email mfarid@hs.uci.eduPurpose: To evaluate the efficacy of 0.2% and 0.4% pilocarpine HCl (CSF-1) for the treatment of presbyopia and to determine the contributions of pilocarpine HCl and diclofenac sodium on the efficacy of fixed-dose combination (FDC) formulations.Patients and Methods: This was a Phase 2b, multicenter, randomized, double-masked, parallel-group clinical trial. Adults (45– 64 years) with presbyopia were randomized 1:1:1 to 3 arms (Pilo arm: pilocarpine HCl; Pilo-Diclo FDC arm: pilocarpine HCl with 0.006% diclofenac sodium; Control arm: 0.006% diclofenac sodium). Participants in Pilo and Pilo-Diclo FDC arms received 0.2% pilocarpine HCl (0.2% Pilo or 0.2% Pilo FDC, respectively) from days 1– 8, and 0.4% pilocarpine HCl (CSF-1 or CSF-1-FDC, respectively) from days 8– 15. Primary efficacy endpoint was achievement of ≥ 3-line (15-letter) gain in mesopic, monocular distance-corrected near visual acuity (DCNVA) at 40 cm, 1 hour post-treatment of the study eye on days 8 and 15 in the per protocol (PP) population. Safety endpoints were assessed.Results: One hundred and sixty-six participants were randomized (intent-to-treat, N = 166; PP, n = 160). There were no statistical differences between 0.2% Pilo or 0.2% Pilo FDC versus Control at 1 hour post-treatment on day 8. On day 15, 43.1% and 46.9% of participants receiving CSF-1-FDC (0.4% Pilo FDC) or CSF-1 (0.4% Pilo), respectively, achieved ≥ 3-line gain at 1 hour post-treatment in mesopic DCNVA compared with 16.1% of Control group in the PP population, meeting the primary endpoint (P = 0.0015 and P = 0.0002, respectively). All formulations were well tolerated.Conclusion: CSF-1 demonstrated significant improvements in mesopic DCNVA and favorable safety. Pilocarpine HCl as a single active ingredient, at the concentration of 0.4% (CSF-1), provided a transient, therapeutic effect for presbyopia.Keywords: pilocarpine hydrochloride, presbyopia, minimum effective concentration

The effectiveness of organizations and the satisfaction of customers are both significantly improved by providing outstanding quality. To better meet the needs of their consumers, an increasing number of firms are implementing quality improvement programs such as total quality management (TQM). The major objective of this research paper is to examine the effects of TQM components on the efficiency and effectiveness of UAE higher education institutions (HEIs). The association between TQM components and organization performance was investigated using a quantitative research technique based on a survey study design. The partial least square structural equation model (PLS-SEM) was used to quantify the reflectiveness of 99 data. The study found that TQM has a positive impact on employee satisfaction and service quality in HEIs. It was revealed that TQM has a significant impact on organizational performance, with service quality serving as a mediator. Furthermore, the results revealed that service quality and students’ satisfaction are fully mediating the relationship between TQM and organizational performance. The current study concludes that HEIs are implementing TQM to enhance market performance and comprehend the evolving business trends. The study has added to the body of information about the relationship between TQM elements and organization performance.

As carbon-based nanomaterials have such remarkable physical, chemical, and electrical capabilities, they have become a major focus of materials science study. A thorough examination of several carbon nanomaterial varieties, such as carbon nanotubes, graphene, fullerenes, and carbon nanodiamonds, is given in this review work. These materials all have distinctive qualities that qualify them for particular uses. This work starts by examining the synthesis processes of these nanomaterials, outlining the ways by which they are made and the variables affecting their ultimate characteristics. The specific features of each kind of carbon nanomaterial will then be briefly discussed in this study, along with their size, structure, and special physical and chemical properties. These materials have a wide range of possible uses in several fields. They are employed in the electronics industry to fabricate sensors, high-speed transistors, and other devices. Their high surface area and electrical conductivity make them useful in energy storage devices like supercapacitors and batteries. They are applied to environmental remediation and water purification in environmental science. They are employed in biomedicine for biosensing, bioimaging, and medication delivery. Notwithstanding the encouraging uses, the large-scale synthesis and functionalization of carbon nanomaterials present several difficulties. This review discusses the importance of carbon nanomaterials by studying their multifaceted properties and potential applications in industries. The novelty of this work lies in its detailed examination of the degradation and toxicity of these materials, which is essential for their safe integration into various technological and biomedical applications. By thoroughly analysing recent experimental results, this review aims to bridge the gap between fundamental research and practical applications.

Introduction The majority of paediatric both bone forearm fractures are treated with manipulative reductions and casting; loss of reduction is one of the most commonly reported complications. We aimed to assess the role of cast index and 3-point index as predictor of outcome of a successful closed reduction in distal both bones forearm fractures. Materials and methods This prospective observational study was conducted at the Department of Orthopedics, Kalpana Chawala Government Medical College in Karnal to assess the role of cast index and 3-point index as predictor of outcome of a successful closed reduction in distal both bones forearm fractures. In the present study, 55 patients 16 years old were included irrespective of sex with distal both bones forearm fractures, managed by closed reduction and casting were included. Results Fracture reduction failure was observed in 32.7 % of the patients. Both three-point index and cast index were found to be significantly higher in patients with reduction failure. It was observed that at 2 weeks Area under curve (ROC Curve) for Cast index and Three point index was 0.72 and 0.85 respectively. At 4 weeks, Area under curve for Cast index and Three point index was 0.77 and 0.84 respectively and at 6 weeks 0.74 and 0.86 respectively. Thus, in the present study, CI and 3PI had similar predictability for fracture reduction failure. Discussion There are a few limitations of our study: We could not observe the patients for a longer period of time to know re-modelling in the long term. We did not take in to consideration the severity of fracture, type of anesthesia used (conscious sedation versus General Anesthesia) and the fracture configuration while assessing the outcomes. We also did not collect information about anthropometric parameters like child weight and diameter of the forearm. Conclusion The three-point index and cast index are clinically useful tools to assess the quality of cast molding following closed reduction of pediatric forearm fractures and to predict re-displacement in distal forearm fractures.

Yilin Feng,1 Nandini Venkateswaran,1 Amanda Steele,2 Eric D Rosenberg,3 Preeya K Gupta2,4 1Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 2Triangle Eye Consultants, Raleigh, NC, USA; 3Department of Ophthalmology, New York Medical College, Valhalla, NY, USA; 4Department of Ophthalmology, Tulane University, New Orleans, LA, USACorrespondence: Preeya K Gupta, Email preeyakgupta@gmail.comPurpose: To evaluate the impact of TearCare (TC) treatment on clinical, quality of life, and functional visual outcome metrics in patients with dry eye disease (DED) and meibomian gland disease (MGD).Methods: This is a prospective, single-center clinical trial. Adults with MGD and a DED diagnosis and tear break-up time (TBUT) < 10 seconds were included. All subjects had at least 20/40 vision and no surgery or new treatment for DED within 60 days prior to enrollment. All patients had one baseline visit prior to undergoing TC and one follow-up visit 1 month after TC. At each visit, the meibomian gland secretion score (MGSS), TBUT, and corneal fluorescein staining (KFL) were assessed. DED symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Visual Function Questionnaire 25 (VFQ-25), and the Fatigue Severity Scale. Reading speed was determined through the International Reading Speed Texts (IReST), Minnesota Low Vision Reading Test (MNREAD), and Wilkins Rate of Reading Test (WRRT).Results: Thirty-two subjects were included. The average age was 55.9 years. Sixteen (52%) participants had a clinically significant improvement in reading speed after treatment with TC, defined as > 10 words per minute increase in their IReST score. Improvement on the IReST and the MNREAD reached statistical significance (p = 0.012 and p = 0.028, respectively). OSDI scores significantly decreased and VFQ-25 scores significantly increased after TC treatment (p < 0.001). All of the clinical exam parameters showed statistically significant improvements after treatment (p < 0.001).Conclusion: TC is an effective treatment both clinically and with respect to visual function. Patients who had TC exhibited improvements in quality of life and improved reading speed after a single treatment. This treatment should be frequently considered and utilized to reduce the disease burden of DED related to MGD.Keywords: thermal pulsation, tearcare, meibomian gland dysfunction, dry eye disease, reading speed

Brinda Gupta, Laura Gosa Barrett, Stephen V Liu Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USACorrespondence: Stephen V Liu, Georgetown University, Lombardi Comprehensive Cancer Center, 3800 Reservoir Road NW, Washington, DC, 20007, USA, Tel +1 202 444-2223, Fax +1 202 444-7889, Email stephen.v.liu@gunet.georgetown.eduAbstract: Fusions in neuregulin 1 (NRG1) are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). NRG1 has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring NRG1 fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor. Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of NRG1 fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.Keywords: NSCLC, NRG1, targeted therapy, HER2, HER3

In this article, we study a question of Hong from 1993 related to the minimum spectral radii of the adjacency matrices of connected graphs of given order and size. Hong asked if it is true that among all connected graphs of given number of vertices nn and number of edges ee, the graphs having minimum spectral radius (the minimizer graphs) must be almost regular, meaning that the difference between their maximum degree and their minimum degree is at most one. In this article, we answer Hong’s question positively for various values of nn and ee, and in several cases, we determined the graphs with minimum spectral radius.

Alessandro Fiocchi,1 R Sharon Chinthrajah,2 Ignacio J Ansotegui,3 Panida Sriaroon,4 S Shahzad Mustafa,5 Pranil Raut,6 Briana Cameron,6 Sachin Gupta,1 David M Fleischer7 1Bambino Gesù Childrens’ Hospital IRCCS, Rome, Italy; 2Stanford University, Stanford, CA, USA; 3Hospital Quironsalud Bizkaia, Bilbao, Spain; 4University of South Florida, Tampa, FL, USA; 5Rochester Regional Health & University of Rochester, Rochester, NY, USA; 6Genentech Inc., South San Francisco, CA, USA; 7Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USACorrespondence: David M Fleischer, Section Head, Allergy & Immunology, University of Colorado School of Medicine and Children’s Hospital Colorado, 13123 East 16th Avenue, B518, Aurora, CO, 80045, USA, Tel +1-720-777-4393, Email David.Fleischer@childrenscolorado.orgBackground: The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy.Patients and Methods: We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data.Results: For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy.Conclusion: There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities.Clinical trial registration: NCT00079937; NCT01922037; NCT00252135.Plain Language Summary: Food allergy and asthma are linked and if you have both conditions then you can feel worse. There is a treatment available, called omalizumab, that helps people with asthma and helps people with food allergy, but it’s not clear if it can help people with both conditions. Here, we look at whether omalizumab can help people with bad to very bad asthma (also called moderate to severe asthma) who also have food allergy. We found that omalizumab improved many aspects of a person’s life, including whether they visited the emergency room, were admitted to hospital, their quality of life, whether they missed school or work, and whether their asthma improved. These improvements occurred in all people with moderate to severe asthma, whether they had food allergy or did not have food allergy. This suggests that omalizumab can help people with both conditions.Keywords: asthma, food allergy, food hypersensitivity, healthcare resource use, omalizumab, productivity, quality of life

Abstract Naringin, a flavonoid, exhibits diverse therapeutic properties and has been proven to exert cytotoxic effects on cancer cells. Nevertheless, the precise mechanism of naringin maintaining its cytotoxic effect on glioblastoma (GBM) remains unknown. Thus, the current study aimed to establish a plausible cellular mechanism for Naringin’s inhibition of GBM. We employed various system biology techniques to forecast the primary targets, including gene ontology and cluster analysis, KEGG enrichment pathway estimation, molecular docking, MD (molecular dynamic) simulation and MMPBSA analysis. Glioblastoma target sequences were obtained via DisGeNet and Therapeutic Target Prediction, aligned with naringin targets, and analyzed for gene enrichment and ontology. Gene enrichment analysis identified the top ten hub genes. Further, molecular docking was conducted on all identified targets. For molecular dynamics modelling, we selected the two complexes that exhibited the most docking affinity and the two most prominent genes of the hub identified through analysis of the enrichment of genes. The PARP1 and ALB1 signalling pathways were found to be the main regulated routes. Naringin exhibited the highest binding potential of − 12.90 kcal/mol with PARP1 (4ZZZ), followed by ABL1 (2ABL), with naringin showing a − 8.4 kcal/mol binding score, as determined by molecular docking. The molecular dynamic approach and MM-PBSA investigation along with PCA study revealed that the complex of Naringin, with 4ZZZ (PARP1) and, 2ABL (ABL1), are highly stable compared to that of imatinib and talazoparib. Analyses of the signalling pathway suggested that naringin may have anticancer effects against GBM by influencing the protein PARP and ALB1 levels. Cytotoxicity assay was performed on two different glioblastoma cell lines C6 and U87MG cells. Naringin demonstrates a higher cytotoxic potency against U87MG human glioblastoma cells compared to C6 rat glioma cells.

Preeya K Gupta,1,2 Rolando Toyos,3 John D Sheppard,4 Melissa Toyos,3 Francis S Mah,5 Brian Bird,6 Pamela E Theriot,7 Don Higgins8 1Triangle Eye Consultants, Raleigh, NC, USA; 2Department of Ophthalmology, Tulane University, New Orleans, LA, USA; 3Toyos Clinic, Nashville, TN, USA; 4Virginia Eye Consultants, Norfolk, VA, USA; 5Scripps Clinic, La Jolla, CA, USA; 6Department of Ophthalmology, Eastern Virginia Medical School, Norfolk, VA, USA; 7Lusk Eye Specialists, Shreveport, LA, USA; 8Dry Eye Treatment Center of Connecticut, Plainville, CT, USACorrespondence: John D Sheppard, Virginia Eye Consultants, 241 Corporate Blvd, Norfolk, VA, USA, Tel +1 757 622-2200, Fax +1 757 622-4866, Email jsheppard@cvphealth.comAbstract: Dry eye disease (DED) is a common, multifactorial ocular disease impacting 5% to 20% of people in Western countries and 45% to 70% in Asian countries. Despite the prevalence of DED and the number of treatment approaches available, signs and symptoms of the disease continue to limit the quality of life for many patients. Standard over-the-counter treatment approaches and behavior/environmental modifications may help some cases but more persistent forms often require pharmacological interventions. Approved and investigational pharmaceutical approaches attempt to treat the signs and symptoms of DED in different ways and tend to have varying tolerability among patients. While several pharmacological approaches are the standard for persistent and severe disease, mechanical options provide alternate treatment modalities that attempt to balance efficacy and comfort. Newer approaches target the causes of DED, utilizing novel delivery methods to minimize irritation and adverse events. Here, we review approved and investigational approaches to treating DED and compare patient tolerability.Keywords: dry eye disease, tolerability, safety, pharmaceutical interventions, mechanical interventions

Manufacturing has experienced an immense transformation since the emergence of Industry 4.0. Digitalization has substantially improved production efficiency and product quality, and innovative business models have emerged. The backbone of emerging countries like India comprises small and medium enterprises (SMEs) that provide jobs for millions of families. Small and medium-sized businesses (SMBs) account for around 31% of the nation’s GDP and 43% of 2021–2022 exports, both significant contributors to economic growth when there is a substantial labour pool. Therefore, they are often known as India’s growth engine. Unfortunately, in today’s highly competitive digital market, they fail to keep pace with technological innovations and keep their employees up to date. This article discusses the significance of digitalization for India’s SMEs, addressing the hurdles and the methods to remove them. New consumer markets have been established due to government programs like Make in India, Digital India, and E-Government.

Brian J Nguyen,1 Angela S Gupta,1 Jocelyn He,1,2 Gui-Shuang Ying,1,2 Vatinee Y Bunya,1 Ilaria Macchi,1 Mina Massaro-Giordano1 1Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Ophthalmology, Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Mina Massaro-Giordano, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th St, Philadelphia, PA, 19104, USA, Email mina@pennmedicine.upenn.eduPurpose: This study was to assess corneal epithelial thickness (CET) in patients with Sjogren’s disease (SjD).Methods: A retrospective chart review was conducted of SjD patients from September 2021 to January 2022. Patient demographics, unanesthetized Schirmer’s test, serologic markers, and symptoms as measured by the Ocular Surface Disease Index (OSDI) were reviewed. Epithelial thickness from both eyes was measured using anterior segment OCT at the central 3mm and concentric 5mm, 7mm, and 9mm zones for the superior, temporal, inferior, and nasal corneal quadrants. Associations between corneal epithelial thickness with patient demographics, clinical characteristics, and symptoms were evaluated using regression models.Results: Fifteen SjD patients (100% female) were included with a mean age of 58.4 years. Patients with Sjogren’s disease had a significantly thinner superior corneal epithelium compared to the inferior epithelium (mean 47.7mm vs 53.1mm, p = 0.001). The epithelial thickness mean standard deviation (MSD) was significantly inversely correlated with the unanesthetized Schirmer test (r=− 0.39, p = 0.005), suggesting that an overall variability of CET correlates with decreased aqueous tear production. SS-A, SS-B, ANA, and RF positivity were not associated with any measures of CET.Conclusion: This pilot study suggests that there is significant superior versus inferior thinning of corneal epithelium in Sjogren’s patients. There was a significant correlation between variability of corneal epithelial thickness and decreased tear production in Sjogren’s patients. Further larger studies are needed to understand the relationship of CET with objective and subjective measurements of ocular surface disease.Keywords: Sjogren’s disease, corneal epithelial thickness, anterior segment OCT

Abstract Background The causative agents of Acute Encephalitis Syndrome remain unknown in 68–75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage. Objectives This study employs metagenomic next-generation-sequencing in the investigation of underlying causative etiologies contributing to acute encephalitis syndrome in Nepal. Methods In this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomization was done to include three age groups (15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan Zuckerberg-ID and confirmed with polymerase-chain-reaction. Results Human-alphaherpes-virus 2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata. Conclusion From this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal.

Electric scooters are increasingly gaining popularity in India owing to rising global crude oil prices and rising levels of vehicular pollution. Most of them are currently powered by expensive in-wheel (IW) permanent magnet (PM) brushless DC motors. Owing to their simplicity, and ruggedness while being cost-effective (since they do not employ PMs), switched reluctance motors (SRMs) are a viable alternative. Despite these benefits, SRMs possess drawbacks such as low torque density and inferior efficiency. Recently, a multi-teeth (MT) SRM with an improved performance was reported. However, the design of MTSRM topologies and their electromagnetic performance have not been explored sufficiently. In this paper, a design formula governing the selection of the number of MT and rotor poles for MTSRMs has been proposed. Using this, a novel four-phase 8/18 IW-MTSRM is derived and proposed for an E-scooter. The characteristics of the proposed SRM are numerically compared with a conventional 8/10 SRM based on magnetic characteristics, efficiencies and steady-state operation for the complete torque-speed range. Results indicate that the proposed 8/18 MTSRM has a higher peak torque capacity, torque density, superior drive cycle efficiency and reduced torque ripple. Further, the FEA model is validated experimentally on a downsized 8/18 MTSRM prototype.

IntroductionRobust connections have been identified between the pathophysiology of mental disorders and the functioning of the circadian system. The overarching objective of this study was to investigate the potential for circadian rhythms to be leveraged for therapeutics in mental disorders.MethodsWe considered two approaches to chronotherapy–optimal timing of existing medications (“clocking the drugs”) and redressing circadian abnormalities with small molecules (“drugging the clock”). We assessed whether circadian rhythm-modulating compounds can interact with the prominent drug targets of mental disorders utilizing computational tools like molecular docking and molecular dynamics simulation analysis.ResultsFirstly, an analysis of transcript-level rhythmic patterns in recognized drug targets for mental disorders found that 24-hour rhythmic patterns were measurable in 54.4% of targets in mice and 35.2% in humans. We also identified several drug receptors exhibiting 24-hour rhythmicity involved in critical physiological pathways for neural signaling and communication, such as neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, and dopaminergic and cholinergic synapses. These findings advocate that further research into the timing of drug administration in mental disorders is urgently required. We observed that many pharmacological modulators of mammalian circadian rhythms, including KL001, SR8278, SR9009, Nobiletin, and MLN4924, exhibit stable binding with psychotropic drug targets.DiscussionThese findings suggest that circadian clock-modulating pharmacologically active small molecules could be investigated further for repurposing in the treatment of mood disorders. In summary, the present analyses indicate the potential of chronotherapeutic approaches to mental disorder pharmacotherapy and specify the need for future circadian rhythm-oriented clinical research.

With its exceptional qualities, Incoloy 825 is highly valued in a range of industries, including nuclear power plants, petrochemical plants, and chemical industries. Nevertheless, the unique combination of these properties presents a formidable challenge when it comes to machining Incoloy 825. Its low heat conductivity, rapid strain hardening, strong chemical affinity, and the presence of hard and abrasive particles in its microstructure all contribute to the difficulty. The objective of this study is to examine important factors related to the machinability of Incoloy 825. To achieve this, a hybrid tool called entropy coupled with MOORA will be used to determine the optimal cutting conditions. In order to achieve this, three specific input parameters were chosen: the spindle speed, feed rate, and depth of cut. Meanwhile, the major outcomes taken into account were the cutting force, cutting temperature, material removal rate, roughness of the machined surface, and flank wear. The experiments were conducted using Taguchi’s L27 orthogonal array, following the principles of experimental design. The findings indicate that the proposed hybrid approach is capable of accurately determining the best combination of parameters for cutting the chosen work material and can be employed in structural applications. For turning Incoloy 825, the optimal parametric setting was determined to be a spindle speed of 1,285 rpm, a feed rate of 0.0625 mm·rev−1, and a depth of cut of 0.3 mm.

Matrix metalloproteinases (MMPs) are proteinases released by gingival cells, macrophages and neutrophils, induced by potentially pathogenic periodontal bacteria of the subgingival plaque, which play a critical role in the pathogenesis of periodontal disease. The expression of MMPs is controlled by chromosome 11. Single nucleotide polymorphisms (SNPs) are linked with variations in the secretion of MMPs, resulting in periodontal disease progression. Genetic studies aim to find the markers for early diagnosis and prevention of the related diseases. This systematic review focuses on finding the association between the MMPs and periodontitis among Indians. A literature review was performed, including studies published between January 1 2012 and May 2024 were incorporated. This systematic review included 1,046 participants in seven Indian studies, and substantial evidence was found for an association between MMP-9 (–1562C/T) and periodontitis in Indian population.

Background Ovarian cancer remains a formidable challenge in oncology, necessitating innovative therapeutic approaches. Claudin-6 (CLDN6), a member of the tight junction molecule CLDN family, exhibits negligible expression in healthy tissues but displays aberrant upregulation in various malignancies, including ovarian cancer. Although several therapeutic modalities targeting CLDN6 are currently under investigation, there is still a need for more potent therapeutic options. While T-cell engagers (TCEs) hold substantial promise as potent immunotherapeutic agents, their current efficacy and safety in terms of target antigen selection and T-cell exhaustion due to only CD3 stimulation without co-stimulation must be improved, particularly against solid tumors. To provide an efficacious treatment option for ovarian cancer, we generated SAIL66, a tri-specific antibody against CLDN6/CD3/CD137.Methods Using our proprietary next-generation TCE technology (Dual-Ig), SAIL66 was designed to bind to CLDN6 with one Fab and CD3/CD137 with the other, thereby activating T cells through CD3 activation and CD137 co-stimulation. The preclinical characterization of SAIL66 was performed in a series of in vitro and in vivo studies which included comparisons to a conventional TCE targeting CLDN6 and CD3.Results Despite the high similarity between CLDN6 and other CLDN family members, SAIL66 demonstrated high specificity for CLDN6, reducing the risk of off-target toxicity. In an in vitro co-culture assay with CLDN6-positive cancer cells, we confirmed that SAIL66 strongly activated the CD137 signal in the Jurkat reporter system, and preferentially induced activation of both CD4+ and CD8+ T cells isolated from human peripheral blood mononuclear cells compared to conventional TCEs. In vivo studies demonstrated that SAIL66 led to a more pronounced increase in intratumor T-cell infiltration and a decrease in exhausted T cells compared with conventional CLDN6 TCE by contribution of CD137 co-stimulation, resulting in better antitumor efficacy in tumor-bearing mouse models.Conclusion Our data demonstrate that SAIL66, designed to engage CLDN6, CD3, and CD137, has the potential to enhance antitumor activity and provide a potent therapeutic option for patients with ovarian and other solid tumors expressing CLDN6. Clinical trials are currently underway to evaluate the safety and efficacy of SAIL66.