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Background and Objectives: Sovateltide (Tycamzzi™), an endothelin-B (ET-B) receptor agonist, increases cerebral blood flow, has anti-apoptotic activity, and promotes neural repair following cerebral ischaemic stroke. The objectives of this study were to evaluate the efficacy and safety of sovateltide in adult participants with acute cerebral ischaemic stroke., Methods: This was a randomised, double-blind, placebo-controlled, multicentre, Phase III clinical trial of sovateltide in participants with cerebral ischaemic stroke receiving standard of care (SOC) in India. Patients aged 18-78 years presenting up to 24 h after the onset of symptoms with radiologic confirmation of ischaemic stroke and a National Institutes of Health Stroke Scale score (NIHSS) of ≥ 6 were enrolled. Patients with recurrent stroke, receiving endovascular therapy, or with intracranial haemorrhage were excluded. The study drug (saline or sovateltide [0.3 µg/kg] was administered intravenously in three doses at 3 ± 1 h intervals on Days 1, 3, and 6, and follow-up was 90 days). The Multivariate Imputation by Chained Equations (MICE) was used to impute the missing assessments on the endpoints. An unpaired t-test, two-way analysis of variance with Tukey's multiple comparison test, and the Chi-square test were used for the statistical analysis. The objective was to determine at Day 90 (1) the number of patients with a modified Rankin Scale score (mRS) 0-2, and (2) the number of patients with an NIHSS 0-5 at 90 days., Results: Patients were randomised with 80 patients in the sovateltide and 78 in the control group. Patients received the investigational drug at about 18 h of stroke onset in both control and sovateltide groups. The median NIHSS at randomisation was 10.00 (95% CI 9.99-11.65) in the control group and 9.00 (95% CI 9.11-10.46) in the sovateltide group. Seventy patients completed the 90-day follow-up in the control group and 67 in the sovateltide group. The proportion of intention-to-treat (ITT) patients with mRS 0-2 score at Day 90 post-randomisation was 22.67% higher (odds ratio [OR] 2.75, 95% CI 1.37-5.57); similarly, the proportion of patients with NIHSS score of 0-5 at Day 90 was 17.05% more (OR 2.67, 95% CI 1.27-5.90) in the sovateltide group than in the control group. An improvement of ≥ 2 points on the mRS was observed in 51.28% and 72.50% of patients in the control and sovateltide groups, respectively (OR 2.50, 95% CI 1.29-4.81). Seven of 78 patients (8.97%) in the control group and 7 of 80 (8.75%) in the sovateltide group developed intracranial haemorrhage (ICH). The adverse events were not related to sovateltide., Conclusions: The sovateltide group had a greater number of cerebral ischaemic stroke patients with lower mRS and NIHSS scores at 90 days post-treatment than the control group. This trial supported the regulatory approval of sovateltide in India, but a multinational RESPECT-ET B trial will be conducted for US approval., Trial Registration: Clinical Trials Registry, India (CTRI/2019/09/021373) and the United States National Library of Medicine, ClinicalTrials.gov (NCT04047563)., Competing Interests: Declarations Funding Pharmazz Inc., Willowbrook, IL, USA, funded the study. The funder contributed and reviewed the study design and protocol but had no role in conducting the study, data collection, management, analysis, and interpretation. All the authors had access to the data and have reviewed and approved the preparation and submission of this manuscript for publication. Conflicts of interest Anil Gulati has issued and pending patents and is an employee and stockholder of Pharmazz Inc. No conflicts related to the content of this article are reported by Sikandar Gokuldas Adwani, Pamidimukkala Vijaya, Nilesh Radheshyam Agrawal, TCR Ramakrishnan, Hari Prakash Rai, Dinesh Jain, Nagarjunakonda Venkata Sundarachary, Jeyaraj Durai Pandian, Vijay Sardana, Mridul Sharma, Gursaran Kaur Sidhu, Sidharth Shankar Anand, Deepti Vibha, Saroja Aralikatte, Dheeraj Khurana, Deepika Joshi, Ummer Karadan, Mohd. Shafat Imam Siddiqui. Ethics Approval The study protocol PMZ-1620/CT-3.1/2019) dated April 29, 2019, was approved by the Drugs Controller General of India (DCGI) (DCGI CT NOC. No.: CT/ND/66/2019). Furthermore, each institutional ethics committee reviewed and approved the study protocol before initiating patient enrolment. The trial registration was done at the Clinical Trials Registry, India (CTRI/2019/09/021373) and the United States National Library of Medicine, ClinicalTrials.gov (NCT04047563). Consent to Participate Informed written consent was obtained from patients or their legally authorised representatives. Consent for Publication Not applicable. Code Availability Not applicable. Data and Material The anonymised patient datasets created and/or analysed for the current study can be accessed from the corresponding author at a reasonable request from a bona fide researcher/research group. Authors' Contributions Study concept and design: AG and JDP; Investigation: SGA, PV, NRA, TCRR, HPR, DJ, NVS, JDP, VS, MS, GKS, SSA, DV, SA, DK, DJ, UK, and MSIS; Acquisition of data: SGA, PV, NRA, TCRR, HPR, DJ, NVS, JDP, VS, MS, GKS, SSA, DV, SA, DK, DJ, UK, and MSIS; Analysis and interpretation of data: AG; Drafting of the manuscript: AG; Review of the manuscript: SGA, PV, NRA, TCRR, HPR, DJ, NVS, JDP, VS, MS, GKS, SSA, DV, SA, DK, DJ, UK, and MSIS. All authors contributed to the data collection, had full access to the data room having all the data in the study, and accept responsibility to submit for publication., (© 2024. The Author(s).)

Background: Antimicrobial peptides (AMPs) such as UBI-29-41 offer a distinctive approach for precise detection due to their unique interactions with bacteria and makes them promising candidates for specific and selective imaging. The study was aimed to corroborate the in-house manual synthesis of 68 Ga-NOTA-UBI-29-41, evaluate its uptake in patients with suspected infection, and estimate of patient-specific dosimetry to ensure optimal clinical application. Materials and Methods: 68 Ga-NOTA-UBI-29-41 was synthesized by using a variable amount of UBI-29-41 (60-90 μg) to 555 MBq of Ga-68 in 0.05 M Hydrochloric acid (HCl) and heating the reaction sample for 12 min at 90°C at pH: 3.5-4 to obtain the radiopeptide with high yield and high radiochemical purity (RCP). 68 Ga-NOTA-UBI-29-41 positron emission tomography/Computed tomography (CT) scans at variable timepoints were done to evaluate its biodistribution and maximum uptake time. Furthermore, patient-specific dosimetric estimation was done using the HERMES software. Results: A total of 5 μg/37 MBq (5 μg/mCi) of NOTA-UBI-29-41 for 12 min at 90°C were the optimal parameters to obtain 88%-90% of yield and 98%-99 % of RCP. 68 Ga-NOTA-UBI-29-41 showed expeditious blood clearance and high renal excretion. The optimal time for imaging of infection with 68 Ga-NOTA-UBI-29-41 was found to be at 60 min postinjection ( n = 8). The critical organ was the urinary bladder, receiving an average dose of 138.02 ± 45.92 µSv/MBq, followed by 53.81 ± 13.72 µSv/MBq for kidneys with a mean effective dose of 1.52 ± 0.64 mSv. Conclusion: The protocol for in-house manual labeling of 68 Ga-NOTA-UBI-29-41 was reproducible, providing high yield and RCP. 68 Ga-NOTA-UBI-29-41 administration was found to be safe and nontoxic. The favorable biodistribution and the first-in-human patient-specific dosimetry ensure optimal clinical application.

Objective: This study aimed to investigate the effects of different commercially available complex implant macro designs on stress distributions using Finite element analysis. The experiment is done under varying simulated bone conditions to provide reference for clinical application., Materials and Methods: The study employed the Finite Element Analysis (FEA) method to compare four commercially available complex implant macro designs on a Computer-Aided Design (CAD) model of a maxillary bone segment. The three-dimensional geometrical model of the implants was reconstructed from computed tomography (CT)-slices in Digital Imaging and Communications in Medicine (DICOM) format and contact condition between the implant and the bone was considered as 'Bonded', implying perfect osseointegration. All materials used in the models were assumed to be isotropic, homogeneous, and linearly elastic. The Finite element simulations employed load of 400 N under both axial and non-axial conditions Stresses were analysed under different bone conditions., Results: Average values of von Mises stresses were used for comparing stress levels between implant designs. There was a definite increase in the equivalent stress values from higher density(D1)to lower density (D4) bone conditions for all implants. The percentage of increase ranged from 23.63 to 49.39 on axial loading and 20.39 to 57.19 when subjected to non-axial loading. The equivalent stress values resulted from non-axial loading were 1.78-2.94 times higher than that of axial loading for all implants under all bone densities. Among the complex designs Equinox Myriad Plus implant exhibited the least stress under axial loading (12.749-19.046 MPa) and (37.462-49.217 MPa) for non-axial loading. The stress on the crestal module was higher (1.49-2.99 times) than the overall stress on the implant regardless of the loading direction or bone conditions., Conclusions: Data from the present study shows Equinox Myriad Plus implant generating the least equivalent stress and this can be taken as indicator in the biomechanical performance of the design., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A sustainable photocatalytic approach has been established for trifluoroalkylation of isoquinoline via a three-component Minisci-type reaction using a green solvent. The polarity reversal radical cascade strategy renders the selective addition of an electrophilic CF 3 radical to an olefin to forge a nucleophilic C -centered radical. This multicomponent approach is operationally simple and environmentally benign with various functional groups, viz. aldehydes, acetals, amides, and halides. Mechanistic investigations were carried out to elaborate the reductive quenching catalytic pathway.

Here in, we have designed two new unfused non-fullerene small molecules using asymmetric benzo[1,2-b:3.4-b', 6,5-b"]trithiophene (BTT) as the central donor core and different terminal units i. e., 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (NFA-4) and 1,3-diethyl-2-thioxodi hydropyrimidine-4,6 (1H,5H)-dione (NFA-5) and examined their optical and electrochemical properties. Using a wide band-gap copolymer D18, organic solar cells (OSCs) based on bulk heterojunction of D18:NFA-4 and D18:NFA-5 showed overall power conversion efficiency (PCE) of about 17.07 % and 11.27 %, respectively. The increased PCE for the NFA-4-based OSC, compared to NFA-5 counterpart, is due higher value of short circuit current (J SC ), open circuit voltage (V OC ), and fill factor (FF). Following the addition of small amount of NFA-5 to the binary bulk heterojunction D18:NFA-4, the ternary organic solar cells attained a PCE of 18.05 %, surpassing that of the binary counterparts due to the higher values of which is higher than that for the binary counterparts and attributed to the increased values of J SC , FF, and V OC . The higher value of J SC is linked to the efficient use to excitons transferred from NFA-5 to NFA-4 with a greated dipole moment than NFA-5 and subsequently dissociated into a free charge carrier efficiently., (© 2024 Wiley-VCH GmbH.)

Groundwater pollution caused by fluoride is a significant concern for the global population owing to its toxicity, which has negative health consequences. Industrial discharges, agricultural practices, and improper waste disposal are primary concerns in evaluating the degree of fluoride contamination in the selected districts of Eastern India. In a targeted area sampling approach, exactly 196 samples were collected during pre- and post-monsoon, and precise fluoride detection was performed using Ion-Selective Electrodes. Fluoride levels in pre-monsoon water were observed within a range of 0.02 to 2.7 mg/L, with an average abundance of 0.4 ± 0.50. In post-monsoon, the concentration ranged from 0.02 to 4.7 mg/L (mean 0.53 ± 0.60). The study found that 97 % of groundwater samples had acceptable fluoride levels within the 1.5 mg/L limit during pre and post-monsoon. Moreover, approximately 87 % of the samples exhibit fluoride content below the 1 mg/L limit. The hazard quotient was observed to be 0.17 to 0.58 in adults, 0.23 to 0.79 in children and 0.36 to 1.26 in infants during pre-monsoon, whereas 0.05 to 0.55 in adults, 0.12 to 0.74 in children and 0.11to 1.19 in infants during post monsoon. The above data indicates that infants had the highest risk of fluoride exposure, with a significant negative correlation between fluoride and calcium ions. Fluoride had minimal to no link with other ions, a modest positive correlation with sulfate, and a weak negative relationship with overall hardness and alkalinity across both seasons. The present study contributes towards the identification of fluoride levels in various areas, making society aware of water contamination and its health impacts., 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 B.V. All rights reserved.)

Context.—: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS., Objective.—: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation., Design.—: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule., Results.—: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule., Conclusions.—: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

The deformation behavior of metallic glasses has been shown in prior studies to be often dependent on its structural state, namely higher energy "rejuvenated" state versus lower energy "relaxed" state. Here, the deformation behavior of thermally rejuvenated Zr-Cu-Al-(Ti) bulk metallic glasses (BMGs) was evaluated. Rejuvenation was achieved by cryogenic thermal cycling with increase of free volume measured in terms of enthalpy of relaxation. Hardness, stiffness, and yield strength of the BMGs were all found to decrease while plasticity increased after rejuvenation. More free volume in the rejuvenated BMG resulted in homogeneous plastic deformation as was evident from the high strain rate sensitivity and more pronounced shear band multiplication during uniaxial compression. Shear transformation zone (STZ) volume was calculated by cooperative shear model and correlated well with the change in structural state after rejuvenation. The enhanced plasticity with the addition of 1 at. % Ti as well as after cryogenic thermal cycling was explained by lower activation energy for shear flow initiation due to increased heterogeneity induced in the system. Molecular dynamics simulation demonstrated that the variation in plastic deformation behavior is correlated with local atomic structure changes., (© 2024. The Author(s).)

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)]., (© Journal of the Association of Physicians of India 2024.)

Background: Inoperable malignant bowel obstruction, which results in chronic nausea, vomiting and abdominal pain, often requires nasogastric tube decompression. However, these tubes are often uncomfortable for patients and require hospitalization during the end-of-life care. Cervical esophago-gastric (CEG) decompression tubes are a potential palliative solution. The objective of this study is to present the outcomes of CEG tubes in 11 patients with malignant bowel obstruction., Methods: We performed a retrospective review of patients requiring nasogastric tube decompression who received CEG decompression tubes for inoperable malignant bowel obstructions between 2016-2022. CEG tube placement was performed percutaneously through the left neck using a guidewire and an endoscopic technique., Results: The average age of patients was 58 years (31-72 years), with metastatic colorectal cancer (36.4%) and ovarian cancer (27.3%) being the most common causes of malignant bowel obstruction. All procedures were completed percutaneously, without requiring conversion to open procedures. The morbidity of the procedure was 27%, which included tube dislodgement, local cellulitis, or bleeding at the insertion site. None of the patients required reoperation, with most of the patients successfully treated conservatively. Most patients were discharged home after the procedure (82%); however, 45% were readmitted (mostly due to abdominal pain). Most patients (73%) were able to continue additional chemotherapy after tube placement. The average survival from cancer diagnosis was approximately six months, whereas the average survival after the procedure was about four months. No mortalities occurred due to CEG tube placement., Conclusions: A CEG decompression tube is safe for patients with malignant bowel obstruction. The procedure allows patients to undergo additional chemotherapy and be discharged home with a more comfortable tube.

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness. Materials and Methods This prospective, observational, cross-sectional study (March 2021 to November 2021) enrolled adults with NAFLD, stratified according to the Fibrosis-4 (FIB-4) index (≤1.3, >1.3 and <2.67, ≥2.67), at two sites to assess SWE with five US systems and VCTE with one system. Each participant underwent 12 elastography examinations over two separate days within 1 week, with each day's examinations conducted by a different operator. VCTE and SWE measurements were reported in units of meters per second. The primary end point was the different-day, different-operator reproducibility coefficient (RDC DDDO ) pooled across systems for SWE and individually for VCTE. Secondary end points included system-specific RDC DDDO , same-day, same-operator repeatability coefficient (RC SDSO ), and between-system same-day, same-operator reproducibility coefficient. The planned sample provided 80% power to detect a pooled RDC DDDO of less than 35%, the prespecified performance threshold. Results A total of 40 participants (mean age, 60 years ± 10 [SD]; 24 women) with low ( n = 17), intermediate ( n = 15), and high ( n = 8) FIB-4 scores were enrolled. RDC DDDO was 30.7% (95% upper bound, 34.4%) for SWE and 35.6% (95% upper bound, 43.9%) for VCTE. SWE system-specific RDC DDDO varied from 24.2% to 34.3%. The RC SDSO was 21.0% for SWE (range, 13.9%-35.0%) and 19.6% for VCTE. The SWE between-system same-day, same-operator reproducibility coefficient was 52.7%. Conclusion SWE met the prespecified threshold, RDC DDDO less than 35%, with VCTE having a higher RDC DDDO . SWE variability was higher between different systems. These estimates advance liver US-based noninvasive test qualification by (a) defining expected variability, (b) establishing that serial examination variability is lower when performed with the same system, and (c) informing clinical trial design. ClinicalTrials.gov Identifier NCT04828551 © RSNA, 2024 Supplemental material is available for this article.

Purpose: The influence of two key factors, host length and infection site, on the host-parasite interaction in Ompok bimaculatus (Butter catfish) from Mukutmanipur Dam Lake, were investigated., Methods: Present study involved 192 specimens of Ompok bimaculatus with varying body lengths, subjected to diverse statistical analyses. One-way analysis of variance (ANOVA) was performed for the parasite numbers for three groups (cestode, nematode and trematode). Subsequently, we conducted one-way permutational multivariate analysis of variance (PERMANOVA) followed by pairwise test to assess parasite numbers across three body sites (intestine, mesentery, and bodycavity), employing the Bray-Curtis index. Additionally, Principal Coordinate Analysis (PCoA) for the same dataset was performed using the same index. Linear regression analysis was performed for the fish length-cestode number, fish length-nematode number, fish length-trematode number and fish length-total parasite number., Results: One-way ANOVA revealed no significant differences in parasite numbers among the three endo-helminth groups (cestode, nematode, and trematode). The results of PERMANOVA revealed significant differences in parasite numbers across the three body sites of the host fishes (groups) (F = 9.41, p = 0.0001). Pairwise tests further demonstrated significant differences between the intestine-mesentery, intestine-body-cavity, and mesentery-body-cavity. Additionally, Principal Coordinate Analysis (PCoA) unveiled a significant relationship between infection site and parasite number. However, linear regression analysis examining the relationship between fish length and parasite abundance indicated no significant associations., Conclusions: Through a detailed exploration of the statistical analyses, we provide insights into the host-parasite interaction, elucidating both established knowledge and novel findings in fish parasitology., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background & Aims: Cotadutide, a peptide co-agonist at the glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, has demonstrated robust improvements in body weight, glycemia, and hepatic fat fraction (HFF) in patients living with obesity and type 2 diabetes mellitus., Methods: In PROXYMO, a 19-week randomized double-blind placebo-controlled trial, the safety and efficacy of cotadutide (600 μg, 300 μg) or placebo were evaluated in 74 participants with biopsy-proven noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis. Analyses were performed using intent-to-treat and modified intent-to-treat population data., Results: Dose- and time-dependent improvements in HFF, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), markers of liver health, and metabolic parameters were observed with significant improvements after 19 weeks with 600 μg ([least squares] mean difference vs placebo, [95% confidence interval] for absolute HFF: -5.0% [-8.5 to -1.5]; ALT: -23.5 U/L [-47.1 to -1.8]; AST: -16.8 U/L [-33.0 to -0.8]). Incidences of any grade treatment-emergent adverse events (TEAEs) were 91.7%, 76.9%, and 37.5% with cotadutide 600 μg, 300 μg, and placebo, respectively. The majority were gastrointestinal, mild to moderate in severity, and generally consistent with other incretins at this stage of development. TEAEs leading to treatment discontinuation were 16.7%, 7.7%, and 4.2% with cotadutide 600 μg, 300 μg, and placebo, respectively., Conclusions: PROXYMO provides preliminary evidence for the safety and efficacy of GLP-1/GCG receptor co-agonism in biopsy-proven noncirrhotic MASH with fibrosis, supporting further evaluation of this mechanism in MASH., Clinical Trial Registration Number: NCT04019561., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pesticide pollution remains a significant environmental challenge, necessitating the exploration of sustainable alternatives. Biosurfactants are a class of unconventional surface-active chemicals that are produced by microorganisms. Biosurfactants have many applications in treating oil spills, emulsifiers, pharmaceuticals, and agriculture. Compared to chemical surfactants, they have benefits such as biodegradability, less toxicity, and a greener option because they are derived from microbes. Biosurfactants have recently been shown to have the potential to speed up pesticide cleanup. Biosurfactants are used in pesticide remediation because of their exceptional foaming ability, high selectivity, and wide range of pH, salinity, and temperature operating windows. Microbial biosurfactants emerged as potential agents for the treatment of organic waste and agricultural residue. This review unfolds the promising realm of microbial biosurfactants as green solutions for environmental sustainability, particularly in agricultural practices, with special reference to pesticide remediation. This article highlights the escalating need for eco-friendly alternatives, paving the way for discussing biosurfactants. Moreover, the articles discuss in detail various advancements in the field of rapid screening of biosurfactants, either using a conventional approach or via advanced instruments such as GC-MS, HPLC, NMR, FTIR, etc. Furthermore, the article unveils the molecular mechanisms and the microbial genes driving biosurfactant synthesis, offering insights into enhancing production efficiency. Moreover, the article explores diverse applications of microbial biosurfactants in sustainable agriculture, ranging from soil remediation to crop protection. The article also highlights the various functions of microbial biosurfactants for enhancing the decomposition and recycling of organic waste and agricultural residues, emphasizing their potential for sustainable waste management strategies. Overall, the review underscores the pivotal role of microbial biosurfactants as green alternatives for addressing pesticide pollution and advancing environmental sustainability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

An important sensation that warns of potential harm to a specific area of the body is pain. The prevalence of pain-related conditions globally is a significant and growing public health issue. Chronic pain affects an estimated 1.5 billion people worldwide, with prevalence rates varying by region and demographic factors. Along with diabetes, cardiovascular disease, and cancer, pain is among the most frequent medical diseases. Opioid analgesics are the mainstay of current pain therapies, which are ineffective. Opioid addiction and its potentially fatal side effects necessitate novel treatment strategies. Nanotechnology offers potential advantages in pain management by enabling targeted drug delivery, which can enhance the efficacy and reduce the side effects of analgesic medications. Additionally, nanoparticles can be designed to release drugs in a controlled manner, improving pain relief duration and consistency. This approach also allows for the delivery of therapeutics across biological barriers, potentially enhancing treatment outcomes for chronic pain conditions. Nanomedicine enables sensitive and focused treatments with fewer side effects than existing clinical pain medicines; it is worth exploring as a potential solution to these problems. Furthermore, medication delivery systems that use nanomaterials are being used to treat pain. Whether it's the distribution of a single medication or a combination of therapies, this review seeks to summarise the ways in which drug delivery systems based on nanomaterials can be utilised to successfully treat and alleviate pain. For the purpose of writing this paper, we consulted several online libraries, including Pubmed, Science Direct, Pubmed Prime, and the Cochrane Library, to gather fresh and up-to-date material. This overview delves into the ins and outs of pain's pathophysiology, the present state of pain treatment, potential new pain treatment targets, and the various initiatives that have been launched and are still in the works to address pain with nanotechnology. Recent developments in nanomaterials-based scavenging, gene therapy for pain aetiology, and nanoparticle-based medicine delivery for side effect reduction are highlighted. Analgesics have been further covered in our discussion on FDA-approved pharmaceuticals and clinical advancements., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pathophysiology of chronic wounds related to diabetes mellitus is a result of a series of complications induced by hyperglycemia. The symptoms include impaired growth factor production, decreased keratinocyte proliferation and migration, reduced angiogenesis and cytokine synthesis, lowered matrix metalloproteinase (MMP) production, neuropathy, reduced nitric oxide synthase production, decreased fibroblast synthesis and migration, and impaired inflammatory cell functions. This multifaceted mechanism of diabetic wounds needs a suitable novel topical formulation that can deliver the active constituent by a controlled means, target the various stages of wound healing, absorb the wound exudates, and prevent secondary infections. To meet the above requirements, the Clerodendrum glandulosum (CG) extract reduced silver nanoparticle (AgNP) impregnated chitosan-polyethylene glycol (PEG) hydrogel was synthesized. The findings of the physicochemical characterization studies suggested that the hydrogel exhibited excellent formulation characteristics and showed controlled release for seven days, making it suitable for chronic wound healing studies. In subsequent studies, these formulations showed good antioxidant and antimicrobial properties, and hemocompatibility, with the least cytotoxic properties. The results of the diabetic wound healing studies showed a faster wound closure rate and improved extracellular matrix formation. These antioxidant, antimicrobial, anti-inflammatory and wound-healing properties suggest that the CG-AgNP loaded chitosan-PEG hydrogel is a promising material for novel topical formulation of diabetic wounds.

We performed an exhaustive numerical analysis of the two-dimensional Chialvo map by obtaining the parameter planes based on the computation of periodicities and Lyapunov exponents. Our results allowed us to determine the different regions of dynamical behavior, identify regularities in the distribution of periodicities in regions indicating regular behavior, find some pseudofractal structures, identify regions such as the "eyes of chaos" similar to those obtained in parameter planes of continuous systems, and, finally, characterize the statistical properties of chaotic attractors leading to possible hyperchaotic behavior., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Purpose: αvβ6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvβ6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68 Ga. This is a pilot study to assess the potential role of 68 Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvβ6 integrin expression by the tumor tissue on immunohistochemistry (IHC)., Patients and Methods: Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body 68 Ga-Trivehexin PET/CT and 18 F-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for αvβ6 integrin expression. The degree of αvβ6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification., Results: The 68 Ga-Trivehexin PET images demonstrated increased tracer uptake (mean SUV max 5.9 ± 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 ± 2.6). Among various cases of H&NSCC, increased uptakes of 68 Ga-Trivehexin (6.6 ± 4.5) and 18 F-FDG (12.7 ± 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in 18 F-FDG PET (7.98 ± 3.1) and no significant uptake in 68 Ga-Trivehexin PET (2.2 ± 0.34).IHC showed higher expression of αvβ6 integrins in lesions with higher uptake of 68 Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of 68 Ga-Trivehexin PET over 18 F-FDG PET was seen for detection of primary and metastatic lesions., Conclusions: 68 Ga-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing αvβ6 integrin, especially in cases where 18 F-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites., Competing Interests: Conflicts of interest and sources of funding: The author “Jakub Simecek” is the CEO (Chief Executive Officer) of “TRIMT GmbH.” There is no conflict of interest with respect to the other authors. The pharmaceutical “trivehexin” was provided by TRIMT GmbH. The investigators have not received any fee or financial indemnity from TRIMT GmbH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Urban slums are hotspots of infectious diseases like COVID-19 as was seen in the waves of 2020 and 2021. One of the primary reasons why slums are disproportionately affected is their location in inaccessible and uninhabitable zones, crowded and poorly ventilated living spaces, unsanitary conditions and common facilities (water taps, common toilets, etc.). Staying at home during pandemics is hardly an option for slum dwellers as it often means giving up work and even basic necessities., Methodology: This paper aims to understand the habitat vulnerabilities of slums in the two Indian megacities of Pune and Surat which were the worst hit during both waves. The study is done at the level of wards, which is the smallest administrative boundary, taking the habitat vulnerability (congestion and access to basic services). To identify the explanatory variables which increase the vulnerability of slums to infectious diseases, literature study is done on the triggering factors which affect habitat vulnerability derived from common characteristics and definitions of slum., Results: The aim of the research is to categorize the slums into 3 levels of risk zones and map them subsequently., Conclusion: This study will help in formulating a model to prioritize the allocation of sparse resources in developing countries to tackle the habitat vulnerabilities of the slum dwellers especially during health emergencies of contagious diseases like COVID-19., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Panda S and Ray SS.)

A convergent strategy for the first total synthesis of the lipopeptide bacilotetrin C has been developed. The key features of this synthesis include Crimmins acetate aldol, Steglich esterification, and macrolactamization. Twenty-nine variants of the natural product were prepared following a systematic structure-activity relationship study, where some of the designed analogues showed promising cytotoxic effects against multiple human carcinoma cell lines. The most potent analogue exhibited a ∼37-fold enhancement in cytotoxicity compared to bacilotetrin C in a triple-negative breast cancer (MDA-MB-231) cell line at submicromolar doses. The study further revealed that some of the analogues induced autophagy in cancer cells to the point of their demise at doses much lower than those of known autophagy-inducing peptides. The results demonstrated that the chemical synthesis of bacilotetrin C with suitable improvisation plays an important role in the development of novel anticancer chemotherapeutics, which would allow future rational design of novel autophagy inducers on this template., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

A commonly accepted standard protocol for noninvasive techniques for the genetic evaluation of an embryo remains elusive due to inconclusiveness regarding the volume of spent media to be acquired and the possibility of acquiring the same for subsequent analysis. Single embryo culture is imperative for standardizing noninvasive preimplantation testing using cell-free DNA (cf-DNA) released by individual developing embryos. This study aims to compare the development dynamics of single-drop embryonic culture against with group embryonic culture to establish a standardized protocol for noninvasive Preimplantation Genetic Testing (PGT) in bovine. A total of 239 cumulus-oocyte complexes were aspirated and subjected to in vitro maturation and fertilization. Among these, 120 embryos of day 3 were transferred to single-drop culture until the blastocyst stage. The single-drop culture drops were prepared using microdrops of 30 μL. At the blastocyst stage, spent media from all single-drop embryos were utilized for extracting cell-free genomic DNA to standardize the protocol. The blastocyst rate indicates no significant difference between the two culture methods, suggesting that single-drop culture is suitable for the process. Additionally, the extracted spent media yielded sufficient quantities of cf-DNA, supporting its potential use for PGT ( p  < 0.05). These findings support the hypothesis that single-drop embryo culture is a viable method for cf-DNA extraction and confirm the potential of using DNA fragments from spent media as a reliable source for noninvasive PGT., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica , predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P . javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC 50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

Background: Epithelial cell adhesion molecule (EpCAM) has been widely studied as a tumor antigen due to its expression in varieties of solid tumors. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extracellular (EpEX) and intracellular (EpICD) domains. In colorectal cancer (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and β-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes that; however, remains unclear whether Wnt signaling is modulated by EpICD activity., Methods: Patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and various CRC cell lines were used to study the roles of EpCAM and EpICD in Wnt receptor expression. Fluorescence and confocal microscopy were used to analyze tumors isolated from PDX and other xenograft models as well as CRC cell lines. EpCAM signaling was intervened with our humanized form of EpCAM neutralizing antibody, hEpAb2-6. Wnt receptor promoters under luciferase reporters were constructed to examine the effects of EpICD. Luciferase reporter assays were performed to evaluate promoter, γ-secretase and Wnt activity. Functional assays including in vivo tumor formation, organoid formation, spheroid and colony formation experiments were performed to study Wnt related phenomena. The therapeutic potential of EpCAM suppression by hEpAb2-6 was evaluated in xenograft and orthotopic models of human CRC., Results: EpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the β-Catenin destruction complex (GSK3β and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our hEpAb2-6 antibody blocked EpICD-mediated upregulation of Wnt receptor expressions and conferred therapeutic benefits in both PDX and orthotopic models of human CRC., Conclusions: This study uncovers relevant functions of EpCAM where Wnt receptors are upregulated via the transcriptional co-factor activity of EpICD. The resultant enhancement of Wnt signaling induces γ-secretase activity further stimulating EpICD cleavage and its nuclear translocation. Our humanized anti-EpCAM antibody hEpAb2-6 blocks these mechanisms and may thereby provide therapeutic benefit in CRC., (© 2024. The Author(s).)

Background: Dermatology is an ideal specialty for artificial intelligence (AI)-driven image recognition to improve diagnostic accuracy and patient care. Lack of dermatologists in many parts of the world and the high frequency of cutaneous disorders and malignancies highlight the increasing need for AI-aided diagnosis. Although AI-based applications for the identification of dermatological conditions are widely available, research assessing their reliability and accuracy is lacking., Objective: The aim of this study was to analyze the efficacy of the Aysa AI app as a preliminary diagnostic tool for various dermatological conditions in a semiurban town in India., Methods: This observational cross-sectional study included patients over the age of 2 years who visited the dermatology clinic. Images of lesions from individuals with various skin disorders were uploaded to the app after obtaining informed consent. The app was used to make a patient profile, identify lesion morphology, plot the location on a human model, and answer questions regarding duration and symptoms. The app presented eight differential diagnoses, which were compared with the clinical diagnosis. The model's performance was evaluated using sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F 1 -score. Comparison of categorical variables was performed with the χ 2 test and statistical significance was considered at P<.05., Results: A total of 700 patients were part of the study. A wide variety of skin conditions were grouped into 12 categories. The AI model had a mean top-1 sensitivity of 71% (95% CI 61.5%-74.3%), top-3 sensitivity of 86.1% (95% CI 83.4%-88.6%), and all-8 sensitivity of 95.1% (95% CI 93.3%-96.6%). The top-1 sensitivities for diagnosis of skin infestations, disorders of keratinization, other inflammatory conditions, and bacterial infections were 85.7%, 85.7%, 82.7%, and 81.8%, respectively. In the case of photodermatoses and malignant tumors, the top-1 sensitivities were 33.3% and 10%, respectively. Each category had a strong correlation between the clinical diagnosis and the probable diagnoses (P<.001)., Conclusions: The Aysa app showed promising results in identifying most dermatoses., (©Shiva Shankar Marri, Warood Albadri, Mohammed Salman Hyder, Ajit B Janagond, Arun C Inamadar. Originally published in JMIR Dermatology (http://derma.jmir.org), 02.07.2024.)

Background: The interaction between the recipient area and the graft is one of the key factors in the success of periodontal plastic surgery. This randomized controlled, split-mouth, double-blinded clinical trial aimed to compare the clinical and aesthetic outcomes of epithelialized palatal graft (EPG) and gingival unit graft (GUG) in achieving root coverage in localized (Recession Type 1) RT1 recession defects., Methods: Twenty participants with forty bilateral recession defects randomly received EPG or GUG surgical treatment modalities for each of the recession defects. Clinical measurements recorded at baseline and after six months included recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), keratinized tissue width (KTW), and the average width of mesial and distal interdental papilla (aWIDP)., Results: There was a statistically significant greater mean root coverage (MRC) percentage at GUG sites (80.68 ± 16.12%) in comparison to EPG sites (71.05 ± 17.23%) ( p  = 0.01). The treatment satisfaction ( p  = 0.009) and aesthetic satisfaction ( p  < 0.001) experienced were significantly better for GUG as compared to EPG. The regression model ( R 2  = 0.56) significantly predicted MRC percentage in GUG sites with baseline RD ( β  = -12.49; p  = 0.02) and aWIDP ( β  = -9.31; p  = 0.02)., Conclusion: GUG showed a better MRC, aesthetics and increased KTW. Root coverage procedures often need to suffice the dual objective of coverage and aesthetics at the same time. GUG is a simple modification of the conventional EPG that can provide better clinical and aesthetic outcomes., (© 2024 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background: The clinical and radiographic efficacy of bone grafts and biomaterials, such as platelet-rich plasma and platelet-rich fibrin (PRF), for reconstructing lost periodontal structures has been well documented. However, there is limited data regarding the presence of demineralized freeze-dried bone allograft (DFDBA) in an environment with abundant growth factors provided by platelet concentrates., Objectives: The aim of the study was to compare the clinical and radiographic effectiveness of DFDBA with PRF versus DFDBA alone in the treatment of intrabony defects., Material and Methods: Twenty-four intrabony defects in contralateral sites were randomly assigned to either the DFDBA group or the DFDBA combined with PRF group. Clinical parameters, including the plaque index (PI), the gingival index (GI), probing pocket depth (PPD), relative attachment level (RAL), and radiographic bone fill (RBF), were measured at baseline, and at 6 and 9 months. Paired and unpaired t-tests were used for intraand intergroup comparisons., Results: Both the PI and the GI showed statistically significant improvements from baseline to 9 months. However, the intergroup comparisons did not reveal any significant differences (p < 0.05) between the groups with regard to clinical and radiographic measurements from baseline to 9 months., Conclusions: Platelet-rich fibrin in combination with DFDBA did not show any additional benefit in terms of reconstructive output in the treatment of intrabony defects compared to the use of DFDBA alone.

Background: This article aims to compare clinical efficacy of newly introduced PowerScope 2 appliance with Forsus FRD in the treatment of Skeletal Class II malocclusion., Methods: This randomized controlled trial studied 40 patients at two centers (20 patients at each center, divided into two groups of 10 patients each as Group 1: Forsus FRD and Group 2: PowerScope 2 appliance. The skeletal, dental, soft tissue, and airway changes were noted at T0 (pretreatment), T1 (preappliance therapy), and T2 (postappliance therapy). Acoustic Pharyngometry (Eccovision® Acoustic Pharyngometer) was done to ascertain changes in mean airway volume and area with both modalities noninvasively. Treatment duration and chairside time in appliance installation and removal were noted. Patient comfort was compared using a customized questionnaire survey., Results: A significant change was observed in skeletal, dental, soft tissue, and airway parameters after treatment with both modalities ( p -value <0.05 for all) with no significant intergroup difference ( p -value >0.05). Chairside time spent in appliance insertion was significantly lower with PowerScope 2 appliance (10.33 min) as compared to the Forsus FRD appliance (18.28 min) ( p -value <0.05). Visual Analogue Scale scores for parameters such as problems in mastication, problems in speech, and problems in oral hygiene maintenance were significantly lower with PowerScope 2 appliance as compared to the Forsus FRD appliance ( p -value <0.05)., Conclusions: Although both modalities are effective in the management of Class II malocclusion, the PowerScope 2 appliance scores better in terms of lesser chairside time in appliance installation and better patient comfort., (© 2023 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

India is renowned for its mango diversity, with more than 1000 genotypes reported. However, the Himalayan plains bear some elite genotypes which supposed to bear high postharvest value, the systemic postharvest study of which is yet to be attempted. The aim of present study is to evaluate the postharvest quality and ripening behviour of these important genotypes. Thus, 15 un-explored mango genotypes of this region were selected and evaluated for ripening behaviour and detailed postharvest profiling via internal (total phenolic and total flavonoid content), nutritional attributes (Brix: acid ratio, total carotenoid concentration, ascorbic acid content and antioxidant activity), sensory evaluation, fruit softening enzymes (polygalactouronase, pectin methylesterase and lipoxygenase), shelf life attributes (respiration rate, physiological loss in weight and storage life in days) external attributes (fruit weight, fruit firmness, peel thickness, fruit shape and dry seed weight) and mineral contents (Calcium, potassium and phosphorous) under ambient storage (25 ± 4 °C and 65 ± 5 % RH). The results revealed that the highest total flavonoid content (682.40 μg g -1 ), ascorbic acid (46.88 mg 100 g -1 ) and antioxidant activity (4.84 μmol TE g -1 ) exhibited by 'Sukul'. The total phenolic content was recorded as the highest in 'Safed Malda' (510.42 μg GAE g-1 FW), and total carotenoid concentration was recorded as the highest in 'Sipiya' (7.30 mg 100 g-1) 'Zardalu' (7.04 mg 100 g-1) and 'Mithua' (6.98 mg 100 g-1). Interestingly, genotypes such as 'Sukul', Sipiya' and 'Krishna Bhog 'exhibited a 4-5 days higher storage life than other selected genotypes. Screened genotypes exhibited a high diversity of nutritional and biochemical contents. The results of this study bear practical utility for research (quality improvement programme) and the processing industry., Competing Interests: The authors declare no conflict of 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:The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corresponding authors is associate editor of this journal. 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., (© 2024 The Authors.)

A strategy for Co(III)-catalyzed C(sp 2 )-H alkenylation of N -protected isoquinolones with 1,4-naphthoquinones has been disclosed. The developed protocol was efficiently applied for diversely substituted isoquinolones. Preliminary mechanistic experiments revealed the involvement of a five-membered cobaltacycle as an intermediate. Deuterium labeling experiments suggested the reversible nature of the C-H activation step. The scale-up reaction was also carried out, and the product was utilized as a chemosensor to detect Fe 3+ ions.

A mild protocol for hydroacylation of enones through photosensitization of acyl silanes with thioxanthone under blue light (455 nm) irradiation is reported. A Brønsted acid is used as a cocatalyst in the reaction. The versatility of the method is demonstrated through inter- and intramolecular hydroacylation reaction. The hydroacylation product is applied for synthesizing an anti-HCV agent. Mechanistic insights are also provided through control experiments., (© 2024 Wiley-VCH GmbH.)

Meteorin (Metrn) and Meteorin-like (Metrnl) are homologous secreted proteins involved in neural development and metabolic regulation. In this study, we have performed de novo structure prediction and analysis of both Metrn and Metrnl using Alphafold2 (AF2) and RoseTTAfold (RF). Based on the domain and structural homology analysis of the predicted structures, we have identified that these proteins are composed of two functional domains, a CUB domain and an NTR domain, connected by a hinge/loop region. We have identified the receptor binding regions of Metrn and Metrnl using the machine-learning tools ScanNet and Masif. These were further validated by docking Metrnl with its reported KIT receptor, thus establishing the role of each domain in the receptor interaction. Also, we have studied the effect of non-synonymous SNPs on the structure and function of these proteins using an array of bioinformatics tools and selected 16 missense variants in Metrn and 10 in Metrnl that can affect the protein stability. This is the first study to comprehensively characterize the functional domains of Metrn and Metrnl at their structural level and identify the functional domains, and protein binding regions. This study also highlights the interaction mechanism of the KIT receptor and Metrnl. The predicted deleterious SNPs will allow further understanding of the role of these variants in modulating the plasma levels of these proteins in disease conditions such as diabetes.Communicated by Ramaswamy H. Sarma.

Citrus Huanglongbing (HLB) caused by ' Candidatus Liberibacter asiaticus' (CLas) is the most devastating citrus disease worldwide. CLas induces systemic and chronic reactive oxygen species (ROS) production, which has been suggested to be a primary cause of cell death in phloem tissues and subsequent HLB symptoms. Mitigating oxidative stress caused by CLas using horticultural approaches has been suggested as a useful strategy to reduce HLB damages. To provide information regarding the application timing to mitigate ROS, we investigated monthly dynamics of CLas concentration, CLas-triggered ROS, and phloem cell death in the bark tissues of asymptomatic and symptomatic branches of HLB-positive Hamlin and Valencia sweet orange trees in the field. Healthy branches in the screenhouse were used as controls. CLas concentration exhibited significant variations over the course of the year, with two distinct peaks observed in Florida citrus groves-late spring/early summer and late fall. Within both Hamlin and Valencia asymptomatic tissues, CLas concentration demonstrated a negative correlation with the deviation between the monthly average mean temperature and the optimal temperature for CLas colonization in plants (25.7°C). However, such a correlation was not evident in symptomatic tissues of Hamlin or Valencia sweet oranges. ROS levels were consistently higher in symptomatic or asymptomatic branches than in healthy branches in most months. ROS concentrations were higher in symptomatic branches than in asymptomatic branches in most months. CLas triggered significant increases in ion leakage in most months for asymptomatic and symptomatic branches compared with healthy controls. In asymptomatic branches of Hamlin, a positive correlation was observed between CLas concentration and ROS concentrations, CLas concentration and ion leakage levels, as well as ROS and ion leakage. Intriguingly, such a relationship was not observed in Valencia asymptomatic branches or in the symptomatic branches of Hamlin and Valencia. This study sheds light on the pathogenicity of CLas by providing useful information on the temporal dynamics of ROS production, phloem cell death, and CLas growth, as well as provides useful information in determining the timing for application of antioxidants and antimicrobial agents to control HLB., Competing Interests: The author(s) declare no conflict of interest.

Finger millet (Eleusine coracana) is an essential staple crop in many regions of Africa and Asia, valued for its nutritional content and resilience in challenging agro-ecological conditions. The enhancement of finger millet through genomic resources and breeding methods represents a promising avenue for addressing food and nutritional security. Current efforts in this field have harnessed genomic technologies to decipher the crop's genetic diversity and identify key traits related to yield, disease resistance, and nutritional content. These insights have facilitated the development of improved varieties through selective breeding, accelerating the crop's adaptation to changing environmental conditions. In the future, continued advancements in genomics and breeding methodologies hold the potential to further enhance finger millet's resilience, nutritional value, and productivity, ultimately benefiting both farmers and consumers. This review article synthesizes the current state of research and development in finger millet enhancement through the integration of genomic resources and innovative breeding methods. The utilization of these insights in selective breeding has already yielded promising results in developing improved finger millet varieties that meet the evolving needs of farmers and consumers. Moreover, this article discusses potential future interventions, including the continued advancement of genomics, precision breeding, and sustainable agricultural practices. These interventions hold the promise of further enhancing finger millet's adaptability to changing climates, its nutritional quality, and its overall productivity, thereby contributing to food security and improved livelihoods in finger millet-dependent regions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to hyperglycemia and associated long-term systemic complications and even death. Immunotherapy demonstrates beta cell function-preserving potential; however, its impact on C-peptide levels, a definitive biomarker of beta cell function, and endogenous insulin secretion remain unclear. A systematic review of various immunotherapeutic interventions is hence needed for a comprehensive assessment of their effectiveness as well as identifying research gaps and influencing future research and clinical decisions. An extensive literature search was done in PubMed, Scopus, and Cochrane Library databases using precise keywords and filters to identify relevant studies. Three independent reviewers assessed eligibility according to predetermined eligibility criteria, and data was extracted. The Cochrane risk of bias assessment tool (RoB 2.0) was used to evaluate the quality and validity of the included studies. A senior reviewer resolved discrepancies and differences of opinion between independent reviewers. A total of 11 studies were included, with 1464 study participants. Both Phase II and III trials were included. Within the included studies, four studies assessed the anti-CD3 monoclonal antibody otelixizumab as an intervention. Another anti-CD3 monoclonal antibody, teplizumab, was assessed as an intervention in four studies, whereas two studies assessed the anti-CD20 antibody rituximab and one study assessed abatacept as its interventional drug. Otelixizumab demonstrated benefits at higher doses but was associated with adverse effects like Ebstein-Barr virus reactivation and cytomegalovirus infection, while at lower doses it failed to show a significant difference in C-peptide levels or glycosylated hemoglobin (HbA1c). Teplizumab, on the other hand, showed promise in reducing C-peptide loss and exogenous insulin requirements and was associated with adverse events such as rash, lymphopenia, urinary tract infection, and cytokine release syndrome. However, these reactions were only associated with therapy initiation, and they subsided on their own. Rituximab improved C-peptide responses, and abatacept therapy demonstrated reduced loss of C-peptide, improved C-peptide levels, and lowered HbA1c. Teplizumab, rituximab, otelixizumab, and abatacept show potential for preserving beta cell function by reducing C-peptide loss in patients with type I diabetes mellitus. However, careful monitoring of adverse reactions, particularly viral infections and cytokine release syndrome, is necessary for the safe implementation of these therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Roy et al.)

Purpose: The current study was taken up to estimate the prevalence of Single Sided Deafness (SSD) in a tertiary healthcare hospital in Mumbai. Also to determine the acceptance of Contralateral routing of offside signal (CROS) devices by individuals with SSD., Method: A retrospective study design was followed to collect data from September 2020 to September 2022. The data were collected by reviewing the files of the cases diagnosed with Single-Sided Deafness in a tertiary health care hospital in Mumbai., Result: The prevalence of SSD was found to be 24% for the given period. It was observed that 50 out of 4456 took a free trial and 2 bought the device., Conclusion: The poor acceptance and purchase of CROS are attributed to the cost, and missed benefits of true binaural hearing in localization and hearing in noise. These benefits can be achieved by using CI, however, the cost and fear of surgery refrained the participants. Also, participants were observed to learn great use of communication repair strategies. Therefore, it is required to counsel individuals with SSD for CI and provide knowledge about care for the better with regular audiological follow-up., Competing Interests: Ethical ConsiderationsThe study was considered post-ethics committee approval. The approval was received on 30/9/2022 (ECARP/2022/95) from the hospital. The data was collected considering the Helsinki Declaration using all non-invasive and standard techniques. This being a retrospective study permission was received from the head of the department and hospital ethics committee board. The authors have no conflict of interest and have received no funding for the research., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Targeted alpha therapy (TAT) using lead-212 (Pb-212)-labeled peptides presents an attractive option for the treatment of metastatic neuroendocrine tumors (NETs). As Pb-203 presents an accurate diagnostic surrogate to Pb-212, imaging with Pb-203-labelled peptides can be an important prerequisite to assess the feasibility of TAT with Pb-212-labelled agents. Here, we present the imaging data of a patient with metastatic NET with Pb-203 VMT-α-NET, a somatostatin receptor targeting agent, and demonstrate the matching distribution of Pb-203 VMT-α-NET with Ga-68 DOTANOC., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Nuclear Medicine.)

Aim and Objectives: The aim of this study is to comparatively analyse the compressive and tensile strength of different types of record base materials made of different materials and processing techniques., Materials and Methodology: The compressive and tensile strength of 4 types of injection moulded materials were compared with a control of conventional compression moulded material. Twenty test specimens (10 tensile and 10 compressive) were fabricated from each material. A test was done using the Instron 3382 (Norwood, MA, USA) universal testing machine., Results: Compressive and tensile test values showed significant differences between the record base resin groups tested for both compressive and tensile strength tests (p=0.00). The mean tensile strength value was greatest for Group V (66.0 MPa) and lowest for Group III (41.9MPa) and the mean compressive strength value was greatest for Group I (74.5 MPa) followed by Group V (70.2 MPa) and lowest for Group III (10.8 MPa)., Conclusion: Injection moulded acetal resin showed the highest tensile strength value; it was comparable to that of conventional compression moulded polymethyl methacrylate (PMMA). Compression moulding is reported to have the highest compressive strength values followed by injection moulded acetal resin material. Injection moulded acetal resin material attributed to its advantages and superior strength value, can be used as a material of choice in various clinical scenarios., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, R et al.)

Background: Cellular resistance to cisplatin has been one of the major obstacles in the success of combination therapy for many types of cancers. Emerging evidences suggest that exosomes released by drug resistant tumour cells play significant role in conferring resistance to drug sensitive cells by means of horizontal transfer of genetic materials such as miRNAs. Though exosomal miRNAs have been reported to confer drug resistance, the exact underlying mechanisms are still unclear., Methods and Results: In the present study, mature miRNAs secreted differentially by cisplatin resistant and cisplatin sensitive HepG2 cells were profiled and the effect of most significantly lowered miRNA in conferring cisplatin resistance when horizontally transferred, was analysed. we report miR-383 to be present at the lowest levels among the differentially abundant miRNAs expressed in exosomes secreted by cisplatin resistant cells compared to that that of cisplatin sensitive cells. We therefore, checked the effect of ectopic expression of miR-383 in altering cisplatin sensitivity of Hela cells. Drug sensitivity assay and apoptotic assays revealed that miR-383 could sensitise cells to cisplatin by targeting VEGF and its downstream Akt mediated pathway., Conclusion: Results presented here provide evidence for the important role of miR-383 in regulating cisplatin sensitivity by modulating VEGF signalling loop upon horizontal transfer across different cell types., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Tongue extramedullary plasmacytoma (EMP) with regional lymph node metastases is a very rare pathology. Despite being a rare entity, extramedullary plasmacytoma should be considered a differential diagnosis in cases of a mass or ulcer in the tongue. A 60-year-old lady presents with an ulcerative lesion over the right lateral border of the tongue with dimensions 3.5 × 2 cm for one year. Initially, on histopathological examination, a possibility of plasma cell neoplasm was suspected; on further IHC, serum protein electrophoresis, and radiological investigations, a definite diagnosis of solitary EMP of the right lateral border of the tongue with regional nodal metastases was confirmed. The patient received radiotherapy for the primary disease along with the involved neck nodal sites., Competing Interests: Conflict of InterestThe authors report no conflicts of interest related to this study., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Goodpasture syndrome is a rare autoimmune disease which affects young adults with a male preponderance and can be triggered at any point in life with a classical clinical triad of rapidly progressive glomerulonephritis, diffuse pulmonary haemorrhage and circulating anti-glomerular basement membrane antibody (anti-GBM antibody). Here we are presenting a case of a young man with hypertension in his early 20s who presented with fatigue, recurrent haemoptysis, breathlessness and decreased urine output without features of infection. He was diagnosed at an early stage of the disease with the help of clinical, serological and radiological findings. An early diagnosis with effective treatment using plasma exchange, intravenous high-dose methylprednisolone, and cyclophosphamide showed a rapid improvement in the patient's condition with an immediate decrease in anti-GBM titres and proteinuria., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)