Search

The main objective of this paper is finding new types of discrete transforms with tuning factor t. This is not only analogy to the continuous Laplace transform but gives discrete Laplace-Fibonacci transform (LFt). This type of Laplace-Fibonacci transform is not available in the continuous case. The LFt generates uncountably many outcomes when the parameter t varies on (0,∞). This possibility is not available in the existing Laplace transform. All the formulae and results derived are verified by MATLAB.

Background: COVID-19, the novelty and uncertainty of the virus make critical for health authorities to prepare appropriate plans for the treatment as well as prevention of the infection. It is, therefore, utmost important for health professionals to update their knowledge of Covid-19. Materials And Methods: A web-based cross sectional survey was conducted among health care students during April-2020. 30 questions were developed related to knowledge on COVID-19 and distributed randomly among health care students. Simple descriptive statistics were used to analyse the study results. Results: A total of 2453 students participated in the study. Out of given 30 questions related to knowledge on COVID-19, medical students answered on an average 17.75± 6.6 correct answers and exhibited well updated clinical knowledge on the recent pandemic when compared to nursing (15.09± 5.09), dental (14.25± 4.89) and pharmacy students (13.62± 6.2) Conclusion: Study findings demonstrate the importance of increased public health information through trusted information channels and sources. [ABSTRACT FROM AUTHOR]

Candida albicans is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against C. albicans revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2. Here, we report optimization of GW via two complementary approaches, synthesis of bioisosteres possessing an imidazo[1,2-a]pyridine core, and R-group substitution of GW's pyrazolo[1,5-a]pyridine core. Characterization of compounds reveals two 6-cyano derivatives with improved pharmacological properties that retain whole-cell bioactivity and selectivity for fungal Yck2 compared to human CK1α. Efficacy studies in mice indicate both analogs possess single-agent activity against C. albicans resistant to first-line echinocandin antifungals and potentiate non-curative echinocandin treatment. Results validate Yck2 as an antifungal target and encourage further development of inhibitors acting by this previously unexploited mode of action., Competing Interests: Competing interests: L.E.C. and L.W. are co-founders and shareholders in Bright Angel Therapeutics, a platform company for the development of novel antifungal therapeutics. L.E.C. is a Science Advisor for Kapoose Creek, a company that harnesses the therapeutic potential of fungi. All other authors declare no competing interests., (© 2025. The Author(s).)

Candida albicans is a growing health concern as the leading causal agent of systemic candidiasis, a life-threatening fungal infection with a mortality rate of ~40% despite best available therapy. Yck2, a fungal casein kinase 1 (CK1) family member, is the cellular target of inhibitors YK-I-02 (YK) and MN-I-157 (MN). Here, multiplexed inhibitor beads paired with mass spectrometry (MIB/MS) employing ATP-competitive kinase inhibitors were used to define the selectivity of these Yck2 inhibitors across the global C. albicans proteome. The MIB matrix captured 89% of the known and predicted C. albicans protein kinases present in cell lysate. In MIB/MS competition assays, YK and MN demonstrated exquisite selectivity across the C. albicans fungal kinome with target engagement of only three CK1 homologs (Yck2, Yck22, and Hrr25) and a homolog of human p38α (Hog1). Additional chemoproteomics using a custom MN-kinobead identified only one additional C. albicans protein, confirming its remarkable fungal proteome-wide selectivity. To identify new Yck2 inhibitors with selectivity over Hog1, thirteen human CK1 kinase inhibitors were profiled for fungal kinase-binding activity using MIB/MS competition assays and in-cell NanoBRET target engagement assays. A new chemotype of family-selective Yck2 inhibitors with antifungal activity was identified. Together, these findings expand the application of MIB/MS proteomic profiling for non-human kinomes and demonstrate its utility in the discovery and development of selective inhibitors of fungal kinases with potential antimicrobial activity.

Candida albicans is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against C. albicans revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2. Here, we report optimization of GW via two complementary approaches, synthesis of bioisosteres possessing an imidazo[1,2-a]pyridine core, and R-group substitution of GW's pyrazolo[1,5-a]pyridine core. Characterization of compounds synthesized revealed two 6-cyano derivatives with improved pharmacological properties that retained whole-cell bioactivity and selectivity for fungal Yck2 compared to human CK1α. Efficacy studies in mice indicated both analogs possess single-agent activity against C. albicans resistant to first-line echinocandin antifungals and potentiate non-curative echinocandin treatment. Results validate Yck2 as an antifungal target and encourage further development of inhibitors acting by this previously unexploited mode of action., Competing Interests: Conflict of Interest L.E.C. and L.W. are co-founders and shareholders in Bright Angel Therapeutics, a platform company for the development of novel antifungal therapeutics. L.E.C. is a Science Advisor for Kapoose Creek, a company that harnesses the therapeutic potential of fungi. All other authors declare no competing interests.

This study examines the behavior of the Casson nanofluid bioconvection flow around a spinning disc under various influences, including gyrotactic microorganisms, multiple slips, and thermal radiation. Notably, it accounts for the reversible nature of the flow and incorporates the esterification process. The aim of this study is to investigate the influence of reversible chemical reactions on the flow behavior of a Casson nanofluid in the presence of bioconvective microorganisms over a spinning disc. Specifically, the study seeks to understand how the non-Newtonian rheology of Casson fluids, enhanced by nanoparticles, affects heat and mass transfer and how bioconvection driven by motile microorganisms impacts the reaction kinetics and fluid dynamics. The significance of studying chemical reactions in Casson nanofluid flow with bioconvective microorganisms over a spinning disc lies in its broad applicability to fields such as chemical engineering, biomedical engineering, environmental science, and nanotechnology. Using the right variables to change the nonlinear partial differential equations (PDEs) that govern the problem into a system of ordinary differential equations (ODEs) is a key step toward finding numerical solutions. Using numerical methods such as the bvp4c approach, the study explores the solutions to these intricate equations. Key focus areas include assessing the impacts of different parameters on the thermal field, nanoparticle concentration, and microbiological field. Graphical representations provide information on the velocity, temperature, concentration, and microorganism profiles, elucidating the underlying physical effects. Furthermore, the study evaluates the wall shear stress, the local Nusselt number, the local Sherwood number, and the local motile density number, providing graphical explanations to elucidate these phenomena. Notably, it highlights the distinction in the rate of the motile density number between reversible and irreversible flows concerning Brownian motion and Peclet number. The findings of the theoretical simulations have significant implications for biotechnology and thermal engineering, offering dynamic insights into practical applications within these fields., 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 Ltd.)

The decline in dengue incidence and/or prevalence during the COVID-19 pandemic (2020-22) appears to be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to mosquito vectors due to prevailing lockdowns. There is limited scientific data on dengue virus (DENV) disease during the COVID-19 pandemic. Here, we conducted a community-based, cross-sectional, cluster-randomized survey to assess anti-DENV and anti-SARS-CoV-2 seroprevalence, and also estimated the spatial distribution of DENV-positive aedine mosquito vectors during the COVID-19 pandemic across all the 38 districts of Tamil Nadu, India. Using real-time PCR, the prevalence of DENV in mosquito pools during 2021 was analyzed and compared with the previous and following years of vector surveillance, and correlated with anti-DENV IgM and IgG levels in the population. Results implicate that both anti-DENV IgM and IgG seroprevalence and DENV positivity in mosquito pools were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3.76% of the mosquito pools were positive for DENV. In the human sera, 4.12% were positive for anti-DENV IgM and 6.4% for anti-DENV IgG. While the anti-SARS-CoV-2 levels significantly correlated with overall DENV seropositivity, COVID-19 vaccination status significantly correlated with anti-DENV IgM levels. The study indicates a profound impact of anti-SARS-CoV-2 levels on DENV-positive mosquito pools and seropositivity. Continuous monitoring of anti-DENV antibody levels, especially with the evolving variants of SARS-CoV-2 and the surge in COVID-19 cases will shed light on the distribution, transmission and therapeutic attributes of DENV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Selvavinayagam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present study aimed to determine the presence of Klebsiella pneumoniae and Escherichia coli with extended-spectrum β-lactamase (ESBL)s property from treated wastewater effluents. Treated effluent samples were collected from two major water treatment plants which located at Avaniyapuram and Sakkimangalam, Madurai, Tamil Nadu, India. Among the 51 isolates, 56.86 % represented E. coli (18 from Avaniyapuram and 11 from Sakkimangalam) and 43.14 % were K. pneumoniae (7 from Avaniyapuram and 15 from Sakkimangalam). Based on the ESBL propensity, E. coli was overrepresented in the present study. All the isolates turned positive for ESBL, while 5.88 % of K. pneumoniae and 7.84 % of E. coli were positive for carbapenemases. Further, K. pneumoniae isolates from both sites showed 100 % resistance to beta-lactams, with resistance to other antibiotics such as tetracycline and meropenem. E. coli isolates were 100 % resistant to ceftazidime and cefuroxime, and 88.9 % were resistant to amoxicillin/clavulanate and ceftriaxone. The MAR indices observed in the present study for E. coli and K. pneumoniae were above the threshold value of 0.2 suggested a high risk of environmental contamination. These findings highlighted the need for routine surveillance at appropriate intervals for the presence of ESBL producing pathogens and other MDR pathogens in the environment to provide proper clinical management, develop various counter measures and policies to address and halt the spread of such potential threats., 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 Ltd. All rights reserved.)

Successful development of phage-based therapeutics and their utility predominantly depend on the mode and route of phage administration. Topical and site-directed phage application evokes minimal immune clearance and allows more phage-host adsorption, thereby ensuring higher phage efficacy. However, a notable drawback of conventional topical phage applications is the absence of sustained release. Occlusive emollients guarantee the controlled release of active pharmaceutical ingredients (APIs), thereby facilitating administration, preventing moisture loss, and acting as a skin barrier. In this study, we developed phage and human platelet lysate (h-PL) incorporated cetomacrogol-based creams for combined phage therapy and wound healing. The base material for phage immobilization was formulated by emulsifying paraffin and sterile water with cetomacrogol (emulsifying agent). Specifically, we incorporated a Pseudomonas aeruginosa -infecting lytic phage vB_PaeM_M12PA in the formulation and characterized its genome in this study. Cetomacrogol, a nonionic PEG (polyethylene glycol) based ether, rendered phage stability and allowed initial burst release followed by continuous controlled release of phages from the embedding matrix in the initial 6-8 h. Rheological studies showed that the material has elastic properties with storage moduli ( G ') values ranging from 109.51 ± 2.10 to 126.02 ± 3.13 kPa, indicating frequency-independent deformation. Platelet lysates in the cream acted as wound healing agents, and in vitro evaluation of cell migration and wound healing capacity of h-PL showed a significant enhancement by the sixth hour compared to untreated groups. The phage-incorporated cream showed sustained phage release in solid media and a significant reduction in bacterial growth in liquid cultures. In vivo wound healing studies in 6-week-old Wistar rats with full-thickness excision wounds and subsequent histopathological studies showed that the formulation enhanced wound healing and tissue restoration efficiency. In conclusion, the study unveils a promising approach for integrated phage therapy and wound healing strategies.

The initiation of colorectal cancer is controlled by various factors, including random occurrences and genetic alterations affecting oncogenes and tumor suppressor genes.Curcumin, a significant compound extracted from turmeric, has attracted interest for its robust anticancer properties, particularly regarding its analogs, 2, 6-bisdifurfurylidene cyclohexanone (DFC) and 2, 6-bis (2, 6-dichlorobenzylidene) cyclohexanone (DCC), which were synthesized and assessed for their anticancer efficacy. A combination of spectroscopic techniques and molecular docking methods was utilized to comprehensively evaluate the interaction behaviors of DFC and DCC. The application of density functional theory (DFT) using the B3LYP/6-311G (d, p) basis set facilitated the prediction of spectroscopic properties. The molecular docking investigations conducted using the Glide docking program from Schrodinger Maestro elucidated the interactions of these drugs at the molecular level. In vitro investigations were performed to evaluate the cytotoxic efficacy of the synthesized curcumin analogs. The determined IC 50 values revealed that DFC displayed an IC 50 of approximately 82 μM, and DCC exhibited a significantly lower IC 50 of around 10 μM. This notable disparity highlights the potential of DFC and DCC as a more efficacious cytotoxic agent and further research be conducted on the produced chemicals in the future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Meganathan C reports administrative support was provided by Sri Sai Ram Engineering College. Meganathan C reports a relationship with Sri Sai Ram Engineering College that includes: employment. 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.)

Despite their widespread impact on human health, there are no approved drugs for combating alphavirus infections. The heterocyclic β-aminomethyl vinyl sulfone RA-0002034 ( 1a ) is a potent irreversible covalent inhibitor of the alphavirus nsP2 cysteine protease with broad-spectrum antiviral activity. Analogs of 1a that varied each of the three regions of the molecule were synthesized to establish structure-activity relationships for the inhibition of Chikungunya (CHIKV) nsP2 protease and viral replication. The vinyl sulfone covalent warhead was highly sensitive to modifications. However, alterations to the core five-membered heterocycle and aryl substituent were well tolerated. The 5-(2,5-dimethoxyphenyl)pyrazole ( 1o ) and 4-cyanopyrazole ( 8d ) analogs exhibited k inact ratios >9000 M K i ratios >9000 M -1 s -1 . 3-Arylisoxazole ( 10 ) was identified as an isosteric replacement for the five-membered heterocycle, which circumvented the intramolecular cyclization of pyrazole-based inhibitors like 1a . A ligand-based model of the enzyme active site was developed to aid the design of nsP2 protease inhibitors as potential therapeutics against alphaviruses.

In December 2023, we observed a notable shift in the COVID-19 landscape, when JN.1 omicron emerged as the predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive clinical specimens, followed by sequence analysis. Mutations within the spike protein sequences were analysed and compared with the previously reported lineages and sub-lineages, to identify the potential impact of the unique mutations on protein structure and possible alterations in the functionality. Several unique and dynamic mutations were identified herein. Molecular docking analysis showed changes in the binding affinity, and key interacting residues of wild-type and mutated structures with key host cell receptors of SARS-CoV-2 entry viz., ACE2, CD147, CD209L and AXL. Our data provides key insights on the emergence of newer variants and highlights the necessity for robust and sustained global genomic surveillance of SARS-CoV-2., (© 2024. The Author(s).)

Background: Dengue is a vector-borne viral disease impacting millions across the globe. Nevertheless, akin to many other diseases, reports indicated a decline in dengue incidence and seroprevalence during the COVID-19 pandemic (2020-22). This presumably could be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to vectors due to lockdowns. Scientific evidence on dengue virus (DENV) disease during the COVID-19 pandemic is limited globally., Methods: A cross-sectional, randomized cluster sampling community-based survey was carried out to assess anti-dengue IgM and IgG and SARS-CoV-2 IgG seroprevalence across all 38 districts of Tamil Nadu, India. The prevalence of DENV in the Aedes mosquito pools during 2021 was analyzed and compared with previous and following years of vector surveillance for DENV by real-time PCR., Findings: Results implicate that both DENV-IgM and IgG seroprevalence and mosquito viral positivity were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3·76% of mosquito pools were positive for DENV. In the human sera, 4·12% were positive for DENV IgM and 6·4% were positive for DENV IgG. The anti-SARS-CoV-2 antibody titres correlated with dengue seropositivity with a significant association whereas vaccination status significantly correlated with dengue IgM levels., Interpretation: Continuous monitoring of DENV seroprevalence, especially with the evolving variants of the SARS-CoV-2 virus and surge in COVID-19 cases will shed light on the transmission and therapeutic attributes of dengue infection., Competing Interests: Declaration of interests There are no conflicts of interest to disclose by any authors.

A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution., (© 2024 Wiley Periodicals LLC.)

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Selvavinayagam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tuberculosis (TB) control is complicated by the emergence of drug resistance. Promising strategies to prevent drug resistance are the targeting of nonreplicating, drug-tolerant bacterial populations and targeting of the host, but inhibitors and targets for either are still rare. In a cell-based screen of ATP-competitive inhibitors, we identified compounds with in vitro activity against replicating Mycobacterium tuberculosis ( Mtb ), and an anilinoquinazoline (AQA) that also had potent activity against nonreplicating and persistent Mtb . AQA was originally developed to inhibit human transforming growth factor receptor 1 (TGFBR1), a host kinase that is predicted to have host-adverse effects during Mtb infection. The structure-activity relationship of this dually active compound identified the pyridyl-6-methyl group as being required for potent Mtb inhibition but a liability for P450 metabolism. Pyrrolopyrimidine ( 43 ) emerged as the optimal compound that balanced micromolar inhibition of nonreplicating Mtb and TGFBR1 while also demonstrating improved metabolic stability and pharmacokinetic profiles.

Hemolysis, a crucial feature of Sickle cell disease (SCD), is a key player for cellular activation leading to various complications including thrombosis. In response to hemolysis, platelets get activated and release components that are necessary for further platelet activation and aggregation. Thus, it is believed that platelets contribute to the development of thrombotic complications. Platelets in SCD are expected to be affected due to common cause of hemolysis. To measure the surface markers of platelets including P-Selectin, Phosphatidyl Serine and integrin αIIbβ3 in SCD patients and healthy controls in order to understand the status of the platelets in SCD. To measure the surface markers of activated platelets using flow cytometry. Since mitochondria and calcium play an important role in cellular functions, the mitochondrial membrane potential and calcium content of platelets in SCD were also evaluated using flow cytometry. In the present study, we have observed significant increase of calcium level in SCD platelets. Further, the loss of mitochondrial membrane potential in SCD platelets was found to be significantly higher when compared to platelets of healthy controls. Though the surface markers of activated platelets in SCD remain unchanged, increased level of calcium and mitochondrial membrane potential loss suggest that the platelets in SCD are more prone to become activated. In order to understand the status of the platelets in SCD, apart from the surface markers, it is also important to assess the calcium levels and mitochondrial membrane potential of platelets., Competing Interests: Conflict of interestThe authors have no conflicts of interests., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 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.)

Background: Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India., Methods: Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients., Findings: Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population., Interpretation: Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants., Funding: National Health Mission (India), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA)., Competing Interests: STS and SR are funded by the National Health Mission, Tamil Nadu (680/NGS/NHMTNMSC/ENGG/2021) for the Directorate of Public Health and Preventive Medicine, WGS facility. EMS is supported by the Indian Council of Medical Research (ICMR) Grant No. 45/2/2020-DDI/BMS and a Core Research Grant (CRG) of the Department of Science and Technology-Science and Engineering Research Board (DST-SERB), Government of India (File No. CRG/2019/006096). ML is supported by grants through AI52731, the Swedish Research Council, the Swedish, Physicians against AIDS Research Foundation, the Swedish International Development Cooperation Agency, SIDA SARC, VINNMER for Vinnova, Linköping University Hospital Research Fund, CALF, and the Swedish Society of Medicine. VV is supported by the Office of Research Infrastructure Programs (ORIP/NIH) base grant P51 OD011132 to ENPRC. AM is supported by a Start-up Grant No. 12020/04/2018-HR, Department of Health Research, Government of India. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work., (© 2023 The Author(s).)

Background: Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy ., Methods: We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay., Results: Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold., Conclusions: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings., Competing Interests: CONFLICTS OF INTEREST The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

Diabetic retinopathy (DR) and diabetic macular edema (DME) are forms of eye illness caused by diabetes that affects the blood vessels in the eyes, with the ground occupied by lesions of varied extent determining the disease burden. This is among the most common cause of visual impairment in the working population. Various factors have been discovered to play an important role in a person's growth of this condition. Among the essential elements at the top of the list are anxiety and long-term diabetes. If not detected early, this illness might result in permanent eyesight loss. The damage can be reduced or avoided if it is recognized ahead of time. Unfortunately, due to the time and arduous nature of the diagnosing process, it is harder to identify the prevalence of this condition. Skilled doctors manually review digital color images to look for damage produced by vascular anomalies, the most common complication of diabetic retinopathy. Even though this procedure is reasonably accurate, it is quite pricey. The delays highlight the necessity for diagnosis to be automated, which will have a considerable positive significant impact on the health sector. The use of AI in diagnosing the disease has yielded promising and dependable findings in recent years, which is the impetus for this publication. This article used ensemble convolutional neural network (ECNN) to diagnose DR and DME automatically, with accurate results of 99 percent. This result was achieved using preprocessing, blood vessel segmentation, feature extraction, and classification. For contrast enhancement, the Harris hawks optimization (HHO) technique is presented. Finally, the experiments were conducted for two kinds of datasets: IDRiR and Messidor for accuracy, precision, recall, F-score, computational time, and error rate., Competing Interests: The authors declare no conflict of interest.

Site-selective functionalization of unactivated C(sp 3 )-H centers is challenging because of the ubiquity and strength of alkyl C-H bonds. Herein, we disclose a position-selective C(sp 3 )-C(sp 2 ) cross-coupling reaction. This process engages C(sp 3 )-H bonds and aryl bromides, utilizing catalytic quantities of a photoredox-capable molecule and a nickel precatalyst. Using this technology, selective C-H functionalization arises owing to a 1,6-hydrogen atom transfer (HAT) process that is guided by a pendant alcohol-anchored sulfamate ester. These transformations proceed directly from N-H bonds, in contrast to previous directed, radical-mediated, C-H arylation processes, which have relied on prior oxidation of the reactive nitrogen center in reactions with nucleophilic arenes. Moreover, these conditions promote arylation at secondary centers in good yields with excellent selectivity.

The present experimental study aims to make advancements in the daily production of freshwater by a single solar still, with the ultimate goal of increasing its efficiency. The experiment was carried out in the solar still with and without integration at four different water masses within the basin, and metrics such as water, glass, basin temperature, and drinkable water generated were measured. The results showed that the daily distillate collected from the integrated system using 2.5 kg/h of mass flow in the parabolic concentrator produced 2.99 kg at the minimum water mass of 20 kg placed in the basin. When the flow velocity of water in the parabolic concentrator is raised from 2.5 to 5 kg/h, the amount of freshwater generated decreases from 2.99 to 2.66 kg. Compared to traditional single slope solar still, the potable water generated increases by roughly 18.24, 18.29, and 18.33% for water mass of 30, 40, and 50 kg, respectively, with the mass flow rate of water in the serpentine tubes as 2.5 kg/h. The results also reveals that, in addition to the PTC collector, the mass flowrate of fluid in the serpentine tube arrangement submerged in the basin affects daily solar efficiency. There is a significant reduction of about 1-2.3% in the daily efficiency of the system with increased mass flow rate of fluid in the serpentine tube arrangement. Similarly, the daily efficiency in all the cases reduces with increased water depth., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Selvavinayagam, Yong, Joseph, Hemashree, Tan, Zhang, Rajeshkumar, Kumaresan, Kalpana, Kalaivani, Monika, Suvaithenamudhan, Kannan, Murugesan, Narayanasamy, Palani, Larsson, Shankar and Raju.)

D-dimer is an established biomarker of thromboembolism and severity in COVID-19. We and others have recently reported the dysregulation of tissue factor pathway inhibitor (TFPI), FXIII, fibrinolytic pathway, inflammatory markers, and tissue injury markers, particularly in severe COVID-19. However, association of these markers with thromboembolism in COVID-19 remains elusive. The correlation analyses between these markers in patients with moderate (non-ICU) and severe COVID-19 (ICU) were performed to delineate the potential pathomechanisms and impact of thromboembolism. We observe a negative correlation of plasma TFPI ( r 2 = 0.148, P = 0.035), FXIII ( r 2 = 0.242, P = 0.006), and plasminogen ( r 2 = 0.27, P = 0.003) with D-dimer, a biomarker of thromboembolism, levels in these patients. Further analysis revealed a strong positive correlation between fibrinolytic markers tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) ( r 2 = 0.584, P < 0.0001). Interestingly, a significant positive correlation of PAI-1, but not tPA, was observed with platelets and endothelial cells dysfunction markers P-selectin ( r 2 = 0.184, P = 0.01) and soluble CD40 ligand (sCD40 L) ( r 2 = 0.163, P = 0.02). Moreover, calprotectin (S100A8/A9) and cystatin C (CST3), previously linked with thromboembolism, exhibited positive correlations with each other ( r 2 = 0.339, P = 0.0007) and with the level of D-dimer independently in COVID-19. Finally, the tissue injury marker myoglobin demonstrated a strong positive correlation with D-dimer ( r 2 = 0.408, P = 0.0001). Taken together, inverse correlations of TFPI and FXIII with D-dimer suggest the TF pathway activation and aberrant fibrin polymerization in COVID-19 patients. The elevated level of PAI-1 is potentially contributed by activated platelets and endothelial cells. S100A8/A9 may also play roles in impaired fibrinolysis and thromboembolism, in part, through regulating the CST3. These findings strengthen the understanding of thromboembolism and tissue injury and may help in better management of thromboembolic complications in COVID-19 patients.

Aims: Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague., Main Methods: GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay., Key Findings: Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r 2  = 0.238, P = 0.006), EPO (r 2  = 0.18, P = 0.01) and EGF (r 2  = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r 2  = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r 2  = 0.199, P = 0.01), EPO (r 2  = 0.115, P = 0.02), and EGF (r 2  = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin., Significance: Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, it is unclear when particularly platelet activation markers and coagulation factors dysregulated during the pathogenesis of COVID-19. Here, we sought to assess the levels of coagulation and platelet activation markers at moderate and severe stages of COVID-19 to understand the pathogenesis., Methods: To understand this, hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases) were recruited. Phenotypic and molecular characterizations were performed employing basic coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), D-Dimer, and tissue factor pathway inhibitor (TFPI). The flow cytometry-based multiplex assays were performed to assess FXI, anti-thrombin, prothrombin, fibrinogen, FXIII, P-selectin, sCD40L, plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and D-Dimer., Results: The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases, which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed fibrinogen induction in both moderate and severe patients. Interestingly, an elevated PAI-1 more prominently in moderate, and tPA particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of the disease., Conclusions: In summary, induction of soluble P-selectin, sCD40L, fibrinogen, and PAI-1 suggests the activation of platelets and coagulation system at the moderate stage before COVID-19 patients require intensive care. These findings would help in designing better thromboprophylaxis to limit the COVID-19 severity., (© 2022 John Wiley & Sons Ltd.)

Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.

Endodontically treated teeth (ETT) are structurally and esthetically compromised. Conventionally, after endodontic therapy, the tooth is restored with full-coverage crowns to improve their fracture resistance and ensure their long-term success rate. However, the tooth preparation required for these restorations can result in the significant loss of enamel and dentin. The periodontal health will be affected if the margin of prosthesis is extended subgingival. Restoring ETT using minimally invasive methods is an effective way to preserve the remaining tooth structure. This case series show cases restoration of four endodontically treated mandibular first molars with extensive subgingival caries restored with short fiber-reinforced composite resin (everX Posterior, GC Europe N.V. Interleuvenlaan, Leuven), with 2-year follow-up., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Conservative Dentistry.)

Many studies have reported the association of VEGF -1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF- 1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p -values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case-control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF- 1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy., Competing Interests: None declared., (Thieme. All rights reserved.)