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•This study evaluated the humoral antibody response after first and second doses of SARS-CoV-2 vaccine CovishieldTM and CovaxinTM in Indian health-care workers.•Combined results of both vaccines showed 95% seropositivity to anti-spike antibody, 21–36 days after the second completed dose.•Seropositivity rates were higher in Covishield recipients compared to Covaxin in the propensity-matched analysis of SARS-CoV-2 naïve participants.•Gender, presence of comorbidities and the type of vaccine received were independent predictors of antibody response after the second dose. We assessed the humoral immune response of both ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) vaccines in Indian health care workers (HCW). A Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naïve and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate, Geometric Mean Titre [GMT] and 95% Confidence Interval [CI]) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the results of anti-spike antibody response after first and two completed doses. Among the 515 HCW (305 Male, 210 Female) who took two doses of both vaccines, 95.0% showed seropositivity to anti-spike antibody. However, both seropositivity rate and GMT (95% CI) of anti-spike antibody was significantly higher in Covishield vs. Covaxin recipients (98.1 vs. 80.0%; 129.3 vs. 48.3 AU/mL; both p < 0.001). This difference persisted in 457 SARS-CoV-2 naïve and propensity-matched (age, sex and BMI) analysis of 116 participants. Age > 60-years, males, people with any comorbidities, and history of hypertension (HTN) had a significantly less anti-spike antibody GMT compared to age ≤ 60 years, females, no comorbidities and no HTN respectively, after the completion of two doses of either vaccine. Gender, presence of comorbidities, and vaccine type were independent predictors of antibody seropositivity rate and anti-spike antibody titre levels in multiple logistic and log transformed linear regression analysis. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. Both vaccines elicited good immune response after two doses, although seropositivity rates and GMT of anti-spike antibody titre was significantly higher in Covishield compared to Covaxin recipients.

In recent years, bioactive compounds are in high demand in the pharmaceuticals and naturopathy, due to their health benefits to human and plants. Microorganisms synthesize these compounds and some enzymes either alone or in association with plants. Microbes residing inside the plant tissues, known as endophytes, also produce an array of these compounds. Endophytic actinomycetes act as a promising resource of biotechnologically valuable bioactive compounds and secondary metabolites. Endophytic Streptomyces sp. produced some novel antibiotics which are effective against multi-drug-resistant bacteria Antimicrobial agents produced by endophytes are eco-friendly, toxic to pathogens and do not harm the human. Endophytic inoculation of the plants modulates the synthesis of bioactive compounds with high pharmaceutical properties besides promoting growth of the plants. Hydrolases, the extracellular enzymes, produced by endophytic bacteria, help the plants to establish systemic resistance against pathogens invasion. Phytohormones produced by endophytes play an essential role in plant development and drought resistance management. The high diversity of endophytes and their adaptation to various environmental stresses seem to be an untapped source of new secondary metabolites. The present review summarizes the role of endophytic bacteria in synthesis and modulation of bioactive compounds.

Botrytis cinerea Pers. Fr. (teleomorph: Botryotinia fuckeliana) is a necrotrophic fungal pathogen that attacks a wide range of plants. This updated pathogen profile explores the extensive genetic diversity of B. cinerea, highlights the progress in genome sequencing, and provides current knowledge of genetic and molecular mechanisms employed by the fungus to attack its hosts. In addition, we also discuss recent innovative strategies to combat B. cinerea. Taxonomy Kingdom: Fungi, phylum: Ascomycota, subphylum: Pezizomycotina, class: Leotiomycetes, order: Helotiales, family: Sclerotiniaceae, genus: Botrytis, species: cinerea. Host range B. cinerea infects almost all of the plant groups (angiosperms, gymnosperms, pteridophytes, and bryophytes). To date, 1606 plant species have been identified as hosts of B. cinerea. Genetic diversity This polyphagous necrotroph has extensive genetic diversity at all population levels shaped by climate, geography, and plant host variation. Pathogenicity Genetic architecture of virulence and host specificity is polygenic using multiple weapons to target hosts, including secretory proteins, complex signal transduction pathways, metabolites, and mobile small RNA. Disease control strategies Efforts to control B. cinerea, being a high‐diversity generalist pathogen, are complicated. However, integrated disease management strategies that combine cultural practices, chemical and biological controls, and the use of appropriate crop varieties will lessen yield losses. Recently, studies conducted worldwide have explored the potential of small RNA as an efficient and environmentally friendly approach for combating grey mould. However, additional research is necessary, especially on risk assessment and regulatory frameworks, to fully harness the potential of this technology. Botrytis cinerea is a generalist fungal phytopathogen with high genetic diversity that utilizes diverse signalling cascades to infect a wide range of hosts.

Background The phase 3 PREEMPT clinical trials confirmed the efficacy and safety of 155 U – 195 U onabotulinumtoxinA for individuals with chronic migraine (CM) and is the licensed dose in Canada and Europe. This analysis aimed to analyze the efficacy and safety parameters of 155 U – 195 U onabotulinumtoxinA in participants with CM from the real-world REPOSE study. Methods REPOSE (NCT01686581) was a 2-year, prospective, observational, noninterventional, open-label study that described the real-world use of onabotulinumtoxinA in adults with CM in Europe. Participants received onabotulinumtoxinA approximately every 12 weeks and were monitored for 24 months after starting treatment. Data on participant-estimated mean headache-day frequency in the last month (MHD), Migraine-Specific Quality of Life Questionnaire (MSQ) scores, and adverse events (AEs) were collected at each treatment visit. Participants in the safety analysis population (those who received at least one dose of onabotulinumtoxinA) were stratified into two groups based on the dosage received at four or more treatment visits: 155 U onabotulinumtoxinA and 156 U – 195 U onabotulinumtoxinA groups. Results A total of 641 participants were enrolled at 77 centers. Of those, 218 participants received 155 U ≥ 4 treatment visits, and 77 participants received 156 U–195 U onabotulinumtoxinA ≥ 4 treatment visits. Between-group baseline characteristics were similar. Reductions from baseline in MHD frequency were observed at both doses (156 U – 195 U range, -8.7 to -14.2 MHDs; 155 U range, -8.2 to -11.9 MHDs). Mean change from baseline in MSQ domain scores improved across administration visits for both 155 U onabotulinumtoxinA and 156 U – 195 U onabotulinumtoxinA groups. Treatment with 156 U – 195 U onabotulinumtoxinA was safe and generally well-tolerated with no new safety signals identified. Adverse drug reactions (ADR) were reported in 51/218 in the 155 U group and 10/77 participants in the 156 U – 195 U group; serious adverse drug reactions were 3/218 and 1/77, respectively. The most frequently reported ADR across both dose groups was eyelid ptosis, followed by neck pain, musculoskeletal stiffness. Conclusions These real-world findings of the safety and efficacy of the 155 U – 195 U onabotulinumtoxinA doses are consistent with data from the PREEMPT clinical trials as a treatment option for CM patients. Trial registration NCT01686581. Name of registry: ClinicalTrials.gov. URL of registry: Date of retrospective registration: September 18, 2012. Date of enrolment of first patient: July 23, 2012.

Violence against women remains a pervasive global issue, with substantial repercussions on their physical, mental, and societal well-being. This study investigates the prevalence and trends of gender-based violence in Lucknow, India, a city renowned for its cultural heritage but currently grappling with a rising incidence of crimes against women. The study employs a blend of qualitative and quantitative techniques, including semi-structured interviews, focus group discussions, and participant observation, to examine the impact of legal changes and educational qualifications on the occurrence of crimes targeting women. The results indicate a significant correlation between legal reforms and the prevalence of gender-based violence, emphasising the crucial role of legislative frameworks in addressing this societal problem. Moreover, the study highlights the influence of educational attainment on awareness of laws safeguarding women, underscoring the importance of education in fostering societal change and efforts to mitigate harm. Despite certain advancements, the occurrence of violence against women is still impacted by societal attitudes and perspectives. This underscores the significance of enacting all-encompassing policies that integrate legal, educational, and sociological activities. This study deepens our understanding of the many factors that influence gender-based violence and offers valuable insights for devising strategies to create safer environments for women in Lucknow and other regions.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomically defined subsets) or in combination with standard cytotoxic therapy, thus far, has proven disappointing in PDAC; however, novel therapies are evolving with increased integration of genomic profiling along with a better understanding of the tumor microenvironment and immunology. A small but important sub-group of patients have some of these agents available in the clinics for use. Olaparib was recently approved by the US Food and Drug Administration for maintenance therapy in germline BRCA1/2 mutated PDAC following demonstration of survival benefit in a phase 3 trial . Pembrolizumab is approved for patients with defects in mismatch repair/microsatellite instability. PDAC with wild-type KRAS represents a unique subgroup who have enrichment of potentially targetable oncogenic drivers. Small-molecule inhibitors including ERBB inhibitors (e.g., afatinib, MCLA-128), TRK inhibitors (e.g., larotrectinib, entrectinib), ALK/ROS inhibitor (e.g., crizotinib), and BRAF/MEK inhibitors are in development. In a small subset of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.

Favipiravir (FAV) has become a promising antiviral agent for the treatment of COVID-19. Herein, a green, fast, high-sample-throughput, non-instrumental, and affordable analytical method is proposed based on surfactant-assisted dispersive liquid–liquid microextraction (SA-DLLME) combined with thin-layer chromatography–digital image colourimetry (TLC-DIC) for determining favipiravir in biological and pharmaceutical samples. Triton X-100 and dichloromethane (DCM) were used as the disperser and extraction solvents, respectively. The extract obtained after DLLME procedure was spotted on a TLC plate and allowed to develop with a mobile phase of chloroform:methanol (8:2, v/v). The developed plate was photographed using a smartphone under UV irradiation at 254 nm. The quantification of FAV was performed by analysing the digital images’ spots with open-source ImageJ software. Multivariate optimisation using Plackett–Burman design (PBD) and central composite design (CCD) was performed for the screening and optimisation of significant factors. Under the optimised conditions, the method was found to be linear, ranging from 5 to 100 µg/spot, with a correlation coefficient (R2) ranging from 0.991 to 0.994. The limit of detection (LOD) and limit of quantification (LOQ) were in the ranges of 1.2–1.5 µg/spot and 3.96–4.29 µg/spot, respectively. The developed approach was successfully applied for the determination of FAV in biological (i.e., human urine and plasma) and pharmaceutical samples. The results obtained using the proposed methodology were compared to those obtained using HPLC-UV analysis and found to be in close agreement with one another. Additionally, the green character of the developed method with previously reported protocols was evaluated using the ComplexGAPI, AGREE, and Eco-Scale greenness assessment tools. The proposed method is green in nature and does not require any sophisticated high-end analytical instruments, and it can therefore be routinely applied for the analysis of FAV in various resource-limited laboratories during the COVID-19 pandemic.

Recent developments in three-dimensional (3D) printing technology offer immense potential in fabricating scaffolds and implants for various biomedical applications, especially for bone repair and regeneration. As the availability of autologous bone sources and commercial products is limited and surgical methods do not help in complete regeneration, it is necessary to develop alternative approaches for repairing large segmental bone defects. The 3D printing technology can effectively integrate different types of living cells within a 3D construct made up of conventional micro- or nanoscale biomaterials to create an artificial bone graft capable of regenerating the damaged tissues. This article reviews the developments and applications of 3D printing in bone tissue engineering and highlights the numerous conventional biomaterials and nanomaterials that have been used in the production of 3D-printed scaffolds. A comprehensive overview of the 3D printing methods such as stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and ink-jet 3D printing, and their technical and clinical applications in bone repair and regeneration has been provided. The review is expected to be useful for readers to gain an insight into the state-of-the-art of 3D printing of bone substitutes and their translational perspectives.