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Abstract This comprehensive examination delves into the multifaceted characteristics of edible flowers, underlining their significance as sources of natural ingredients and their medicinal properties. The review commences with an introductory section emphasizing edible flowers' cultural and health importance. It proceeds to explore the botanical diversity of edible flowers, encompassing their geographical distribution. Emphasis is placed on the bioactive constituents of these flowers, with a focus on their potential health benefits and various molecular targets for the treatment of several chronic disorders. Culinary and medicinal uses are examined, illustrating their adaptability across diverse cultural contexts. Their nutritional richness is highlighted through comparative analysis. Safety considerations and regulatory frameworks ensure consumer protection. Future prospects underscore innovation, discussing potential applications in the food industry and avenues for further research. The analysis concludes by summarizing key findings and discussing future implications, highlighting the intriguing potential of edible flowers as natural components for various applications in food, health, and beyond. Graphical abstract

Abstract Background While assisted reproductive technologies (ART) have helped many people experiencing infertility become pregnant, the ART process can take a psychological toll. This study examined whether and how perceived stress- and depression-related symptoms vary among individuals at different stages of the infertility and ART process, and whether ART-specific stressors and emotional support are associated with mental health symptomatology. Methods Data were collected using an online REDCap survey administered between July 2021 and March 2022. The survey was administered to 240 participants who had experienced infertility, including those who had not yet accessed ART, those undergoing ART but who were not yet pregnant, those currently pregnant through ART, and those who had given birth in the last year through ART. Each participant completed the Cohen Perceived Stress Scale (range 0–40) and the Edinburgh Depression Scale (range 0–30). Participants who had undergone ART were asked about their experience of ART-specific stressors and how helpful partner and provider support had been during the ART process. Survey data were analyzed using ANOVA and multivariate linear regressions. Results 88% of participants reported medium or high levels of perceived stress, and 43.8% of respondents showed probable indications of depression. Perceived stress and depression symptoms were significantly higher for individuals currently undergoing, but not yet pregnant from, ART treatments. These effect sizes were substantial; for example, depression scores in this group were five points higher than among currently pregnant individuals and nine points higher than among postpartum individuals. For the subset of participants who had used or were currently undergoing ART (N = 221), perceived social stigma and the physical and time demands of ART were significantly associated with higher stress and depression symptoms, while partner emotional support was associated with lower perceived stress. Conclusions The ART process exacerbates perceived stress and depression symptoms among individuals experiencing infertility. Given the potential long-term impacts on both parent and child wellbeing, clinicians and policymaking groups, including the American Society for Reproductive Medicine (ASRM), should consider making access to mental health services a standard of care during infertility treatment.

Background & Hypothesis: Cognitive impairment is common in patients being evaluated for a kidney transplant (KT). The association between pretransplant cognitive function and posttransplant outcomes is unclear. Study Design: We performed a prospective cohort study to assess the association between pretransplant cognitive function and clinically relevant posttransplant outcomes. Setting and Population: In this single center study, participants from the transplant clinic were evaluated during their pretransplant clinic visits and followed prospectively. Outcomes: Our primary outcome measure was allograft function. Secondary outcomes were length of hospitalization for KT, hospital readmission within 30 and 90 days, graft loss, graft rejection within 90 days and 1 year, and mortality. Analytic Approach: We measured cognitive function with the Montreal Cognitive Assessment (MoCA) test. We assessed the association of pretransplant MoCA score with posttransplant outcomes; we used linear mixed effects models to assess the association with the change in estimated glomerular filtration rate, Poisson regression for length of hospitalization, Cox proportional hazard model for graft loss and mortality, and a logistic regression model for readmission and rejection. Results: We followed 501 participants for 2.7 ± 1.5 years. The mean age of the patients was 53 ± 14 years and the mean pretransplant MoCA score was 25 ± 3. Lower pretransplant MoCA scores did not adversely affect the primary outcome of allograft function or the secondary outcomes. Although higher MoCA scores predicted a higher decline in graft function (β = −0.28, 95% CI: −0.55 to −0.01, P = 0.04), the effect was small and not clinically significant. Older age was associated with longer hospitalization, lower likelihood of rejection, and higher mortality. Deceased donor KT (vs living donor KT) was associated with longer hospitalization but better graft function. Longer time receiving dialysis before KT was associated with longer hospitalization. A history of diabetes mellitus was associated with higher mortality. Limitations: Single center study limiting generalizability. Conclusions: Pretransplant MoCA scores were not associated with the primary outcome of allograft function or the secondary outcomes. Plain-Language Summary: Cognitive impairment (problems with memory and thinking) is common in patients with kidney disease. Cognitive impairment is associated with problems following instructions and remembering to take medications. Medical adherence is important in kidney transplant recipients, and inability to follow instructions and missed doses of immunosuppression increases the risk of rejection of the transplanted kidney. However, kidney transplantation also improves cognition. Hence, transplant centers wonder if cognitive impairment before transplant affects clinical outcomes after kidney transplant. We tried to answer this question by assessing cognitive function before transplantation and examining whether pretransplant cognitive function affects graft function, length of hospitalization, readmission after transplantation, rejection, and death. We did not find any strong link between cognitive function before transplant and these outcomes.

Abstract Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource’s (ClinGen’s) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen’s BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders.

Pulp revascularization is an emerging treatment modality in endodontics aimed at preserving the vitality and function of immature permanent teeth with necrotic pulp and apical periodontitis. This review provides a comprehensive examination of the current state of pulp revascularization, encompassing its rationale, clinical procedures, indications, contraindications, advantages, limitations, and potential future prospects. By critically analyzing the existing literature and clinical experiences, this review aims to offer insights into the efficacy, challenges, and potential advancements in the field of pulp revascularization.

Abstract INTRODUCTION Alzheimer's disease (AD) blood biomarkers show promise for clinical diagnosis but their reliability in chronic kidney disease (CKD) is debated. This study investigates the impact of kidney transplant (KT) on AD biomarkers in CKD. METHODS We assessed AD biomarkers in 46 CKD patients pre‐KT, at 12 weeks and 12 months post‐KT, with baseline measures from 13 non‐CKD controls. Using linear mixed models, we examined associations with participant groups, estimated glomerular filtration rate (eGFR) and cognition. RESULTS CKD patients showed elevated levels of neurofilament light (117 ± 72 vs. 11 ± 5 pg/mL), phosphorylated tau 181 (75 ± 42 vs. 13 ± 8 pg/mL), glial fibrillary acidic protein (193 ± 127 vs. 94 ± 39 pg/mL), amyloid β 42 (17 ± 5 vs. 5 ± 1 pg/mL), and amyloid β 40 (259 ± 96 vs. 72 ± 17 pg/mL) compared to controls. Post‐KT, biomarker levels approached normal with improved eGFR, paralleled by enhanced cognitive function. DISCUSSION AD blood biomarker elevations in CKD are reversible with improved kidney function through KT. Highlights AD biomarker levels are extremely high in severe CKD. AD biomarker levels are higher in patients with kidney failure on dialysis when compared to CKD patients not on dialysis. These elevations in AD biomarker levels in kidney failure are reversable and decrease dramatically after kidney transplantation. The change in biomarker levels after transplantation align with changes in kidney function. The change in biomarker levels after transplantation align with changes in cognitive function.

Drought, a detrimental abiotic stress, disturbs many vital processes critical to plant growth and development resulting in subpar crop yield. Unconventional measures such as biofertilizers and nanofertilizers have been reported as reliable solutions to this, however, outcomes vary greatly depending upon the type of organism/particle and its mode of delivery. Seed priming involves treating seeds with organic/inorganic chemicals to ameliorate drought stress by boosting pre-germinative metabolism, maintaining water potential, scavenging free radicals, etc. Therefore, this study determined the effect of biopriming and nanopriming on germination percentage (GP), leaf water status (LWS), proline, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and survial percentage (SP) of BG-4958 (Drought tolerant) and ICC-1882 (Drought sensitive) chickpea varieties exposed to polyethylene glycol (PEG) induced moderate (5 %) and severe drought (10 %) at flowering with no drought acting as a control. Experimental setup had three groups, control (untreated), bioprimed with plant growth promoting endophytic bacteria (PGPEB), and nanoprimed with CuNPs synthesised from PGPEB and their chemical counterparts). Crop analysis after 15 DDS (Days to drought stress) revealed that priming significantly altered the physio-biochemical parameters. Consortium and N2X led highest increment in GP and SP for DT and DS varieties, respectively, whereas N1X showed highest increase in LWS of both. Highest accumulation of proline was observed with consortium and N1 (X & Y) in DS variety while only biological CuNPs accumulated proline for DT variety. MDA and H₂O₂ decreased significantly in treated groups thereby reducing oxidative damage with non-significant variations in DT. Lower concentrations of biological CuNPs were found to be more effective in modulating the physio-biochemical machinery of chickpea under drought than their higher concentration as well as chemical counterparts. This study deepens our understanding of the beneficial role of PGPEB and biosynthesized CuNPs in alleviating the adverse effects of drought in chickpea.

Introduction: In this communication the focus is on the summarization of the complex molecular pathways that Ginkgo biloba Linn. utilizes to treat metabolic syndromes, a major international health concern marked by interrelated risk factors like obesity, insulin resistance, dyslipidaemia, and hypertension. Method: Several databases, including the Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and PubChem, were used while literature review was conducted. The use of suitable keywords like mechanism of Ginkgo biloba, pharmacological activities of medicinal plants, herbal remedies in metabolic syndromes etc. was made. It was attempted that all the English language articles published between 1980 and 2023 were referred. Results: Numerous molecular mechanisms contribute to the development of various metabolic syndromes and their risk factors. These mechanisms include insulin resistance, chronic low-grade inflammation, increased oxidative stress, dysregulation of lipid metabolism, impaired mitochondrial function, and others. This review summarizes the ways in which Gingko biloba, through modification of ROS formation, blocking the activation of NADPH oxidases, modifying the expression of antioxidant enzymes, downregulating MAPKs and AP-1, increasing cAMP, deactivating Stat5, activating the AMPK signalling pathway, influencing Stat3/JAK2, NF-κB, Nrf-2, mTOR, HGF/c-Met, Wnt/β-catenin, and BMP signalling pathways, modifying the mitochondrial transmembrane potential, etc., can alleviate disorders related to metabolic dysfunction. Discussion: The therapeutic properties of Ginkgo biloba Linn. and its constituents, including its anti-inflammatory, antioxidant, anti-apoptotic, and apoptotic activities, have drawn attention in recent years. In response to the growing public demand for novel therapeutics, prospective novel medicines may be produced by comprehending their molecular mechanisms and signalling networks.

Code fragments with identical or similar functionality are called code clones. This study aims to detect semantic clones in Java-based programs, focusing on the method-level granularity. To accomplish this, our approach extracts and compares both semantical and structural features of Java methods and applies certain heuristics to obtain the final result set. The semantics of a method are often described by its documentation, while its structural details are characterized by its implementation within the code body. However, Java methods may not always be accompanied by descriptive documentation. To address this, we have employed a Generative AI tool named ChatGPT, which has the ability to understand the given code and generate its documentation. To compare the documentation of methods, we have used various corpus-based and knowledge-based information retrieval (IR) techniques. However, for comparing a method’s structural details, we tokenized the method’s body and applied an information retrieval technique called VSM (Vector Space Modelling) on the tokenized body. Additionally, we also extracted and compared certain method-level metrics for this purpose. Further, while doing the semantical comparison of methods, eight IR variants are formed based on the internal processing requirements of different IR techniques. The technique proposed in this paper relies on the textual and metrics-based analysis of Java programs with few parsing requirements, making it lightweight and less computation-intensive. To examine the efficiency of the proposed technique, we have validated it using a semantic clone benchmark. The results show that the proposed technique detects semantic clones with high recall values ranging from 67% to 81% and precision values ranging from 60% to 96% for different IR variants explored in our research.

Abstract 3D bioprinting holds great promise for meeting the increasing need for transplantable tissues and organs. However, slow printing, interlayer mixing, and the extended exposure of cells to non‐physiological conditions in thick structures still hinder clinical applications. Here the DeepFreeze‐3D (DF‐3D) procedure and bioink for creating multilayered human‐scale tissue mimetics is presented for the first time. The bioink is tailored to support stem cell viability, throughout the rapid freeform DF‐3D biofabrication process. While the printer nozzle is warmed to room temperature, each layer solidifies at contact with the stage (‐80 °C), or the subsequent layers, ensuring precise separation. After thawing, the encapsulated stem cells remain viable without interlayer mixing or delamination. The composed cell‐laden constructs can be cryogenically stored and thawed when needed. Moreover, it is shown that under inductive conditions the stem cells differentiate into bone‐like cells and grow for months after thawing, to form large tissue‐mimetics in the scale of centimeters. This is important, as this approach allows the generation and storage of tissue mimetics in the size and thickness of human tissues. Therefore, DF‐3D biofabrication opens new avenues for generating off‐the‐shelf human tissue analogs. It further holds the potential for regenerative treatments and for studying tissue pathologies caused by disease, tumor, or trauma.

Abstract Background Intraocular inflammation is common after anterior or posterior segment surgery. They typically manifest either as non-infectious inflammation of the anterior or posterior segment, known as toxic anterior or posterior segment syndrome (TPSS), or as sterile or infective endophthalmitis. In this report, we describe a rare case of TPSS following vitreoretinal surgery, presenting as hemorrhagic retinal vasculitis. Case presentation A 58-year-old male diagnosed with a left eye acute rhegmatogenous retinal detachment underwent an uneventful primary pars plana vitrectomy with silicone oil endotamponade on the same day of presentation. At presentation, there were no signs of intraocular inflammation, and his visual acuity in the affected eye was 20/200. Results The retina was well-attached with silicone oil in place on the first post-operative day. Along the inferior retinal periphery, a hemorrhagic occlusive vasculitis was observed. Clinical examination revealed retained intraocular cotton fiber along the inferotemporal quadrant over the retinal surface. In addition to the standard post-operative medications, a course of systemic steroids (40 mg per day of Prednisolone tablets) was started. At the end of the first post-operative week, clinical signs of hemorrhagic retinal vasculitis were beginning to resolve, and by the end of the fourth post-operative week, they had completely resolved. Conclusion This report describes an unusual diagnosis of TPSS after vitreoretinal surgery, most likely due to the presence of an intraocular cotton fiber. This excessive inflammation of the posterior segment usually responds to a course of topical and systemic steroids.

This article presents a Multimodal database consisting of 222 images of 76 people wherein 111 are OCTA images and 111 are color fundus images taken at the Natasha Eye Care and Research Institute of Pune Maharashtra, India. Nonmydriatic fundus images were acquired using a confocal SLO widefield fundus imaging Eidon machine. Nonmydriatic OCTA images were acquired using the Optovue Avanti Edition machine Initially, the clinical approach described in this article was used to obtain the retinal images. Following that, the dataset was categorized by two experienced eye specialists. To identify instances of Non-Proliferative Diabetic Retinopathy (NPDR) with their various stages, medical professionals and scholars can use this data. Research scholars and ophthalmologists can utilize the data created to develop the initial stages of automated identification techniques for diabetic retinopathy (DR).

Background. Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. Methods. We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Results. Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Conclusions. Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.

Objective – During the COVID-19 pandemic, the majority of post-secondary institutions in British Columbia remained closed for a prolonged period, and volume on the provincial consortia chat service, AskAway, increased significantly. This study was designed to evaluate the content of AskAway transcripts for the 2019-2020 and 2020-2021 academic years to determine if the content of questions varied during the pandemic. Methods – The following programs were used to evaluate the dataset of more than 70,000 transcripts: R, Python (pandas), Voyant Tools and Linguistic Inquiry and Word Count (LIWC). Results – Our findings indicate that the content of questions remained largely unchanged despite the COVID-19 pandemic and the related increase in volume of questions on the AskAway chat service. Conclusion – These findings suggest that the academic libraries covered by this study were well-poised to provide continued support of patrons through the AskAway chat service, despite an unprecedented closure of physical libraries, a significant increase in chat volume, and a time of global uncertainty.

Komagataella phaffii (a.k.a. Pichia pastoris) requires histidine for optimal growth when cultured in a medium containing yeast extract, peptone (YP), and acetate (YPA). We demonstrate that HIS4‐deficient, K. phaffii strain GS115 exhibits a growth defect on YP‐media containing acetate, but not on other carbon sources. K. phaffii X33, a prototroph, grows better than K. phaffii GS115 (his4), a histidine auxotroph in YPA. Normal growth of GS115 is restored either by the expression of HIS4 or by culturing in YPA containing ≥0.6 mM histidine. In the presence of histidine, expression of several genes is altered, including those encoding key subunits of mitochondrial ATP synthase, transporters of amino acids and nutrients, as well as biosynthetic enzymes. Thus, histidine should be included as an essential component for optimal growth of K. phaffii histidine auxotrophs cultured in YPA.

Background: Tobacco cessation motivation majorly depends on self-efficacy and sense of coherence. Hence the aim and objective of the present study was to explore how self-efficacy (SE) in addition to sense of coherence (SOC) affected tobacco cessation motivation and readiness among slum dwellers during the COVID-19 health emergency. Materials and Methods: The ongoing research was a cross-sectional, descriptive questionnaire study. The research started in November and ended in December 2020. The research took place in primary health centres located in Ajmer's urban slums. In this analysis, east, west, north and south directions of Ajmer were chosen at random from each direction, and each slum had an associated primary health centre (PHC). From these 16 PHCs, people coming from slum areas were interviewed. The questionnaire consisted of demographic details, tobacco motivation and readiness, SOC and SE. Results: The majority of study participants (178, 56.7%) were not seriously considering reducing their tobacco intake. The majority of study subjects had poor sense of coherence {137 (43.6%)}, self-efficacy {141 (44.9%)} and tobacco cessation motivation and readiness {156 (49.7%)}. Using the logistic regression model, it was discovered that study participants with high SE and a high SOC had a substantial impact on successful tobacco cessation motivation and readiness (P = 0.01*), (P = 0.00*). Conclusion: It was concluded that the study participants with high self-efficacy and high sense of coherence had a significant impact on good tobacco cessation motivation and readiness.

Introduction: Multiple Myeloma (MM) is a clonal expansion of B lineage plasma cells in bone marrow. MM accounts for 10-15% of haematological malignancies and 1% of all malignant diseases. Though, the aetiology of the disease is largely unknown, various factors have been found to increase the incidence of MM. The present comprehensive research work on MM in the Malwa region of central India is an attempt to establish on clinicodemographic, haematological, biochemical and radiological parameters and finally to stage them according to Durie Salmon Staging (DSS) system. Aim: To study clinicopathological profile of patients with MM. Materials and Methods: The present ambispective study was conducted on total 70 cases of MM reported in the Department of Pathology at Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India, from July 2012 to June 2020. The study design included retrospective studies from July 2012 to December 2018 (six years and five months) and prospective studies from November 2017 to April 2019 (one year and five months). The demographic data of patients’ including history and clinical findings were recorded. Complete Blood Count (CBC) was done in all cases. Biochemical investigations were also done. Urine samples of all patients were screened for the presence of Bence Jones protein. Biochemical parameters and staging of MM patients was done. Statistical analysis prepared in excels spreadsheet and quantitative data were presented as proportions. Results: The study included a total of 70 cases of MM diagnosed on peripheral smear and/or bone marrow examination. The male:female ratio was 2.1:1, with a male preponderance. The results of the present study, reported 48 (68.57%) patients were male and 22 (31.43%) patients were females. In the present investigation, the authors diagnosed serum Lactate Dehydrogenase (LDH) levels were estimated in 63, out of 70 patients. Out of which, 25 (39.69%) patients had levels 480 U/L, respectively. Conclusion: The present study, underlines the association between clinical presentation, laboratory parameters and radiological findings in establishing the diagnosis of MM. The present study emphasises not only the role of a bone marrow aspiration and biopsy in establishing a diagnosis of MM, but also, assessing the plasma cell burden in the marrow.

Gupta et al. demonstrate that targeting isoform-specific TGFβ leads to an increase in the anti-tumor response when compared to pan-TGFβ inhibition, due to enhanced CD8 T cell function. The authors also report that combining TGFβ inhibition with immune checkpoint blockade results in improved tumor control.

Abstract Background The progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV. Methods We performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters. Results Mean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p

Abstract Background In an effort to encourage Family Planning (FP) adoption, since 1952, the Government of India has been implementing various centrally sponsored schemes that offer financial incentives (FIs) to acceptors as well as service providers, for services related to certain FP methods. However, understanding of the role of FIs on uptake of FP services, and the quality of FP services provided, is limited and mixed. Methods A qualitative descriptive study was conducted in Chatra and Palamu districts of Jharkhand state. A total of 64 interviews involving multiple stakeholders were conducted. The stakeholders included recent FP acceptors or clients, FP service providers of public health facilities including Accredited Social Healthcare Activists (ASHAs), government health officials managing FP programs at the district and state level, and members of development partners supporting FP programs in Jharkhand. Data analysis included both inductive and deductive strategies. It was done using the software Atlas ti version 8. Results It has emerged that there is a strong felt need for FP among majority of the clients, and FIs may be a motivator for uptake of FP methods only among those belonging to the lower socio economic strata. For ASHAs, FI is the primary motivator for providing FP related services. There may be a tendency among them and the nurses to promote methods which have more financial incentives linked with them. There are mixed opinions on discontinuing FIs for clients or replacing them with non-financial incentives. Delays in payment of FIs to both clients and the ASHAs is a common issue and adversely effects the program. Conclusion FIs for clients have limited influence on their decision to take up a FP method while different amounts of FIs for ASHAs and nurses, linked with different FP methods, may be influencing their service provision. More research is needed to determine the effect of discontinuing FI for FP services.

The methylotrophic yeast Komagataella phaffii (a.k.a. Pichia pastoris) harbors a methanol utilization (MUT) pathway, enabling it to utilize methanol as the sole source of carbon. The nexus between transcription factors such as Mxr1p and Trm1p and chromatin-modifying enzymes in the regulation of genes of MUT pathway has not been well studied in K. phaffii. Using transcriptomics, we demonstrate that Gcn5, a histone acetyltransferase, and Gal83, one of the beta subunits of nuclear-localized SNF1 (sucrose non-fermenting 1) kinase complex are essential for the transcriptional regulation by the zinc finger transcription factors Mxr1p and Trm1p. We conclude that interactions among Gcn5, Snf1, Mxr1p, and Trm1p play a critical role in the transcriptional regulation of genes of MUT pathway of K. phaffii.

The seminal discovery of paclitaxel from endophytic fungus Taxomyces andreanae was a milestone in recognizing the immense potential of endophytic fungi as prolific producers of bioactive secondary metabolites of use in medicine, agriculture, and food industries. Following the discovery of paclitaxel, the research community has intensified efforts to harness endophytic fungi as putative producers of lead molecules with anticancer, anti-inflammatory, antimicrobial, antioxidant, cardio-protective, and immunomodulatory properties. Endophytic fungi have been a valuable source of bioactive compounds over the last three decades. Compounds such as taxol, podophyllotoxin, huperzine, camptothecin, and resveratrol have been effectively isolated and characterized after extraction from endophytic fungi. These findings have expanded the applications of endophytic fungi in medicine and related fields. In the present review, we systematically compile and analyze several important compounds derived from endophytic fungi, encompassing the period from 2011 to 2022. Our systematic approach focuses on elucidating the origins of endophytic fungi, exploring the structural diversity and biological activities exhibited by these compounds, and giving special emphasis to the pharmacological activities and mechanism of action of certain compounds. We highlight the tremendous potential of endophytic fungi as alternate sources of bioactive metabolites, with implications for combating major global diseases. This underscores the significant role that fungi can play in the discovery and development of novel therapeutic agents that address the challenges posed by prevalent diseases worldwide.

Bacterial adaptation through frame-shifting insertions and deletions (indels) could be reversed by secondary introduction of a frame-restoring indel. Here, the authors develop ScarTrek, a program that scans genomic data for different indels, and analyze 5977 clinical M. tuberculosis isolates for indel frequency.

Aortic and pulmonary valves share a common developmental origin from the embryonic arterial trunk so there are chances of involvement of both semilunar valves in process of congenital malformation involving one semilunar valve. But in reported literature, this is a rare association. We are reporting 4 infants with bicuspid morphology of both semilunar valves and their different clinical presentation.

A diverse set of environmental contaminants have raised a concern about their potential adverse effects on endocrine signaling. Robust and widely accepted battery of in vitro assays is available to assess the disruption of androgenic and estrogenic pathways. However, such definitive systems to investigate effects on the disruption of thyroid pathways by the xenobiotics are not yet well established. One of the major “Molecular Initiating Events” (MIEs) in thyroid disruption involves targeting of thyroid peroxidase (TPO), a key enzyme involved in thyroid hormone synthesis. TPO catalyzes mono- and diiodination of L-Tyrosine (L-Tyr) to generate 3-Iodo-l-tyrosine (MIT) and 3,5-Diiodo-l-tyrosine (DIT), respectively, followed by the coupling of iodinated tyrosine rings to generate thyroid hormones, 3,3’5-Triiodo-l-thyronine (T3) and Levothyroxine (T4).We sought to develop a robust, sensitive, and rapid in vitro assay systems to evaluate the effects of test chemicals on the multiple catalytic activities of thyroid peroxidase. Simple in vitro assays were designed to study TPO mediated distinct reactions using a single LC-MS/MS method.Herein, we describe a battery of assays to investigate the iodination of L-Tyr to MIT and DIT, MIT to DIT as well as, T3 to T4 catalyzed by rat thyroid TPO. Importantly, two sequential reactions involving mono- and diiodination of L-Tyr could be analyzed in a single assay. The assay that monitors in vitro conversion of DIT to T4 was developed to study the coupling of tyrosine rings. Enzyme kinetics studies revealed distinct characteristics of multiple reactions catalyzed by TPO. Further, the known TPO inhibitors were used to assess their potency towards individual TPO substrates and reactions. The resultant half maximum inhibitory concentration (IC50) values highlighted differential targeting of TPO catalyzed reactions by the same inhibitor. Overall results underscore the need to develop more nuanced approaches that account for distinct multiple catalytic activities of TPO.

ObjectiveTo develop and evaluate a sepsis prediction model for the general ward setting and extend the evaluation through a novel pseudo-prospective trial design.DesignRetrospective analysis of data extracted from electronic health records (EHR).SettingSingle, tertiary-care academic medical center in St. Louis, MO, USA.PatientsAdult, non-surgical inpatients admitted between January 1, 2012 and June 1, 2019.InterventionsNone.Measurements and Main ResultsOf the 70,034 included patient encounters, 3.1% were septic based on the Sepsis-3 criteria. Features were generated from the EHR data and were used to develop a machine learning model to predict sepsis 6-h ahead of onset. The best performing model had an Area Under the Receiver Operating Characteristic curve (AUROC or c-statistic) of 0.862 ± 0.011 and Area Under the Precision-Recall Curve (AUPRC) of 0.294 ± 0.021 compared to that of Logistic Regression (0.857 ± 0.008 and 0.256 ± 0.024) and NEWS 2 (0.699 ± 0.012 and 0.092 ± 0.009). In the pseudo-prospective trial, 388 (69.7%) septic patients were alerted on with a specificity of 81.4%. Within 24 h of crossing the alert threshold, 20.9% had a sepsis-related event occur.ConclusionsA machine learning model capable of predicting sepsis in the general ward setting was developed using the EHR data. The pseudo-prospective trial provided a more realistic estimation of implemented performance and demonstrated a 29.1% Positive Predictive Value (PPV) for sepsis-related intervention or outcome within 48 h.

Here, Colangeli et al. use a human household contact cohort to measure the rate of mutation and evolution of Mycobacterium tuberculosis strains and find that long term latency is characterized by reduced mutation rates compared to latency in the first year, coinciding with clinical risk of developing active TB.

Abstract Background Post-transplant weight gain affects 50–90% of kidney transplant recipients adversely affecting survival, quality of life, and risk for diabetes and cardiovascular disease. Diet modification and physical activity may help prevent post-transplant weight gain. Methods for effective implementation of these lifestyle modifications are needed. The objective of this study is to assess the feasibility and acceptability of a remotely delivered nutrition and physical activity intervention among kidney transplant recipients. Secondary aims were to estimate the effectiveness of the intervention in producing changes in physical activity, qualify of life, fruit and vegetable intake, and consumption of whole grains and water from baseline to 6 months. Methods A randomized controlled study for stable kidney transplant recipients between 6 and 12 months post-transplantation was conducted. Participants were randomly assigned 1:1 to a technology-based, lifestyle modification program (intervention) or to enhanced usual care (control). Results The first 10 kidney transplant recipients screened were eligible and randomized into the intervention and control groups with no significant between-group differences at baseline. Health coaching attendance (78%) and adherence to reporting healthy behaviors (86%) were high. All participants returned for final assessments. The weight in controls remained stable, while the intervention arm showed weight gain at 3 and 6 months. Improvements were found for physical activity, quality of life, and fruit and vegetable intake in both groups. All participants would recommend the program to other transplant recipients. Conclusions Our data suggest that a remotely delivered televideo nutrition and physical activity intervention is feasible and valued by patients. These findings will aid in the development of a larger, more prescriptive, randomized trial to address weight gain prevention. Trial registration Clinicaltrials.gov Identifier NCT03697317 . Retrospectively registered on October 5, 2018.

Background: Post fever uveoretinal sequelae (PFURS) are the various uveoretinal manifestations seen after a systemic febrile illness in an immunocompetent individual caused by bacteria, viruses, and protozoa. These may be the result of a direct invasion by the pathogen or by indirect mechanism mediated through immune mechanisms. Method: The authors aim to review the ocular manifestations, utility of relevant diagnostic tests, management, and prognosis of PFURS. A comprehensive literature search was conducted on PubMed and Google Scholar databases with the search words “retinitis”, “choroiditis”, “neuroretinitis”, “macular edema”, “maculopathy”, “multifocal retinitis”, “chikungunya”, “dengue”, “West Nile”, “typhoid”, and “rickettsiosis”. Only articles published or translated into English language were considered. The key data were extracted, evaluated, and combined. Results: The authors search yielded 95 articles for the period between 1986 and May 2020. Painless blurring of vision was the most common symptom. Patients can have varied posterior segment manifestations, including vitritis, focal and multifocal patches of retinitis which could be unilateral or bilateral, optic nerve involvement, serous detachment at the macula, macular oedema, and localised involvement of the retinal vessels in the form of beading of the vessel wall, tortuosity, and perivascular sheathing. Conclusion: PFURS presents with a similar morphological pattern irrespective of the aetiology and follows a preset natural course before resolution. Treatment may or may not be required. Treating physicians need to be aware of this important ophthalmic condition even after complete resolution of fever.

Objectives:To study the incidence of dry eye and its determinants in patients undergoing cataract surgery.Materials and Methods:One hundred twenty patients with senile cataract underwent Schirmer’s test, tear break-up time (TBUT) test, lissamine green staining of the cornea and conjunctiva, and Ocular Surface Disease Index (OSDI) for evaluation of dry eye preoperatively and again at first and second follow-up examinations at 1 week and 1 month after cataract surgery.Results:Mean age of the patients was 59.25+9.77 years and 73 (60.8%) were men. None of the patients had dry eye at the time of enrollment as per the criteria of our study. Postoperatively, Schirmer’s test values ranged from 12-35 mm and 8-24 mm at first and second follow-ups, respectively. Mean TBUT was 13.16±2.45 and 9.64±2.20 seconds, while lissamine green staining score was 3 in 67 (55.8%) and 1 in 67 (55.8%) subjects at first and second follow-up, respectively. OSDI values ranged from 1-30 and 10-33 with a mean of 25.97±5.34 and 11.96±7.47 respectively at first and second follow-up. At first follow-up, 89.1% of the 56 patients who underwent phacoemulsification were found to have grade 2 dry eye (p

Abstract Background Mobile Clinics represent an untapped resource for our healthcare system. The COVID-19 pandemic has exacerbated its limitations. Mobile health clinic programs in the US already play important, albeit under-appreciated roles in the healthcare system. They provide access to healthcare especially for displaced or isolated individuals; they offer versatility in the setting of a damaged or inadequate healthcare infrastructure; and, as a longstanding community-based service delivery model, they fill gaps in the healthcare safety-net, reaching social-economically underserved populations in both urban and rural areas. Despite an increasing body of evidence of the unique value of this highly adaptable model of care, mobile clinics are not widely supported. This has resulted in a missed opportunity to deploy mobile clinics during national emergencies such as the COVID-19 pandemic, as well as using these already existing, and trusted programs to overcome barriers to access that are experienced by under-resourced communities. Main text In March, the Mobile Healthcare Association and Mobile Health Map, a program of Harvard Medical School’s Family Van, hosted a webinar of over 300 mobile health providers, sharing their experiences, challenges and best practices of responding to COVID 19. They demonstrated the untapped potential of this sector of the healthcare system in responding to healthcare crises. A Call to Action: The flexibility and adaptability of mobile clinics make them ideal partners in responding to pandemics, such as COVID-19. In this commentary we propose three approaches to support further expansion and integration of mobile health clinics into the healthcare system: First, demonstrate the economic contribution of mobile clinics to the healthcare system. Second, expand the number of mobile clinic programs and integrate them into the healthcare infrastructure and emergency preparedness. Third, expand their use of technology to facilitate this integration. Conclusions Understanding the economic and social impact that mobile clinics are having in our communities should provide the evidence to justify policies that will enable expansion and optimal integration of mobile clinics into our healthcare delivery system, and help us address current and future health crises.

This research article presents the participation of frequency linked pricing control (FPC) scheme for frequency and voltage control ancillary services in multi-area power system having automatic load frequency control (ALFC) loop and automatic voltage regulator (AVR) loop and integrated with doubly fed induction generator (DFIG) based wind farms. Mutual coupling effects are shown between the two loops by extending linearised ALFC system to include excitation model using AVR loop. FPC based on availability based tariff (ABT) mechanism is used under small load perturbations in power system to provide secondary control to reset frequency and voltage to their nominal values. Dynamic participation of DFIG based wind farms is shown by using modified inertial control scheme to inject active power quickly into the power system, thereby arresting deviations in frequency and voltage during transient conditions. Results reveal that coordinated action of DFIG based wind farms under FPC environment provides better dynamic frequency and voltage responses by reducing their deviations from nominal values.

Congenital coronary artery anomalies occur either in isolation or in association with other congenital heart disease. With the advent of multimodality imaging, the number of incidentally detected anomalies of coronary origin has risen over the last decade. The clinical presentation of these anomalies can range from being asymptomatic to serious morbidity and mortality, including sudden cardiac death in children and adolescents. We review the most common coronary anomalies and various echocardiographic views used to image the coronary arteries origin, size, and flow.

Introduction: Over the past few years, the demographic profile of lung cancer has changed. However, most reports are limited by small numbers, short follow-up period, and show an inconsistent pattern. A comprehensive evaluation of changing trends over a long period has not been done. Materials and Methods: Consecutive lung cancer patients were studied over a 10-year period from January 2008 to March 2018 at the All India Institute of Medical Sciences, New Delhi, and relevant clinical information, and survival outcomes were analyzed. Results: A total of 1862 patients were evaluated, with mean (SD) age of 59 (11.1) years, and comprising 82.9% males. Majority were smokers (76.2%) with median smoking index of 500 (interquartile range [IQR]: 300–800). Adenocarcinoma (ADC) was the most common type (34%), followed by squamous cell carcinoma (SCC – 28.6%) and small cell lung cancer (SCLC) (16.1%). Over the 10-year period, ADC increased from 9.5% to 35.9%, SCC from 25.4% to 30.6%, and non-small cell lung cancer -not otherwise specified (NSCLC-NOS) decreased from 49.2% to 21.4%. The proportion of females with lung cancer increased although smoking rates remained similar. Majority of NSCLC (95%) continued to be diagnosed at an advanced stage (3 or 4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements were present in 25.3% and 11.5% ADC patients, respectively. The median overall survival was 8.8 months (IQR 3.7–19) for all patients and 12.57 (IQR 6.2–28.7) months among the 1013 patients who were initiated on specific treatment (chemotherapy, targeted therapy, radiotherapy, or surgery). Never-smokers were younger, more likely to be female and educated, had a higher prevalence of ADC and EGFR/ALK mutations, and had better survival. Conclusion: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival.

The rapid development of safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a necessary response to coronavirus outbreak. Here, we developed PRAK-03202, the world's first triple antigen virus-like particle vaccine candidate, by cloning and transforming SARS-CoV-2 gene segments into a highly characterized S. cerevisiae-based D-Crypt™ platform, which induced SARS CoV-2 specific neutralizing antibodies in BALB/c mice. Immunization using three different doses of PRAK-03202 induced an antigen-specific (spike, envelope, and membrane proteins) humoral response and neutralizing potential. Peripheral blood mononuclear cells from convalescent patients showed lymphocyte proliferation and elevated interferon levels suggestive of epitope conservation and induction of T helper 1-biased cellular immune response when exposed to PRAK-03202. These data support further clinical development and testing of PRAK-03202 for use in humans.

Determination of viral load through cycle threshold (Ct) values may act as a predictor of severity and outcomes in patients with corona virus disease 2019 (COVID-19). However, variable literature is available regarding this relationship. Our study attempted to explore this association and the effect of various socio-demographic and clinical parameters on severity and outcome of COVID-19. Retrospective analysis of records of 731 patients whose nasopharyngeal/ oropharyngeal swabs were subjected to cartridge based nucleic acid amplification (CBNAAT) on Cepheid Xpert Xpress SARS-Cov-2 was done. Cycle threshold (Ct) values of N2 and E genes were studied in relation to severity and outcome of COVID-19. The viral load as determined by Ct values was classified as high (32). Association of socio-demographic and clinical parameters with respect to severity and outcome was also studied. Severity and mortality were significantly more in elder individuals, those belonging to the rural background, those with symptoms >7 days in duration before presentation and those with increasing number of co-morbidities (Severity: p32, in comparison when it was upto 25, and when between 25.1 and 32 (severity: p=0.032 and 0.003 respectively, mortality: p=0.018 and

Brucellosis is the main zoonotic disease worldwide. Cardiovascular complications, though rare are the most common cause of morbidity and mortality in patients with this infection. There are reported cases of endocarditis, aortoarteritis and peripheral arteritis as cardiovascular complications of Brucella but pulmonary arteritis has not been reported. Here we present the case of a 9-year-old child with pulmonary arteritis caused by Brucella melitensis. Pulmonary arteritis in a structurally normal heart is a very rare entity and causative organism of Brucella species makes it even rarer.

Key Clinical Message We report a patient with developmental delay, autism, epilepsy, macrocephaly, facial dysmorphism, gastrointestinal, and behavioral issues due to EXT2 compound heterozygous likely pathogenic variants. This case report expands the EXT2 gene mutation database and the clinical spectrum of patients with deficiencies in the heparan sulfate pathway.

Mediastinal lymphadenopathy is often associated with tuberculosis, especially in a high burden country like India. We present a case of an asymptomatic female, who had mediastinal lymphadenopathy and middle lobe collapse, both of which pointed towards a diagnosis of tuberculosis. Patient was later diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA) on basis of clinical, radiological and serological findings. Hence, even in a high burden country and in background of bronchial asthma, ABPA should be kept as a differential diagnosis in patients presenting with mediastinal lymphadenopathy

Allergic rhinitis (AR) is a chronic allergen specific, IgE-mediated hypersensitivity disorder which significantly impairs the quality of life in affected patients. Many aeroallergens and molds are responsible for AR. This study was conducted to find prevalence of Aspergillus fumigatus skin hypersensitivity in patients of AR by skin prick test (SPT). 150 clinically diagnosed AR patients visiting our OPD were enrolled. Skin hypersensitivity for Aspergillus f. was done by SPT in all the enrolled patients. Chi square test and Student’s t-test were applied for statistical analysis. Out of 150 patients, 60 (40%) were positive for Aspergillus fumigatus SPT. Majority of the positive patients had persistent AR and among those 39/60 (65%) had moderate to severe persistent AR and 12/60 (20%) had mild persistent AR. Our study concluded that there is high (40%) prevalence of Aspergillus f. skin hypersensitivity among AR patients. The hypersensitivity to Aspergillus f. was found more in severe AR patients and it was statistically significant.

Summary: Phosphatidylserine (PS) is exposed on the surface of apoptotic cells and is known to promote immunosuppressive signals in the tumor microenvironment (TME). Antibodies that block PS interaction with its receptors have been shown to repolarize the TME into a proinflammatory state. Radiation therapy (RT) is an effective focal treatment of isolated solid tumors but is less effective at controlling metastatic cancers. We found that tumor-directed RT caused an increase in expression of PS on the surface of viable immune infiltrates in mouse B16 melanoma. We hypothesize that PS expression on immune cells may provide negative feedback to immune cells in the TME. Treatment with an antibody that targets PS (mch1N11) enhanced the anti-tumor efficacy of tumor-directed RT and improved overall survival. This combination led to an increase in proinflammatory tumor-associated macrophages. The addition of anti-PD-1 to RT and mch1N11 led to even greater anti-tumor efficacy and overall survival. We found increased PS expression on several immune subsets in the blood of patients with metastatic melanoma after receiving tumor-directed RT. These findings highlight the potential of combining PS targeting with RT and PD-1 pathway blockade to improve outcomes in patients with advanced-stage cancers.

IntroductionImproving hypertension management is a national priority that can decrease morbidity and mortality. Evidence-based hypertension management guidelines advocate self-measured BP (SMBP), but widespread implementation of SMBP is lacking. The purpose of this study was to describe the perspective of primary care physicians (PCPs) on SMBP to identify the barriers and facilitators for implementing SMBP.MethodsWe collected data from PCPs from a large health system using semi-structured interviews based on the Theoretical Domains Framework (TDF). Responses were recorded, transcribed, and qualitatively analyzed into three overarching TDF domains based on the Behavior Change Wheel (BCW): 1) Motivation 2) Opportunity and 3) Capabilities. The sample size was based on theme saturation.ResultsAll 17 participating PCPs believed that SMBP is a useful, but underutilized tool. Although individual practices varied, most physicians felt that the increased data points from SMBP allowed for better hypertension management. Most felt that overcoming existing barriers would be difficult, but identified several facilitators: physician support of SMBP, the possibility of having other trained health professionals to assist with SMBP and patient education; improving patient engagement and empowerment with SMBP, and the interest of the health system in using technology to improve hypertension management.ConclusionPCPs believe that SMBP can improve hypertension management. There are numerous barriers and facilitators for implementing SMBP. Successful implementation in clinical practice will require implementation strategies targeted at increasing patient acceptability and reducing physician workload. This may need a radical change in the current methods of managing hypertension.

Introduction Mobile clinics provide an efficient manner for delivering healthcare services to at-risk populations, and there is a need to understand their economics. This study analyzes the costs of operating selected mobile clinic programs representing service categories in dental, dental/preventive, preventive care, primary care/preventive, and mammography/primary care/preventive. Methods The methodology included a self-reported survey of 96 mobile clinic programs operating in Texas, North Carolina, Georgia, and Florida; these states did not expand Medicaid and have a large proportion of uninsured individuals. Data were collected over an 8-month period from November 2016 to July 2017. The cost analyses were conducted in 2018, and were analyzed from the provider perspective. The average annual estimated costs; as well the costs per patient in each mobile clinic program within different service delivery types were assessed. Costs reported in the study survey were classified into recurrent direct costs and capital costs. Results Results indicate that mean operating costs range from about $300 000 to $2.5 million with costs increasing from mammography/primary care/preventive delivery to dental/preventive. The majority of mobile clinics provided dental care followed by dental/preventive. The cost per patient visit for all mobile clinic service types ranged from $65 to $529, and appears to be considerably less than those reported in the literature for fixed clinic services. Conclusion The overall costs of all delivery types in mobile clinics were lower than the costs of providing care to Medicare beneficiaries in federally funded health centers, making mobile clinics a sound economic complement to stationary healthcare facilities.