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Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation. Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models. Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment. Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Trivalent phosphine catalysis is mostly utilized to activate the carbon‐carbon multiple bonds to form carbanion intermediate species and is highly sensitive to certain variables. Random manual multi‐variables are critical for understanding the batch disabled regeneration of trivalent phosphine chemistry. We need the artificial intelligence‐based system which can change the variable based on previously conducted failed experiment. Herein, we report an auto‐optimized electro‐micro‐flow reactor platform for the in‐situ reduction of stable P(V) oxide to sensitive P(III) and further utilized the method for Corey‐Fuchs reaction. [ABSTRACT FROM AUTHOR]

Current evidence for medical therapies for diabetic kidney disease (DKD) is largely based on large-scale clinical trials. These trials, however, often exhibit heterogeneity in participant characteristics and baseline kidney function. These differences may lead to misinterpretation in clinical practice, such that treatment effects from different trials are directly compared and generalized to broader populations beyond the population in which each trial was conducted. This is particularly relevant if comparisons on efficacy and safety are made when the underlying study populations are distinctly different. Indeed, key clinical trials evaluating sodium-glucose transport protein-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonist (nsMRA), and glucagon-like peptide-1 receptor agonist (GLP-1RA) differed in recruitment requirements (inclusion/exclusion criteria), resulting in differences in the severity of the underlying kidney disease as well as risk factor profiles. Moreover, these trials defined their primary and secondary outcomes differently. Collectively, these factors lead to distinct study populations with different baseline risks for DKD progression in the placebo arm in each clinical trial. Consequently, a direct head-to-head comparison of the treatment effect between treatments using relative risk measures from placebo-controlled clinical trials alone is not recommended. In addition, healthcare professionals should be equipped to understand the specific target population of clinical trials to avoid over-generalization when drawing conclusions from these trials. Plain Language Summary: The medicines approved to help people with compromised kidney function were developed based on clinical trials that differed in many ways. There is a risk that clinical trials may be incorrectly compared and generalized by healthcare providers. In this review, the authors highlight the importance of interpreting clinical trial results cautiously while being mindful of the study population features. Key clinical trials for the treatment of diabetic kidney disease had different recruitment requirements for participants, a wide range of kidney disease severity, and different risks of disease progression in the comparison arm that did not receive the treatment during the trial. The conclusion of this review is to highlight the inappropriateness of comparing these medicines with each other using the results of clinical trials alone. It is important for the medical community to understand the specific types of patients that were involved in the clinical trials, to avoid unjustified conclusions. [ABSTRACT FROM AUTHOR]

This document provides concise and factual information about the synthesis and characterization of various compounds derived from biphenyl. The compounds were synthesized using different methods and techniques, such as flow reactors and microreactors. The yields and melting points of the synthesized compounds were reported, and their spectroscopic data matched values reported in the literature. The authors acknowledge the support and encouragement of the Director of the CSIR-IICT, and additional supporting information for the article is available online. [Extracted from the article]

Background: Urban poor face a disproportionate burden of ill health and high out-of-pocket expenditure (OOPE), creating a severe unmet need for affordable and quality health care. This article highlights the impact of health insurance on OOPE and catastrophic healthcare expenditure among the urban poor of India. Methods: The study uses randomly collected household data from a baseline survey conducted in the states of Rajasthan and Uttar Pradesh. Separate Insurance impact models have been generated for the analysis. Results: Mean out-of-pocket health expenses is higher in the private health facility for the inpatient care but in case of outpatient care, the expenditure was more in public. Expenditure on medicine constitutes the largest part of the total OOPE. Insurance impact model shows that coverage on medicine alone can reduce medical impoverishment by 85% in the case of Outpatient Deparment (OPD) and 71% in the case of Inpatient Department (IPD). The urban poor preferred private facility for treatment in case of illness, albeit when it comes to delivery, they prefer public facility Conclusions: Study findings indicate overt reliance on private health care must be regulated, to reduce OOPE among the urban poor. Also, effective universal health insurance can go a long way in reducing the OOPE with availability of free medicines and diagnostics in the public health facilities. [ABSTRACT FROM AUTHOR]

Over the past few decades, many batch process strategies have been developed that allow activated C(sp3)–O bonds to facilitate the synthesis of cross-electrophile coupling products. However, in these processes, a transition metal catalyst or an organic photocatalyst with a stoichiometric amount of oxidant or a reductant is the prerequisite. Indeed, the expensive catalyst, reductant, and oxidant and low surface-to-volume ratio for the gas–liquid reaction serve as major challenges in the field of cross-electrophile coupling and organosulfur chemistry. Herein, we report an electro-micro-flow induced cross-electrophile coupling of activated C(sp3)–O bonds with CO2 to generate aliphatic carboxylic acids via sequential reactions of sulfonium salts followed by replacement of CO2 with CS2, an aldehyde, a ketone, and electron-deficient olefins, to obtain the corresponding dithiol acid, deoxygenated Barbier-type product, and 1,4-addition product. [ABSTRACT FROM AUTHOR]

Background The prespecified on-treatment analysis of ASCEND-ND (NCT02876835) raised concerns about a higher relative risk of cancer-related adverse events (AEs) with daprodustat vs darbepoetin in patients with anaemia of CKD. This concern was not observed in dialysis patients in ASCEND-D (NCT02879305). Methods ASCEND-ND randomized 3872 patients to daprodustat or darbepoetin. ASCEND-D randomized 2964 patients to daprodustat or conventional erythropoiesis-stimulating agents (ESAs). In both studies ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). The prespecified on-treatment approach examined relative risks for cancer AEs up to the last dose date + 1 day. In these analyses, owing to different dosing intervals between arms, Cox models were used to estimate the daprodustat effect by various follow-up periods (censoring at last dose date, last dose date + dosing intervals, or end of study). Results In ASCEND-ND, the safety of daprodustat vs darbepoetin on cancer-related AEs depended on the duration of follow-up after last dose date: hazard ratio (HR) 1.04 [95% confidence interval (CI) 0.77, 1.40] at end of study [HR 1.12 (95% CI 0.81, 1.56) for last dose date + dosing interval; HR 1.50 (95% CI 1.04, 2.15) for last dose date + 1 day]. In ASCEND-D, no excess risk of cancer-related AEs was observed with any model examined. Conclusions Prespecified on-treatment analyses for cancer-related AEs appeared to result in biased risk estimates in ASCEND-ND by preferentially under-counting events from patients assigned to darbepoetin. Analyses accounting for longer darbepoetin dosing intervals, or extending follow-up, resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D, where ESA comparator dosing intervals are closer to daprodustat. Trial registration The ASCEND-ND trial is registered with ClinicalTrials.gov (NCT02876835); the ASCEND-D trial is registered with ClinicalTrials.gov (NCT02879305). [ABSTRACT FROM AUTHOR]