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Aim: The precise estimation and replication of skin color are crucial for maxillofacial prosthesis. The study aimed to evaluate facial skin color with a colorimeter and suggest a skin shade guide and formula for color estimation. Settings and Design: An observational study conducted in the department of prosthodontics. Materials and Methods: Study was conducted on 368 individuals of Indian origin in age range of 20–45 years. The facial skin color was assessed in malar regions using SkinColorCatch colorimetric device and individual topography angle (ITA) and CIELAB L*a*b* values were noted. Statistical Analysis Used: K-means clustering was utilized to propose a shade guide for maxillofacial prosthesis with 24 skin shades. Logistic regression analysis was conducted to propose a formula to estimate skin shade of the individuals. Results: Based on cluster analysis, 368 subjects were divided into three clusters with similar characteristic as Cluster 1 with dark skin color in 88 (23.91%) subjects, Cluster 2 with medium skin color in 224 (60.87%) subjects, and Cluster 3 with light skin color in 56 (15.22%) subjects. The mean ITA and L*a*b* values for cluster 1 were −47.04° ±14.77°, 34.53 ± 4.31, 8.55 ± 2, 11.42 ± 3.7033, respectively. The mean ITA angle and L*a*b* values for Cluster 2 were 4.29° ±11.34° 51.67 ± 3.42, 8.79 ± 3.13, 21.36 ± 2.38, respectively. The mean ITA and L*a*b* values for Cluster 3 were 34.65 ± 4.29°, 62.66 ± 3.08, 6.53 ± 1.79, 17.73 ± 2.39, respectively. The proposed shade guide comprised a total of 24 different shades that were categorized into three primary colors according to three distinct clusters, each of which was further broken down into eight subclusters containing various shades within each cluster. Logistic regression analysis gave an equation as follows: Y =12.43 + 0.186X (Y = Predicted skin color, X = ITA angle). Conclusions: Twenty-four facial skin shade tabs have been proposed based on ITA angle and CIELAB values. This comprehensive approach to categorize the shades will ensure a detailed and organized system for selecting and matching colors in maxillofacial prosthesis.

Abstract Alcohol consumption leads to neuroinflammation and blood‒brain barrier (BBB) damage, resulting in neurological impairment. We previously demonstrated that ethanol-induced disruption of barrier function in human brain endothelial cells was associated with mitochondrial injury, increased ATP and extracellular vesicle (EV) release, and purinergic receptor P2 × 7R activation. Therefore, we aimed to evaluate the effect of P2 × 7R blockade on peripheral and neuro-inflammation in ethanol-exposed mice. In a chronic intermittent ethanol (CIE)-exposed mouse model, P2 × 7R was inhibited by two different methods: Brilliant Blue G (BBG) or gene knockout. We assessed blood ethanol concentration (BEC), brain microvessel gene expression by using RT2 PCR array, plasma P2 × 7R and P-gp, serum ATP, EV-ATP, number of EVs, and EV mtDNA copy numbers. An RT2 PCR array of brain microvessels revealed significant upregulation of proinflammatory genes involved in apoptosis, vasodilation, and platelet activation in CIE-exposed wild-type animals, which were decreased 15–50-fold in BBG-treated–CIE-exposed animals. Plasma P-gp levels and serum P2 × 7R shedding were significantly increased in CIE-exposed animals. Pharmacological or genetic suppression of P2 × 7R decreased receptor shedding to levels equivalent to those in control group. The increase in EV number and EV-ATP content in the CIE-exposed mice was significantly reduced by P2 × 7R inhibition. CIE mice showed augmented EV-mtDNA copy numbers which were reduced in EVs after P2 × 7R inhibition or receptor knockout. These observations suggested that P2 × 7R signaling plays a critical role in ethanol-induced brain injury. Increased extracellular ATP, EV-ATP, EV numbers, and EV-mtDNA copy numbers highlight a new mechanism of brain injury during alcohol exposure via P2 × 7R and biomarkers of such damage. In this study, for the first time, we report the in vivo involvement of P2 × 7R signaling in CIE-induced brain injury.

Abstract Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach to knockout expression of Kindlin-2 in both androgen-independent and dependent prostate cancer cell lines, and the effects of Kindlin-2 suppression on oncogenic properties of these prostate cancer cell lines was examined. Adhesion to extracellular matrix proteins was markedly blunted, consistent with the control of integrin function by Kindlin-2. Migration across matrices was also affected. Anchorage independent growth was markedly suppressed. These observations indicate that Kindlin-2 regulates hallmark features of prostate cancer cells. In androgen expressing cells, testosterone-stimulated adhesion was Kindlin-2-dependent. Furthermore, tumor growth of a prostate cancer cell line lacking Kindlin-2 and implanted into the prostate gland of immunocompromised mice was markedly blunted and was associated with suppression of angiogenesis in the developing tumor. These results establish a key role of Kindlin-2 in prostate cancer progression and suggest that Kindlin-2 represents an interesting therapeutic target for treatment of prostate cancer.

Abstract Functional blockade of the transforming growth factor-beta (TGFβ) signalling pathway improves the efficacy of cytotoxic and immunotherapies. Here, we conducted a phase 1b study (ClinicalTrials.gov., NCT03143985) to determine the primary endpoints of safety, tolerability, and maximal tolerated dose (200 mg twice daily) for the orally-available TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed and/or refractory multiple myeloma (RRMM) patients who had received ≥2 lines of chemoimmunotherapy. Secondary endpoints demonstrated sustained clinical responses, favorable pharmacokinetic parameters and a 6-month progression-free survival of 82%. Vactosertib combined with pomalidomide was well-tolerated at all dose levels and displayed a manageable adverse event profile. Exploratory analysis indicated that vactosertib co-treatment with pomalidomide also reduced TGFβ levels in patient bone marrow as well as the level of CD8+ T-cells that expressed the immunoinhibitory marker PD-1. In vitro experiments indicated that vactosertib+pomalidomide co-treatment decreased the viability of MM cell lines and patient tumor cells, and increased CD8+ T-cell cytotoxic activity. Vactosertib is a safe therapeutic that demonstrates tumor-intrinsic activity and can overcome immunosuppressive challenges within the tumor microenvironment to reinvigorate T-cell fitness. Vactosertib offers promise to improve immunotherapeutic responses in heavily-pretreated MM patients refractory to conventional agents.

The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery.

Abstract We make decisions by comparing values, but it is not yet clear how value is represented in the brain. Many models assume, if only implicitly, that the representational geometry of value is linear. However, in part due to a historical focus on noisy single neurons, rather than neuronal populations, this hypothesis has not been rigorously tested. Here, we examine the representational geometry of value in the ventromedial prefrontal cortex (vmPFC), a part of the brain linked to economic decision-making, in two male rhesus macaques. We find that values are encoded along a curved manifold in vmPFC. This curvilinear geometry predicts a specific pattern of irrational decision-making: that decision-makers will make worse choices when an irrelevant, decoy option is worse in value, compared to when it is better. We observe this type of irrational choices in behavior. Together, these results not only suggest that the representational geometry of value is nonlinear, but that this nonlinearity could impose bounds on rational decision-making.

Background: A healthy child can make way for a healthy adult. Some of the factors that can be used to determine the health of a young child are nutritional status of the child, the developmental milestones achieved, and frequency of illness. Objectives: The health status of children and associated factors are determined. Methods: This is a community-based cross-sectional study with 271 participants. The height and weight of the child were measured; questions were asked regarding developmental milestones achieved and frequent illnesses. An interview schedule was used to enquire about the determinants of health status. Descriptive statistics were done; Chi-square test and regression were used to determine association between the health status of children and determinants. Results: A total of 127 (46.86%) were found to have a good health status. Family type (Chi square value 9.568; P value = 0.002), birth spacing (Chi square 20.540; P value < 0.001), term or pre-term birth (Chi square 4.598; P value = 0.032), chronic medical problem in the child (Chi square 11.074; P value = 0.001), and immunization status of the child (Chi square 5.666; P value = 0.017) were found to have significant association with the health status of the child. By logistic regression, pre-term child birth and family type were found to have higher odds. Conclusion: For better health of the child, specific focus on birth spacing, term birth of baby, better care of the ill, and complete immunization play vital roles.

RNA-sequencing (RNA-seq) is a gold-standard method to profile genome-wide changes in gene expression. RNA-seq uses high-throughput sequencing technology to quantify the amount of RNA in a biological sample. With the increasing popularity of RNA-seq, many variations on the protocol have been proposed to extract unique and relevant information from biological samples. 3' Tag-Seq (also called TagSeq, 3' Tag-RNA-Seq, and Quant-Seq 3' mRNA-Seq) is one RNA-seq variation where the 3' end of the transcript is selected and amplified to yield one copy of cDNA from each transcript in the biological sample. We present a simple, easy-to-use, and publicly available computational workflow to analyze 3' Tag-Seq data. The workflow begins by trimming sequence adapters from raw FASTQ files. The trimmed sequence reads are checked for quality using FastQC and aligned to the reference genome, and then read counts are obtained using STAR. Differential gene expression analysis is performed using DESeq2, based on differential analysis of gene count data. The outputs of this workflow are MA plots, tables of differentially expressed genes, and UpSet plots. This protocol is intended for users specifically interested in analyzing 3' Tag-Seq data, and thus normalizations based on transcript length are not performed within the workflow. Future updates to this workflow could include custom analyses based on the gene counts table as well as data visualization enhancements. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Running the 3' Tag-Seq workflow Support Protocol: Generating genome indices.

Background: Thalassemia major is a genetic disorder characterized by severe anemia and the need for lifelong blood transfusions. Aims and Objectives: The aim of this study was to investigate the clinical profile of transfusion-dependent thalassemia major children with reference to serum ferritin levels and liver function. Materials and Methods: A prospective observational study included 100 children aged 1–12 years with beta-thalassemia major, who were receiving blood transfusions. Clinical data, including growth parameters, serum ferritin levels, and liver function tests, were collected. Descriptive and inferential statistical analyses were performed. Results: The study population predominantly consisted of children aged 1–5 years (54%) and males (51%). Hindu children accounted for 85% of the participants. Most children were diagnosed with thalassemia major before the age of 1 year (84%) and were diagnosed through Hb electrophoresis (77%). The majority of children received blood transfusions every 15–30 days (49%). Pre-transfusion hemoglobin levels ranged from