Miracle-dz/UniFAR-FTUs huggingface dataset:
YouTube as a source of information about pulpotomy and pulp capping: a cross sectional reliability analysis

Objectives The purpose of this study was to critically evaluate the quality, reliability and educational content of the information of vital pulp treatment videos available on YouTube. Materials and Methods The keywords “pulpotomy” and “pulp capping” were searched on YouTube on 5th July 2020, until 60 English language videos of each search term with a duration shorter than 15 minutes were acquired. Video characteristics were recorded and Video Power Index (VPI) was calculated. Reliability and educational quality of videos were evaluated using the Modified DISCERN score, the Journal of American Medical Association (JAMA) benchmark criteria and Global Quality Scores (GQS). Videos were categorized by uploading source. Results Regarding pulpotomy, 31.7% of the videos were uploaded by specialists and 68.3% were directed by non-specialists. In the case of pulp capping, the corresponding percentages were 45% and 55%, respectively. Videos uploaded by specialists had significantly higher modified DISCERN, JAMA and GQS scores compared to those uploaded by non-specialists. Endodontists tended to have the highest reliability and VPI scores. Conclusions YouTube videos on vital pulp treatment contain low educational quality or incomplete information. Low popularity of dental pulp capping and pulpotomy videos may be attributed to the specialized nature of these procedures. As YouTube represents an important source for patient information about different health topics, reliable informative videos should be uploaded by specialized dental professionals.
Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells

Objectives: This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD). Background: Calcific aortic valve disease is a chronic disease presenting with aortic valve degeneration and mineralization. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells (AVICs). Methods: We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical (IHC) analysis. ELISA was used to measure GLP-1 in serum of the Control (n = 197) and CAVD groups (n = 200). The effect of GLP-1 on the calcification of AVICs and the regulation of calcific gene expression were also characterized. Results: The GLP-1 concentration in the calcific aortic valves was 39% less than that in the control non-calcified aortic valves. Its concentration in serum was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 level was independently associated with CAVD risk. In vitro, GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and it down-regulated RUNX2, MSX2, BMP2, and BMP4 expression but up-regulated SOX9 expression. Conclusions: A reduction in GLP-1 was associated with CAVD, and GLP-1 participated in the mineralization of AVICs by regulating specific calcific genes. GLP-1 warrants consideration as a novel treatment target for CAVD.
Soluble Biomarkers with Prognostic and Predictive Value in Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy

Simple Summary Immunotherapy, most notably immune checkpoint inhibitors (ICIs), has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. Biological markers can help to improve patient selection. However, currently available markers such as PD-1 and its ligand (PD-L1) have important limitations. For this reason, new biomarkers obtained by non-invasive methods are urgently needed. In the present review, we describe recent advances in the development of novel soluble biological markers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with immunotherapy. Abstract Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers—including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)—have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the development of novel soluble biomarkers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with ICIs. We also describe the potential use of these biomarkers as prognostic indicators of treatment response and toxicity.
Risk Factors of Biochemical Failure in Locally Advanced Carcinoma Prostate Treated With Definitive External Beam Radiotherapy and Androgen Deprivation Therapy: Experience From Tertiary Care Center in North India

Background Locally advanced prostate cancer (LACAP), despite external beam radiotherapy (EBRT) along with antiandrogen therapy (ADT) has risk of prostate-specific antigen (PSA) progression. Furthermore, number of studies have emphasized on different prognostic factors. The purpose of our study is to analyze risk factors for biochemical failure (BF) in these patients treated at our institute. Methods Our study is a single-institution retrospective observational done at a tertiary care center in North India. Between January 2018 and December 2020, we retrospectively identified 34 patients managed at our institute as per multidisciplinary board (MBD). Demographic, clinical, radiological, pathological and treatment-related parameters were assessed as potential risk factors. End-point of the study was to find significant risk factors for BF. Statistical analysis was done on SPSS, version 20 (IBM Corp., Armonk, NY). Results All eligible patients received EBRT with ADT as per institution policy. Mean follow-up period was 20 months during which two (5.9%) patients had BF at a mean of 30 months after EBRT. Four-year PSA-progression-free survival rate was 73%. On univariate analysis, prognostic factors associated with high risk of BF were Gleason score and clinical T stage. Conclusion In summary, prognostic factors for high risk of BF leading to clinical progression are Gleason score 9 or 10 and clinical T3b stage.
Design and Optimization of New Enteric Nanoparticles of Ceftriaxone for Oral Delivery: In vitro and in vivo Assessments

Purpose Development of new strategies for oral delivery of existing antibiotics administered exclusively through intravenous route is one of the global priorities of pharmaceutical research. The encapsulation of these active pharmaceutical agents within nanosized natural products offers several traits due to their tunable surface properties. Ceftriaxone (CTX) is an injectable, third-generation cephalosporin that suffers poor oral bioavailability. Methods In the present study, ionic gelation of two biopolymers, namely chitosan (CH) and shellac (SH), was implemented to consolidate CTX, within elegant nanoparticles (NPs) for oral administration that would increase its bioavailability and sustainability. Quality by design approach (23 full factorial design) was adopted to optimize CTX-loaded nanoparticles. The optimized formula (F2) was characterized through transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). In vitro release behavior and stability study were also evaluated. Pharmacokinetic studies of enteric-coated hard gelatin capsules (HGCs) loaded with F2-NPs were finally assessed. Results The optimized spherical F2-NPs had a mean particle size of 258 nm, zeta potential of about +30.1 and appreciable drug entrapment efficiency of 83%. The in vitro drug release profile of F2-NPs in pH 7.4 experienced biphasic configuration with an initial burst release for an hour, followed by a sustained release over 15 h with Higuchi model and non-Fickian diffusion mechanism (R2=0.9852). High stability upon storage at refrigerated and room temperature for 3 months and good flow properties (θ= 32.2 and HR= 1.13) of the optimized formula were also conferred. In vivo pharmacokinetic assessment in rabbits fruitfully displayed 92% absolute bioavailability of CTX. Conclusion The obtained results provide evidence for the potential combination of CH and SH in NPs preparation to enhance the oral bioavailability of CTX.
Antagonism of Cerebral High Mobility Group Box 1 Ameliorates Dendritic Cell Dysfunction in Sepsis

Sepsis has emerged as a global health issue, and accounts for millions of deaths in intensive care units. Dysregulation of the immune response reportedly contributes to the pathogenesis and progression of this lethal condition, which involves both the dysfunction of immune cells and incompetent immunomodulatory mechanisms. High mobility group box 1 (HMGB1) is known as a later inflammatory mediator and is critically involved in the severity and prognosis of sepsis by inducing intractable inflammation and dysfunction of various immune cells. In the present study, we found that intracerebroventricular (ICV) injection of Box A, a specific antagonist of HMGB1, restored the dysregulated response of splenic dendritic cells (DCs) in septic mice by enhancing the expression of surface molecules, including CD80, CD86, and MHC-II, as well as improving DC priming of T lymphocytes. Cerebral HMGB1 was also confirmed to have potent inhibitory effects on DC functions when administrated by ICV injection in normal mice. The brain cholinergic system was found to mediate the immunomodulatory effects of central HMGB1, as it exhibited enhanced activity with persistent HMGB1 exposure. Furthermore, the inhibitory effects of cerebral HMGB1 on the response of peripheral DCs were also blocked by α7nAchR gene knockout. These findings provide novel insight into the relationship between cerebral HMGB1 and splenic DC dysfunction during sepsis, which is, at least in part, dependent on cholinergic system activity.
Consequences of Peri-Implant Bone Loss in the Occlusal Load Transfer to the Supporting Bone in terms of Magnitude of Stress, Strain, and Stress Distribution: A Finite Element Analysis

Methods Three models of a single internal connection bone level-type implant inserted into a posterior mandible bone section were constructed using a 3D finite element software: one control model without marginal bone loss and two test models, both with a circumferential peri-implant bone defect, one with a 3 mm high defect and the other one 6 mm high. A 150 N static load was tested on the central fossa at 6° relative to the axial axis of the implant. Results The results showed differences in the magnitude of strain and stress transferred to the bone between models, being the higher strain found in the trabecular bone around the implant with greater marginal bone loss. Stress distribution differed between models, being concentrated at the cortical bone in the control model and at the trabecular bone in the test models. Conclusion Marginal bone loss around dental implants under occlusal loading influences the magnitude and distribution of the stress transferred and the deformation of peri-implant bone, being higher as the bone loss increases.
The association between the belief in coronavirus conspiracy theories, miracles, and the susceptibility to conjunction fallacy

Summary Previous research has shown that people who endorse conspiracy theories are more prone to the conjunction fallacy: the tendency to perceive conjunct events as more probable than constituent events. The present study examined the relationship between specific beliefs (belief in conspiracy theories, religiosity) and the susceptibility to conjunction errors (CEs) in specific domains. A total of 500 participants was presented with brief scenarios from the domains “coronavirus conspiracy,” “miraculous healing,” and a control condition. Each scenario included one statement about a separate event and a second statement about two joint events co‐occurring. The participants estimated the probability of each statement. Results showed that the number of CEs made in the coronavirus domain was only associated with the belief in conspiracy theories, while general religiosity was only associated with CEs for scenarios describing miraculous healings. The assessed beliefs were not associated with CEs made in the control condition. Results suggest that distinct beliefs are uniquely associated with the susceptibility to conjunction errors in particular domains.
New‐onset atrial fibrillation in critically ill patients with coronavirus disease 2019 (COVID‐19)

Mortality in critically ill patients with coronavirus disease 2019 (COVID‐19) is high, therefore, it is essential to evaluate the independent effect of new‐onset atrial fibrillation (NOAF) on mortality in patients with COVID‐19. We aimed to determine the incidence, risk factors, and outcomes of NOAF in a cohort of critically ill patients with COVID‐19.
Water deprivation compromises maternal physiology and reproductive success in a cold and wet adapted snake Vipera berus

Abstract Droughts are becoming more intense and frequent with climate change. These extreme weather events can lead to mass mortality and reproduction failure, and therefore cause population declines. Understanding how the reproductive physiology of organisms is affected by water shortages will help clarify whether females can adjust their reproductive strategy to dry conditions or may fail to reproduce and survive. In this study, we investigated the consequences of a short period of water deprivation (2 weeks) during early pregnancy on the physiology and behaviour of a cold- and wet-adapted ectotherm (Vipera berus). We also examined water allocation to developing embryos and embryonic survival. Water-deprived females exhibited significant dehydration, physiological stress and loss of muscle mass. These effects of water deprivation on water balance and muscle loss were correlated with the number of developing embryos. While water-deprived females maintained water transfer to embryos at the expense of their own maintenance, water deprivation also led to embryonic mortality. Overall, water deprivation amplifies the reproductive costs of water allocation to support embryonic development. The deleterious impacts of water deprivation on female current reproductive performance and on potential survival and future reproduction could lead to severe population declines in this species.
Association Between Efficacy of Immune Checkpoint Inhibitors and Sex: An Updated Meta-Analysis on 21 Trials and 12,675 Non-Small Cell Lung Cancer Patients

Background Mounting randomized clinical trials have proved that immune checkpoint inhibitors (ICIs) achieved better overall survival (OS) and progression-free survival (PFS) than chemotherapy drugs for advanced non-small cell lung cancer (NSCLC) patients. However, some literatures have indicated that different sexes might not have equal immune response. Also, no agreement reached on the issue whether therapeutic benefit of ICIs is related to sex. Objectives To explore the association between efficacy of ICIs for NSCLC patients and their sexes and summarize overall treatment-related adverse events (TRAEs) in an exploratory manner. Methods We performed this systematic review and meta-analysis of all potentially relevant studies retrieved from PubMed, EMBASE, and the Cochrane Library until June 2021, for eligible randomized controlled trials (RCTs) comparing immunotherapy with chemotherapy in advanced NSCLC patients. Literature screening, summary data extraction was performed independently and in duplicate. The pooled hazard ratio (HR) and 95% confidence interval (CI) of OS, PFS and TRAEs were calculated, applying STATA software and random-effects models. This study was registered in international prospective register of systematic reviews (PROSPERO), number CRD42020210797. Results Twenty-one trials involving 12,675 NSCLC patients were included. For patients with advanced NSCLC, ICIs significantly prolonged the OS (males: HR 0.73, 95%CI 0.67-0.79; females: HR 0.73, 95%CI 0.61-0.85) and PFS (males: HR 0.62, 95%CI 0.55-0.70; females: HR 0.68, 95%CI 0.55-0.81) versus chemotherapy. Overall, there was no statistical difference between their sexes (OS: P = 0.97; PFS: P = 0.43), respectively. Owing to insufficient TRAEs data of different sexes, we only found immunotherapy for NSCLC patients had more all-grades (RR 0.88; 95%CI 0.82-0.95) and 3-5 grades (RR 0.60; 95%CI 0.47-0.75) AEs compared with chemotherapy. Conclusion Our findings indicated that the interaction between immunotherapy efficacy and different sexes was equally evident. Overall, patients with NSCLC could obtain more benefits from ICIs than chemotherapy regimen regardless of their sexes. Systematic Review Registration PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020210797.
Green synthesis of silver nanoparticles from aqueous leaf extract of Pomegranate (Punica granatum) and their anticancer activity on human cervical cancer cells

Plants contain different important phytochemicals that can be used as a potential treatment for various ailments including cancer. The green synthesis of silver nanoparticles from the extract of different plant parts has gained a wide range of engrossment among the researchers due to its unique optical and structural property. The aim of this study is green synthesis of silver nanoparticles from the aqueous leaf extract of pomegranate (Punica granatum) and to investigate its anticancer activity on human cervical cancer cells (HeLa). The synthesis of silver nanoparticle was depicted by the colour change from golden yellowish to dark brownish, UV-visible spectral analysis gave a characteristic surface plasmon absorption peak at . Further morphological characterization was done by Zeta potential where the size analysis was depicted to be 46.1 nm and zeta potential as . Fourier transform infrared spectroscopy (FTIR) inferred 3 intense sharp peaks at , , , confirmed the presence of flavonoids and polyphenols. The scanning electron microscopy (SEM) analysis with energy diffraction spectroscopy (EDS) confirmed the presence of silver nanoparticles with size ranged from to . X-ray diffraction (XRD) confirmed the crystallographic nature of silver. The cell proliferation activity of nanoparticles was tested by 3, −4, 5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay where the inhibitory concentration () was found at inhibiting of HeLa cell line. The anticancer activity of nanoparticles was determined by lactate dehydrogenase (LDH) assay where showed of cytotoxicity. Furthermore, the anticancer property of nanoparticles was confirmed by the DNA fragmentation assay.
Corynebacterium Bovis: A Rare Case of Persistent Bacterial Keratitis and Corneal Perforation

We report a rare case of severe, non-contact lens-related Corynebacterium bovis corneal infection on a background of viral keratitis, resulting in corneal abscess formation with subsequent corneal perforation. An 89-year-old Caucasian lady presented with a significant epithelial defect and a dense stromal infiltrates on a background of herpes zoster keratitis, ultimately resulting in corneal perforation. Enrichment culture obtained from corneal scraping isolated the unusual organism Corynebacterium bovis. This was treated with a combination of culture-directed, targeted course of antibiotics and surgical interventions. To the best of our knowledge, this is the first reported case of profuse bacterial keratitis secondary to Corynebacterium bovis infiltration, on a background of viral keratitis, resulting in corneal abscess formation and subsequent perforation. This report highlights this rare bacterium’s characteristics including its pathogenicity in causing severe corneal disease, particularly in immunosuppressed environments such as in this case, apparent antibiotic sensitivities & resistance, and potential transmission route.
Concentrated growth factor regulates the macrophage-mediated immune response

Abstract Concentrated growth factor (CGF) is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering. The host immune response, particularly macrophage activity, plays a critical role in injury repair and tissue regeneration. However, the biological effect of CGF on the immune response is not clear. To enrich the theoretical groundwork for clinical application, the present study examined the immunoregulatory role of CGF in macrophage functional activities in vitro. The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets, and it was biocompatible with macrophages. Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages. CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression, as detected by cell morphology and surface marker expression. A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin-1β while inducing expression of the chemokine regulated on activation, normal T cell expressed and secreted. Mechanistically, the AKT signaling pathway was activated, and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF. Our findings reveal that CGF induces a favorable immune response mediated by macrophages, which represents a promising strategy for functional tissue regeneration.