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This survey paper investigates the empirical findings of academic work that explores the nexus between the highly innovative Twitter happiness sentiment index and a range of financial assets. An integrated overview of econometric outcomes and the relevant investment policy implications are provided. It is revealed that investor happiness reinforces the safe haven abilities of gold. Moreover, major stock indices are highly influenced by the happiness index especially at higher quantiles. Reverse causality between the happiness index and stock indices is also detected but in a weaker level. This survey contributes to better understanding investment decisions based on behavioural finance and provides evidence about the nexus of investor sentiment estimation with the financial sector nowadays. JEL Classification numbers: G15, G40, Q02. Keywords: Investor happiness, Investor sentiment, Twitter, Survey, Gold, Stock prices.

One of the mechanisms used by epigenetic therapy is the elevation of host cell-derived double stranded RNA (dsRNA) baseline levels through overexpression of genomic repetitive elements especially Alu retroelements. The dsRNAs trigger immunogenic responses since immune system cannot distinguish between endogenous and exogenous dsRNAs derived from viral infections; hence called “Viral mimicry response”. These dsRNAs are recognized by pattern recognition receptors (PRRs) such as MDA-5 which further induce inflammatory responses through interferon secretion. However, the response is limited through the function of some editing enzymes such as ADAR1 which destabilizes the formation of dsRNAs and renders the therapy less efficient through attenuating interferon secretion by immune cells. Since, some cancer cells can survive even after ADAR1 inhibition, it is speculated that there might be other mechanism which contribute to dsRNA destabilization. Since dsRNA formation derived from retroelement transcripts mimics viral infections, we tried to review the mechanistic approaches applied during host-pathogen interaction to highlight a possible candidate which might be cogitable for further investigations in epigenetic therapy. dsRNAs produced by RNA viruses are sensed by PRRs and activate nuclear factor erythroid 2 p45-related factor 2 (NRF2) which further downregulates STING protein and attenuates IFN release. RNA viruses such as SARS-CoV-2 have the potential to impair NRF2 signaling and eliminate its inhibitory effect from STING, leading to excessive release of IFNs and destroy pulmonary cells through cytokine release storm (CRS). Here, we briefly explain that NRF2, in a very downstream side of anti-viral response, might be a potential candidate target in combination with epigenetic therapy to circumvent the limitations in cancer epigenetic therapy.

The current review sought to highlight the significance of nanotechnology in food systems with the most recent developments in nanotechnology applications in the oil and fat industries. The definition and classification of nanotechnology (using bottom-up and top-down approaches) are covered first, followed by its importance to the food industry and food safety. The authentication and detection of adulteration are a few applications of nanotechnology that have been addressed in the oils and fats industry. The presence of dangerous chemicals and food packaging byproducts, including, plasticizers, was identified. Some applications of nanotechnology in lipids systems were mentioned.

Objectives: Transcranial magnetic stimulation (TMS) has been suggested as a non-invasive stimulation treatment modality in bipolar disorder. However, the efficacy of repetitiver TMS in acute phase mania is unclear. The aim of this study is to assess the efficacy of theta burst stimulation (TBS) as an add-on therapy in the treatment of acute phase mania stimulation both right and left dorsolateral prefrontal cortex (DLPFC) in a randomized and sham-controlled design. Material and Methods: Forty right-handed patients between 18 and 59 years were randomly allocated to active and sham groups. Then, intermittent TBS (right DLPFC) and cTBS (left DLPFC) sessions (half an hour apart) were delivered in two sessions per day for 5 days in a week. Youngs Mania Rating Scale (YMRS) and Clinical global impression-Bipolar Disorder (CGI-BP) were assessed at baseline and at 7th and 21st days. Results: Our study fails to show a significant effect on of active stimulation in comparison to sham over psychopathology YMRS (F = 0.300; P ≤ 0.612), CGIBP-S (F = 0.432; P = 0.562), CGIBP-P (F = 0.202; P = 0.701), and CGIBP-W (F = 200; P = 0.705) in intention to treat protocol across 21 days. Minimal side effects were reported and none of the patients discontinued TBS citing side effects. Conclusion: We conclude that it is safe and well tolerated yet has inconclusive short-term therapeutic benefits. Trials using better localization technique with large sample, longer duration, and better dosing protocols are needed.

Objectives: Depression is theorized to result from “cognitive constriction” and problem-solving deficits, making an individual vulnerable to suicidal thoughts and acts. The present study explored the relationships between metacognitive beliefs, ruminations, and executive functions in patients with depression with suicidal ideation and without suicidal ideation. Material and Methods: Fifty patients of clinical depression (n = 25 depression with suicidal ideation, n = 25 depression without suicidal ideation) were recruited using purposive sampling. All participants completed the sociodemographic data sheet, Modified Scale for Suicidal Ideation, Metacognition Questionnaire 30, Ruminative Response Scale, Cognitive Flexibility Scale and Hamilton Rating Scale for Depression, and executive functions tests such as Wisconsin Card Sorting Test and Eriksen Flanker Test. Results: Metacognition and rumination responses were significantly higher in patients with depression with suicidal ideation than in patients without suicidal ideation. In addition, cognitive flexibility is higher in patients with depression without suicidal ideation, and executive deficits were higher in depression with suicidal ideation than without suicidal ideation. Conclusion: The findings support the role of metacognitive beliefs, ruminations, and executive deficits in maintaining suicidal ideations in depression.

Delayed–release dimethyl fumarate (DMF), Tecfidera®, is approved globally for treating relapsing-remitting multiple sclerosis. The disposition of DMF was determined in humans after administration of a single oral dose of [14C]DMF, and the total recovery was estimated to be between 58.4% to 75.0%, primarily through expired air.The absorption of [14C]DMF-derived radioactivity was rapid, with Tmax at 1h postdose. Glucose was the predominant circulating metabolite, accounting for ∼60% of the total extractable radioactivity. Cysteine and N-acetylcysteine conjugates of mono- or di-methyl succinate were found to be the major urinary metabolites.In vitro studies showed that [14C]DMF was mainly metabolised to MMF, and fumarase exclusively converted fumaric acid to malic acid and did not catalyse the conversion of fumaric acid esters to malic acid. DMF was observed to bind with human serum albumin through Michael addition to the Cys-34 residue when exposed to human plasma.These findings indicate that DMF undergoes metabolism via hydrolysis, GSH conjugation, and the TCA cycle, leading to the formation of citric acid, CO2, and water. These ubiquitous and well-conserved metabolism pathways minimise the risk of drug-drug interactions and reduce variability related to pharmacogenetics and ethnicity. Delayed–release dimethyl fumarate (DMF), Tecfidera®, is approved globally for treating relapsing-remitting multiple sclerosis. The disposition of DMF was determined in humans after administration of a single oral dose of [14C]DMF, and the total recovery was estimated to be between 58.4% to 75.0%, primarily through expired air. The absorption of [14C]DMF-derived radioactivity was rapid, with Tmax at 1h postdose. Glucose was the predominant circulating metabolite, accounting for ∼60% of the total extractable radioactivity. Cysteine and N-acetylcysteine conjugates of mono- or di-methyl succinate were found to be the major urinary metabolites. In vitro studies showed that [14C]DMF was mainly metabolised to MMF, and fumarase exclusively converted fumaric acid to malic acid and did not catalyse the conversion of fumaric acid esters to malic acid. DMF was observed to bind with human serum albumin through Michael addition to the Cys-34 residue when exposed to human plasma. These findings indicate that DMF undergoes metabolism via hydrolysis, GSH conjugation, and the TCA cycle, leading to the formation of citric acid, CO2, and water. These ubiquitous and well-conserved metabolism pathways minimise the risk of drug-drug interactions and reduce variability related to pharmacogenetics and ethnicity.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and its global health burden is increasing. COPD is characterized by emphysema, mucus hypersecretion, and persistent lung inflammation, and clinically by chronic airflow obstruction and symptoms of dyspnea, cough, and fatigue in patients. A cluster of pathologies including chronic bronchitis, emphysema, asthma, and cardiovascular disease in the form of hypertension and atherosclerosis variably coexist in COPD patients. Underlying causes for COPD include primarily tobacco use but may also be driven by exposure to air pollutants, biomass burning, and workplace related fumes and chemicals. While no single animal model might mimic all features of human COPD, a wide variety of published models have collectively helped to improve our understanding of disease processes involved in the genesis and persistence of COPD. In this review, the pathogenesis and associated risk factors of COPD are examined in different mammalian models of the disease. Each animal model included in this review is exclusively created by tobacco smoke (TS) exposure. As animal models continue to aid in defining the pathobiological mechanisms of and possible novel therapeutic interventions for COPD, the advantages and disadvantages of each animal model are discussed.

The rise in offshore oil and gas operations, maritime shipping, and tourism in northern latitudes enhances the risk of oil spills to sub-Arctic and Arctic coastal environments. Therefore, there is a need to understand the potential adverse effects of petroleum on key species in these areas. Here, we investigated the effects of oil exposure on the early life stages of capelin (Mallotus villosus), an ecologically and commercially important Barents Sea forage fish species that spawns along the coast of Northern Norway. Capelin embryos were exposed to five different concentrations (corresponding to 0.5–19 µg/L total PAHs) of water-soluble fraction (WSF) of crude oil from 6 days post fertilization (dpf) until hatch (25 dpf), and development of larvae in clean seawater was monitored until 52 dpf. None of the investigated endpoints (embryo development, larval length, heart rate, arrhythmia, and larval mortality) showed any effects. Our results suggest that the early life stages of capelin may be more robust to crude oil exposure than similar life stages of other fish species.

In our daily life, we are exposed to numerous industrial chemicals that may be harmful to the retina, which is a delicate and sensitive part of our eyes. This could lead to irreversible changes and cause retinal diseases or blindness. Current retinal environmental health studies primarily utilize animal models, isolated mammalian retinas, animal- or human-derived retinal cells, and retinal organoids, to address both pre- and postnatal exposure. However, as there is limited toxicological information available for specific populations, human induced pluripotent stem cell (hiPSC)-induced models could be effective tools to supplement such data. In order to obtain more comprehensive and reliable toxicological information, we need more appropriate models, novel evaluation methods, and computational technologies to develop portable equipment. This review mainly focused on current toxicology models with particular emphasis on retinal organoids, and it looks forward to future models, analytical methods, and equipment that can efficiently and accurately evaluate retinal toxicity.

Background: The use of left placket single muscle flap covered anastomosis in proximal gastrectomy has not been reported in the literature. The occurrence of gastroesophageal reflux after proximal gastrectomy is closely related to the mode of digestive tract reconstruction. The currently available digestive tract reconstruction approach affects patient’s postoperative quality of life due to the disadvantages of gastroesophageal reflux and anastomotic stenosis. Therefore, the use of left open flap single muscle flap covered anastomosis in proximal gastrectomy may improve the postoperative quality of life of patients. We present a case report and literature review to illustrate the therapeutic results of left-opening single muscle flap covered anastomosis in proximal gastrectomy. Case presentation: Two male patients with average age of 70.5 years and average BMI of 20.5 underwent laparoscopic proximal gastrectomy with an intraoperative left open flap single muscle flap covered overlap anastomosis. The average duration of surgery was 277.5 min, with average intraoperative bleeding of 100 ml, and no anastomotic stenosis was detected by contrast examination on the sixth postoperative day. The postoperative exhaust time was 3 days in both cases, liquid diet was given for 7 days and discharged from the hospital on the 8th day after operation. On an average 19 lymph nodes were dissected. The postoperative pathological stages were T3N2M0 and T1bN0M0. No gastroesophageal reflux or anastomotic fistula was detected in the recent follow-up. Conclusion: The application of the left flap covering the overlap anastomosis in laparoscopic proximal gastrectomy has achieved good results. Multi center large sample clinical studies are needed to further determine its role in gastroesophageal reflux.

Numerous animal studies have shown that the decrease in the tissue Nicotinamide Adenine Dinucleotide (NAD+) levels during aging are closely related to age-related physiological decline and that the administration of NAD+ precursors restore NAD+ levels and promotes health and prolongs lifespan. Therefore, in order to demonstrate whether NAD+ supplementation by NAD+ precursors mitigate age-related physiological dysfunction including muscle weakness in older men. We conducted a placebo-controlled, randomized, double-blind, parallel-group study in which Nicotinamide mononucleotide (NMN) was administered to healthy older men for 12 weeks. In this commentary, we overview reported human NAD+-related clinical trials including our NMN study.

The recent development of the International Medullary Thyroid Cancer Grading System (IMTCGS) provided clinicians with a tool to predict for disease outcomes after undergoing resection based on histologic features. However, its impact on the clinical management of patients is still under investigation. Utilizing the IMTCGS, we evaluated the association of grade with postoperative surveillance markers. High-grade tumors, when compared to low-grade, had a significantly more rapid calcitonin doubling time with a vast majority of high-grade patients having doubling times

Background: Pectus Carniatum (PC) is a term used for ranges of different chest wall deformities. Compressive bracing is one of the treatment approaches recommended for this group of the subjects. The aim of this review was to determine the efficiency of bracing on PC deformity based on available literature. Method: A search was done in some data bases include ISI web of Sciences, Scopus, PubMed and Medline. Pectus Carniatum was used with in combination with brace and orthosis. The quality assessment of the selected papers was done by use of Down and Black tool. Result: 25 papers was obtained based on the mentioned key words. 6 papers were selected for final analysis. The quality of the selected studies varied between 4 and 18. The results of the studies confirmed that compressive orthosis is a safe and effective method which can be used instead of surgery in treatment of PC. Conclusion: It is recommended to use braces in treatment of PC deformities. It is recommended to do a big study with more number of subjects, with long follow up period and also evaluate the effects of brace on deformity correction and quality of life.

Established in vitro assays for regulatory testing of skin sensitisation partly suffer from only moderate sensitivity, specificity, and predictivity when testing specific groups of chemicals. This may be due to limited biomarker response in vitro in cell types that interact as crucial players of in vivo skin sensitisation pathogenesis. Here, we propose a molecular approach to overcome this limitation. In our model, we apply genome editing and blocking of immunoregulatory molecules to increase the range of biomarker modulation by sensitising chemicals. To this end, aryl hydrocarbon receptor (AhR) knockout was done by CRISPR/Cas9 technology in THP-1 cells and combined with Programmed Cell Death-Ligand (PD-L)1 blockade. AhR-knockout THP-1 in coculture with HaCaT keratinocytes showed increased CD54 expression compared to wild type cells after stimulation with 10 µmol/L dinitrochlorobenzene (DNCB) that was further enhanced by anti-PD-L1. After stimulation of AhR-knockout THP-1 with 200 µmol/L mercaptobenzothiazol or 10 µmol/L DNCB, cocultivated Jurkat T cells significantly increased expression of T cell receptor-associated CD3. No such increase was detected after prior treatment of THP-1 with 150 µmol/L of irritant sodium lauryl sulphate. Additionally, higher levels of inflammatory cytokines MIP-3α, MIP-1β, TNF-α, and IL-8 were found in supernatants of enhanced loose-fit co-culture based sensitisation assay (eLCSA) after substance treatment. Hence, eLCSA allowed to discriminate between sensitisers and non-sensitisers. Thus, inhibition of immunoinhibitory pathway signalling by combining AhR knockout and PD-L1 antibody blockage into an assay involving main acting cell types in skin sensitisation may increase sensitivity and specificity of such assays and allow potency derivation.

Performing risk assessments (RA) on household use of flexible polyurethane (PU) foams requires access to reliable data about emission and migration of potential diamine impurities. A toluene diisocyanate (TDI) and a methylene diphenyl diisocyanate (MDI) based foam were thermally treated to enable measurements on samples with defined concentrations of the corresponding diamines, toluene diamine (TDA), and methylene dianiline (MDA). The thermally treated foams used for emission testing contained up to 15 mg.kg−1 of TDA and 27 mg.kg−1 of MDA. Those used for migration testing contained 5.1 mg.kg−1 of TDA and 14.1 mg.kg−1 of MDA. Stability of the thermally generated diamines was sufficient for testing over a 37-day period. Analytical techniques that did not decompose the polymer matrix were applied. Emission rates for TDA and MDA isomers were less than the limit of quantitation (LOQ) of 0.008–0.07 μg.m−2.h−1. Migration was studied using samples of the same thermally treated foams over a 35-day period. Quantifiable migration of MDA from the MDI-based foam was only observed on Days 1 and 2. From Day 3 onward, migration rates were less than the LOQ. Quantifiable migration of TDA from the TDI-based foam rapidly decreased with time and was only observed on Days 1 thru 3. From Day 4 onward, migration rates were less than the LOQ. Theoretically, the migration rate should be inversely proportional to the square root of time (t) as t−0.5. This relationship was confirmed by the experimental data and enables extrapolating migration values to more extended time periods to conduct RAs.

Repeated chronic fluoride (F) exposure for prolonged duration through water, air, and food causes F poisoning in the form of fluorosis in both humans and domestic and wild animals. However, among domestic equine animals, horses (Equus caballus) and donkeys (Equus asinus), chronic F poisoning caused by industrial fluoride pollution and fluoridated drinking water has been well studied. But these studies in these animals are still very limited. On the other hand, the sample size of these animals in these studies is also very small. Nevertheless, these studies are important from the point of view of veterinary medicine and toxicology. In these animals, F-induced diverse toxic effects or pathognomonic signs such as dental mottling or light to deep brownish staining on enamel surface of teeth, lameness, stiffness, skeletal abnormalities, crooked legs, hoof deformities, pain in joints, weight loss, unthriftiness, poor health, standing with an arched back, difficulty eating, rough hair coats, allergy or urticaria, anaemia, colic, diarrhoea, constipation, retention of urine, repeated abortions, and sterility have been reported. At the mean F concentration, in the range of 1.4 to 3.3 ppm in the drinking water, the prevalence of osteo-dental fluorosis in horses and donkeys has been found to be 78.7% and 100%, respectively. In present communication, chronic F poisoning in domesticated equine animals, horses and donkeys and its prevention in these animals have been focused. Simultaneously, research gaps have also been highlighted for researchers and veterinary scientists to do some advanced research works on these animals.

Novichoks represent the fourth generation of chemical warfare agents with paralytic and convulsive effects, produced clandestinely during the Cold War by the Soviet Union. This novel class of organophosphate compounds is characterised by severe toxicity, which, for example, we have already experienced three times (Salisbury, Amesbury, and Navalny's case) as a society. Then the public debate about the true nature of Novichoks began, realising the importance of examining the properties, especially the toxicological aspects of these compounds. The updated Chemical Warfare Agents list registers over 10,000 compounds as candidate structures for Novichoks. Consequently, conducting experimental research for each of them would be a huge challenge. Additionally, due to the enormous risk of contact with hazardous Novichoks, in silico assessments were applied to estimate their toxicity safely. In silico toxicology provides a means of identifying hazards of compounds before synthesis, helping to fill gaps and guide risk minimisation strategies. A new approach to toxicology testing first considers the prediction of toxicological parameters, eliminating unnecessary animal studies. This new generation risk assessment (NGRA) can meet the modern requirements of toxicological research. The present study explains, using QSAR models, the acute toxicity of the Novichoks studied (n = 17). The results indicate that the toxicity of Novichoks varies. The deadliest turned out to be A-232, followed by A-230 and A-234. On the other hand, the "Iranian" Novichok and C01-A038 compounds turned out to be the least toxic. Developing reliable in silico methods to predict various parameters is essential to prepare for the upcoming use of Novichoks.

Introduction: The effectiveness of simulation in medicine for teaching and assessing procedural skills is well documented; however, simulation technologies are not always available due to the high cost of simulators and lack of specific training. With the advances in digital modeling and 3D printing, we can create less expensive, more specific, and more readily available models to represent these tricky procedures, allowing for more robust training of our medical professionals. Methods: The process begins with a radiological scan that is segmented to capture the anatomies associated with the desired condition. We tested two different methods for fabrication; one made on a multi-material poly jet printer and the other using a selective laser sintering (SLS) TPU printer. Results: Our first method produced a model that was not adequate for our use case. The second method produced a model that worked for our use case and captured the geometry well. The SLS printer proved more durable, mechanically accurate, and feasible for simulating massive hemoptysis than method 1. This model was used in the airway management simulations with the PCCM Fellows and was deemed exempt by COMIRB 21-3067, the institutional review board of the University of Colorado Denver | Anschutz Medical Campus. Conclusion: Our method proved to be successful in producing models that are high-detailed, inexpensive, and reproducible to teach specific medical procedures.