Investigating the Attitudes of Adolescents and Young Adults Towards JUUL: Computational Study Using Twitter Data.

Background: Increases in electronic nicotine delivery system (ENDS) use among high school students from 2017 to 2019 appear to be associated with the increasing popularity of the ENDS device JUUL.

Objective: We employed a content analysis approach in conjunction with natural language processing methods using Twitter data to understand salient themes regarding JUUL use on Twitter, sentiment towards JUUL, and underage JUUL use.

Methods: Between July 2018 and August 2019, 11,556 unique tweets containing a JUUL-related keyword were collected.

Limbic-predominant age-related TDP-43 encephalopathy in Black and White decedents.

Objective: The association of limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathologic change (LATE-NC) with cognition and dementia was assessed in community-dwelling Black elders, and racial differences in these associations were tested.

Methods: Black (n = 76) and White (n = 152) decedents from 4 longitudinal clinical pathologic studies of aging were matched 2 to 1 by age at death, sex, years of education, dementia status, and follow-up time. LATE-NC detected by immunohistochemistry was dichotomized into none/mild and moderate/severe groups.

The insufficiency of ATG4A in macroautophagy.

During autophagy, LC3 and GABARAP proteins become covalently attached to phosphatidylethanolamine on the growing autophagosome. This attachment is also reversible. Deconjugation (or delipidation) involves the proteolytic cleavage of an isopeptide bond between LC3 or GABARAP and the phosphatidylethanolamine headgroup.

Negative feedback regulation by HuR controls TRIM21 expression and function in response to UV radiation.

The E3 ubiquitin ligase TRIM21 plays a crucial role as a negative regulator of innate immune responses. Recent evidence has also indicated the involvement of TRIM21 in the genotoxic stress response and suppressing tumorigenesis. Our previous work has demonstrated a new function of TRIM21 in inhibiting p53 protein synthesis by degrading the RNA-binding protein HuR in response to UV radiation.

Phytochemical composition analysis and evaluation of medicinal properties and cytotoxicity of five wild weeds: A comparative study.

Medicinal plants are a source of phytochemicals and they are used for the treatment of several oxidative stress-related or other diseases for their effectiveness, low toxicity and easy availability. Five traditionally used and less characterized herbaceous weeds of West Bengal, India, namely, , , , and , were investigated for the current research study. Aqueous and 70% ethanolic extracts of the leaves were analyzed for estimation of essential phytochemicals and to evaluate their antioxidant status, medicinal properties and cytotoxic effects.

Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand.

Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound , which exhibited target engagement in autoradiography (ARG) studies in brain slices from HD mouse models and postmortem human HD samples.

Separating Hydrocarbon Mixtures by Driving the Components in Opposite Directions: High Degree of Separation Factor and Energy Efficiency.

A radically different approach for separation of molecular mixtures is proposed. A judicious combination of levitation effect observed in zeolites with a counter intuitive Landauer blow torch effect provides driving forces for the two components of the mixture to move in opposite directions. Using nonequilibrium Monte Carlo simulations, we illustrate the efficacy of the method for separating real mixtures of both linear n-pentane and its branched isomer, neopentane, and linear n-hexane and its branched isomer, 2,2-dimethylbutane.

Palbociclib and beyond for the treatment of HR + HER2- metastatic breast cancer: an Asian-Pacific perspective and practical management guide on the use of CDK4/6 inhibitors.

Breast cancer is the most frequent cancer amongst women worldwide including in Asia where the incidence rate is rapidly increasing. Even with treatment, around 30% of patients with early breast cancer progress to metastatic disease, with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer the most common phenotype. First-line endocrine therapy targeting the estrogen receptor signaling pathway provides a median progression-free survival or time to progression of 6-15 months in HR + HER2- metastatic breast cancer.

Rab7 of Plasmodium falciparum is involved in its retromer complex assembly near the digestive vacuole.

Background: Intracellular protein trafficking is crucial for survival of cell and proper functioning of the organelles; however, these pathways are not well studied in the malaria parasite. Its unique cellular architecture and organellar composition raise an interesting question to investigate.

Methods: The interaction of Plasmodium falciparum Rab7 (PfRab7) with vacuolar protein sorting-associated protein 26 (PfVPS26) of retromer complex was shown by coimmunoprecipitation (co-IP).

Voltage-controlled NiO/ZnO p-n heterojunction diode: a new approach towards selective VOC sensing.

Metal oxide resistive gas sensors suffer from poor selectivity that restricts their practical applicability. Conventional sensor arrays are used to improve selectivity which increased the system complexity. Here, we have proposed a novel NiO/ZnO-based p-n junction single-diode device for selective sensing of several volatile organic compounds (VOCs) simultaneously by tuning bias voltage.

Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.

Background: Premutation size (55-199 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome, but it is unclear whether smaller "gray" zone expansions of 41-54 repeats are also associated with movement disorders. The objectives of this study were to determine the association between the FMR1 gene gray zone expansions, AGG interspersions, and the presence of parkinsonism and motor and cognitive function in an elderly community-based population.

Methods: Automated FMR1 polymerase chain reaction was performed on existing samples from 2 longitudinal aging studies whose subjects agreed to brain donation.

Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and feared side effects in cancer patients undergoing chemotherapy. Scientific evidence proves its detrimental impact on a patient's quality of life (QoL), treatment compliance, and overall healthcare cost. Despite the CINV-management landscape witnessing a radical shift with the introduction of novel, receptor-targeting antiemetic agents, this side effect remains a chink in the armor of a treating oncologist.

The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.

Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well.

Synthesis, Biodistribution, and Radiation Dosimetry of a Novel mGluR5 Radioligand: F-AZD9272.

The metabotropic glutamate receptor subtype mGluR5 has been proposed as a potential drug target for CNS disorders such as anxiety, depression, Parkinson's disease, and epilepsy. The AstraZeneca compound AZD9272 has previously been labeled with carbon-11 and used as a PET radioligand for mGluR5 receptor binding. The molecular structure of AZD9272 allows one to label the molecule with fluorine-18 without altering the structure.

PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [F]PF-06684511.

Purpose: Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [F]PF-06684511 estimated in non-human primates was relatively high.

Protein assembled nano-vehicle entrapping photosensitizer molecules for efficient lung carcinoma therapy.

The efficiency of drug depends not only on its potency but also on its ability to reach the target sites in preference to non-target sites. In this regard, protein assembled nanocarrier is the most promising strategy for intracellular anti-cancer drug delivery. The key motive of this study is to fabricate biocompatible protein assembled nanocarrier conjugated photosensitizer system for stimuli-responsive treatment of lung carcinoma.

A Clinicopathological Report of a 93-Year-Old Former Street Boxer With Coexistence of Chronic Traumatic Encephalopathy, Alzheimer's Disease, Dementia With Lewy Bodies, and Hippocampal Sclerosis With TDP-43 Pathology.

Chronic traumatic encephalopathy (CTE) was recently recognized as a new tauopathy in which multifocal perivascular phosphorylated tau aggregates accumulate in neurons, astrocytes, and neurites at the depths of the cortical sulci. Traumatic brain injury (TBI) in early or mid-life is known to be associated with an increased risk of dementia in late life. This case report describes a 93-year-old former street boxer with a premortem diagnosis of severe dementia, who showed pathological evidence of the coexistence of Alzheimer's disease, CTE, dementia with Lewy bodies, and hippocampal sclerosis with TDP-43 pathology.

PET Molecular Imaging of Phosphodiesterase 10A: An Early Biomarker of Huntington's Disease Progression.

Background: Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease.

Objectives: To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [ F]MNI-659.

Methods: The cross-sectional study (NCT02061722) included 45 Huntington's disease gene-expansion carriers stratified into four disease stages (early and late premanifest and Huntington's disease stages 1 and 2) and 45 age- and sex-matched healthy controls.

Status of pesticide residues in water, sediment, and fishes of Chilika Lake, India.

Chilika Lake is the largest coastal lagoon in Asia and the second largest in the world covering an area of 1100 km and spread over three districts of Odisha state of India. It is the first Indian wetland designated as a wetland of international importance under the Ramsar Convention in 1981. The lake ecosystem sustains large and diversified resources of plants and animals including fisheries.

Mainstreaming genetic counseling for testing into oncology clinics - Indian perspective.

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%-65% cumulative lifetime risk of developing breast cancer and an 11%-39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years.

Tannic acid and vitamin E loaded PLGA nanoparticles ameliorate hepatic injury in a chronic alcoholic liver damage model via EGFR-AKT-STAT3 pathway.

Tannic acid and vitamin E loaded-poly D, L-lactide-co-glycolic acid (PLGA) nanoparticles (NP) were developed to achieve hepatoprotection in alcoholic liver disease mice model. PLGA NPs were formed by emulsion solvent evaporation and characterized and delivered to mice. Histology studies were performed, serum enzyme levels of AST, ALT and inflammatory cytokines were checked using ELISA kits.

Potential for imaging the high-affinity state of the 5-HT receptor: a comparison of three PET radioligands with differing intrinsic activity.

Background: Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT receptors. The 5-HT receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand.

Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review.

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence.

Development of a F-labeled PET radioligand for imaging 5-HT receptors: [F]AZ10419096.

Introduction: In the last decade PET has been useful in studying and understanding the 5-HT receptor. [C]AZ10419369 and [C]P943 have been applied as radioligands in these studies. Both use carbon-11 (t = 20.

Clinical Presentation and Outcomes of Phaeochromocytomas/Paragangliomas in Neurofibromatosis Type 1.

Patients with neurofibromatosis type 1 (NF1) are at risk of developing phaeochromocytomas/paragangliomas (PHAEO/PG). Unlike in other familial PHAEO/PG syndromes, there are no published guidelines regarding screening in asymptomatic or normotensive patients with NF1. This strategy may be associated with preventable morbidities in those patients who ultimately present with symptomatic PHAEO/PG.