Bright and fast scintillation of organolead perovskite MAPbBr3 at low temperatures

The purpose of this review is to evaluate progress inmolecular epidemiology over the past 24 years in canceretiology and prevention to draw lessons for futureresearch incorporating the new generation of biomarkers.Molecular epidemiology was introduced inthe study of cancer in the early 1980s, with theexpectation that it would help overcome some majorlimitations of epidemiology and facilitate cancerprevention. The expectation was that biomarkerswould improve exposure assessment, document earlychanges preceding disease, and identify subgroupsin the population with greater susceptibility to cancer,thereby increasing the ability of epidemiologic studiesto identify causes and elucidate mechanisms incarcinogenesis. The first generation of biomarkers hasindeed contributed to our understanding of riskandsusceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes havebeen mounted to reduce riskfrom several importantenvironmental carcinogens. Several new and promisingbiomarkers are now becoming available for epidemiologicstudies, thanks to the development of highthroughputtechnologies and theoretical advances inbiology. These include toxicogenomics, alterations ingene methylation and gene expression, proteomics, andmetabonomics, which allow large-scale studies, includingdiscovery-oriented as well as hypothesis-testinginvestigations. However, most of these newer biomarkershave not been adequately validated, and theirrole in the causal paradigm is not clear. There is a needfor their systematic validation using principles andcriteria established over the past several decades inmolecular cancer epidemiology.

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Konkurrenz zwischen Stieleiche und Buche auf Lothar-Sturmflächen | Competition between pedunculate oak and European beech on Lothar windthrow areas

Schweizerische Zeitschrift fur Forstwesen ◽

10.3188/szf.2009.0114 ◽

2009 ◽

Vol 160 (5) ◽

pp. 114-123 ◽

Cited By ~ 4

Author(s):

Daniel Otto ◽

Sven Wagner ◽

Peter Brang

Keyword(s):

Large Scale ◽

Early Stage ◽

Tree Height ◽

European Beech ◽

Threshold Value ◽

Test Methods ◽

Permanent Plots ◽

Pedunculate Oak ◽

Competitive Pressure ◽

Competition Index

The competitive pressure of naturally regenerated European beech (Fagus sylvatica) saplings on planted pedunculate oak (Quercus robur) was investigated on two 1.8 ha permanent plots near Habsburg and Murten (Switzerland). The plots were established with the aim to test methods of artificial oak regeneration after large-scale windthrow. On both plots, 80 oaks exposed to varying levels of competitive pressure from at most 10 neighbouring beech trees were selected. The height of each oak as well as stem and branch diameters were measured. The competitive pressure was assessed using Schütz's competition index, which is based on relative tree height, crown overlap and distance from competing neighbours. Oak trees growing without or with only slight competition from beech were equally tall, while oaks exposed to moderate to strong competition were smaller. A threshold value for the competition index was found above which oak height decreased strongly. The stem and branch diameters of the oaks started to decrease even if the competition from beech was slight, and decreased much further with more competition. The oak stems started to become more slender even with only slight competition from beech. On the moderately acid beech sites studied here, beech grow taller faster than oak. Thus where beech is competing with oak and the aim is to maintain the oak, competitive pressure on the oak must be reduced at an early stage. The degree of the intervention should, however, take the individual competitive interaction into account, with more intervention if the competition is strong.

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Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

Scientific Reports ◽

10.1038/s41598-021-85293-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Geetika Nehra ◽

Shannon Andrews ◽

Joan Rettig ◽

Michael N. Gould ◽

Jill D. Haag ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Brain Tumors ◽

Nasal Mucosa ◽

Brain Cancer ◽

Intranasal Administration ◽

High Performance ◽

Early Stage ◽

Plasma Concentrations ◽

Perillyl Alcohol ◽

Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

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Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

International Journal of Molecular Sciences ◽

10.3390/ijms22157917 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7917

Author(s):

Hideaki Kaneto ◽

Tomohiko Kimura ◽

Masashi Shimoda ◽

Atsushi Obata ◽

Junpei Sanada ◽

...

Keyword(s):

Large Scale ◽

Cell Function ◽

Apoptotic Cell ◽

Early Stage ◽

Insulin Biosynthesis ◽

Protective Effects ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Glucose Toxicity

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

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Understanding the Processes Causing the Early Intensification of Hurricane Dorian through an Ensemble of the Hurricane Analysis and Forecast System (HAFS)

Atmosphere ◽

10.3390/atmos12010093 ◽

2021 ◽

Vol 12 (1) ◽

pp. 93

Author(s):

Andrew Hazelton ◽

Ghassan J. Alaka ◽

Levi Cowan ◽

Michael Fischer ◽

Sundararaman Gopalakrishnan

Keyword(s):

Tropical Cyclone ◽

Large Scale ◽

Early Stage ◽

Early Period ◽

Storm Track ◽

Key Factors ◽

Complex Interplay ◽

Forecast System ◽

Model Initialization

The early stages of a tropical cyclone can be a challenge to forecast, as a storm consolidates and begins to grow based on the local and environmental conditions. A high-resolution ensemble of the Hurricane Analysis and Forecast System (HAFS) is used to study the early intensification of Hurricane Dorian, a catastrophic 2019 storm in which the early period proved challenging for forecasters. There was a clear connection in the ensemble between early storm track and intensity: stronger members moved more northeast initially, although this result did not have much impact on the long-term track. The ensemble results show several key factors determining the early evolution of Dorian. Large-scale divergence northeast of the tropical cyclone (TC) appeared to favor intensification, and this structure was present at model initialization. There was also greater moisture northeast of the TC for stronger members at initialization, favoring more intensification and downshear development of the circulation as these members evolved. This study highlights the complex interplay between synoptic and storm scale processes in the development and intensification of early-stage tropical cyclones.

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Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555219873068 ◽

2019 ◽

Vol 25 (1) ◽

pp. 9-20 ◽

Cited By ~ 2

Author(s):

Olivia W. Lee ◽

Shelley Austin ◽

Madison Gamma ◽

Dorian M. Cheff ◽

Tobie D. Lee ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

High Throughput ◽

High Throughput Screening ◽

Drug Targets ◽

Large Scale ◽

Early Stage ◽

Cancer Cell Line ◽

Hek 293 ◽

Cytotoxic Compounds

Cell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes, and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed the cell-based cytotoxicity of nearly 10,000 compounds in the National Institutes of Health, National Center for Advancing Translational Sciences annotated libraries and more than 100,000 compounds in a diversity library against four normal cell lines (HEK 293, NIH 3T3, CRL-7250, and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity, and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitute a valuable resource for the scientific community and provide insight into the extent of cytotoxic compounds in screening libraries, allowing for the identification and avoidance of compounds with cytotoxicity during high-throughput screening campaigns.

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Separation of Fe from Mn in the Cryogenian Sedimentary Mn Deposit, South China: Insights from Ore Mineral Chemistry and S Isotopes from the Dawu Deposit

Minerals ◽

10.3390/min11050446 ◽

2021 ◽

Vol 11 (5) ◽

pp. 446

Author(s):

Zhiming Xu ◽

Chengquan Wu ◽

Zhengwei Zhang ◽

Jinhong Xu ◽

Xiyao Li ◽

...

Keyword(s):

South China ◽

Large Scale ◽

Early Stage ◽

Sulfur Isotopes ◽

Mineral Chemistry ◽

Manganese Carbonate ◽

Separation Mechanism ◽

Geochemical Properties ◽

Stage Separation ◽

Fe Content

Manganese and Fe have similar geochemical properties in the supergene environment. Separation of Mn and Fe is an important process for the formation of high-grade sedimentary manganese deposits. Large-scale manganese carbonate deposits (total reserves of approximately 700 Mt) were formed during the interglacial of the Sturtian and Marinoan in South China. The orebodies are hosted in the black rock series at the basal Datangpo Formation of the Cryogenian period. The Fe contents in ores range from 1.15 to 7.18 wt.%, with an average of 2.80 wt.%, and the average Mn/Fe ratio is 8.9, indicating a complete separation of Mn and Fe during the formation of manganese ores. Here, we present element data of manganese carbonates and sulfur isotopes of pyrite from the Dawu deposit, Guizhou, China, aiming to investigate the separation mechanism of Mn and Fe and the ore genesis. The Fe in ores mainly occurs as carbonate (FeCO3) and pyrite (FeS2). The Mn, Ca, Mg and Fe exist in the form of isomorphic substitutions in manganese carbonate. The contents of FeCO3 in manganese carbonates are similar in different deposits, with averages of 2.6–2.8 wt.%. The whole-rock Fe and S contents have an obvious positive correlation (R = 0.69), indicating that the difference of whole-rock Fe content mainly comes from the pyrite content. The δ34SV-CDT of pyrite varies from 40.0 to 48.3‰, indicating that the pyrite formed in a restricted basin where sulfate supply was insufficient and the sulfate concentrations were extremely low. Additionally, the whole-rock Fe content is negatively correlated with the δ34S values of the whole-rock and pyrite, with correlation coefficients of −0.78 and −0.83, respectively. Two stages of separations of Mn and Fe might have occurred during the mineralization processes. The reduced seawater became oxidized gradually after the Sturtian glaciation, and Fe2+ was oxidized and precipitated before Mn2+, which resulted in the first-stage separation of Mn and Fe. The residual Mn-rich and Fe-poor seawater flowed into the restricted rift basin. Mn and Fe were then precipitated in sediments as oxyhydroxide as the seawater was oxidized. At the early stage of diagenesis, organic matter was oxidized, and manganese oxyhydroxide was reduced, forming the manganese carbonate. H2S was insufficient in the restricted basin due to the extremely low sulfate concentration. The Fe2+ was re-released due to the lack of H2S, resulting in the second-stage separation of Mn and Fe. Finally, the manganese carbonate deposit with low Fe and very high δ34S was formed in the restricted basin after the Sturtian glaciation.

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Accessing Voluntary HIV Testing in the Construction Industry: A Qualitative Analysis of Employee Interviews from the Test@Work Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084184 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4184

Author(s):

Sarah Somerset ◽

Catrin Evans ◽

Holly Blake

Keyword(s):

Sexual Health ◽

Hiv Testing ◽

Construction Industry ◽

Large Scale ◽

Early Stage ◽

Structured Interview ◽

Health Check ◽

Public Health Issue ◽

Health Awareness ◽

Health Checks

HIV, globally, remains a significant public health issue and community HIV testing can help to identify those with HIV at an early stage of disease. The workplace offers a prime location for provision of opt-in HIV testing as part of wider health promotion initiatives. The construction industry offers a key opportunity for HIV testing provision in a generally male-dominated group exhibiting some risky behaviors related to HIV. The intervention was an optional one-off individual health check with tailored health advice and signposting, offered to the construction workforce in health check events delivered as part of a large-scale multi-site research program called Test@Work. The events were undertaken at 10 participating organizations (21 events across 16 different sites), none had previously offered sexual health awareness or HIV testing to their workforce. Participants were invited to participate in a semi-structured interview following general health checks which included HIV testing. Out of 426 employees attending the health check events, 338 (79.3%) consented to interview on exit. Accessing HIV testing at work was valued because it was convenient, quick, and compatible with work demands. Interviewees identified HIV risks for construction including drug use, high numbers of sexual partners and job-related exposures, e.g., to used needles. Health seeking in construction was limited by stigma and low support, with particular barriers for non-permanent workers. The organization of the construction industry is complex with multiple organizations of different sizes having responsibility for varying numbers of employees. A disparity between organizational policies and employment circumstances is evident, and this generates significant health inequalities. To combat this, we recommend that organizations in the construction sector offer their employees awareness-raising around health behaviors and health protection in packages, such as toolbox talks. We recommend these be accompanied by annual health checks, including sexual health awareness and opt-in workplace HIV testing. This approach is highly acceptable to the workforce in the industry and removes barriers to access to healthcare.

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Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma

10.21203/rs.3.pex-963/v1 ◽

2021 ◽

Author(s):

Lin Huang ◽

Kun Qian

Keyword(s):

Machine Learning ◽

Lung Adenocarcinoma ◽

Cancer Detection ◽

High Performance ◽

Large Scale ◽

Early Cancer ◽

Early Stage ◽

Early Cancer Detection ◽

Ionization Mass ◽

Efficient Test

Abstract Early cancer detection greatly increases the chances for successful treatment, but available diagnostics for some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA for large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning of serum metabolic patterns to detect early-stage LA. We extract direct metabolic patterns by the optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 second using only 50 nL of serum. We define a metabolic range of 100-400 Da with 143 m/z features. We diagnose early-stage LA with sensitivity~70-90% and specificity~90-93% through the sparse regression machine learning of patterns. We identify a biomarker panel of seven metabolites and relevant pathways to distinguish early-stage LA from controls (p < 0.05). Our approach advances the design of metabolic analysis for early cancer detection and holds promise as an efficient test for low-cost rollout to clinics.

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Following the discovery of anti-MDA5 Ab, the clinical understanding of dermatomyositis has been improved

10.31219/osf.io/j2t5f ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Large Scale ◽

Early Stage ◽

Total Mortality ◽

Epidemiological Studies ◽

Respiratory Physiology ◽

Prognostic Indicators ◽

Current Standard ◽

Incurable Disease ◽

Triple Treatment ◽

Risk Categorization

Knowledge about clinically amyopathic dermatomyositis has exploded in the last two decades, especially after the discovery of anti-MDA5 Ab. The disease's likely genesis and pathophysiological processes have been studied in a number of scientific and epidemiological studies. Thanks to a slew of new large-scale cohort studies, the clinical characteristics of MDA5+ DM may be better identified. In addition, several prognostic indicators have been discovered, such as respiratory physiology measures and serum biomarkers, which have helped to enhance risk categorization in clinical practice and restrict the design of future clinical studies. Quantitative evaluation of pulmonary HRCT data may be the trend of imaging testing in MDA5+ DM-ILD. The current standard of treatment for MDA5+ DM-ILD is "triple treatment" with JAK inhibitors, which has been proven in recent trials to significantly improve the survival of early-stage patients. Total mortality in this incurable disease, however, is still shockingly high, especially in advanced-stage patients. There is still a pressing need for a more effective and well-evidenced treatment approach for MDA5+ DM-ILD.

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