Notes

Discovery involving carbapenemase making enterobacteria utilizing an ion delicate field impact transistor sensing unit.
Creating Unsymmetrical-Coordinated Fischer Site in Oxide-Supported Rehabilitation Causes regarding Improved Area Task as well as Stability.
Influence on total well being through multimodality strategy for united states: a new randomised manipulated viability tryout associated with medical procedures vs . absolutely no surgical procedure in multimodality treatment method within most likely resectable phase III-N2 NSCLC (the actual PIONEER tryout).

Primary squamous cell carcinoma (SCC) of the kidney parenchyma is extremely rare, with only seven cases reported to date. Herein, we present a case of primary with colon invasion.

A 61-year-old man presented right flank pain for 5months. Computed tomography (CT) showed multiple renal stones and a necrotic mass in the lower pole of the right kidney, which was suspicious for ascending colon invasion. There was no history of radiation or occupational exposure to chemicals. Radical nephrectomy, right hemicolectomy, and lymph node dissection were performed. The kidneys showed a solid mass with multiple renal stones. The tumor comprised nests of atypical squamous cells and keratin pearls; however, the renal pelvis was normal. 18-Fluorodeoxyglucose-positron emission tomography/CT failed to demonstrate other primary site. Therefore, the patient was diagnosed as primary SCC of the kidney. The patient did not receive adjuvant therapy and was alive during follow-up for 6months after surgery.

SCC of the urinary tract is considered to be the result of squamous metaplasia of the urothelium, which may potentially progress to SCC. Squamous metaplasia may be caused by chronic irritation. However, the mechanism of SCC remains unclear. Although the prognosis of SCC is similar to that of urothelial carcinoma when compared stage for stage, SCC tends to be diagnosed at a more advanced stage.

This is a rare case of kidney SCC with adjacent organ invasion. Additional studies are required to further our understanding of this rare tumor and improve diagnosis and treatment.
This is a rare case of kidney SCC with adjacent organ invasion. Additional studies are required to further our understanding of this rare tumor and improve diagnosis and treatment.Congenital red and green color blindness is the most X-linked recessive disorder in humans caused by deletions or gross structural rearrangements of the visual pigment gene array that lead to altered the functions of visual pigments in their retina differ from normal. The incidence is about 7-10% in male and close association of X-linked recessive disorders (such as hemophilia A, hemophilia B, duchenne muscular dystrophy). However, the traditional genetic analysis methods are time-consuming and low-efficiencies. Therefore, the purpose of the study is to develop a rapid method for genotyping of red and green pigment genes. We describe herein the first method for simultaneous evaluation of ten exons in the red and green pigment genes for genetic analysis. A forward specific primers with identifiable universal fluorescent multiplex PCR (FSIUFM-PCR) method utilized one universal primer (containing two universal non-human sequences) and forward specific primers in the multiplex PCR reaction system for simultaneously fluorescent labeling of eleven gene fragments (ten exons in red and green pigment genes and one internal standard). All the PCR products were analyzed on capillary electrophoresis with short-end injection, which had the advantage of high resolution and rapid separation. Of all 80 detected individuals, 7 subjects with color vision deficiencies (including 3 subjects only had red exons 1-5, 4 subjects had a specific red-green or green-red hybrid gene and 73 subjects with normal color vision). All genotyping results showed good agreement with DNA sequencing data. This method provided a better potential technique for genotyping and identifying of red and green pigment genes. In addition, FSIUFM-PCR method will be useful in many fields, such as diagnosis of diseases, analysis of polymorphisms and quantitative assay.In the decades since female social dominance was first described in strepsirrhine primates, researchers have sought to uncover the proximate and ultimate explanations for its development. In the females of various female-dominant species, androgens have been implicated as regulators of behavior and/or predictors of seasonal fluctuations in aggression (the 'Female Masculinization Hypothesis'). Males, more generally, respond to changing social demands via seasonal fluctuations in androgen-mediated behavior (the 'Challenge Hypothesis'), that may also entail changes in activation of the hypothalamic-pituitary-adrenal axis. Here, we explore if androgens, glucocorticoids, and intersexual behavior fluctuate seasonally in the female-dominant, blue-eyed black lemur (Eulemur flavifrons), with potential consequences for understanding female aggression and male deference. Across two studies conducted during the breeding and nonbreeding seasons, we assessed rates of mixed-sex, dyadic social behavior (aggression and affiliation) and concentrations of fecal glucocorticoid metabolites (Study 1) and serum sex hormones (androstenedione, testosterone, and estradiol; Study 2). Our results align with several predictions inspired by the Female Masculinization and Challenge Hypotheses for intersexual relations During the breeding season, specifically, both aggression and androstenedione peaked in females, while female-initiated affiliation decreased, potentially to facilitate female resource access and reproductive control. By comparison, all target hormones (androgens, estrogen, and glucocorticoids) peaked in males, with glucocorticoid concentrations potentially increasing in response to the surge in female aggression, and unusually high estrogen concentrations year-round potentially facilitating male deference via male-initiated affiliation. These results suggest complex, seasonally and hormonally mediated behavior in Eulemur flavifrons.In this study, pellet-type biofilter media was developed with rice husk and applied in a wet scrubber system for odor removal. The lab-scale bioscrubber system was operated for 200 days to evaluate odorous gas removal (i.e., NH3, H2S, methyl mercaptan, and dimethyl sulfide), and the removal mechanism of odor gases was studied by analyzing the behavior of nitrogen and sulfur compounds in circulation water of bioscrubber system. The rice husk pellets supplied the organic carbon source and phosphoric acid necessary for microbial growth, allowing the system to continue successfully for 200 days without any maintenance technology. By analyzing the behavior of the nitrogen and sulfur compounds in the circulation water, we confirmed that the odor gas removal resulted from various mechanisms, including adsorption and biodegradation. learn more Ammonia gas was absorbed by the rice husk pellets and accumulated in the circulation water as nitrite under conditions of sufficient alkalinity and above pH 7. Conversely, when the alkalinity and pH decreased, nitrite was rapidly converted to nitrate. However, H2S gas was oxidized to sulfate and continuously accumulated in the circulation water regardless of the pH and alkalinity. In addition, it was confirmed that the decrease in nitrate in the bioscrubber system was due to heterotrophic denitrification by the organic carbon source supply and autotrophic denitrification by sulfur gas. During the operation of the rice husk pellet bioscrubber for 8 months, under low solubility condition, more than 99% of NH3 and H2S were removed and about 85% of methyl mercaptan (MM) and dimethyl sulfide (DMS) were removed.Ecological infrastructure (EI) planning can promote regional nature conservation efficiency and enhance ecosystem functions. link2 Watershed-scale EI research is a research hotspot in landscape ecology. This study proposed a method framework to develop EI planning in large river basins based on the connectivity of ecological processes and the integrity of ecosystems in the whole basin, as well as the typical ecological problems in each sub-basin. The framework included three parts determining the protective EI i.e. the spatial range of the watershed ecological networks; quantifying and mapping the functional EI i.e. the typical ecosystem functions within each sub-basin; and integrating ecological networks and key ecosystem function area into an EI planning based on their spatial overlap and functional synergy. The method framework was applied in the Yellow River Basin. Results showed that spatial range of ecological networks of the basin accounted for 35.8% of the study area. Key ecosystem function area including ee conservation in the watershed and promote the specific ecosystem functions. It is also applicable to river management and watershed territorial spatial planning in other large river basins.The Virtual Special Issue entitled "Tackling Water Security" is mainly focused on water availability, water quality, management, governance, biotic or abiotic emerging contaminants and policy development in the Anthropocene. link= learn more The issue is further dedicated to highlight the new opportunities and approaches to elevate the efficiency of water treatment and wastewater reuse. It has undergone an open call for papers and rigorous peer-review process, where each submission has been evaluated by the panel of experts. 43 articles have been selected from 85 submissions that represents the ongoing research and development activities. The message that emerged explicitly from nearly a hundred submissions to this special issue is that there is an urgent global need for cross-cutting approaches for the rational, quick, cost-effective and sustainable solutions for tackling water-security in the Anthropocene.China's forests were severely degraded by human activities during the latter half of the 20th century. Therefore, China enacted ambitious programs of natural forest protection and afforestation to protect and expand forests. Yet it is unclear how the programs, especially the designation of forest reserves, have affected forest cover and fragmentation. We evaluated the effectiveness of China's national forest reserves designated since 1990 in conserving forests, by analyzing four forest metrics (i.e., percentage forest cover, mean forest patch size, mean forest patch radius of gyration, and forest patch cohesion index) derived from a newly produced 30 m annual China land cover dataset from 1990 to 2019. We found that overall forest cover increased and fragmentation decreased from baseline years, when reserves were designated, to 2019 in both reserves and their surrounding areas, and only the increase in forest cover relative to baseline was significantly greater in reserves than in surrounding areas. The designation time of reserves under national protection had no considerable effect on changes in the four metrics, but for zonation, the core zone showed a significantly higher increase in forest patch cohesion index relative to baseline than the buffer and transition zones. Nevertheless, forest cover declined and fragmentation increased in highly forested reserves, suggesting destructive human activities and ineffective management. Thus, forest protection and regeneration programs were moderately successful. We recommend that there is significant improvement needed to ensure greater protection of existing forests and reduction of threats to promote effective management.Adsorption is the primary mechanism of antibiotic removal in wastewater treatment plants, wherein the extracellular polymeric substances (EPS) of the activated sludge play an important role. Due to their complex characteristics, the effect of EPS components on antibiotic adsorption is unknown. Therefore, in this study, the role of main components of EPS in antibiotic adsorption was explored using enzymatic treatment. The results revealed that proteinase K and α-amylase can efficiently hydrolyse the proteins and polysaccharides of EPS. The protein content of EPS reduced from 31.25 mg/g VSS to 21.53, 18.75, and 10.76 mg/g VSS, after treatment with proteinase K, α-amylase and their combination, respectively; the polysaccharides content also observed a similar decrease from 15.20 mg/g VSS to 8.22, 7.83, and 6.03 mg/g VSS, respectively. The humic substance in EPS was stable during enzymatic treatment. The equilibrium adsorption capacity of activated sludge treated by enzyme for trimethoprim (TMP)- a typical antibiotic, was significantly increased from 2.19 μg/g VSS to 4.68, 5.34, and 8.36 μg/g VSS after treatment with proteinase K, α-amylase and their mixture. The adsorption process was adequately described by pseudo-second-order kinetic model. A multivariable linear regression model was subsequently used to quantify the adsorption capacity of activated sludge for TMP considering the concentration of EPS components. The modelling and validated results showed that the model could satisfactorily predict the TMP adsorption capacity. The results of this study can provide new insights into the role of EPS on antibiotic transformation in biological wastewater treatment systems.Population projection models are important tools for conservation and management. They are often used for population status assessments, for threat analyses, and to predict the consequences of conservation actions. Although conservation decisions should be informed by science, critical decisions are often made with very little information to support decision-making. Conversely, postponing decisions until better information is available may reduce the benefit of a conservation decision. When empirical data are limited or lacking, expert elicitation can be used to supplement existing data and inform model parameter estimates. The use of rigorous techniques for expert elicitation that account for uncertainty can improve the quality of the expert elicited values and therefore the accuracy of the projection models. One recurring challenge for summarizing expert elicited values is how to aggregate them. Here, we illustrate a process for population status assessment using a combination of expert elicitation and dataidered. We discuss the benefits and limitations associated with each method and their relevance to the population status assessment. We note a difference in the temporal scope or inference between the literature-based estimates that provided insights about historical changes, whereas the expert-based estimates were forward looking. Therefore, conducting an expert-elicitation in addition to using parameter estimates from the literature improved our understanding of our species of interest.Climate change is projected to transform US agriculture, particularly in places reliant on limited irrigation water resources. As water demand and scarcity increase simultaneously over the coming decades, water managers and growers will need to optimize water use on their irrigated lands. Understanding how growers maintain high yields in arid, water stressed places, while conserving water, is of key importance for the future of US agriculture in the West. We explore water use management and trends in irrigated agriculture in the Western US using operator-level USDA-NASS Farm and Ranch Irrigation Survey/Irrigation and Water Management Survey data aggregated for the first time to the county-scale. In this exploration, we build the first county-level, openly accessible dataset linking farm(er) characteristics to irrigation behaviors in the West. We find notable spatial and temporal variability in Western irrigation practices, with neighboring counties exhibiting large differences in efficiency, water use, and crop yields, as well as in the sources of information, scheduling methods, and technological improvements employed. To produce effective management initiatives in the West, we call for the express and open dissemination of USDA irrigation data at sub-state scales. These data will contribute to our understanding of irrigated production and could support a pathway that will prepare growers for a more resilient agricultural future.Sites polluted by dense non-aqueous phases (DNAPLs) constitute an environmental concern. In situ chemical oxidation (ISCO) application is limited since oxidation often occurs in the aqueous phase and contaminants are usually hydrophobic. In this work, ISCO enhanced by the surfactant addition (S-ISCO) was studied for a complex liquid mixture of chlorinated organic compounds (COCs) using persulfate (PS) activated by alkali (PSA) as oxidant and Emulse-3® as a commercial non-ionic surfactant. The reaction between E3 and PSA was investigated in the absence and presence of solubilized COCs in the following concentration ranges COCs 1.2-50 mM, PS 84-336 mM, NaOHPS molar ratio of 2, and surfactant concentration 1-10 g·L-1. In the experiments carried out in the absence of COCs, the unproductive consumption of PS was studied. The higher the surfactant concentration, the lower the ratio PS consumed to the initial surfactant concentration due to more complex micelle structures hindering the oxidation of surfactant molecules. This hindering effect was also noticed in the oxidation of solubilized COCs. The reduction of chlorobenzenes by PSA was negligible at surfactant concentrations above 2.5 g·L-1, independently of the COCs concentration solubilized. Instead, a surfactant concentration of about 1 and PS concentration of 168 mM yielded a significant decrease in the time required to abate a mass of DNAPL, compared with an ISCO process, with a bearable increase in the unproductive consumption of PS.China has been experiencing serious and recurrent incidences of air pollution in recent years. The frequency and timespans of such incidences are uncertain because of variable urban weather conditions, especially temperature, that inhibit the productivity of manufacturing companies. Matching data about listed manufacturing companies in China's Yangtze River Delta urban cluster from 2003 to 2018 with data on urban air pollution and weather, we explored the effects of air pollution on corporate productivity and the moderating role of temperature. We found that air pollution significantly inhibited the productivity of these companies, which decreased by about 0.1% for 1% increase in the concentration of PM2.5. Regarding industry heterogeneity, high-energy-consumption and low-technology manufacturing industries were more sensitive to the negative effects of air pollution. Furthermore, we concluded that low temperatures played an important role in causing significant increases in the negative effects of air pollution. In the fall and winter (October to January), the lower the temperatures resulted in stronger inhibitory effects of air pollution on corporate productivity. When the average daily temperature is 0°C-3°C, the moderating effects of temperature are even more obvious. To minimize the inhibitory effects of air pollution on productivity, governments and companies should implement positive adaptions to simultaneously confront air pollution and temperature change.
The purpose of this review was to explore how professional identity is formed and shaped within pre-registration physiotherapy curricular.

A scoping review using the PRISMA guidelines from the Joanna Briggs Institute to capture a range of evidence describing how professional identity has been formed and shaped in pre-registration physiotherapy curricular.

Databases searched included PubMed 1996-Present, Embase 1974-Present, CINAHL 1961-Present, ProQuest Health and Medical Collection 1938-Present and Google Scholar (2004-Present). Additional studies were identified by scanning reference lists and hand searching for relevant articles.

The research team collaboratively designed the data charting table and two project leads independently extracted and screened the data as per guidance from the Joanna Briggs Institute Reviewers Manual. A meta-synthesis was conducted in this scoping review to identify common themes from qualitative research to provide a deeper understanding of literature. To ensure feasibilysiotherapy curricular involved to assist in shaping and forming professional identity in pre-registration physiotherapy students. The results of this review can provide a foundation level into the understanding of what professional identity is, although further research is required to understand how it could be best implemented in pre-registration physiotherapy curricular.FMS-like tyrosine kinase 3 (FLT3) enzyme overexpression and mutations are the most common molecular abnormalities associated with acute myeloid leukemia (AML). In addition, recent studies investigated the role of tropomyosin receptor kinase A (TrKA) enzyme fusions in promoting AML growth and survival. Based on these premises, targeting both kinases using dual inhibitors would constitute a promising therapeutic approach to target resistant AML. Guided by ligand-based design and structure simplification of the FLT3 inhibitor, quizartinib, we developed a benzimidazole-based small molecule, 4ACP, that exhibited nanomolar activity against wild-type FLT3, FLT3-Internal tandem duplications (FLT3-ITD), and FLT3-D835Y (FLT3-TKD) mutation (IC50 = 43.8, 97.2, and 92.5 nM respectively). Additionally, 4ACP demonstrated potent activity against colon cancer KM12 cell line (IC50 = 358 nM) and subsequent mechanistic deconvolution identified TrKA enzyme as a second plausible target (IC50 = 23.6 nM) for our compound. 4ACP manifested preferential antiproliferative activity against FLT3-ITD positive AML cell lines (MV4-11 IC50 = 38.8 ± 10.7 nM and MOLM-13 IC50 = 54.9 ± 4.1 nM), while lacking activity against FLT3-ITD negative AML cell lines. Western blot analysis confirmed 4ACP ability to downregulate ERK1/2 and mTOR signaling downstream of FLT3-ITD in AML cells. Furthermore, 4ACP prompted apoptotic and necrotic cell death and G0/G1 cell cycle arrest as indicated by cell cycle analysis. 4ACP did not show cytotoxic effects on normal BNL and H9c2 cells and demonstrated decreased activity against c-Kit enzyme, hence, indicating lower probability of synthetic lethal toxicity and a relatively safer profile. In light of these data, 4ACP represents a novel FLT3/TrKA dual kinase inhibitor for targeted therapy of AML.Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery. Solubility improvement of poorly soluble lead compounds without losing potency is a challenging task for the medicinal chemist in a drug discovery setup. Solubility is an important factor not only to dissipate or liquefy a substance but also to attain an optimal concentration of drug in systemic circulation required for the desired therapeutic effect. It has been estimated that more than forty percent of newly developed molecules are practically insoluble in water. Molecules with poor solubility not only cause difficulty for in vitro and in vivo assays but also add significant burdens to drug development in the form of longer time taken and increased cost to optimize the solubility. To tackle this problem, different techniques are being used such as physical, chemical, and miscellaneous methods to enhance solubility. Among them, the medicinal chemistry approach focussed on structural modification is a versatile and unique approach in way that it can also improve other pharmacokinetic/physicochemical parameters simultaneously. In this review, we have begun with brief introduction of solubility and its role followed by recent successful examples of different structural modification tactics reported in the literature including synthesis of prodrugs, hydrophilic and ionizable group insertion, addition & removal of hydrogen bonding, bioisosterism, disruption of molecular symmetry and planarity. Moreover, we have included a section on the obstacles in the solubility optimization and also summarised different in silico tools with potential application in solubility prediction. Overall, this review encompasses various successfully used solubility optimization examples using structure modification.
Systemic amyloidosis is a group of diseases characterized by the deposition of amyloid protein in multiple organs throughout the body and causing their dysfunction. As amyloid deposition is observed at an early phase and is highly specific to systemic amyloidosis, noninvasive detection of amyloid is considered useful for the early diagnosis of systemic amyloidosis. In this study, we designed and synthesized a novel radiolabeled amyloid imaging probe, sodium (E)-4-amino-3-((4-(6-iodobenzothiazol-2-yl)phenyl)diazenyl)naphthalene-1-sulfonate (1), which combines two amyloid-binding compounds, thioflavin-T and Congo-red, and evaluated its effectiveness in diagnosing amyloidosis.

A tributyltin precursor was synthesized through a 5-step reaction from 2-amino-6-bromobenzothiazole, and [
I]1 was synthesized by an iododestannylation reaction with a tributyltin precursor. Mouse models of amyloid A (AA) amyloidosis, a type of systemic amyloidosis, were prepared by intraperitoneal injection of amyloid-enhancing factod 1 as a nuclear imaging probe for diagnosing AA amyloidosis.The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18 y, n = 28,871, 51% female) without inflammation [C-reactive protein (CRP) 6.6%, suggestive of a quiescent, balanced immune system.
Serological assays for SARS-CoV-2 have a critical role not only in diagnosis of COVID-19, but also in assessing the degree and duration of response of specific antibodies against the virus obtained through infection or vaccination. We present the results obtained with a competitive immunoenzymatic method (Chorus SARS-CoV-2 "Neutralizing" Ab) for quantitative determination of total neutralizing anti-S1 SARS-CoV-2 antibodies (IgG, IgM, and IgA) in human serum obtained on a disposable device with the Chorus TRIO instrument using a recombinant strong neutralizing antibody as tracer.

A total of 694 sera were evaluated for SARS-CoV-2 neutralizing antibodies 407 uninfected, 201 symptomatic subjects, 37 post-infection patients, and 49 vaccinated. Sixty-eight of the previous sera were used to compare the Chorus SARS-CoV-2 "Neutralizing" Ab results with those obtained with micro-neutralization of the Alpha and original variants. A set of 74 positive sera for other respiratory infections were analyzed to evaluate the possible cross reaction to SARS-CoV-2 virus.

Of the 694 samples, only 3 had discordant results between micro-neutralization and values measured by Chorus SARS-CoV-2 "Neutralizing" Ab 1 false negative and 2 false positives. Values of sensitivity and specificity were very high percent positive agreement (sensitivity) 99.6% (95% CI 97.7 - 99.9) and percent negative agreement (specificity) 99.6% (95% CI 98.0 -99.9). Concordance was high with a Gwet's Ac1 of 0.992. No significant differences were observed between the alpha and original variants.

The Chorus SARS-CoV-2 "Neutralizing" Ab test was highly sensitive and specific, and varies from most other currently available tests since it analyzes only antibodies with viral-neutralizing capacity.
The Chorus SARS-CoV-2 "Neutralizing" Ab test was highly sensitive and specific, and varies from most other currently available tests since it analyzes only antibodies with viral-neutralizing capacity.
To identify, evaluate, and summarise evidence about advanced practice nurses' (APNs') job satisfaction in cancer care and its related factors.

A systematic review was performed including a narrative synthesis. Relevant evidence was identified from searches of three databases Medline (PubMed), EBSCO (CINAHL), and PsychInfo. This systematic review searched for relevant articles published in English between 2000 and 2020. A structured process according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was followed. link2 The articles critical appraisal was based on the Mixed-Methods Appraisal Tool. Narrative data synthesis was based on the extracted data (study characteristics, type of questionnaire, level of job satisfaction, related factors, and risk of bias).

Just four articles met the inclusion criteria and were included in the systematic review. Job satisfaction of APNs providing cancer care in different care settings varied from low to high. Satisfying factors werand patient group-related factors on job satisfaction.
Artificial Intelligence (AI), in particular, machine learning (ML) has shown promising results in coronary artery disease (CAD) or cardiovascular disease (CVD) risk prediction. Bias in ML systems is of great interest due to its over-performance and poor clinical delivery. The main objective is to understand the nature of risk-of-bias (RoB) in ML and non-ML studies for CVD risk prediction.

PRISMA model was used to shortlisting 117 studies, which were analyzed to understand the RoB in ML and non-ML using 46 and 32 attributes, respectively. The mean score for each study was computed and then ranked into three ML and non-ML bias categories, namely low-bias (LB), moderate-bias (MB), and high-bias (HB), derived using two cutoffs. Further, bias computation was validated using the analytical slope method.

Five types of the gold standard were identified in the ML design for CAD/CVD risk prediction. The low-moderate and moderate-high bias cutoffs for 24ML studies (5, 10, and 9 studies for each LB, MB, and HB) and 14 non-ML (3, 4, and 7 studies for each LB, MB, and HB) were in the range of 1.5 to 1.95. Bias
<Bias
by ∼43%. A set of recommendations were proposed for lowering RoB.

ML showed a lower bias compared to non-ML. For a robust ML-based CAD/CVD prediction design, it is vital to have (i) stronger outcomes like death or CAC score or coronary artery stenosis; (ii) ensuring scientific/clinical validation; (iii) adaptation of multiethnic groups while practicing unseen AI; (iv) amalgamation of conventional, laboratory, image-based and medication-based biomarkers.
ML showed a lower bias compared to non-ML. For a robust ML-based CAD/CVD prediction design, it is vital to have (i) stronger outcomes like death or CAC score or coronary artery stenosis; (ii) ensuring scientific/clinical validation; (iii) adaptation of multiethnic groups while practicing unseen AI; (iv) amalgamation of conventional, laboratory, image-based and medication-based biomarkers.Mechano-electric feedbacks (MEFs), which model how mechanical stimuli are transduced into electrical signals, have received sparse investigation by considering electromechanical simulations in simplified scenarios. In this paper, we study the effects of different MEFs modeling choices for myocardial deformation and nonselective stretch-activated channels (SACs) in the monodomain equation. We perform numerical simulations during ventricular tachycardia (VT) by employing a biophysically detailed and anatomically accurate 3D electromechanical model for the left ventricle (LV) coupled with a 0D closed-loop model of the cardiocirculatory system. We model the electromechanical substrate responsible for scar-related VT with a distribution of infarct and peri-infarct zones. Our mathematical framework takes into account the hemodynamic effects of VT due to myocardial impairment and allows for the classification of their hemodynamic nature, which can be either stable or unstable. By combining electrophysiological, mechanical and hemodynamic models, we observe that all MEFs may alter the propagation of the transmembrane potential. In particular, we notice that the presence of myocardial deformation in the monodomain equation may change the VT basis cycle length and the conduction velocity but do not affect the hemodynamic nature of the VT. Finally, nonselective SACs may affect VT stability, by possibly turning a hemodynamically stable VT into a hemodynamically unstable one.Silymarin is used as a hepatoprotective agent since ancient times which could be via its potent anti-oxidant effect. However, the mode of silymarin for the hepatoprotective effect has not been established with the targets involved in hepatic cirrhosis. The present study investigated the multiple interactions of the flavonolignans from Silybum marianum with targets involved in hepatic cirrhosis using a series of system biology approaches. Chemo-informative tools and databases i.e. DIGEP-Pred and DisGeNET were used to predict the targets of flavonolignans and proteins involved in liver cirrhosis respectively. Further, STRING was used to enrich the protein-protein interaction for the flavonolignans-modulated targets. Similarly, molecular docking was performed using AutoDock Vina. Additionally, molecular dynamics simulation and MM-PBSA calculations were carried out for the lead-hit complexes by GROMACS. Thirteen flavonolignans were identified from S. marianum, in which silymonin exhibited the highest drug-likeness score i.e. 1.09. Similarly, CTNNB1 was found to be regulated by the 12 different flavonolignans and was majorly expressed within the compound(s)-protein(s)-pathway(s) network. Further, silymonin had the highest binding affinity; binding energy -9.2 kcal/mol with the CTNNB1 and formed very stable hydrogen bond interactions with Arg332, Ser336, Lys371, and Arg475 throughout 100 ns molecular dynamic production run. link3 The binding free energy of CTNNB1-silymonin complex was found to be -15.83 ± 2.71 kcal/mol. The hepatoprotective property of S. marianum may be due to the presence of silymonin and silychristin; this could majorly modulate CTNNB1, HMOX1, and CASP8 in combination with other flavonolignans. Our findings further suggest designing the in-vitro and in-vivo studies to validate the interaction of flavonolignans with identified targets to strengthen present findings of S. marianum as a hepatoprotective..Atrial fibrillation (AF) is the most common supraventricular cardiac arrhythmia, resulting in high mortality rates among affected patients. AF occurs as episodes coming from irregular excitations of the ventricles that affect the functionality of the heart and can increase the risk of stroke and heart attack. Early and automatic prediction, detection, and classification of AF are important steps for effective treatment. For this reason, it is the subject of intensive research in both medicine and engineering fields. The latter research focuses on three axes prediction, classification, and detection. Knowing that AF is often asymptomatic and that its episodes are often very short, its automatic early detection is a very complicated but clinically important task to improve AF treatment and reduce the risks for the patients. This article is a review of publications from the past decade, focusing on AF episode prediction, detection, and classification using wavelets and artificial intelligence (AI). Forty-five articles were selected of which five are about AF in general, four articles compare accuracy, recall and precision between Fourier transform (FT) and wavelets transform (WT), and thirty-six are about detection, classification, and prediction of AF with WT 15 are based on deep learning (DL) and 21 on conventional machine learning (ML). Of the thirty-six studies, thirty were published after 2015, confirming that this particular research area is very important and has great potential for future research.The present study mimicked daily life exposure to plastic food package bags and evaluated its effects on the reproductive and neurobehavioral responses using zebrafish model. Gas chromatography-mass spectrometer (GC/MS) full scan analysis revealed that phthalic acid, isobutyl octyl ester (DEHP) and its metabolites were the main leachate from plastic bags. Our results demonstrated that during the eight weeks exposure, leaching from plastic bags treated with boiling water (P-high group) significantly affected the spawn egg production, embryo hatching and larval malformation rate. Cross-spawning trails between zebrafish collected from the controls and P-high group at the end of eight weeks showed that these adverse effects were more severe in the offspring derived from paternal exposure than those derived from the maternal exposure, suggesting leached chemicals may have a more pronounced effect in sperm than in eggs. In addition, P-high group male testis weight, sperm motility and sperm swimming velocities were decreased significantly. After eight weeks treatment, neurobehavioral tests demonstrated significant changes in the swimming speed during free swimming and light-dark stimulation in the adult zebrafish from P-high group, with the effects being more severe in the males than females. P-high group males also showed altered response in the light/dark explore and mirror attacks assays.In this work, the use of chemical reduction combined with microbial stabilization to remediate Cr(VI) in contaminated soil was systematically investigated. The effectiveness, phytotoxicity and microbial diversity resulting from the combination of ferrous sulfate with microbial stabilization by biogas solid residue (BSR) were determined. The stabilization experiments showed that the optimum Cr(VI) conversion rate of 99.92% was achieved with an Fe (II)/Cr(VI) molar ratio of 31, a BSR dose of 5.2% (wt), and a water content of 40%. Under these conditions, the residual Cr(VI) content was 0.80 mg/kg, which satisfied the risk screening value (≤ 5.7 mg/kg) for soil contamination of land for general development in China. The remaining Cr(VI) level was stable for 90 days during the chemical reduction and biogenic stabilization process. Moreover, Zucconi test analysis suggested that the soil phytotoxicity to Brassica campestris L. disappeared. The results of microbial diversity analysis indicated that the bacterial community changed significantly during chemical reduction and microbial stabilization processes, and Bacillus, Pseudomonas and Psychrobacter may participate in the reduction of Cr(VI) into Cr(III).long non-coding RNAs (lncRNAs), as tumor suppressors or oncogenes, have been identified to play key roles in tumorigenesis. The present study explored the roles and potential mechanisms of LINC00960 in osteosarcoma (OS). In vitro study showed that silencing LINC00960 inhibited proliferation, migration and invasion of 143B and MG63. In vivo study demonstrated that knockdown of LINC00960 repressed tumor growth. Further investigation revealed that LINC00960 could regulate SALL4 by sponging miR-107 to promote the progression of OS. Together, LINC00960 is a tumor oncogene in the development and prognosis of OS, which may be a new therapeutic target for OS.Intrinsically photosensitive retinal ganglion cells (ipRGCs) are able to synthesize the photosensitive protein melanopsin, which is involved in the regulation of circadian rhythms, the papillary light reflex and other nonimaging visual functions. To investigate whether ipRGCs are involved in mediating the light modulation of sleep-wakefulness in rodents, melanopsin knockout mice (MKO), melanopsin-only mice (MO) and coneless, rodless, melanopsin knockout mice (TKO) were used in this study to record electroencephalogram and electromyography variations in the normal 1212 h lightdark cycle, and 1 h and 3 h light pulses were administered at 1 h after the light was turned off. In the normal 1212 h light-dark cycle, the WT, MKO and MO mice had a regular day-night rhythm and no significant difference in wakefulness, rapid eye movement (REM) or nonrapid eye movement (NREM) sleep. However, TKO mice could not be entrained according to the light-dark cycle and exhibited a free-running rhythm. Extending the light pulse durations significantly changed the sleep and wakefulness activities of the WT and MO mice but did not have an effect on the MKO mice. These results indicate that melanopsin significantly affects REM and NREM sleep and that ipRGCs play an important role in light-induced sleep in mice.We screened pre-approved drugs for the survival of the Hu5/KD3 human myogenic progenitors. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, promoted the proliferation and survival of Hu5/KD3 cells. Meclozine increased expression of MyoD, but reduced expression of myosin heavy chain and suppressed myotube formation. Withdrawal of meclozine, however, resumed the ability of Hu5/KD3 cells to differentiate into myotubes. We examined the effects of meclozine on mdx mouse carrying a nonsense mutation in the dystrophin gene and modeling for Duchenne muscular dystrophy. Intragastric administration of meclozine in mdx mouse increased the body weight, the muscle mass in the lower limbs, the cross-sectional area of the paravertebral muscle, and improved exercise performances. Previous reports show that inhibition of phosphorylation of ERK1/2 improves muscle functions in mouse models for Emery-Dreifuss muscular dystrophy and cancer cachexia, as well as in mdx mice. We and others previously showed that meclozine blocks the phosphorylation of ERK1/2 in cultured cells. We currently showed that meclozine decreased phosphorylation of ERK1/2 in muscles in mdx mice but not in wild-type mice. This was likely to be one of the underlying mechanisms of the effects of meclozine on mdx mice.Studies have shown that the higher prevalence of colorectal cancers among patients with inflammatory bowel disease. Thus, proinflammatory stimulus due to a high-fat diet may impose a higher risk on the development of colorectal cancer. In the present study, we applied a transcriptomic approach to characterize the molecular mechanism(s) by which high-fat feeding aggravates colitis-associated colorectal cancer (CAC). A high-fat diet was supplied in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model for 10 weeks and then the severity of CAC and global gene expression in colon were assessed. Although consumption of high-fat diet did not significantly aggravate CAC, it substantially changed gene expression profile in colon. In AOM/DSS treated mice (AD group) and AD mice fed a high-fat diet (AD + HF group), 34 and 54 DEGs were enriched in 'pathways in cancer', respectively. Notably, high-fat diet upregulated the expression of genes associated with spliceosome and ribosome biogenesis, and downregulated the expression of genes associated with lipid catabolism in mice treated with AOM/DSS. In addition, we identified that DEGs between the AD and AD + HF groups, were enriched in 'metabolic pathways', especially amino acid and nucleotide metabolism. Taken together, this study provides the molecular mechanism in understanding the high-fat diet-mediated CAC development.
Atherosclerosis is driven by an inflammatory process of the vascular wall. The novel orphan G-protein coupled receptor 5B of family C (GPRC5B) is involved in drosophila sugar and lipid metabolism as well as mice adipose tissue inflammation. Here, we investigated the role of GPRC5B in the pro-atherogenic mechanisms of hyperglycemia and vascular inflammation.

Immortalized and primary endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) were used for stimulation with high glucose or different cytokines. Adenoviral- or plasmid-driven GPRC5B overexpression and siRNA-mediated knockdown were performed in these cells to analyze functional and mechanistic pathways of GPRC5B.

In ECs and VSMCs, stimulation with high glucose, TNFα or LPS induced a significant upregulation of endogenous GPRC5B mRNA and protein levels. GPRC5B overexpression and knockdown increased and attenuated, respectively, the expression of the pro-inflammatory cytokines TNFα, IL-1β, IL-6 as well as the pro-atherogenic vascular adhesipendent positive feedback loop via Fyn and NFκB. Thus, GPRC5B warrants further attention as a novel pharmacological target for the treatment of vascular inflammation and possibly atherogenesis.Viral respiratory infection causes inflammatory lung disease. Chitinase 3-like 1 (CHI3L1) contributes to airway inflammation, but its role in human airway epithelial cells following viral infection is unclear. Thus, we investigated whether CHI3L1 regulates inflammatory responses caused by viral infections in airway epithelial cells. Human bronchial epithelial cells, BEAS-2B, were stimulated with a synthetic analog of viral double-stranded RNA, polyinosinicpolycytidylic acid (poly(IC)). To confirm the specific role of CHI3L1, CHI3L1 was knocked down in BEAS-2B cells using shRNA lentivirus. The expression of CHI3L1 and proinflammatory cytokines such as IL-8 and phosphorylation of mitogen-activated protein kinase (MAPK) pathways were analyzed. In addition to poly(IC), BEAS-2B cells were infected with the human respiratory syncytial virus (RSV) A2 strain, and CHI3L1 and IL-8 expression was analyzed. Stimulating the cells with poly(IC) increased CHI3L1 and IL-8 expression, whereas IL-8 expression was abrogated in CHI3L1 knockdown BEAS-2B cells. learn more Poly(IC) stimulation of BEAS-2B cells resulted in phosphorylation of MAPK pathways, and inhibition of MAPK pathways significantly abolished IL-8 secretion. Phosphorylation of MAPK pathways was diminished in CHI3L1 knockdown BEAS-2B cells. Infection with RSV increased CHI3L1 and IL-8 expression. IL-8 expression induced by RSV infection was abrogated in CHI3L1 knockdown cells. In conclusion, CHI3L1 may be involved in IL-8 secretion by regulating MAPK pathways during respiratory viral infections in airway epithelial cells.The advent of high-throughput sequencing has allowed to profoundly interrogate the molecular landscape of non-small cell lung cancer (NSCLC) in the last years. These findings constitute the opportunity to better stratify these patients in order to address specific treatments to well-defined oncogene-restricted subgroups. Among them, BRAF-mutated lung cancers represent around 4% of NSCLC, thus identifying a clinically relevant population that should be aptly managed. Pivotal phase II trials have demonstrated the efficacy of combinatorial treatment - dabrafenib plus trametinib, targeting both BRAF and MEK - for patients harboring V600E mutations, making this specific BRAF alteration a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, around half of BRAF+ NSCLC patients remain orphan of targeted approaches. Here we review the available evidence, mainly from a clinical perspective, of therapeutic strategies for both V600E and non-V600 patients, in terms of small molecule, immune checkpoint inhibitors and forthcoming integrated strategies. link3 Looking at on-going clinical trials, a special attention is dedicated to emergent molecules and combinatorial strategies that not only will improve outcomes of classical V600E, but also will make concrete the chance of tailored treatments for the majority of BRAF-mutated patients.Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.Repeated interactions with automated systems are known to affect how agents experience their own actions and choices. The present study explores the possibility of partially restoring sense of agency in operators interacting with automated systems by providing additional information about the system's decision, i.e. its confidence. To do so, we implemented an obstacle avoidance task with different levels of automation and explicability. Levels of automation were varied by implementing conditions in which the participant was free or not free to choose which direction to take, whereas levels of explicability were varied by providing or not providing the participant with the system's confidence in the direction to take. We first assessed how automation and explicability interacted with participants' sense of agency, and then tested whether increased self-agency was systematically associated with greater confidence in the decision and improved system acceptability. The results showed an overall positive effect of system assistance. Providing additional information about the system's decision (explicability effect) and reducing the cognitive load associated with the decision itself (automation effect) was associated with stronger sense of agency, greater confidence in the decision, and better performance. In addition to the positive effects of system assistance, acceptability scores revealed that participants perceived "explicable" systems more favorably. These results highlight the potential value of studying self-agency in human-machine interaction as a guideline for making automation technologies more acceptable and, ultimately, improving the usefulness of these technologies.In the contexts of language learning and music processing, hand gestures conveying acoustic information visually influence perception of speech and non-speech sounds (Connell et al., 2013; Morett & Chang, 2015). Currently, it is unclear whether this effect is due to these gestures' use of the human body to highlight relevant features of language (embodiment) or the cross-modal mapping between the visual motion trajectories of these gestures and corresponding auditory features (conceptual metaphor). To address this question, we examined identification of the pitch contours of lexical tones and non-speech analogs learned with pitch gesture, comparable dot motion, or no motion. Critically, pitch gesture and dot motion were either congruent or incongruent with the vertical conceptual metaphor of pitch. Consistent with our hypotheses, we found that identification accuracy increased for tones learned with congruent pitch gesture and dot motion, whereas it remained stable or decreased for tones learned with incongruent pitch gesture and dot motion.
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