Search Results (14)

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) harbors one of the most mutated genomes. There are limited data on the genomic profile and its predictive potential for response to immunotherapy with PD-1 inhibitors in cSCC. Methods: This study retrospectively reviewed cSCC patients treated with PD-1 inhibitor monotherapy at a single institution. Clinical characteristics, treatment outcomes, PD-L1 expression, tumor mutation burden (TMB), and genomic profile in tumor and blood were analyzed. Logistic regression and a support vector classifier were used to validate identified biomarkers of significance. Results: Twenty-five patients were evaluable for response and had genomics tested in tumor and/or blood. Of the total, 80% of patients achieved an objective response: 40% complete response (CR), 32% partial response (PR) for more than 6 months, and 8% stable disease (SD) for more than 1 year; 20% of patients progressed on treatment. With a median follow-up of 21 months, progression-free survival (PFS) was 28 months in responders vs. 3 months in non-responders (p = 0.00001). Median PD-L1 was 25% in responders vs. 10% in non-responders (p = 0.39). There was no difference in median TMB between responders and non-responders. Eight gene mutations were significantly more frequent in non-responders than in responders: CDK12 (p = 0.005), CTCF (p = 0.033), CTNNB1 (p = 0.033), IGF1R (p = 0.038), IKBKE (p = 0.016), MLH1 (0.033), QKI (p = 0.016), and TIPARP (p = 0.033). A support vector model of these genes classified responders and non-responders with an accuracy of 0.88 in the training data and 1.0 in the testing data. Conclusions: PD-1 inhibitor monotherapy produces an impressive response. Eight gene mutations were significantly more frequent in non-responders. PD-L1 and TMB were inconclusive in predicting treatment response to anti-PD-L1. Full article

This study highlights the intricate relationship between Gray-Level Co-occurrence Matrix (GLCM) metrics and machine learning model performance in the context of plant disease identification. It emphasizes the importance of rigorous dataset evaluation and selection protocols to ensure reliable and generalizable classification outcomes. Through a comprehensive examination of publicly available plant disease datasets, focusing on their performance as measured by GLCM metrics, this research identified dataset_2 (D2), a database of leaf images, as the top performer across all GLCM analyses. These datasets were then utilized to train the DarkNet19 deep learning model, with D2 exhibiting superior performance in both GLCM analysis and DarkNet19 training (achieving about 91% testing accuracy) according to performance metrics such as accuracy, precision, recall, and F1-score. The datasets other than dataset_1 and 2 exhibited significantly low classification performance, particularly in supporting GLCM analysis. The findings underscore the need for transparency and rigor in dataset selection, particularly given the abundance of similar datasets in the literature and the growing trend of utilizing deep learning methods in future scientific research. Full article

Metabolic-dysfunction-associated steatotic liver disease (MASLD), which affects 30 million people in the US and is anticipated to reach over 100 million by 2030, places a significant financial strain on the healthcare system. There is presently no FDA-approved treatment for MASLD despite its public health significance and financial burden. Understanding the connection between point mutations, liver enzymes, and MASLD is important for comprehending drug toxicity in healthy or diseased individuals. Multiple genetic variations have been linked to MASLD susceptibility through genome-wide association studies (GWAS), either increasing MASLD risk or protecting against it, such as PNPLA3 rs738409, MBOAT7 rs641738, GCKR rs780094, HSD17B13 rs72613567, and MTARC1 rs2642438. As the impact of genetic variants on the levels of drug-metabolizing cytochrome P450 (CYP) enzymes in human hepatocytes has not been thoroughly investigated, this study aims to describe the analysis of metabolic functions for selected phase I and phase II liver enzymes in human hepatocytes. For this purpose, fresh isolated primary hepatocytes were obtained from healthy liver donors (n = 126), and liquid chromatography–mass spectrometry (LC–MS) was performed. For the cohorts, participants were classified into minor homozygotes and nonminor homozygotes (major homozygotes + heterozygotes) for five gene polymorphisms. For phase I liver enzymes, we found a significant difference in the activity of CYP1A2 in human hepatocytes carrying MBOAT7 (p = 0.011) and of CYP2C8 in human hepatocytes carrying PNPLA3 (p = 0.004). It was also observed that the activity of CYP2C9 was significantly lower in human hepatocytes carrying HSD17B13 (p = 0.001) minor homozygous compared to nonminor homozygous. No significant difference in activity of CYP2E1, CYP2C8, CYP2D6, CYP2E1, CYP3A4, ECOD, FMO, MAO, AO, and CES2 and in any of the phase II liver enzymes between human hepatocytes carrying genetic variants for PNPLA3 rs738409, MBOAT7 rs641738, GCKR rs780094, HSD17B13 rs72613567, and MTARC1 rs2642438 were observed. These findings offer a preliminary assessment of the influence of genetic variations on drug-metabolizing cytochrome P450 (CYP) enzymes in healthy human hepatocytes, which may be useful for future drug discovery investigations. Full article

We investigate the prospects for the direct detection of dark matter (DM) particles, incident on the upper atmosphere. A recent work relating the burst-like temperature excursions in the stratosphere at heights of ≈38–47 km with low speed incident invisible streaming matter is the motivation behind this proposal. As an example, dark photons could match the reasoning presented in that work provided they constitute part of the local DM density. Dark photons emerge as a U(1) symmetry within extensions of the standard model. Dark photons mix with real photons with the same total energy without the need for an external field, as would be required, for instance, for axions. Furthermore, the ionospheric plasma column above the stratosphere can resonantly enhance the dark photon-to-photon conversion. Noticeably, the stratosphere is easily accessible with balloon flights. Balloon missions with up to a few tons of payload can be readily assembled to operate for months at such atmospheric heights. This proposal is not limited to streaming dark photons, as other DM constituents could be involved in the observed seasonal heating of the upper stratosphere. Therefore, we advocate a combination of different types of measurements within a multi-purpose parallel detector system, in order to increase the direct detection potential for invisible streaming constituents that affect, annually and around January, the upper stratosphere. Full article

Mitochondria contain connexins, a family of proteins that is known to form gap junction channels. Connexins are synthesized in the endoplasmic reticulum and oligomerized in the Golgi to form hemichannels. Hemichannels from adjacent cells dock with one another to form gap junction channels that aggregate into plaques and allow cell–cell communication. Cell–cell communication was once thought to be the only function of connexins and their gap junction channels. In the mitochondria, however, connexins have been identified as monomers and assembled into hemichannels, thus questioning their role solely as cell–cell communication channels. Accordingly, mitochondrial connexins have been suggested to play critical roles in the regulation of mitochondrial functions, including potassium fluxes and respiration. However, while much is known about plasma membrane gap junction channel connexins, the presence and function of mitochondrial connexins remain poorly understood. In this review, the presence and role of mitochondrial connexins and mitochondrial/connexin-containing structure contact sites will be discussed. An understanding of the significance of mitochondrial connexins and their connexin contact sites is essential to our knowledge of connexins’ functions in normal and pathological conditions, and this information may aid in the development of therapeutic interventions in diseases linked to mitochondria. Full article

Objectives: To review the risk of airborne infections in schools and evaluate the effect of intervention measures reported in field studies. Background: Schools are part of a country’s critical infrastructure. Good infection prevention measures are essential for reducing the risk of infection in schools as much as possible, since these are places where many individuals spend a great deal of time together every weekday in a small area where airborne pathogens can spread quickly. Appropriate ventilation can reduce the indoor concentration of airborne pathogens and reduce the risk of infection. Methods: A systematic search of the literature was conducted in the databases Embase, MEDLINE, and ScienceDirect using keywords such as school, classroom, ventilation, carbon dioxide (CO₂) concentration, SARS-CoV-2, and airborne transmission. The primary endpoint of the studies selected was the risk of airborne infection or CO₂ concentration as a surrogate parameter. Studies were grouped according to the study type. Results: We identified 30 studies that met the inclusion criteria, six of them intervention studies. When specific ventilation strategies were lacking in schools being investigated, CO₂ concentrations were often above the recommended maximum values. Improving ventilation lowered the CO₂ concentration, resulting in a lower risk of airborne infections. Conclusions: The ventilation in many schools is not adequate to guarantee good indoor air quality. Ventilation is an important measure for reducing the risk of airborne infections in schools. The most important effect is to reduce the time of residence of pathogens in the classrooms. Full article

Stormwater regulations require erosion and sediment control practices to be implemented during construction to prevent discharging polluted water offsite and mitigate downstream effects. Sediment basins are a common practice used to detain suspended sediment from stormwater runoff by providing residence time and storage to promote gravitational settling. Sediment basin design, and thus pollutant removal efficiency, vary regionally due to local design standards and preferences. This manuscript presents the results of a case study from Highway U.S. 30 construction in Tama County, Iowa, USA where two sediment basin systems were created within a conveyance channel by constructing an earthen berm across the channel to detain sediment-laden stormwater. A dewatering riser pipe was routed through the earthen berm to provide primary dewatering. The in-channel sediment basin was constructed with a 3% slope and a 10 ft. bottom width. The first system consisted of one basin created by a single earthen berm damming sediment-laden runoff, whereas the second system included two earthen berms, creating two in-channel sediment basins in series. Field monitoring was conducted on in-situ basins by deploying a rain gauge and automated water samplers positioned at the inflow and discharge points of a (a) single basin and (b) two basins in series within a roadside channel. During the monitoring period, no maintenance or dredging was recorded. Water samples were taken from the monitored basins at regular time intervals and analyzed for turbidity. Inflow turbidities often reached magnitudes up to the 10³ NTU and discharge samples indicated negligible turbidity reduction after residence. On several occasions, the in-channel sediment basins acted as a sediment source, with discharge turbidities measuring higher than inflow. Despite their initial performance, there was interest in improving the in-channel basin design due to the potential to maximize length-to-width flow ratios, and use of existing infrastructure, which reduced the amount of right of way needed for basin construction, installation time and cost. As a result, several potential design improvements and techniques were recommended to enhance in-channel sediment basin performance. Full article

Adolescent health and well-being are of great concern worldwide, and adolescents encounter particular challenges, vulnerabilities and constraints. The dual challenges of adolescent parenthood and obesity are of public health relevance because of the life-altering health and socioeconomic effects on both the parents and the offspring. Prevention and treatment strategies at the individual and population levels have not been successful in the long term, suggesting that adolescent pregnancy and obesity cannot be managed by more of the same. Here, we view adolescent obese pregnancy through the lens of the social contract with youth. The disruption of this contract is faced by today’s adolescents, with work, social and economic dilemmas which perpetuate socioeconomic and health inequities across generations. The lack of employment, education and social opportunities, together with obesogenic settings, increase vulnerability and exposure to lifelong health risks, affecting their offspring’s life chances too. To break such vicious circles of disadvantage and achieve sustainable solutions in real-world settings, strong efforts on the part of policymakers, healthcare providers and the community must be oriented towards guaranteeing equity and healthy nutrition and environments for today’s adolescents. The involvement of adolescents themselves in developing such programs is paramount, not only so that they feel a sense of agency but also to better meet their real life needs. Full article

This research aimed to study consumers’ trends and the consumption of foods obtained through organic farming in two different countries, Portugal and Turkey. A questionnaire survey was used, applied through internet tools as a result of COVID-19 pandemic restrictions. For the treatment of data, we used basic statistics complemented with a tree classification, aimed at evaluating the influence of sociodemographic factors on the knowledge about this type of food. The results showed that the consumption patterns are relatively similar in both countries, with many participants consuming organic foods, especially vegetables and fruits, consuming them mostly two or three meals per week. The strongest motivations to consume organic foods include benefits for human health and lower environmental impacts, while the most substantial reason not to consume is the higher price. It was also found that in both countries, people have good knowledge about the advantages of organic foods over conventional ones. Finally, the perception of the value attributed by society to organic foods was considerably higher in Portugal. These results confirm the apparent trend of making more sustainable food choices, which is motivated by the perceived negative impact of conventional agriculture on ecosystems and health. Full article

Of all driving functions, one of the critical maneuvers is the lane merge. A cooperative Nonlinear Model Predictive Control (NMPC)-based optimization method for implementing a highway lane merge of two connected autonomous vehicles is presented using solutions obtained by the direct multiple shooting method. A performance criteria cost function, which is a function of the states and inputs of the system, was optimized subject to nonlinear model and maneuver constraints. An optimal formulation was developed and then solved on a receding horizon using direct multiple shooting solutions; this is implemented using an open-source ACADO code. Numerical simulation results were performed in a real-case scenario. The results indicate that the implementation of such a controller is possible in real time, in different highway merge situations. Full article

Climate studies based on global climate models (GCMs) project a steady increase in annual average temperature and severe heat extremes in central North America during the mid-century and beyond. However, the agreement of observed trends with climate model trends varies substantially across the region. The present study focuses on two different locations: Des Moines, IA and Austin, TX. In Des Moines, annual extreme temperatures have not increased over the past three decades unlike the trend of regionally-downscaled GCM data for the Midwest, likely due to a “warming hole” over the area linked to agricultural factors. This warming hole effect is not evident for Austin over the same time period, where extreme temperatures have been higher than projected by regionally-downscaled climate (RDC) forecasts. In consideration of the deviation of such RDC extreme temperature forecasts from observations, this study statistically analyzes RDC data in conjunction with observational data to define for these two cities a 95% prediction interval of heat extreme values by 2040. The statistical model is constructed using a linear combination of RDC ensemble-member annual extreme temperature forecasts with regression coefficients for individual forecasts estimated by optimizing model results against observations over a 52-year training period. Full article

In this paper, Hematoxylin and Eosin (H&E) stained liver images are classified by using both Local Binary Patterns (LBP) and one dimensional SIFT (1-D SIFT) algorithm. In order to obtain more meaningful features from the LBP histogram, a new feature vector extraction process is implemented for 1-D SIFT algorithm. LBP histograms are extracted with different approaches and concatenated with color histograms of the images. It is experimentally shown that,with the proposed approach, it possible to classify the H&E stained liver images with the accuracy of $88\%$ . Full article

The first thing to do in wind turbine blade design is to select tip speed ratio. Generally speaking, the speed ratio depends on the profile type used and the number of blades. Various speed ratios could be chosen for different types of profiles with different number of blades. Therefore, an optimization procedure should be applied to find the best ratio since this directly affects the energy generated from the turbine and in turn the investment made. This study presents a procedure to assess the optimum speed ratios for various profile types used in practice with various numbers of blades. Full article