Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular characterization of clinical responses to PD‐1/PD‐L1 inhibitors in non‐small cell lung cancer: Predictive value of multidimensional immunomarker detection for the efficacy of PD‐1 inhibitors in Chinese patients

According to multiple studies, the objective response rate of PD‐1/PD‐L1 inhibitors in the second‐line treatment of unscreened non‐small cell lung cancer (NSCLC) is only approximately 20%. Predictive biomarkers of treatment efficacies are still under investigation. In selected NSCLC patients with PD‐L1 expression ≥ 50%, the response rate of pembrolizumab in first‐line treatment can reach 44.8%. Moreover, patients with a higher tumor mutation burden (TMB) tend to achieve a better response with nivolumab. Besides PD‐L1 expression and TMB, taking all these indicators into consideration would hypothetically maximize the clinical response in a specific subgroup of patients. Our study aims to accumulate large and complete samples and clinical data to verify the biomarkers and their cutoff values related to the efficacy of PD‐1/PD‐L1 inhibitors in Chinese NSCLC patients, and to construct a comprehensive predictive model by combining multi‐omics data with contemporary machine learning techniques. NSCLC patients administered treatment of anti‐PD‐1/PD‐L1 antibodies or a combination with other drugs have been enrolled. The estimated enrollment is 250 participants. A sophisticated predictive model of immunotherapy response in the Chinese population has not yet been developed. It is clinically and practically imperative to comprehensively evaluate the possible indicators of Chinese NSCLC patients through multiple test platforms, such as next generation sequencing, PCR, or immunohistochemistry. This study is registered in the Chinese Clinical Trial Registry (ChiCTR1900021395).
Ligand-Based Stability Changes in Duplex DNA Measured with a Microscale Electrochemical Platform

Development of technologies for rapid screening of DNA secondary structure thermal stability and the effects on stability for binding of small molecule drugs is important to the drug discovery process. In this report, we describe the capabilities of an electrochemical, microdevice-based approach for determining the melting temperatures (Tm) of electrode-bound duplex DNA structures. We also highlight new features of the technology that are compatible with array development and adaptation for high-throughput screening. As a foundational study to exhibit device performance and capabilities, melting-curve analyses were performed on 12-mer DNA duplexes in the presence/absence of two binding ligands: diminazene aceturate (DMZ) and proflavine. By measuring electrochemical current as a function of temperature, our measurement platform has the ability to determine the effect of binding ligands on Tm values with high signal-to-noise ratios and good reproducibility. We also demonstrate that heating our three-electrode cell with either an embedded microheater or a thermoelectric module produces similar results. The ΔTm values we report show the stabilizing ability of DMZ and proflavine when bound to duplex DNA structures. These initial proof-of-concept studies highlight the operating characteristics of the microdevice platform and the potential for future application toward other immobilized samples.
Anti-miRNA21 and resveratrol-loaded polysaccharide-based mesoporous silica nanoparticle for synergistic activity in gastric carcinoma

Abstract Anti-miR21 and resveratrol (RSV)-loaded mesoporous silica nanoparticles (MSNs) conjugated with hyaluronic acid (HA) were developed to enhance therapeutic efficacy in gastric carcinoma. The surface conjugation of HA, which acts as a targeting ligand to the overexpressed CD44 receptor on gastric cancer cells, was clearly identified by the presence of a greyish shell on the dark MSNs. Confocal laser-scanning microscopy and flow cytometry analysis showed higher cellular internalisation of HA/RSVmirNP compared to RSVmirNP. In vitro cytotoxicity and apoptosis assays confirmed the superior anticancer effect of the optimised formulation and synergistic effects of anti-miR21 and RSV in gastric cancer cells. Importantly, HA/RSVmirNP showed significant (p < .001) reductions in the tumour burden compared to the other group. Indeed, HA/RSVmirNP showed a threefold higher tumour regression effect compared to that of free RSV and a twofold tumour regression effect compared to that of RSVmirNP, indicating its anticancer efficacy. The percentage of TUNEL-positive cells was significantly higher in HA/RSVmirNP-treated cells compared to any other group, indicating that the mechanism underlying the superior anticancer efficacy of HA/RSVmirNP included apoptosis and cell necrosis. Thus, a combination of anti-miR21 and RSV in a targeted nanocarrier might be a promising drug delivery system for gastric cancer therapy.
Risk Factors for Brucella Seroprevalence in Peri-Urban Dairy Farms in Five Indian Cities

Brucellosis is endemic among dairy animals in India, contributing to production losses and posing a health risk to people, especially farmers and others in close contact with dairy animals or their products. Growing urban populations demand increased milk supplies, resulting in intensifying dairy production at the peri-urban fringe. Peri-urban dairying is under-studied but has implications for disease transmission, both positive and negative. In this cross-sectional study, five Indian cities were selected to represent different geographies and urbanization extent. Around each, we randomly selected 34 peri-urban villages, and in each village three smallholder dairy farms (defined as having a maximum of 10 dairy animals) were randomly selected. The farmers were interviewed, and milk samples were taken from up to three animals. These were tested using a commercial ELISA for antibodies against Brucella abortus, and factors associated with herd seroprevalence were identified. In all, 164 out of 1163 cows (14.1%, 95% CI 12.2–16.2%) were seropositive for Brucella. In total, 91 out of 510 farms (17.8%, 95% CI 14.6–21.4%) had at least one positive animal, and out of these, just seven farmers stated that they had vaccinated against brucellosis. In four cities, the farm-level seroprevalence ranged between 1.4–5.2%, while the fifth city had a seroprevalence of 72.5%. This city had larger, zero-grazing herds, used artificial insemination to a much higher degree, replaced their animals by purchasing from their neighbors, were less likely to contact a veterinarian in case of sick animals, and were also judged to be less clean. Within the high-prevalence city, farms were at higher risk of being infected if they had a young owner and if they were judged less clean. In the low-prevalence cities, no risk factors could be identified. In conclusion, this study has identified that a city can have a high burden of infected animals in the peri-urban areas, but that seroprevalence is strongly influenced by the husbandry system. Increased intensification can be associated with increased risk, and thus the practices associated with this, such as artificial insemination, are also associated with increased risk. These results may be important to identify high-risk areas for prioritizing interventions and for policy decisions influencing the structure and development of the dairy industry.
Physical Parameters Affecting Liquid Penetration and Wetting of Fabrics

Abstract : The purpose of this research is the development and evaluation of a test procedure for determining the water repellency of films and fabrics of military interest. The approach selected has been used by several investigators. The method determines the critical surface tension (gamma sub c) of the material by measuring the angle of contact between the fabric and a series of liquids of different surface tensions. A camera microscope system is used to obtain the contact angles. Young's equation and theoretical equations proposed by other researchers are used to analyze test results. Data obtained on several experimental films was analyzed using the approaches of Fowkes and Good. For practical purposes both approaches gave similar results. However, analysis of data reveals a fundamental limitation of the method. When applied to materials of low surface energy, particularly the rough surface of a water repellent woven fabric, a long extrapolation is required to obtain (gamma sub c). Keywords: Fabrics, Contact angle, Surface tension, Wetting, Liquid penetration, Critical surface tension.
Secondary prevention after stroke/transient ischemic attack: A randomized audit and feedback trial

The clinical benefits of use of secondary preventive pharmacotherapy in ischemic stroke/TIA have been previously demonstrated. A potential target for facilitating the use of recommended medications is primary care physicians. Therefore, we carried out an audit and feedback intervention aimed at primary care centers. The aim was to improve the use of secondary preventive stroke medications and diagnosis recording in ischemic stroke/TIA.
Pharmacokinetics of monoamine oxidase B inhibitors in Parkinson’s disease: current status

ABSTRACT Introduction: Brain function depends considerably on the neurotransmission of biogenic monoamines. Their metabolism employs monoamine oxidase-B in neuronal and glial cells. Inhibition of monoamine oxidase-B elevates biogenic amine levels. Accordingly, monoamine oxidase-B inhibitors provide a symptomatic effect via dopamine on motor symptoms in patients with Parkinson’s disease. Areas covered: This narrative review aims to describe the pharmacokinetic characteristics of the available reversible and irreversible monoamine oxidase B inhibitors for the treatment of Parkinson’s disease in daily practice. All these compounds are administered on a daily basis. Expert opinion: Reversibility or irreversibility of available monoamine oxidase-B inhibition is not relevant, due to their daily intake and half-life in clinical practice. Irreversible monoamine oxidase-B inhibitors slowed the progression of neuronal dying in experimental models of Parkinson’s disease. In patients, concomitant inhibition of monoamine oxidase-B caused less increase of levodopa dosages over five years. The curve of levodopa increment diverged from the placebo curve. This reduced need for L-dopa monotherapy may be discussed as an indirect biomarker for disease severity and reflects a disease-modifying effect. In case of a symptomatic effect only, parallel curves would have occurred. Long-term L-dopa treatment should be combined with monoamine oxidase-B inhibitors when tolerated by patients.
Heterogeneous Patterns of Marijuana Use Motives Using Latent Profile Analysis

Abstract Background: Given that marijuana use is often associated with detrimental physical and mental health problems, research examining motives for its use is critical for effective remedial and preventive treatment. To date, the majority of research on marijuana use motives has used variable-centered analyses, which overlooks potentially meaningful heterogeneous response patterns and the associations of those patterns with other risk/protective factors. Methods: To address this gap, in the current study, we conducted a person-centered analysis (latent profile analysis) to identify subgroups of participants based on endorsed marijuana use motives, and examined the construct validity of the optimal class solution (covariates included sociodemographic (e.g., age), psychiatric (e.g., depression), and marijuana-use indices (e.g., use-frequency, use-related problems). Participants were 898 college students (Mage = 20.93, SDage = 3.10; 68.9% female) who completed an anonymous online survey examining substance use and psychological well-being, were 18 years or older, and endorsed lifetime marijuana use. Data were collected November 2016 through February 2018. Results: Results identified four unique classes of coping, conformity, social, and enhancement marijuana use motives: (a) “Low Motives” (37.6%), (b) “High Conformity” (4.9%), (c) “Low Conformity” (45.8%), and (d) “High Motives” (11.7%). In terms of covariates, higher motive classes tended to report more frequent and problematic use. The two classes uniquely characterized by conformity motives only differed on past-month marijuana use frequency. Conclusions/Importance: The current findings provide evidence that specific classes of motives were not only associated with marijuana use frequency and problems but other risk and protective factors, such as anxiety sensitivity and social support.
Remote Control of Greenhouse Vegetable Production with Artificial Intelligence—Greenhouse Climate, Irrigation, and Crop Production

The global population is increasing rapidly, together with the demand for healthy fresh food. The greenhouse industry can play an important role, but encounters difficulties finding skilled staff to manage crop production. Artificial intelligence (AI) has reached breakthroughs in several areas, however, not yet in horticulture. An international competition on “autonomous greenhouses” aimed to combine horticultural expertise with AI to make breakthroughs in fresh food production with fewer resources. Five international teams, consisting of scientists, professionals, and students with different backgrounds in horticulture and AI, participated in a greenhouse growing experiment. Each team had a 96 m2 modern greenhouse compartment to grow a cucumber crop remotely during a 4-month-period. Each compartment was equipped with standard actuators (heating, ventilation, screening, lighting, fogging, CO2 supply, water and nutrient supply). Control setpoints were remotely determined by teams using their own AI algorithms. Actuators were operated by a process computer. Different sensors continuously collected measurements. Setpoints and measurements were exchanged via a digital interface. Achievements in AI-controlled compartments were compared with a manually operated reference. Detailed results on cucumber yield, resource use, and net profit obtained by teams are explained in this paper. We can conclude that in general AI performed well in controlling a greenhouse. One team outperformed the manually-grown reference.
Augmentative and Alternative Communication (AAC) Advances: A Review of Configurations for Individuals with a Speech Disability

High-tech augmentative and alternative communication (AAC) methods are on a constant rise; however, the interaction between the user and the assistive technology is still challenged for an optimal user experience centered around the desired activity. This review presents a range of signal sensing and acquisition methods utilized in conjunction with the existing high-tech AAC platforms for individuals with a speech disability, including imaging methods, touch-enabled systems, mechanical and electro-mechanical access, breath-activated methods, and brain–computer interfaces (BCI). The listed AAC sensing modalities are compared in terms of ease of access, affordability, complexity, portability, and typical conversational speeds. A revelation of the associated AAC signal processing, encoding, and retrieval highlights the roles of machine learning (ML) and deep learning (DL) in the development of intelligent AAC solutions. The demands and the affordability of most systems hinder the scale of usage of high-tech AAC. Further research is indeed needed for the development of intelligent AAC applications reducing the associated costs and enhancing the portability of the solutions for a real user’s environment. The consolidation of natural language processing with current solutions also needs to be further explored for the amelioration of the conversational speeds. The recommendations for prospective advances in coming high-tech AAC are addressed in terms of developments to support mobile health communicative applications.
Bacillus Spp.: Efficient Biotic Strategy to Control Postharvest Diseases of Fruits and Vegetables

Postharvest diseases significantly reduce the shelf-life of harvested fruits/vegetables worldwide. Bacillus spp. are considered to be an eco-friendly and bio-safe alternative to traditional chemical fungicides/bactericides due to their intrinsic ability to induce native anti-stress pathways in plants. This review compiles information from multiple scientific databases (Scopus, ScienceDirect, GoogleScholar, ResearchGate, etc.) using the keywords “postharvest diseases”, “Bacillus”, “Bacillus subtilis”, “biocontrol”, “storage”, “losses”, and “fruits/vegetables”. To date, numerous examples of successful Bacillus spp. application in controlling various postharvest-emerged pathogens of different fruits/vegetables during handling, transportation, and storage have been described in the literature. The mechanism/s of such action is/are still largely unknown; however, it is suggested that they include: i) competition for space/nutrients with pathogens; ii) production of various bio-active substances with antibiotic activity and cell wall-degrading compounds; and iii) induction of systemic resistance. With that, Bacillus efficiency may depend on various factors including strain characteristics (epiphytes or endophytes), application methods (before or after harvest/storage), type of pathogens/hosts, etc. Endophytic B. subtilis-based products can be more effective because they colonize internal plant tissues and are less dependent on external environmental factors while protecting cells inside. Nevertheless, the mechanism/s of Bacillus action on harvested fruits/vegetables is largely unknown and requires further detailed investigations to fully realize their potential in agricultural/food industries.
Genes’ Interactions: A Major Contributor to the Malignant Transformation of Endometriosis

The genetic and epigenetic factors that contribute to the malignant transformation of endometriosis are still under investigation. The objective of the present study was to investigate the genetic link between endometriosis and cancer by examining and correlating the latest clinical observations with biological experimental data. We collected updated evidence about the genetic relationship between endometriosis and cancers by conducting a comprehensive search of PubMed and Scopus databases, focusing on the papers published between January 2018 and January 2019. New insights into the mechanism of the malignant transformation of endometriosis have been published recently. The use of state-of-the-art techniques and methods, such as the genome-wide association study analysis and the weighted gene co-expression analysis, have significantly altered our understanding of the association between endometriosis and endometriosis-associated cancer development. Interestingly, the interactions formed between genes seem to play a pivotal role in the phenotypic expression of mutations. Therefore, the effect of single nucleotide polymorphisms and the function of the expression quantitative trait loci on genes’ expression have been the subject of many recent works. In addition, it has been discovered that genes, the mutations of which have been related to the development of endometriosis, play a role as hub genes. This may lead to new areas of research for understanding the mechanism of malignant transformation of the disease. Significant steps forward have been made towards the identification of factors that control the malignant transformation of endometriosis. Still, due to rarity of the event, a better-organized scheme for sampling on a global level should be adopted.
No vaginal estrogen therapy arm in an RCT trial on genitourinary syndrome of menopause is a concern

Flint et al. are to be congratulated for formulating a randomized controlled trial (RCT) in the management of genitourinary syndrome of menopause (GSM). However, the exclusion of vaginal estrogen as a treatment arm in the trial is disruptive to the natural course of evidence-based medicine, disingenuous to the current evidence surrounding the treatment of GSM, and places participating women at risk of not receiving vaginal estrogen therapy as the current goldstandard treatment for GSM. The only published RCT comparing vaginal estrogen and a carbon dioxide laser is not referenced by the authors and demonstrated that the estrogen group had improved scores on the vaginal health index, a lower rate of dyspareunia on the validated self-completed Female Sexual Function Index, and a lower rate of pain post treatments when compared to the carbon dioxide vaginal laser. The trial, by excluding vaginal estrogen as a first-line treatment option, unduly promotes the role of laser therapy for this condition to participants and readers, and is counterintuitive to the recent action of the Food and Drug Administration in forcing the laser manufacturers to remove any assertions of efficacy or safety of this therapy for the treatment of GSM in promotional material. This methodological problem could be easily addressed with the inclusion of an estrogen arm in the trial. Furthermore, the authors declare no conflict of interest in the trial; however, both recruiting institutions in this trial are also listed on ClinicalTrials.gov as participating sites in an RCT comparing Fotona YaG vaginal laser therapy and sham treatment for stress urinary incontinence (SUI). This SUI trial is co-sponsored by Fotona, a company whose YaG laser therapy product also forms one arm of the current study protocol. The authors’ research collaboration with Fotona is a potential conflict of interest that should be declared to the readers.
Detc2003/dac-48785 Design Space Visualization and Its Application to a Design by Shopping Paradigm

We have developed a data visualization interface that facilitates a design by shopping paradigm, allowing a decision-maker to form a preference by viewing a rich set of good designs and use this preference to choose an optimal design. Design automation has allowed us to implement this paradigm, since a large number of designs can be synthesized in a short period of time. The interface allows users to visualize complex design spaces by using multi-dimensional visualization techniques that include customizable glyph plots, parallel coordinates, linked views, brushing, and histograms. As is common with data mining tools, the user can specify upper and lower bounds on the design space variables, assign variables to glyph axes and parallel coordinate plots, and dynamically brush variables. Additionally, preference shading for visualizing a user's preference structure and algorithms for visualizing the Pareto frontier have been incorporated into the interface to help shape a decision-maker's preference. Use of the interface is demonstrated using a satellite design example by highlighting different preference structures and resulting Pareto frontiers. The capabilities of the design by shopping interface were driven by real industrial customer needs, and the interface was demonstrated at a spacecraft design conducted by a team at Lockheed Martin, consisting of Mars spacecraft design experts. 1. INTRODUCTION Balling [1] proposes a design by shopping paradigm, where a decision-maker first explores a design space and then chooses an optimal solution from a set of possible designs. This paradigm gives more control to decision-makers compared to traditional optimization approaches by allowing them to form their design preferences after visualizing the entire design space, and then choose an optimal design that is based on this preference. The design by shopping paradigm can be classified as an a posteriori articulation of preference to solve a multiobjective optimization [2]. This approach is more attractive to decision-makers than an a priori approach, because design exploration is followed by a selection process in which the decision-makers have control [1]. Balling states the need for research in two areas to support this process: 1. interactive graphical computer tools to assist decision-makers in the shopping process, and 2. efficient methods for obtaining Pareto frontiers. The focus in our research is to develop a graphical user interface that allows a decision-maker to visualize the design space and implement a design by shopping paradigm. The following functionality was incorporated into the interface: 1. Assign variables to glyph and parallel coordinate …