Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis

Background: The benefit of dual antiplatelet therapy (DAPT) for reducing ischemic events is greatest in the early period of acute coronary syndrome, and recent randomized controlled trials have investigated the unguided de-escalation strategy of changing potent P2Y12 inhibitors to less potent or reduced-dose P2Y12 inhibitors 1 month after acute coronary syndrome. However, it remains unclear which strategy is more effective and safer: the uniform unguided de-escalation strategy versus the personalized guided selection of DAPT with genotype or platelet function tests. Methods: PubMed, EMBASE, and Cochrane Central were searched for articles published from database inception to September 10, 2021. Randomized controlled trials investigating DAPT using clopidogrel, low-dose prasugrel, standard-dose prasugrel, ticagrelor, unguided de-escalation strategy, and guided selection strategy for patients with acute coronary syndrome were included. Hazard ratios and relative risk estimates were extracted from each study. The estimates were pooled using a random-effects network meta-analysis. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and major bleeding. Results: This study included 19 randomized controlled trials with 69 746 patients. Compared with guided selection of DAPT, unguided de-escalation of DAPT was associated with a decreased risk of the primary safety outcome (hazard ratio, 0.48 [95% CI, 0.33–0.72]) without increased risks of major adverse cardiovascular events (hazard ratio, 0.82 [95% CI, 0.53–1.28]) or any secondary outcomes. The results were similar when the guided selection strategy was divided into platelet function–guided and genotype-guided strategies. Conclusions: Compared with guided selection of DAPT, unguided de-escalation of DAPT decreased bleeding without increasing ischemic events in patients after acute coronary syndrome. If a strategy of de-escalation is chosen, these findings do not support the routine use of personalized guiding tests. Registration: URL: https://www.crd. york.ac. uk/PROSPERO/; Unique identifier: CRD42021273082.
EBV-associated NK and T-cell lymphoid neoplasms

Purpose of review Epstein-Barr virus (EBV)-associated neoplasms derived from natural killer (NK) or T cells comprise a group of clinically and biologically heterogenous disorders affecting children and adults, which are overall rare but more prevalent in Asia and South America. This review focuses on neoplasms presenting in the adulthood, addressing recent genomic discoveries as well as therapeutic developments in these highly aggressive disorders. Recent findings Distinct molecular subtypes of extranodal NK/T-cell lymphomas (ENKTCLs) have been described, with differences in cell of origin, EBV pattern, genomic alterations, clinical characteristics, response to asparaginase-based therapies and to more recent approaches targeting molecular aberrations of the lymphoma. For the last two decades, progress in the clinical management of ENKTCL was based on L-asapraginase containing combinations and the incoroperation of radiotherapy. A subset of cases with PDL1-2 structural alterations may be more responsive to treatment with immune checkpoint inhibitors. Primary nodal EBV+ lymphomas derived from T or NK cells have distinctive features separating them from both peripheral T-cell lymphoma not otherwise specified and ENKTCL. Treatment algorithms correspond to those for advanced ENKTCL. Summary With better understanding of lymphomagenesis, genomic landscape and immunologic aspects of the diseases, future treatment options will include targeted therapies including immune checkpoint inhibitors and novel antibodies.
Tissue engineering approaches and generation of insulin-producing cells to treat type 1 diabetes

Abstract Tissue engineering (TE) has become a new effective solution to a variety of medical problems, including diabetes. Mesenchymal stem cells (MSCs), which have the ability to differentiate into endodermal and mesodermal cells, appear to be appropriate for this function. The purpose of this review was to evaluate the outcomes of various researches on the insulin-producing cells (IPCs) generation from MSCs with TE approaches to increase efficacy of type 1 diabetes treatments. The search was performed in PubMed/Medline, Scopus and Embase databases until 2021. Studies revealed that MSCs could also differentiate into IPCs under certain conditions. Therefore, a wide range of protocols have been used for this differentiation, but their effectiveness is very different. Scaffolds can provide a microenvironment that enhances the MSCs to IPCs differentiation, improves their metabolic activity and up-regulate pancreatic-specific transcription factors. They also preserve IPCs architecture and enhance insulin production as well as protect against cell death. This systematic review offers a framework for prospective research based on data. In vitro and in vivo evidence suggests that scaffold-based TE can improve the viability and function of IPCs.
Association of Long-Acting Injectable Antipsychotics and Oral Antipsychotics With Disease Relapse, Health Care Use, and Adverse Events Among People With Schizophrenia

Key Points Question Are long-acting injectable antipsychotics (LAIAs) associated with a lower risk of disease relapse, health care use, and adverse events compared with oral antipsychotics among people in Hong Kong with schizophrenia? Findings In this 16-year, population-based, self-controlled case series study of 70 396 individuals with a diagnosis of schizophrenia, 23 719 were prescribed LAIAs and oral antipsychotics. There were 48% fewer psychiatric hospitalizations, 47% fewer hospitalizations for schizophrenia, 44% fewer suicide attempts, and 37% fewer all-cause hospitalizations during full treatment periods with LAIAs alone, without an increased risk of adverse events; this association was also observed when excluding the first 90 days of treatment. Meaning This study suggests that clinicians should more broadly consider the long-term use of LAIAs for people with schizophrenia.
Serum levels of neuron-specific enolase as a prognostic factor for disease progression in patients with GET/NEN in the pancreas and the small intestine

The aim of this study was to assess the usefulness of neuron-specific enolase (NSE) concentrations as a prognostic factor in patients with neuroendocrine neoplasms and to determine the relationship between NSE and clinicopathological features. Serum NSE levels were measured in 179 NEN patients before treatment. It was found that NSE levels in patients with a primary pancreatic location were higher compared to patients with a small intestine lesion (P = 0.015). NSE levels were significantly higher in patients with primary pancreatic location with histological grade G2 compared with the group with low-grade G1 (P = 0.047). Patients with initial liver involvement showed significantly higher NSE levels compared to patients with tumour location in the pancreas (P = 0.009). Statistical analysis confirmed that higher NSE levels were associated with disease progression (P = 0.001) in both the overall study group and in patients with tumours in the pancreas and small intestine. During treatment monitoring, an increase in median NSE concentrations was observed in patients with persistent progression with subsequent blood draws, and a decrease in NSE concentrations was observed in patients with disease stabilisation. We showed that NSE concentrations have prognostic value for progression-free survival in addition to primary liver involvement. In conclusion, the most important results of the study include the demonstration of an association between NSE concentrations and clinical status, which confirms its usefulness in patient monitoring and as a potential predictive indicator for progression-free survival in patients with NENs.
Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

Limbus-derived stromal/mesenchymal stem cells (LMSCs) are vital for corneal homeostasis and wound healing. However, despite multiple pre-clinical and clinical studies reporting the potency of LMSCs in avoiding inflammation and scarring during corneal wound healing, the molecular basis for the ability of LMSCs remains unknown. This study aimed to uncover the factors and pathways involved in LMSC-mediated corneal wound healing by employing RNA-Sequencing (RNA-Seq) in human LMSCs for the first time. We characterized the cultured LMSCs at the stages of initiation (LMSC−P0) and pure population (LMSC−P3) and subjected them to RNA-Seq to identify the differentially expressed genes (DEGs) in comparison to native limbus and cornea, and scleral tissues. Of the 28,000 genes detected, 7800 DEGs were subjected to pathway-specific enrichment Gene Ontology (GO) analysis. These DEGs were involved in Wnt, TGF-β signaling pathways, and 16 other biological processes, including apoptosis, cell motility, tissue remodeling, and stem cell maintenance, etc. Two hundred fifty-four genes were related to wound healing pathways. COL5A1 (11.81 ± 0.48) and TIMP1 (20.44 ± 0.94) genes were exclusively up-regulated in LMSC−P3. Our findings provide new insights involved in LMSC-mediated corneal wound healing.
Association of a common genetic variant with Parkinson’s disease is mediated by microglia

Studies of multiple neurodegenerative disorders have identified many genetic variants that are associated with risk of disease throughout a lifetime. For example, Parkinson’s disease (PD) risk is attributed in part to both coding mutations in the leucine-rich repeat kinase 2 (LRRK2) gene and to a common noncoding variation in the 5′ region of the LRRK2 locus, as identified by genome-wide association studies (GWAS). However, the mechanisms linking GWAS variants to pathogenicity are largely unknown. Here, we found that the influence of PD-associated noncoding variation on LRRK2 expression is specifically propagated through microglia and not by other cell types that express LRRK2 in the human brain. We find microglia-specific regulatory chromatin regions that modulate the LRRK2 expression in human frontal cortex and substantia nigra and confirm these results in a human-induced pluripotent stem cell–derived microglia model. We showed, using a large-scale clustered regularly interspaced short palindromic repeats interference (CRISPRi) screen, that a regulatory DNA element containing the single-nucleotide variant rs6581593 influences the LRRK2 expression in microglia. Our study demonstrates that cell type should be considered when evaluating the role of noncoding variation in disease pathogenesis and sheds light on the mechanism underlying the association of the 5′ region of LRRK2 with PD risk. Description Noncoding variation near the LRRK2 gene is linked to Parkinson’s disease through microglia-specific regulatory mechanisms. Microglia modulates PD risk Previous studies have identified variants in the LRRK2 gene that are associated with an increased risk of developing Parkinson’s disease (PD). Here, Langston and colleagues studied the mechanisms of LRRK2 variants to PD and showed that the disease risk is determined by microglial cells. Studying PD-associated LRRK2 variants in patient-derived tissue and iPSC-derived microglia, the authors identified a quantitative trait in microglia, suggesting that, although this cell type expresses LRRK2 in lower amounts compared to other cell types, it might be critical for determining the PD risk. The cell type–specific baseline expression and effect on disease pathophysiology might not be predictive of the mechanisms mediating this and other disease-associated variants in noncoding gene regions.
A sampling, exposure and receptor framework for identifying factors that modulate behavioural responses to disturbance in cetaceans

Abstract The assessment of behavioural disturbance in cetacean species (e.g. resulting from exposure to anthropogenic sources such as military sonar, seismic surveys, or pile driving) is important for effective conservation and management. Disturbance effects can be informed by Behavioural Response Studies (BRSs), involving either controlled exposure experiments (CEEs) where noise exposure conditions are presented deliberately to meet experimental objectives or in opportunistic contexts where ongoing activities are monitored in a strategic manner. In either context, animal‐borne sensors or in situ observations can provide information on individual exposure and disturbance responses. The past 15 years of research have greatly expanded our understanding of behavioural responses to noise, including hundreds of experiments in nearly a dozen cetacean species. Many papers note limited sample sizes, required knowledge of baseline behaviour prior to exposure and the importance of contextual factors modulating behavioural responses, all of which in combination can lead to sampling biases, even for well‐designed research programs. It is critical to understand these biases to robustly identify responses. This ensures outcomes of BRSs help inform predictions of how anthropogenic disturbance impacts individuals and populations. Our approach leverages concepts from the animal behaviour literature focused on helping to avoid sampling bias by considering what shapes an animal's response. These factors include social, experience, genetic and natural changes in responsiveness. We developed and applied a modified version of this framework to synthesise current knowledge on cetacean response in the context of effects observed across marine and terrestrial taxa. This new ‘Sampling, Exposure, Receptor’ framework (SERF) identifies 43 modulating factors, highlights potential biases, and assesses how these vary across selected focal species. In contrast to studies that identified variation in ‘Exposure’ factors as a key concern, our analysis indicated that factors relating to ‘Sampling’ (e.g. deploying tags on less evasive individuals, which biases selection of subjects), and ‘Receptor’ (e.g. health status or coping style) have the greatest potential for weakening the desired broad representativeness of BRSs. Our assessment also highlights how potential biases could be addressed with existing datasets or future developments.
Suitability of monotypic and mixed diets for development, population growth and predation capacity of Typhlodromus bagdasarjani (Acari: Phytoseiidae)

Abstract We quantified the life table parameters and predation capacity of a generalist predatory mite, Typhlodromus bagdasarjani Wainstein and Arutunjan on five monotypic diets, including Tetranychus urticae Koch (TSSM) eggs in the presence (SW) and absence (SN) of webs, Trialeurodes vaporariorum Westwood (GHWF) eggs (G), honeydew (H), and maize pollen (M) as well as three mixed diets, including SN + M, SN + G, and G + M. Our results showed that the individuals fed on the mixed diets had a considerably shorter developmental time and pre-oviposition period (APOP), higher oviposition days, higher fecundity and population growth rate than those raised on the monotypic diets. Furthermore, we found that the mixed diet of TSSM and GHWF eggs was the most favorable diet, resulted in the highest fecundity and population growth rate, shortest developmental time and APOP. While TSSM eggs alone in the presence of webs and honeydew were the worst diets resulted in the longest developmental time, lower oviposition day, higher fecundity and population growth rate. Our data determined that TSSM has more nutritional benefits than GHWF for T. bagdasarjani. We observed the positive effects of pollen addition to prey on the predatory mite's immature and adult life-history characters; however, it reduced the predation rate. Overall, maize pollen could enhance ecosystem services provided against spider mites and whiteflies by positively impacting the increase of T. bagdasarjani population. This predator may be more effective when two prey species are available than when only one species is present.
The Effect of Correlated Colour Temperature on Physiological, Emotional and Subjective Satisfaction in the Hygiene Area of a Space Station

The hygiene area is one of the most important facilities in a space station. If its environmental lighting is appropriately designed, it can significantly reduce the psychological pressure on astronauts. This study investigates the effect of correlated colour temperature (CCT) on heart rate, galvanic skin response, emotion and satisfaction in the hygiene area of a space station. Forty subjects participated in experiments in a hygiene area simulator with a controlled lighting environment. The lighting conditions included 2700 K, 3300 K, 3600 K, 5000 K and 6300 K; physiological responses (heart rate, galvanic skin response), as well as emotion and satisfaction, were recorded. The results showed that CCT significantly influenced the participants’ physiological and subjective responses in the space station hygiene area. 6300 K led to the best emotion and satisfaction levels, the highest galvanic skin response and the lowest heart rate. The opposite was true for 2700 K.
Theory of Quanta

1: The Birth of Quantum Theory. 1.1: The radiation of an ideal black body. 1.2: Line spectra and Bohr's model of the atom. 1.3: The quantum conditions of Bohr-Sommerfield. 1.4: Waves of matters. Comments. Problems. 2: Classical Physics - Quantum Physics. 2.1: The difficulties of classical theory. 2.2: The successes of quantum theory. 2.3: Problems with interpretation of quantum theory. 2.4: Quantum theory (1930. Problems. II: Schrodinger's Equation and the Interpretation of its Solutions. 3: Schrodinger's Equation. 3.1: The Schrodinger equation with time. 3.2: The time-dependent Schrodinger equation. Comments. Problems. 4: The Probabilistic Interpretation of the Wavefunction. Comments. Problems. 5: The Motion of a Free Particle in Wave Mechanics. 5.1: The spreading of wave packets. 5.2: The initial problem for Schrodinger's free particle equation. 5.3: The Gaussian wave packet. Comments. Problems. 6: The Momentum of a Particle and the Fourier Transformation of the Wavefunction. Comments. Problems. 7: Description of Experiments in Wave Mechanics and the Heinsberg Uncertainty Principle. 7.1: Heisenberg's uncertainty principle. 7.2: The entropic uncertainty principle. Comments. Problems. 8: A Charged Particle in an Electromagnetic Field. Comments. Problems. 9: The Hydrodynamic Formulation of Wave Mechanics. 9.1: The motion of the probability fluid in an electromagnetic field. Comments. Problems. 10: The Spin of the Elctron and Pauli's Equation. 10.1: The magnetic moment vector. 10.2: Pauli's equation. 10.3: The Stern-Gerlach experiments. Comments. Problems. 11: The Hydrodynamic Picture of Wave Mechanics of a Particle with Spin. Comments. Problems. 12: Ehrenfest's Equations. 12.1: A particle with spin in the electromagnetic field. Problems. 13: Descriptiopn of Particle Motion in Phase Space -- Wigner's Function. Comments. Problems. 14: Mixed States. 14.1: An unpolarized beam as a mixed state. Comments. Problems. III: Solutions of Schrodinger's Equation. 15: Classification of Solutions to Schrodinger's Equation. 15.1: Scattering states. 15.2: The completeness of the set of bound and scattering state wavefunctions. 15.3: Orthogonality of the wavefunctions. 15.4: Development of the system in time. 15.5: Bound and scattered states. Problems. 16: Bound States and Energy. 16.1: The three-dimensional spherically symmetric potential well. Comments. Problems. 17: Scattering States and Collision Cross-sections. 17.1: One-dimensional scattering. 17.2: The method of integral equations. 17.3: Three-dimensional scattering. 17.4: The scattering amplitude. 17.5: The S matrix. 17.6: Collision cross-section. 17.7: The optical theorem. Comments. Problems. 18: Partial Waves and Wave Effects in Scattering. 18.1: Phase shifts. 18.2: The spherical potential hump. 18.3: The Ramsauer-Townsend effect. 18.4: The extinction paradox. Comments. Problems. 19: Resonance States. Problems. 20: The Coulomb Potential. 20.1: Bound states. 20.2: Scattering states. Comments. Problems. 21
Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task

Abstract Background Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide. Method 136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences. Results On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA. Conclusions These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.
Larval Competition Between Aedes albopictus and Aedes aegypti (Diptera: Culicidae) in Argentina: Coexistence and Implications in the Distribution of the Asian Tiger Mosquito

Abstract Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) are worldwide vectors of dengue and yellow fever viruses. These species coexist in many countries and the biotic interactions between them can influence their abundances and distributions. In Argentina, Ae. aegypti is widely distributed in the north and center regions of the country, with temperate and subtropical climate, while both are sympatric only in the northeastern area of the subtropical region. Interspecific and intraspecific larval competition for food was evaluated to assess if their interaction influences on patterns of abundance and distribution. Finite rates of increase and survivorship for each species were estimated and the effects of mosquito density ratio and detritus availability were determined. The Lambda (λ′) index of population performance of both showed there is no competitive exclusion pattern. However, survival of Ae. albopictus was negatively affected by the presence of Ae. aegypti. These results suggest one possible explanation for the codominance pattern of both species display in rural regions of the southernmost distribution of Ae. albopictus in South America. They also show Ae. aegypti as a potential biotic barrier for the expansion of Ae. albopictus as was reported in regions of the United States.