Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect biomarkers of nanoparticle-exposed workers: A scoping review

The widespread and increasing use of engineered nanomaterials (i.e., particulate materials measuring 1–100 nanometers (nm) in at least one dimension) poses a potential health and safety risk to exposed workers. The unique properties of nanomaterials have made nanomaterials useful in multiple industries. However, their production and use may compromise worker health, presenting an emerging occupational health hazard, the acute and chronic effects of which have not been fully assessed. In this scoping review, we critically assess the literature on biomarkers of effect from nanoparticles and discuss the utility of biomonitoring as a means of assessing the physiological effects of nanoparticle exposure among nanotechnology workers. Multiple databases were queried based on select inclusion and exclusion criteria according to PRISMA guidelines, and articles were independently screened by two topic experts. Of 286 articles initially retrieved, 28 were included after screening and eligibility. The reviewed articles indicated that sensitive effect biomarkers could reflect early health effects of exposure to nanoparticles in the workplace and may be useful for monitoring toxicological effects and associated risks.
Insights into the Y chromosome human diversity in Uruguay

With regard to the origin of its population and microevolutionary processes, Uruguay exhibits distinctive features that distinguish it from other countries in Latin America, while at the same time sharing several similarities. In this article, we will focus on the variability of paternal genetic lineages in two geographical regions with different histories that can be considered as examples of distinct populations for the continent. In general terms, the genetic diversity is a result of different demographic processes related to the American conquest and colonisation. These resulted in distinct ancestral components which vary geographical and depend on the distribution by sex within these components. In Uruguay, native maternal haplogroups are significantly more frequent in the North. Although there are several studies about the geneticvariability of Uruguay, little is known about male genetic lineages.
The minichromosome maintenance complex drives esophageal basal zone hyperplasia

Eosinophilic esophagitis (EoE) is a chronic gastrointestinal disorder characterized by food antigen–driven eosinophilic inflammation and hyperproliferation of esophageal mucosa. By utilizing a large-scale, proteomic screen of esophageal biopsies, we aimed to uncover molecular drivers of the disease. Proteomic analysis by liquid chromatography–tandem mass spectrometry identified 402 differentially expressed proteins (DEPs) that correlated with the EoE transcriptome. Immune cell–related proteins were among the most highly upregulated DEPs in EoE compared with controls, whereas proteins linked to epithelial differentiation were primarily downregulated. Notably, in the inflamed esophageal tissue, all 6 subunits of the minichromosome maintenance (MCM) complex, a DNA helicase essential for genomic DNA replication, were significantly upregulated at the gene and protein levels. Furthermore, treating esophageal epithelial cells with a known inhibitor of the MCM complex (ciprofloxacin) blocked esophageal epithelial proliferation. In a murine model of EoE driven by overexpression of IL-13, ciprofloxacin treatment decreased basal zone thickness and reduced dilated intercellular spaces by blocking the transition of epithelial cells through the S-phase of the cell cycle. Collectively, a broad-spectrum proteomic screen has identified the involvement of the MCM complex in EoE and has highlighted MCM inhibitors as potential therapeutic agents for the disease.
TARPγ2 Is Required for Normal AMPA Receptor Expression and Function in Direction-Selective Circuits of the Mammalian Retina

Abstract AMPA receptors (AMPARs) are the major mediators of fast excitatory neurotransmission in the retina as in other parts of the brain. In most neurons, the synaptic targeting, pharmacology, and function of AMPARs are influenced by auxiliary subunits including the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is unclear which TARP subunits are present at retinal synapses and how they influence receptor localization and function. Here, we show that TARPɣ2 (stargazin) is associated with AMPARs in the synaptic layers of the mouse, rabbit, macaque, and human retina. In most species, TARPɣ2 expression was high where starburst amacrine cells (SACs) ramify and transcriptomic analyses suggest correspondingly high gene expression in mouse and human SACs. Synaptic expression of GluA2, GluA3, and GluA4 was significantly reduced in a mouse mutant lacking TARPɣ2 expression (stargazer mouse; stg), whereas GluA1 levels were unaffected. AMPAR-mediated light-evoked EPSCs in ON-SACs from stg mice were ∼30% smaller compared with heterozygous littermates. There was also loss of a transient ON pathway-driven GABAergic input to ON-SACs in stg mutants. Direction-selective ganglion cells in the stg mouse showed normal directional tuning, but their surround inhibition and thus spatial tuning was reduced. Our results indicate that TARPɣ2 is required for normal synaptic expression of GluA2, GluA3, and GluA4 in the inner retina. The presence of residual AMPAR expression in the stargazer mutant suggests that other TARP subunits may compensate in the absence of TARPɣ2.
Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers

Abstract In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development. Graphical abstract
The quest for good genes: Epigamic traits, fitness, MHC and multilocus heterozygosity in the guppy

The ‘good genes’ hypothesis for the evolution of male secondary sexual traits poses that female preferences for such traits are driven by indirect genetic benefits. However, support for the hypothesis remains ambiguous, and, in particular, the genetic basis for the benefits has rarely been investigated. Here, we use seminatural populations of Trinidadian guppies to investigate whether sexually selected traits (orange, black and iridescent colouration, gonopodium length and body size) predict fitness measured as the number of grandoffspring, a metric that integrates across fitness components and sexes. Furthermore, we tested whether two potential sources of genetic benefits—major histocompatibility complex (MHC) genotypes and multilocus heterozygosity (MLH)—are significant predictors of fitness and of the size of sexually selected traits. We found a significant, nonlinear effect of the area of black pigmentation and male body size on the number of grandoffspring, suggesting stabilizing selection on black area, and nonlinear selection favouring small body size. MLH was heritable (h2 = 0.14) and significantly predicted the number of grandoffspring, indicating the potential for genetic benefits based on heterozygosity. We also found support for local heterozygosity effects, which may reflect a noneven distribution of genetic load across the genome. MHC genotype was not significantly associated with any tested fitness component, or with the load of Gyrodactylus parasites. Neither MHC nor MLH was significant predictor of sexually selected traits. Overall, our results highlight the role of heterozygosity in determining fitness, but do not provide support for male sexually selected traits being indicators of genetic quality.
Fundamental Issues, Technology Development, and Challenges of Boiling Heat Transfer, Critical Heat Flux, and Two-Phase Flow Phenomena with Nanofluids

ABSTRACT This paper presents a comprehensive and critical review of studies on nucleate pool boiling heat transfer, flow boiling heat transfer, critical heat flux (CHF), and two-phase flow phenomena with nanofluids. First, general analysis of the available studies on the relevant topics is presented. Then, studies of physical properties of nanofluids are discussed. Next, boiling heat transfer, CHF phenomena, and the relevant physical mechanisms are explored. Finally, future research needs have been identified according to the review and analysis. As the first priority, the physical properties of nanofluids have a significant effect on the boiling and CHF characteristics but the lack of the accurate knowledge of the physical properties has greatly limited the studies. Fundamentals of boiling heat transfer and CHF phenomena with nanofluids have not yet been well understood. Flow regimes are important in understanding the boiling and CHF phenomena and should be focused on. Two-phase pressure drops of nanofluids should also be studied. Furthermore, economic evaluation of the enhancement technology with nanofluid should be considered for the new heat transfer enhancement technology with nanofluids. Finally, applied research should be targeted to achieve an enabling practical heat transfer and CHF enhancement technology for engineering application with nanofluids.
Trabecular bone structure of the proximal capitate in extant hominids and fossil hominins with implications for midcarpal joint loading and the dart-thrower's motion.

OBJECTIVES This research examines whether the distribution of trabecular bone in the proximal capitates of extant hominids, as well as several fossil hominin taxa, is associated with the oblique path of the midcarpal joint known as the dart-thrower's motion (DTM). MATERIALS AND METHODS We analyzed proximal capitates from extant (Pongo n = 12; Gorilla n = 11; Pan n = 10; fossil and recent Homo sapiens n = 29) and extinct (Australopithecus sediba n = 2; Homo naledi n = 1; Homo floresiensis n = 2; Neandertals n = 3) hominids using a new canonical holistic morphometric analysis, which quantifies and visualizes the distribution of trabecular bone using relative bone volume as a fraction of total volume (rBV/TV). RESULTS Homo sapiens and Neandertals had a continuous band of high rBV/TV that extended across the scaphoid, lunate, and hamate subarticular regions, but other fossil hominins and extant great apes did not. A. sediba expressed a distinct combination of human-like and Pan-like rBV/TV distribution. Both H. floresiensis and H. naledi had high rBV/TV on the ulnar-side of the capitate but low rBV/TV on the radial-side. CONCLUSION The proximal capitates of H. sapiens and Neandertals share a distinctive distribution of trabecular bone that suggests that these two species of Homo regularly load(ed) their midcarpal joints along the full extent of the oblique path of the DTM. The observed pattern in A. sediba suggests that human-like stress at the capito-scaphoid articular surface was combined with Pan-like wrist postures, whereas the patterns in H. floresiensis and H. naledi suggest their midcarpal joints were loaded differently from that of H. sapiens and Neandertals.
Can prospect theory explain the disposition effect? An analysis based on value function

Purpose The prospect theory is potentially an essential ingredient in modeling the disposition effect. However, many scholars have tried to explain the disposition effect with the help of prospect theory and they came to opposite conclusions. The purpose of this paper is to examine the impact of value function of the prospect theory on predicting the disposition effect. Design/methodology/approach Lagrange multiplier optimization and dynamic programming method are used to solve the representative investor’s optimal portfolio choice problem. Furthermore, numerical simulation is used to compare the prediction ability of different types of value function. Findings The authors support that the value function has a crucial role in predicting the disposition effect with prospect theory, i.e. the curvature and boundedness of the value function may influence the performance of applying the prospect theory in the disposition effect. They conclude that a piecewise negative exponential value function can predict the disposition effect, while others like the piecewise power value function may not. Originality/value Extant literature about modeling the disposition effect with the prospect theory mostly focus on the time when gain-loss utility occurs or the selection of reference point. This paper based on the value function properties provides a new perspective in analyzing the crucial role that value function has in predicting financial market anomalies.
Targets for obstructive sleep apnea pharmacotherapy: principles, approaches, and emerging strategies

ABSTRACT Introduction Obstructive sleep apnea (OSA) is a common and serious breathing disorder. Several pathophysiological factors predispose individuals to OSA. These factors are quantifiable, and modifiable pharmacologically. Areas covered Four key pharmacotherapeutic targets are identified and mapped to the major determinants of OSA pathophysiology. PubMed and Clinicaltrials.gov were searched through April 2023. Expert opinion Target #1: Pharyngeal Motor Effectors. Increasing pharyngeal muscle activity and responsivity with noradrenergic-antimuscarinic combination is central to recent breakthrough OSA pharmacotherapy. Assumptions, knowledge gaps, future directions, and other targets are identified. #2: Upper Airway Sensory Afferents. There is translational potential of sensitizing and amplifying reflex pharyngeal dilator muscle responses to negative airway pressure via intranasal delivery of new potassium channel blockers. Rationales, advantages, findings, and potential strategies to enhance effectiveness are identified. #3: Chemosensory Afferents and Ventilatory Control. Strategies to manipulate ventilatory control system sensitivity by carbonic anhydrase inhibitors are supported in theory and initial studies. Intranasal delivery of agents to stimulate central respiratory activity are also introduced. #4: Sleep-Wake Mechanisms. Arousability is the fourth therapeutic target rationalized. Evolving automated tools to measure key pathophysiological factors predisposing to OSA will accelerate pharmacotherapy. Although not currently ready for general clinical settings, the identified targets are of future promise.
Global well-being, anxiety, social isolation, and emotional support among hospitalists during COVID-19 and Mpox outbreaks

ABSTRACT Objective The Coronavirus Disease-19 (COVID-19) pandemic caused a decline in hospitalist wellness. The COVID-19 pandemic has evolved, and new outbreaks (i.e. Mpox) have challenged healthcare systems. The objective of the study was to assess changes in hospitalist wellness and guide interventions. Methods We surveyed hospitalists (physicians and advanced practice providers [APPs]), in May 2021 and September 2022, at a healthcare system’s 16 hospitals in four US states using PROMIS® measures for global well-being, anxiety, social isolation, and emotional support. We compared wellness score between survey periods; in the September 2022 survey, we compared wellness scores between APPs and physicians and evaluated the associations of demographic and hospital characteristics with wellness using logistic (global well-being) and linear (anxiety, social isolation, emotional support) regression models. Results In May 2021 vs. September 2022, respondents showed no statistical difference in top global well-being for mental health (68.4% vs. 57.4%) and social activities and relationships (43.8% vs. 44.3%), anxiety (mean difference: +0.8), social isolation (mean difference: +0.5), and emotional support (mean difference: −1.0) (all, p ≥ 0.05). In September 2022, in logistic regression models, APPs, compared with physicians, had lower odds for top (excellent or very good) global well-being mental health (odds ratio [95% CI], 0.31 [0.13–0.76]; p < 0.05). In linear regression models, age <40 vs. ≥40 years was associated with higher anxiety (estimate ± standard error, 2.43 ± 1.05; p < 0.05), and concern about contracting COVID-19 at work was associated with higher anxiety (3.74 ± 1.10; p < 0.01) and social isolation (3.82 ± 1.21; p < 0.01). None of the characteristics showed association with change in emotional support. In September 2022, there was low concern for contracting Mpox in the community (4.6%) or at work (10.0%). Conclusion In hospitalists, concern about contracting COVID-19 at work was associated with higher anxiety and social isolation. The unchanged wellness scores between survey periods identified opportunities for intervention. Mpox had apparently minor impact on wellness.
Predictive impact of human papillomavirus circulating tumor DNA in treatment response monitoring of HPV‐associated cancers; a meta‐analysis on recurrent event endpoints

HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be used as a promising marker for predicting recurrence in HPV‐related cancers remains to be validated. Here we conducted a systematic review and meta‐analysis to assess its effectiveness in predicting treatment response.
Novel Therapeutics: Can Hydrogels Work to Treat Kidney Disease?

Background: Hydrogels are water-swollen networks that can be made from a variety of natural and synthetic polymers. Numerous chemistries can be utilized to formulate hydrogels that are injectable, enabling facile in situ delivery of therapeutics such as cytokines or cells. Summary: Cells delivered via injectable hydrogels survive injection better than cells injected in saline or media suspension. Several materials have been used to investigate the use of injectable hydrogels to treat animal models of kidney disease. Species studied to date include mice and rats. This review summarizes the various materials, encapsulated therapeutic payloads, and preclinical models of kidney disease employed to investigate hydrogel injection. Transcutaneous measurements of glomerular filtration rate have demonstrated that delivery of hydrogels under the kidney capsule does not impair kidney function. Key Messages: Studies to date have shown the safety and efficacy of hydrogel therapies to treat kidney disease, and numerous studies have demonstrated that hydrogel therapy alone reduces inflammation and fibrosis.
A Nomogram for Predicting Survival in Advanced Non-Small-Cell Lung Carcinoma Patients: A Population-Based Study

Abstract Non-small-cell lung cancer (NSCLC) remains the most common malignant cancer. We identified 43140 advanced NSCLC patients from the SEER database to develop and validate a new prognostic model. The prognostic performance was evaluated by P value, concordance index, net reclassification index, integrated discrimination improvement, and decision curve analysis. The following variables were contained in the final prognostic model: age, sex, race, TNM stage, and grade and treatment options. Compared to the AJCC staging system, this prognostic model is conducive to the implementation of individualized clinical treatment schemes and can be an important part of the precise medical care of NSCLC tumors.
Global smoothness preservation by singular integrals

Here is established that the well-known singular integrals of Picard, Poisson-Cauchy and Gauss- Weierstrass fulfill the "global smoothness preservation" property. J. e. , they "ripple" less than the function they are applied on, that is producing a nice approximation to the unit. The associated inequalities are sharp.
Understanding Acceptability of Group Leisure Activities Used to Address Loneliness Among People Living With Dementia: An Exploratory Mixed-Methods Study

Abstract This mixed-methods complementarity study explored family members’, friends’, and health care providers’ perspectives of acceptability of group leisure activities as an intervention for loneliness experienced by older adults living with dementia. A sample of 25 family members, friends, and health care providers of people living with dementia in ON rated the acceptability of group leisure activities (adapted Treatment Perception and Preference questionnaire) and discussed their ratings in an interview. Quantitative (descriptive statistics) and qualitative (conventional content analysis) results were integrated to understand acceptability. Participants viewed group leisure activities as effective, logical, and suitable for use with people living with dementia. Participants described the need for flexible programs, careful facilitation, and attention to activity selection. Group leisure activities were seen as low risk, but stigmas related to dementia could prevent participation. The findings inform the design of acceptable group leisure activities, promoting their use to address loneliness in people living with dementia.
ADOL - Markovian approximation of rough lognormal model

In this paper we apply Markovian approximation of the fractional Brownian motion (BM), known as the Dobric-Ojeda (DO) process, to the fractional stochastic volatility model where the instantaneous variance is modelled by a lognormal process with drift and fractional diffusion. Since the DO process is a semi-martingale, it can be represented as an \Ito diffusion. It turns out that in this framework the process for the spot price $S_t$ is a geometric BM with stochastic instantaneous volatility $\sigma_t$, the process for $\sigma_t$ is also a geometric BM with stochastic speed of mean reversion and time-dependent colatility of volatility, and the supplementary process $\calV_t$ is the Ornstein-Uhlenbeck process with time-dependent coefficients, and is also a function of the Hurst exponent. We also introduce an adjusted DO process which provides a uniformly good approximation of the fractional BM for all Hurst exponents $H \in [0,1]$ but requires a complex measure. Finally, the characteristic function (CF) of $\log S_t$ in our model can be found in closed form by using asymptotic expansion. Therefore, pricing options and variance swaps (by using a forward CF) can be done via FFT, which is much easier than in rough volatility models.