Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood–brain barrier permeable benzylpiperidin‐4‐yl‐linked benzylamino benzamides as dual cholinesterase inhibitors

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder involving various pathological events. The existing options for managing the disease utterly rely on cholinesterase (ChE) inhibitors. In recent years, the dual inhibition of ChEs as a potential AD therapeutics has substantially attracted the attention of medicinal chemists. Recently, we reported benzyl piperidinyl‐linked methoxy‐naphthamides as dual ChE inhibitors. Herein, we investigated the peripheral anionic binding site‐binding methoxy‐naphthamide fragment that yielded benzyl piperidinyl‐linked benzyl aminobenzamide as another class of dual ChE inhibitors. The 3,5‐dimethoxy benzyl aminobenzamide, 8c1, exhibits inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with half‐maximal inhibitory concentration values of 0.61 and 2.04 µM, respectively. The enzyme kinetics and molecular modeling study indicated the noncompetitive and mixed‐type mode of inhibition for AChE and BChE with ki values of 0.14 and 0.46 µM, respectively. The derivative 8c1 crosses the blood–brain barrier as indicated by the Pe value of 14.34 × 10−6cm/s in the parallel artificial membrane permeability assay. Besides this, it also inhibits the self‐aggregation of amyloid‐β. The results presented herein indicate the potential of benzamide 8c1 for further investigation in preclinical models of AD.
Transzonal projections: Essential structures mediating intercellular communication in the mammalian ovarian follicle

The development of germ cells relies on contact and communication with neighboring somatic cells that provide metabolic support and regulatory signals. In females, contact is achieved through thin cytoplasmic processes that project from follicle cells surrounding the oocyte, extend through an extracellular matrix (ECM) that lies between them, and reach its surface. In mammals, the ECM is termed the zona pellucida and the follicular cell processes are termed transzonal projections (TZPs). TZPs become detectable when the zona pellucida is laid down during early folliculogenesis and subsequently increase in number as oocyte growth progresses. They then rapidly disappear at the time of ovulation, permanently breaking germ‐soma contact. Here we review the life cycle and functions of the TZPs. We begin with an overview of the morphology and cytoskeletal structure of TZPs, in the context of actin‐ and tubulin‐based cytoplasmic processes in other cell types. Next, we review the roles played by TZPs in mediating progression through successive stages of oocyte development. We then discuss two mechanisms that may generate TZPs—stretching at pre‐existing points of granulosa cell‐oocyte contact and elaboration of new processes that push through the zona pellucida—as well as gene products implicated in their formation or function. Finally, we describe the signaling pathways that cause TZPs to be retracted in response to signals that also trigger meiotic maturation and ovulation of the oocyte. The principles and mechanisms that govern TZP behavior may be relevant to understanding communication between physically separated cells in other physiological contexts.
Ergodic conditions and spectral properties for A-contractions

In this paper the canonical representation of an \(A\)-contraction \(T\) on a Hilbert space \(\mathcal{H}\) is used to obtain some conditions concerning the concept of \(A\)-ergodicity studied in [L. Suciu, Orthogonal decompositions induced by generalized contractions, Acta Sci. Math. (Szeged) 70 (2004), 751–765; L. Suciu, On the ergodic \(A\)-contractions, Analele Universitaţii de Vest din Timisoara, Ser. Mat. -Inf. 2 (2004), 115–136; L. Suciu, Ergodic properties for regular \(A\)-contractions, Integral Equations and Operator Theory 56 (2006) 2, 285–299; L. Suciu, Ergodic properties and saturation for \(A\)-contractions, Operator Theory: Advances and Applications; Proceeding of 20th Conference on Operator Theory, Timisoara 2004, Theta 2006, 225–242]. The regular case and the case of \(\mathcal{R}(A)\) closed are considered, and specifically, the \(TT^{*}\)-contractions are studied. Some spectral properties are also given for certain particular class of \(A\)-isometries.
The use of patient experience feedback in rehabilitation quality improvement and codesign activities: Scoping review of the literature

Objective To characterize the literature, reported enablers, and gaps on the use of patient experience feedback for person-centered rehabilitation quality improvement and codesign activities. Design Scoping Review. Data sources Scientific databases (PubMed, CINAHL, Rehabdata, Scopus, Web of Science, ProQuest), website searches (e.g. Beryl Institute), snowballing, and key-informant recommendations. Methods Two independent reviewers performed title and abstract screenings and full-text reviews. Eligibility focused on English-language, peer-reviewed (all time) and gray literature (last five years) that used patient experience feedback in rehabilitation improvement activities. The aims, settings, methods, findings, implications, and reported limitations were extracted, followed by content analyses identifying reported enablers and gaps. Results Among the 901 unique references and 52 full texts reviewed, ten were included: four used patient experience surveys for improving patient experiences; six used codesign methodologies to engage patient feedback in service improvement activities. Implementation enablers included securing managerial support, having a structured methodology and facilitator, using efficient processes, engaging staff experiences, and using appreciative inquiry. Reported study gaps included limited follow-up, low sample sizes, analytical limitations, lack of reported limitations, or narrow range of perspectives (e.g. not from people with severe impairments). Conclusion Few examples of the use of patient experience feedback in quality improvement or codesign activities were found in the rehabilitation literature. Patient experience improvement activities relied exclusively on retrospective survey data, which were not combined with often more actionable forms (e.g. qualitative, real time) of patient experience feedback. Further research might consider design of activities that collect and use patient experience feedback for rehabilitation service improvements.
Policies to Sustain Employment Among Family Caregivers: The Family Caregiver Perspective

The work of caregiving can make it difficult to sustain employment. This study aimed to clarify what family caregivers themselves think is important in remaining employed, as part of work mandated under the Recognize, Assist, Include, Support, and Engage (RAISE) Family Caregivers Act of 2018. Data came from a Request for Information promulgated by the Administration for Community Living, resulting in 1147 family caregiver responses, and 12 focus groups. Findings support many goals identified by caregiver-advocates, such as expanding the Family and Medical Leave Act, and access to paid time off and sick leave; caregivers also value flexible work arrangements. However, the study further revealed a need for supportive work environments that protect caregivers against workplace discrimination and negative attitudes held by both managers and colleagues, and thus for employer education about the caregiving experience as well as caregivers’ needs for workplace supports and benefits, and possibly anti-discrimination legislation.
“Psychological characteristics of functional respiratory disorders in children and adolescents—Pilot study”

Aim of our prospective, multicenter, nonrandomized study was to identify characteristic features and similarities of patients with functional respiratory disorders regarding socio‐familial and behavioral aspects, in comparison with controls in a cross‐sectional analysis using standardized psychological questionnaires. Furthermore, we investigated the longitudinal outcome of symptoms, effects of primary interventions and the stability of psychological traits 6 months after diagnosis and primary intervention.
Comprehensive analysis identifies as a critical prognostic prediction gene in breast cancer

Abstract Background: Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC. Methods: The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan–Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues. Results: The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P < 0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P < 0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC (P < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway. Conclusions: Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
Coping‐resilience profiles and experiences of stress in autistic adults

Emerging studies allude to high stress in autistic adults. Considering the detrimental impact of stress on health outcomes, examining individual resources which may influence the extent to which stress is experienced (e.g., coping and resilience) is vital. Using a person‐focused approach, this study aimed to identify coping‐resilience profiles, and examine their relations to general perceived stress and daily hassles in a sample of autistic adults (N = 86; aged 19–74 years). Cluster analysis identified four coping‐resilience profiles (i.e., high cope/ low resilience, low cope/ high resilience, engage cope/ high resilience, and disengage cope/ low resilience). The high cope/ low resilience and disengage cope/ low resilience groups had significantly higher general perceived stress than the remaining groups. No significant group differences were noted in relation to daily hassles. Jointly addressing coping and resilience may be beneficial on the perceived stress experienced in autistic adults. The use of coping‐resilience profiles may also allow for the personalization of stress management and support options in the autistic adult population.
MULTIVARIATE REGRESSION TREES: A NEW TECHNIQUE FOR MODELING SPECIES-ENVIRONMENT RELATIONSHIPS

Multivariate regression trees (MRT) are a new statistical technique that can be used to explore, describe, and predict relationships between multispecies data and en- vironmental characteristics. MRT forms clusters of sites by repeated splitting of the data, with each split defined by a simple rule based on environmental values. The splits are chosen to minimize the dissimilarity of sites within clusters. The measure of species dis- similarity can be selected by the user, and hence MRT can be used to relate any aspect of species composition to environmental data. The clusters and their dependence on the en- vironmental data are represented graphically by a tree. Each cluster also represents a species assemblage, and its environmental values define its associated habitat. MRT can be used to analyze complex ecological data that may include imbalance, missing values, nonlinear relationships between variables, and high-order interactions. They can also predict species composition at sites for which only environmental data are available. MRT is compared with redundancy analysis and canonical correspondence analysis using simulated data and a field data set.
Clinical outcomes and echocardiographic characteristics between African American and Caucasian patients with acute pulmonary embolism

Background Despite socioeconomic disparities, no association between clinical presentation and poor outcomes explains a higher mortality in African Americans with pulmonary embolism (PE). The objective is to identify the co-morbidities and echocardiographic characteristics associated with increased mortality in African American patients. Methods This is a cross-sectional study of Caucasian or African American patients with PE diagnosed between October 2015 and December 2017 at University of Maryland Medical Center. The outcomes were in-hospital death, length of stay, and bleeding. Results There were 303 African Americans and 343 Caucasians. Caucasians were older (p = 0.007), males (p = 0.01) with history of coronary artery revascularization (CABG (p = 0.001), coronary stents (p = 0.001)), trauma (p = 0.007), and/or recent surgeries (p = 0.0001). African Americans exhibited higher rates of diabetes (p = 0.01), chronic kidney disease (p = 0.0005), and smoking (p = 0.04). Severity of PE was similar between groups and there was no difference in clot burden size. African Americans had more right ventricular strain on Computer Tomography (p = 0.001) and echocardiogram (p = 0.004); also, underfilled left ventricles (p = 0.02) and higher right ventricular systolic pressures (p = 0.001). There was no difference in hospital mortality (7.1% vs. 7.9%, p = 0.71), length of stay (13.1 ± 16.7 vs 12.8 ± 14.9, p = 0.80) and bleeding (9.0% vs.8.3%. p = 0.72). Mortality was higher in African Americans who received advanced therapies (3.8% vs. 18.8%, p = 0.02). The risk of death increased with age (OR 1.04; 95%CI 1.020–1.073) and with advanced therapies (OR 2.43; 95%CI 1.029–5.769). Conclusions Differences in co-morbidities, radiologic findings, and echocardiographic characteristics that may contribute to higher mortality in African American patients, specifically those receiving advanced therapies.
Monitoring nature's calendar from space: Emerging topics in land surface phenology and associated opportunities for science applications

Vegetation phenology has been viewed as the nature's calendar and an integrative indicator of plant‐climate interactions. The correct representation of vegetation phenology is important for models to accurately simulate the exchange of carbon, water, and energy between the vegetated land surface and the atmosphere. Remote sensing has advanced the monitoring of vegetation phenology by providing spatially and temporally continuous data that together with conventional ground observations offers a unique contribution to our knowledge about the environmental impact on ecosystems as well as the ecological adaptations and feedback to global climate change. Land surface phenology (LSP) is defined as the use of satellites to monitor seasonal dynamics in vegetated land surfaces and to estimate phenological transition dates. LSP, as an interdisciplinary subject among remote sensing, ecology, and biometeorology, has undergone rapid development over the past few decades. Recent advances in sensor technologies, as well as data fusion techniques, have enabled novel phenology retrieval algorithms that refine phenology details at even higher spatiotemporal resolutions, providing new insights into ecosystem dynamics. As such, here we summarize the recent advances in LSP and the associated opportunities for science applications. We focus on the remaining challenges, promising techniques, and emerging topics that together we believe will truly form the very frontier of the global LSP research field.
Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta‐analysis

This study aimed to map systemic alterations predisposing to oral squamous cell carcinoma (OSCC) onset. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. Five databases were used to access (1) reports of OSCC co‐occurring in patients with systemic conditions, (2) prevalence of OSCC among these patients, and (3) clinicopathological profiles. Data from more than 1 million patients worldwide showed that Fanconi's anemia, xeroderma pigmentosum, dyskeratosis congenital, chronic fatigue syndrome, and patients post bone marrow transplantation (BMT) present increased risk for OSCC development. The overall prevalence of OSCC in syndromic patients and post‐BMT were 0.65% (95% CI = 0.13–3.11, p < 0.01) and 5.83% (95% CI = 0.00–30.90, p < 0.01), respectively. The certainty of the evidence was moderate. This study demonstrated that some systemic conditions predispose to OSCC. These results present an impact on the screening of OSCC in systemically compromised patients.
Strain propagation in layered two-dimensional halide perovskites

Impulsive light excitation presents a powerful tool for investigating the interdependent structural and electronic responses in layered two-dimensional (2D) halide perovskites. However, detailed understanding of the nonlinear lattice dynamics in these soft hybrid materials remains limited. Here, we explicate the intrinsic strain propagation mechanisms in 2D perovskite single crystals using transient reflection spectroscopy. Ultrafast photoexcitation leads to the generation of strain pulses via thermoelastic (TE) stress and deformation potential (DP) interaction whence their detection proceed via Brillouin scattering. Using a two-temperature model together with strain wave propagation, we discern the TE and DP contributions in strain generation. Hot carrier cooling plays a dominant role in effecting the weak modulation amplitude. Out-of-plane lattice stiffness is reduced by the weak van der Waals bond between organic layers, resulting in a slow strain propagation velocity. Our findings inject fresh insights into the basic strain properties of layered perovskites critical for manipulating their functional properties for new applications.
Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna

Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life.
Second-order BSDEs with general reflection and Dynkin games under uncertainty

The aim of this paper is twofold. First, we extend the results of (32) concerning the existence and uniqueness of second-order reflected 2BSDEs to the case of upper obstacles. Then, under some regularity assumptions on one of the barriers, similar to the ones in (9), and when the two barriers are completely separated, we provide a complete wellposedness theory for doubly reflected second-order BSDEs. We also show that these objects are related to non-standard optimal stopping games, thus generalizing the connection between DRBSDEs and Dynkin games first proved by Cvitanic and Karatzas (10). More precisely, we show that the second order DRBSDEs provide solutions of what we call uncertain Dynkin games and that they also allow us to obtain super and subhedging prices for American game options (also called Israeli options) in financial markets with volatility uncertainty. �
Lagrangian Intersection Theory - Finite dimensional ap - praoch

A Minimum Delay Module Assembly, having unrestricted accessibility for servicing, that provides substantially constant electrical and thermal environments for all portions of the assembly regardless of configuration. The assembly comprises a plurality of vertical page modules in which each page module is vertically hinged to the adjacent page module. Electrical interconnections are provided between the page modules by means of cable assemblies which enter each page module in the edge thereof adjacent said hinges. Individual self contained cooling means are provided for each page module so that the flow of air is up through the bottom of each page module and out through the top thereof. Resilient conduit means may be utilized to supply a pressurized coolant to each page module regardless of the configuration of the module assembly. The complete vertically hinged module assembly is supported on a base assembly, including a foraminous base member sufficiently large to support said hinged module assembly when in the closed position and further including at least one foraminous foldable shelf which folds out of the way when the assembly is in the closed position and folds to a position coplanar with said base member when in the "open for service" position. The base assembly further includes a chamber or space under the base member which provides for an unrestricted flow of air up through said base member.
THREE-DIMENSIONAL HYDRODYNAMICAL SIMULATIONS OF THE SUPERNOVAE-DRIVEN GAS LOSS IN THE DWARF SPHEROIDAL GALAXY URSA MINOR

As is usual in dwarf spheroidal galaxies, today the Local Group galaxy Ursa Minor is depleted of its gas content. How this galaxy lost its gas is still a matter of debate. To study the history of gas loss in Ursa Minor, we conducted the first three-dimensional hydrodynamical simulations of this object, assuming that the gas loss was driven by galactic winds powered only by type II supernovae (SNe II). The initial gas setup and supernova (SN) rates used in our simulations are mainly constrained by the inferred star formation history and the observed velocity dispersion of Ursa Minor. After 3 Gyr of evolution, we found that the gas removal efficiency is higher when the SN rate is increased, and also when the initial mean gas density is lowered. The derived mass-loss rates are systematically higher in the central regions ( < 300 ? > pc), even though such a relationship has not been strictly linear in time and in terms of the galactic radius. The filamentary structures induced by Rayleigh–Taylor instabilities and the concentric shells related to the acoustic waves driven by SNe can account for the inferred mass losses from the simulations. Our results suggest that SNe II are able to transfer most of the gas from the central region outward to the galactic halo. However, other physical mechanisms must be considered in order to completely remove the gas at larger radii.