Miracle-dz/UniFAR-FTUs huggingface dataset:
The Whi2p-Psr1p/Psr2p complex regulates interference competition and expansion of cells with competitive advantage in yeast colonies

Significance Population structure and spatiotemporal dynamics in natural microbial communities largely depend on interactions of constituent cells with each other and the environment. Using a yeast colony model, we identified the Whi2p-Psr1p/Psr2p complex as an important interference competition regulator that strongly influences cell interactions, pattern formation, and adaptive potential in dense yeast populations. In the presence of this complex, the offspring of potentially fitter mutants that emerged in developing colonies rapidly grow and outcompete parental cells by forming papillae specifically localized within the colony. Papillae expansion disrupts colony organization in a manner that resembles tissue disruption by tumor cells. Cells with a dysfunctional complex acquire interaction-specific fitness dominance and rapidly exclude cells with a functional complex from the population. Yeast form complex highly organized colonies in which cells undergo spatiotemporal phenotypic differentiation in response to local gradients of nutrients, metabolites, and specific signaling molecules. Colony fitness depends on cell interactions, cooperation, and the division of labor between differentiated cell subpopulations. Here, we describe the regulation and dynamics of the expansion of papillae that arise during colony aging, which consist of cells that overcome colony regulatory rules and disrupt the synchronized colony structure. We show that papillae specifically expand within the U cell subpopulation in differentiated colonies. Papillae emerge more frequently in some strains than in others. Genomic analyses further revealed that the Whi2p-Psr1p/Psr2p complex (WPPC) plays a key role in papillae expansion. We show that cells lacking a functional WPPC have a sizable interaction-specific fitness advantage attributable to production of and resistance to a diffusible compound that inhibits growth of other cells. Competitive superiority and high relative fitness of whi2 and psr1psr2 strains are particularly pronounced in dense spatially structured colonies and are independent of TORC1 and Msn2p/Msn4p regulators previously associated with the WPPC function. The WPPC function, described here, might be a regulatory mechanism that balances cell competition and cooperation in dense yeast populations and, thus, contributes to cell synchronization, pattern formation, and the expansion of cells with a competitive fitness advantage.
β-Glucocerebrosidase activity in GBA-linked Parkinson disease

Objective To test the relationship between clinically relevant types of GBA mutations (none, risk variants, mild mutations, severe mutations) and β-glucocerebrosidase activity in patients with Parkinson disease (PD) in cross-sectional and longitudinal case-control studies. Methods A total of 481 participants from the Harvard Biomarkers Study (HBS) and the NIH Parkinson's Disease Biomarkers Program (PDBP) were analyzed, including 47 patients with PD carrying GBA variants (GBA-PD), 247 without a GBA variant (idiopathic PD), and 187 healthy controls. Longitudinal analysis comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years (interquartile range, 1–2 years). Results β-Glucocerebrosidase activity was low in blood of patients with GBA-PD compared to healthy controls and patients with idiopathic PD, respectively, in HBS (p < 0.001) and PDBP (p < 0.05) in multivariate analyses adjusting for age, sex, blood storage time, and batch. Enzyme activity in patients with idiopathic PD was unchanged. Innovative enzymatic quantitative trait locus (xQTL) analysis revealed a negative linear association between residual β-glucocerebrosidase activity and mutation type with p < 0.0001. For each increment in the severity of mutation type, a reduction of mean β-glucocerebrosidase activity by 0.85 μmol/L/h (95% confidence interval, −1.17, −0.54) was predicted. In a first longitudinal analysis, increasing mutation severity types were prospectively associated with steeper declines in β-glucocerebrosidase activity during a median 2 years of follow-up (p = 0.02). Conclusions Residual activity of the β-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in PD. β-Glucocerebrosidase activity is a quantitative endophenotype that can be monitored noninvasively and targeted therapeutically.
European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population

Jens Cosedis Nielsen (EHRA Chair), Yenn-Jiang Lin (APHRS Co-Chair), Marcio Jansen de Oliveira Figueiredo (LAHRS Co-Chair), Alireza Sepehri Shamloo, Alberto Alfie, Serge Boveda, Nikolaos Dagres, Dario Di Toro, Lee L. Eckhardt, Kenneth Ellenbogen, Carina Hardy, Takanori Ikeda, Aparna Jaswal, Elizabeth Kaufman, Andrew Krahn, Kengo Kusano, Valentina Kutyifa, Han S. Lim, Gregory Y.H. Lip, Santiago Nava-Townsend, Hui-Nam Pak, Gerardo Rodríguez Diez, William Sauer, Anil Saxena, Jesper Hastrup Svendsen, Diego Vanegas, Marmar Vaseghi, Arthur Wilde, T. Jared Bunch (HRS Co-Chair) ESC Scientific Document Group: Alfred E. Buxton, Gonzalo Calvimontes, Tze-Fan Chao, Lars Eckardt, Heidi Estner, Anne M. Gillis, Rodrigo Isa, Josef Kautzner, Philippe Maury, Joshua D. Moss, Gi-Byung Nam, Brian Olshansky, Luis Fernando Pava Molano, Mauricio Pimentel, Mukund Prabhu, Wendy S. Tzou, Philipp Sommer, Janice Swampillai, Alejandro Vidal, Thomas Deneke (Reviewer Coordinator), Gerhard Hindricks, Christophe Leclercq (ESC-CPG representative)
Noise Reduction Caused by External Events in Wireless Sensor Network

Reliable communication always is an essential critical and challenging task in wireless sensor networks (WSNs). Despite this, WSNs models are prone to disrupting the normal working state because most WSN models are deployed in unattended hostile environments. To ensure secure data processing in a WSNs, many techniques have been proposed to protect data privacy when data are transferred from sensors to base stations. This article focuses on reducing noise, which occurs due to external events, such as harsh weather conditions. We reconstruct the data, which is affected by noise, by using a convolutional autoencoder network. The performance was evaluated in terms of error, and it was proven to be competitive.
Risk of eczema, wheezing and respiratory tract infections in the first year of life: A systematic review of vitamin D concentrations during pregnancy and at birth

Background Allergic conditions and respiratory tract infections (RTIs) are common causes of morbidity and mortality in childhood. The relationship between vitamin D status in pregnancy (mothers), early life (infants) and health outcomes such as allergies and RTIs in infancy is unclear. To date, studies have shown conflicting results. Objective This systematic review aims to gather and appraise existing evidence on the associations between serum vitamin D concentrations during pregnancy and at birth and the development of eczema, wheezing, and RTIs in infants. Data sources PubMed, MEDLINE, ProQuest, Scopus, CINAHL, Cochrane Library and Academic Search Premier databases were searched systematically using specified search terms and keywords. Study selection Articles on the associations between serum vitamin D concentrations during pregnancy and at birth and eczema, wheezing, and RTIs among infants (1-year-old and younger) published up to 31 March 2019 were identified, screened and retrieved. Results From the initial 2678 articles screened, ten met the inclusion criteria and were included in the final analysis. There were mixed and conflicting results with regards to the relationship between maternal and cord blood vitamin D concentrations and the three health outcomes—eczema, wheezing and RTIs—in infants. Conclusion Current findings revealed no robust and consistent associations between vitamin D status in early life and the risk of developing eczema, wheezing and RTIs in infants. PROSPERO registration no. CRD42018093039.
Caregiver–Child Symptom Concordance: Links to Premature Termination From Trauma-Focused Therapy

Abstract Rates of attrition from child trauma-focused treatment are high, yet few predictors of premature termination are known. Caregiver-child symptom discrepancies are common in this population and have been related to treatment outcome. However, research has not examined whether caregiver–child symptom concordance is associated with attrition. The aim of the study was to determine whether pretreatment caregiver–child symptom agreement predicted premature termination from trauma-focused treatment. Two hundred and sixty-nine treatment-seeking children ages 8 to 12 (M = 9.97, SD = 1.49; 64.7% female, 51.3% Black) and their non-offending caregivers were included in the study. Two operational definitions of attrition are as follows: (a) clinician-rated dropout, and (b) whether the child received an adequate dose of treatment (i.e., 12 or more sessions), which were used to more thoroughly examine premature termination. Rates of attrition were high (68.1% clinician-rated premature termination, 37.4% received inadequate dose). Levels of symptom concordance between caregivers and children were low across symptom difficulties (intraclass correlations = .003–.16). Lower levels of discordance for posttraumatic stress symptoms (PTSS) were associated with an increased likelihood of receiving an adequate dose of treatment (odds ratio [OR] = 1.03). Nonetheless, unexpectedly, higher levels of caregiver–child discordance for anxiety symptoms at pretreatment predicted both clinician-rated treatment completion and adequate dose (ORs = .97, .96, respectively). However, caregiver’s and children’s perceptions of children’s trauma-related difficulties may not converge, and thus, both reports are important to assess. Symptom disagreement regarding PTSS may help identify families at risk for attrition.
Time-of-Day Differences in Treatment-Related Habit Strength and Adherence

Abstract Background Many of our daily behaviors are habitual, occurring automatically in response to learned contextual cues, and with minimal need for cognitive and self-regulatory resources. Behavioral habit strength predicts adherence to actions, including to medications. The time of day (morning vs. evening) may influence adherence and habit strength to the degree that stability of contexts/routines varies throughout the day. Purpose The current study evaluates whether patients are more adherent to morning versus evening doses of medication and if morning doses show evidence of greater habit strength than evening doses. Methods Objective adherence data (exact timing of pill dosing) were collected in an observational study by electronic monitoring pill bottles in a sample of patients on twice-daily pills for Type 2 diabetes (N = 51) over the course of 1 month. Results Data supported the hypothesis that patients would miss fewer morning than evening pills. However, counter to the hypothesis, variability in dose timing (an indicator of habit strength) was not significantly different for morning versus evening pills. Conclusions Findings suggest that medication adherence may be greater in the morning than in the evening. However, more research is needed to evaluate the role of habitual action in this greater adherence. Furthermore, future research should evaluate the validity of behavioral timing consistency as an indicator of habit strength.
Multiple Victimizations and Overdose Among Women With a History of Illicit Drug Use

The experiences of violence and overdose are highly prevalent among women who use illicit drugs. This study sought to ascertain whether multiple victimizations during adulthood increase the frequency of women’s overdose. The sample comprised 218 women recruited at Philadelphia harm reduction sites during 2016–2017. Victimization was assessed as exposure to 16 types of adulthood violence. Three measures were constructed for multiple victimizations: continuous and categorical polyvictimization, and predominant violence domain. Negative binomial regression estimated the incidence rate ratio (IRR) of lifetime overdoses from multiple victimizations. Lifetime history of opioid use (88.6%) and drug injection (79.5%) were common. Among overdose survivors (68.5%), the median of lifetime overdoses was 3. The majority of participants (58.7%) were victims of predominantly sexual violence, 26.1% experienced predominantly physical abuse/assault, and 3.7% were victims of predominantly verbal aggression/coercive control. Participants reported a mean of seven violence types; the higher-score category of polyvictimization (9–16 violence types) comprised 41.7% of the total sample. In multivariable models, one-unit increase in continuous polyvictimization was associated with 4% higher overdose rates (IRR: 1.04, 95% confidence interval [CI]: [1.00, 1.08]). Compared to women who were not victimized (11.5%), those in the higher-score category of polyvictimization (IRR: 2.01; 95% CI: [1.06, 3.80]) and exposed to predominantly sexual violence (IRR: 2.10, 95% CI: [1.13, 3.91]) were expected to have higher overdose rates. Polyvictimization and sexual violence amplified the risk of repeated overdose among drug-involved women. Female overdose survivors need to be screened for exposure to multiple forms of violence, especially sexual violence. Findings underscore the need to scale-up victimization support and overdose prevention services for disenfranchised women.
Minocycline attenuates testicular damages in a rat model of ischaemia/reperfusion (I/R) injury

Testicular torsion is a serious urological disease leading to testicular damage. This study aimed to assess the effect of minocycline on testicular ischaemia/reperfusion (I/R) injury caused by testicular torsion/detorsion. Male adult Wistar rats (n = 32) were assigned into four groups of sham, I/R, I/R + minocycline and minocycline. I/R injury was induced by two sets of surgical operations, including the rotation of the left testis (720°, counterclockwise), followed by detorsion after 4 hr. The administration of minocycline was carried out 30 min before detorsion and then continued for 8 weeks. At the end of the 8th week, rats were killed and sampling was done. Johnson's score, the height of seminiferous tubule epithelium, the mean seminiferous tubule diameter, as well as biochemical parameters, SOD, GPx and CAT, were significantly enhanced in the I/R + minocycline group compared with the I/R group. The administration of minocycline led to a marked decrease in expression levels of Caspase‐3, Bax, IL‐1β and TNF‐α genes, and a remarkable increase in expression levels of Bcl‐2, 3β‐HSD and 17β‐HSD3 genes compared with the I/R group. Administration of minocycline could also reduce the rate of germ cell apoptosis (TUNEL staining). Hence, minocycline was useful in the management of testicular torsion/detorsion.
Fear of falling avoidance behavior affects the inter-relationship between vision impairment and diminished mobility in community-dwelling older adults

ABSTRACT Background Age-related decline in vision may contribute to the development of fear of falling (FOF) behavior and reduced mobility, which are related to increased fall risk in older adults. Purpose To investigate the inter-relationship between vision impairment, physical mobility performance, and FOF behavior in community-dwelling older adults. Methods A total of 400 participants from community centers (267 females; age = 74.8 (6.4), range = 65–97 years) participated in this cross-sectional study. Presence of age-related eye diseases (e.g. macular degeneration, cataracts, glaucoma, and retinopathy) and visual acuity (VA) was assessed. Physical mobility and FOF avoidance behavior were assessed using the Timed Up-and-Go (TUG) test and the Fear of Falling Avoidance Behavior Questionnaire (FFABQ). The inter-relationships between parameters were analyzed using mediation model analysis. Results Significant decreases in mobility performance were observed in those with eye disease (eye disease = 9.56 [5.2] sec, no eye disease = 8.54 [2.75] sec; p = .037) and FOF avoidance behavior (avoiders = 12.87 [6.04] sec, non-avoiders = 8.51 [3.56] sec; p < .001). Furthermore, FOF behavior was found to significantly influence the inter-relationship between presence of eye disease and TUG performance (p = .004). VA alone had no significant effect on mobility (p = .69). Conclusion The presence of eye disease and the associated FOF behavior was related to decreased mobility and potentially increased fall risk. We recommend clinicians to inquire about the presence of eye disease and FOF behavior to identify risk factors related to falls in older adults.
Examination of the psychological changes in nurses due to workload in an intensive care unit: a mixed method study

Background: The workload is the impinged stress due to several inter-related factors, including the competence of the intensive care unit nurse. Objectives: The objective of this study was to investigate the workload-related psychological changes in intensive care nurses. Methods: The study had a two-phase explanatory mixed method design. Data were collected through in-depth personal interviews and with other instruments. The obtained data were analyzed with SPSS 18.0 and MAXQDA plus10. Results: The workload of intensive care nurses was 315.8 per minute and the mean TISS 28 score was as high as 65.00. The in-depth interviews with intensive care nurses revealed that participants experienced professional stress due to high workload and went through psychological changes. Conclusion: The study findings demonstrate that psychological symptoms seen in intensive care nurses relate to a high workload. Impact Statement: The results of this study can be used by hospital administrators to create a healthy work environment with a moderated workload and optimized shift schedules so that the mental well-being of nurses can be promoted.
Selinexor for advanced hematologic malignancies

Abstract Recent measures to classify novel molecular targets with therapeutic potential across multiple hematologic tumors have identified the eukaryotic nuclear exporter, exportin 1 (XPO1), as a promising candidate. Molecular agents termed ‘Selective Inhibitors of Nuclear Export’ (SINEs) have been developed to selectively inhibit the essential regulatory functions of XPO1 in the eukaryotic cell and have been extensively studied in pre-clinical and clinical tumor models. Recently, selinexor (XPOVIO™), a first-in-class oral SINE molecule, was granted accelerated approval by the United States FDA for penta-refractory multiple myeloma. To establish a complete profile of this emerging drug candidate, this article reviews evidence collected from recent clinical studies against both solid and liquid tumors, describing selinexor as a promising new anti-cancer pharmaceutic against late-stage and highly aggressive tumors. With management of well-defined and predictable adverse effects, selinexor can be a life-saving therapeutic option in cancer patients with few alternatives.
Fragment linking strategies for structure-based drug design.

Fragment-based drug discovery is a strategy widely used both in academia and pharmaceutical companies, to generate small-molecule protein inhibitors and drug candidates. Among the approaches reported in the literature (growing, linking and merging), the linking approach theoretically offers the opportunity to rapidly gain in binding energy. Nevertheless, this approach is poorly represented when considering the compounds currently in clinical trials. Here, we report an exhaustive view of the cases published so far in the literature, together with the methods used to identify the two initial fragments either simultaneously or successively. We review the different types of linkers published and discuss how these linkers are designed to obtain the lead compound. Mixing merging and linking methods, where the linker is duplicated from a known inhibitor appears as an interesting strategy. To reach super-additivity, we propose to grow one of the fragments in order to minimize the distance between the two binders, and then link the resulting compounds using flexible alkyl-derived linkers.
Methods for spatial and temporal imaging of the different steps involved in RNA processing at single‐molecule resolution

RNA plays a quintessential role as a messenger of information from genotype (DNA) to phenotype (proteins), as well as acts as a regulatory molecule (noncoding RNAs). All steps in the journey of RNA from synthesis (transcription), splicing, transport, localization, translation, to its eventual degradation, comprise important steps in gene expression, thereby controlling the fate of the cell. This lifecycle refers to the majority of RNAs (primarily mRNAs), but not other RNAs such as tRNAs. Imaging these processes in fixed cells and in live cells has been an important tool in developing an understanding of the regulatory steps in RNAs journey. Single‐cell and single‐molecule imaging techniques enable a much deeper understanding of cellular biology, which is not possible with bulk studies involving RNA isolated from a large pool of cells. Classic techniques, such as fluorescence in situ hybridization (FISH), as well as more recent aptamer‐based approaches, have provided detailed insights into RNA localization, and have helped to predict the functions carried out by many RNA species. However, there are still certain processing steps that await high‐resolution imaging, which is an exciting and upcoming area of research. In this review, we will discuss the methods that have revolutionized single‐molecule resolution imaging in general, the steps of RNA processing in which these methods have been used, and new emerging technologies.
Attentional processing and interpretative bias in functional neurological disorder.

OBJECTIVE Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness-relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally. METHODS We compared cognitive task performance of FND, CFS and healthy control (HC) groups. Tasks assessed attentional bias towards illness-relevant stimuli (visual probe task), attentional control (attention network task) and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue and general health. RESULTS Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS and 51 HC participants were included. Whilst participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13 p = 0.002, d = 0.624), individuals with FND did not (t = -1.59, p = 0.118, d = 0.379). Both FND (t = 3.08, p = 0.003, d = 0.759) and CFS (t = 2.74, p = 0.007, d = 0.548) groups displayed worse attentional control than HC. Similarly, FND (t = 3.63, p < 0.001, d = 0.801) and CFS groups (t = 4.58, p < 0.001, d = 0.909) showed more somatic interpretative bias than HC. CONCLUSIONS Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias towards somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.