Miracle-dz/UniFAR-FTUs huggingface dataset:
De-escalation strategies in patients with acute coronary syndrome: a step towards precision medicine

ABSTRACT Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. Areas covered In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. Expert Opinion Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.
Age‐ and sex‐dependent alterations in primary somatosensory cortex neuronal calcium network dynamics during locomotion

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Age‐dependent Ca2+‐mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline based on work done mostly at the single‐cell level and in the slice preparation. Recently, our lab identified age‐ and Ca2+‐related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to test the generalizability of the Ca2+ hypothesis of brain aging. Here, we used in vigilo two‐photon imaging in ambulating mice, to image GCaMP8f in the primary somatosensory cortex (S1), during ambulation and at rest. We investigated aging‐ and sex‐related changes in neuronal networks in the C56BL/6J mouse. Following imaging, gait behavior was characterized to test for changes in locomotor stability. During ambulation, in both young adult and aged mice, an increase in network connectivity and synchronicity was noted. An age‐dependent increase in synchronicity was seen in ambulating aged males only. Additionally, females displayed increases in the number of active neurons, Ca2+ transients, and neuronal activity compared to males, particularly during ambulation. These results suggest S1 Ca2+ dynamics and network synchronicity are likely contributors of locomotor stability. We believe this work raises awareness of age‐ and sex‐dependent alterations in S1 neuronal networks, perhaps underlying the increase in falls with age.
The impact of facilitators and rural immersion on medical student engagement during a child and adolescent mental health videoconference workshop

Objective Child and adolescent mental health (CAMH) disorders are a major public health problem in Australia, especially outside metropolitan areas. The issue is compounded by a shortage of child and adolescent psychiatrists (CAPs). CAMH receives minimal coverage in health professional training, training opportunities are scarce, and support for generalist health professionals, who treat most cases, is lacking. Novel approaches to early medical education and teaching are required to strengthen the available skilled workforce in rural and remote settings. Method This qualitative study explored the factors influencing medical student engagement in a CAMH videoconferencing workshop as part of the Rural Clinical School of WA. Results Our results confirm the priority of personal characteristics of medical educators, over clinical and subject matter expertise, on student learning. This research affirms that general practitioners are well-placed to facilitate recognition of learning experiences, especially given that students may not readily recognise exposure to CAMH cases. Conclusion Our findings support the effectiveness, efficiencies, and benefits of utilising general medical educators in supporting child and adolescent psychiatry expertise in delivering subspecialty training within medical school curricula.
Evaluating biogenic amines and pH levels in farmed rainbow trout (Oncorhynchus mykiss) for freshness assessment during storage

Abstract This study examined the production of eight key biogenic amines (methylamine, tryptamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine) in 120 samples of farmed rainbow trout during various storage conditions, and determined any accompanying variations in pH. The main objective of this study was to identify which of the eight biogenic amines could be used as chemical markers to evaluate the quality of farmed rainbow trout. Histamine and tryptamine were not present in any of the samples, and the levels of cadaverine were inconsistent. The levels of putrescine significantly increased at 0 °C (by day 9), 2 °C (by day 8), and 4 °C (by day 4). Tyramine, spermidine, and spermine levels exhibited fluctuations but had a significant positive correlation with the levels of putrescine. The pH levels slightly increased from their initial values across all storage temperatures, with no significant variations observed. Based on the results, it can be concluded that putrescine may serve as an effective marker of the freshness of farmed rainbow trout during storage.
Administration of agmatine prior to physical or psychological stress in pregnant mice ameliorates behavioural and cognitive deficits in female offspring

Physical or psychological stress experienced by a mother during gestation is often associated with serious behavioural and cognitive deficits in newborns. Investigations of protective agents, which could prevent the adverse outcomes of prenatal stress (PS), are warranted. Agmatine is a neurotransmitter putatively involved in the physiological response to stress, and exogenous administration of agmatine has been shown to produce a variety of neuroprotective effects. In this study, we aimed to assess whether prenatal agmatine exposure could ameliorate behavioural and cognitive deficits in female offspring born to prenatally stressed mice. Pregnant Swiss Webster (SW) mice were exposed to physical or psychological stress from the 11th to 17th days of gestation. Agmatine (37.5 mg/kg, i.p.) was administrated 30 min before the induction of stress for seven consecutive days. The pups were assessed using a variety of behavioural tests and molecular assays on postnatal days 40 to 47. Agmatine attenuated impairments in locomotor activity, anxiety‐like behaviour, and drug‐seeking behaviour associated with both physical and psychological PS. Furthermore, agmatine reduced PS‐induced impairments in passive avoidance memory and learning. Neither PS nor agmatine treatment affected the mRNA expression level of hippocampal brain‐derived neurotrophic factor (BDNF) or tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). Taken together, our findings highlight the protective effects of prenatally administered agmatine on PS‐mediated behavioural and cognitive deficits of the offspring. Future studies are needed to elucidate the underlying mechanisms, which could allow for more targeted prenatal treatments.
Automated time-lapse data segmentation reveals in vivo cell state dynamics

Embryonic development proceeds as a series of orderly cell state transitions built upon noisy molecular processes. We defined gene expression and cell motion states using single-cell RNA sequencing data and in vivo time-lapse cell tracking data of the zebrafish tailbud. We performed a parallel identification of these states using dimensional reduction methods and a change point detection algorithm. Both types of cell states were quantitatively mapped onto embryos, and we used the cell motion states to study the dynamics of biological state transitions over time. The time average pattern of cell motion states is reproducible among embryos. However, individual embryos exhibit transient deviations from the time average forming left-right asymmetries in collective cell motion. Thus, the reproducible pattern of cell states and bilateral symmetry arise from temporal averaging. In addition, collective cell behavior can be a source of asymmetry rather than a buffer against noisy individual cell behavior.
Genetic and non-genetic components of family history of stroke and heart disease: a population-based study among adopted and non-adopted individuals

Background: It is increasingly clear that genetic and non-genetic factors account for the association of family history with disease risk in offspring. We sought to distinguish the genetic and non-genetic contributions of family history of stroke and heart disease on incident events by examining adopted and non-adopted individuals. Methods: We examined associations between family history of stroke and heart disease with incident stroke and myocardial infarction (MI) in 495,640 participants of the UK Biobank (mean age 56.5 years, 55% female) stratified by early childhood adoption status into adoptees (n=5,747) and non-adoptees (n=489,893). We estimated hazard ratios (HRs) per affected nuclear family member, and for polygenic risk scores (PRS) for stroke and MI in Cox models adjusted for baseline age and sex. Results: 12,518 strokes and 23,923 MIs occurred over a 13-year follow-up. In non-adoptees, family history of stroke and heart disease were associated with increased stroke and MI risk, with the strongest association of family history of stroke for incident stroke (HR 1.16 [1.12, 1.19]) and family history of heart disease for incident MI (HR 1.48 [1.45, 1.50]). In adoptees, family history of stroke associated with incident stroke (HR 1.41 [1.06, 1.86]), but family history of heart disease did not associate with incident MI (p>0.5). PRS showed strong disease-specific associations in adoptees and non-adoptees. In non-adoptees, the stroke PRS mediated 6% risk between family history of stroke and incident stroke, and the MI PRS mediated 13% risk between family history of heart disease and MI. Conclusions: Family history of stroke and heart disease increase risk for their respective conditions. Family history of stroke contains a substantial proportion of potentially modifiable non-genetic risk, indicating a need for further research to elucidate these elements for novel prevention strategies, whereas family history of heart disease represents predominantly genetic risk.
Novel minimally invasive treatments for lower urinary tract symptoms: a systematic review and network meta-analysis

ABSTRACT Purpose: To review and compare the effectivity of novel minimally invasive treatments (MITs) to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) in men. Methods: Medline, Embase, and Cochrane databases were searched from January 2010 to December 2022 for randomized controlled trials (RCTs) evaluating MITs, compared to TURP or sham, in men with LUTS. Studies were assessed by risk of bias tool, and evidence by GRADE. Functional outcomes by means of uroflowmetry and IPSS were the primary outcomes, safety and sexual function were secondary outcomes. As part of this review, a network meta-analysis (NMA) was conducted. MITs were ranked based on functional outcome improvement probability. Results: In total, 10 RCTs were included, evaluating aquablation, prostatic urethral lift, prostatic artery embolization (PAE), convective water vapor thermal treatment or temporary implantable nitinol device. All MITs showed a better safety profile compared to TURP. Functional outcome improvement following aquablation were comparable to TURP. In the NMA, aquablation was ranked highest, PAE followed with the second highest probability to improve functional outcomes. Other novel MITs resulted in worse functional outcomes compared to TURP. Level of evidence was low to very low. Conclusions: Five MITs for treatment of LUTS were identified. Aquablation is likely to result in functional outcomes most comparable to TURP. Second in ranking was PAE, a technique that does not require general or spinal anesthesia. MITs have a better safety profile compared to TURP. However, due to high study heterogeneity, results should be interpreted with caution.
Net Dzyaloshinskii–Moriya interaction in defect-enriched ferromagnet

The Dzyaloshinskii–Moriya interaction (DMI), which typically occurs in lattices without space inversion symmetry, can also be induced in a highly symmetric lattice by local symmetry breaking due to any lattice defect. We recently presented an experimental study of polarized small angle neutron scattering (SANS) on the nanocrystalline soft magnet Vitroperm (Fe73Si16B7Nb3Cu1), where the interface between the FeSi nanoparticles and the amorphous magnetic matrix serves as such a defect. The SANS cross sections exhibited the polarization-dependent asymmetric term originating from the DMI. One would naturally expect the defects characterized by a positive and a negative DMI constant D to be randomly distributed and this DMI-induced asymmetry to disappear. Thus, the observation of such an asymmetry indicates that there exists an extra symmetry breaking. In the present work we experimentally explore the possible causes by measuring the DMI-induced asymmetry in the SANS cross sections of the Vitroperm sample tilted in different directions with respect to the external magnetic field. Furthermore, we analyzed the scattered neutron beam using a spin filter based on polarized protons and confirm that the asymmetric DMI signal originates from the difference between the two spin-flip scattering cross-sections.
A review of behavioural rating scales for the assessment of Attention Deficit/Hyperactivity Disorder among adults: Efficacy, best practices, and research recommendations.

This study aimed to improve understanding of the best behavioural rating scales for adult ADHD assessment by mapping and comparing these scales, with a particular focus on the largely unexplored area of detecting feigned or invalid symptom presentation. A comprehensive review and comparison of the most recent literature on behavioural rating scales for adult ADHD assessment was conducted, examining their psychometric properties and the breadth of symptoms they assess. The investigation found that the Conners' Adult ADHD Rating Scales (CAARS), Mind Excessively Wandering Scale (MEWS), and Wender Utah Rating Scale (WURS) emerged as the most precise scales for adult ADHD assessment. The study also noted a growing emphasis on the development of tools to assess feigned or invalid symptom presentation, either as independent measures or integrated within existing scales. Stand-alone tools were found to be more effective than embedded ones, with the ADHD Symptom Infrequency Scale (ASIS) identified as the most precise scale for detecting feigning. Consequently, the review offers recommendations for the most accurate behavioural rating scales in different research-related contexts involving adult ADHD assessment.
Impact of Nurse Leaders Behaviors on Nursing Staff Performance: A Systematic Review of Literature

Nursing leadership is critical in facilitating and improving nurse performance, which is essential for providing quality care and ensuring patient safety. The aim of this study is to explore the relationship between nursing leadership and nurse performance by understanding the leadership behaviors and factors that motivate nurses to perform well. To study the factors that nurses believe motivate them to perform better, a systematic review was undertaken, correlating these factors to leadership behaviors/styles. The PRISMA guidelines were followed to identify relevant articles. After applying the selection criteria, 11 articles were included in the final analysis. Overall, 51 elements that influence nurses’ motivation to perform better were found and categorized into 6 categories, including autonomy, competencies, relatedness, individual nursing characteristics, relationships and support, and leadership styles/practices. It has been discovered that both direct and indirect nursing leadership behaviors affect nurses’ performance. A better understanding of the factors that motivate nurses to perform well and facilitating them in the work environment through leadership behaviors/styles can improve nurses’ performance. There is a need to increase research on nurse leadership and nurses’ performance in the current innovative and technologically integrated work environment to identify new factors of influence.
A genetic algorithm for generating a steiner tree with wire sizing and buffer insertion

This paper proposes a genetic algorithm for generating a rectilinear Steiner tree with wire sizing and buffer insertion for the interconnect optimization problem in VLSI layout design. In the proposed genetic algorithm, each chromosome represents the topological structure of a Steiner tree. An evaluation function is given to map it into the layout of a Steiner tree with wire sizing and buffer insertion. Experimental results show that the algorithm effectively produces Steiner trees better than ones produced by the previous method.
Maternal exposure to zolpidem and risk of specific birth defects

Zolpidem is a non‐benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self‐reported zolpidem use 1 month before pregnancy through to the end of the third month (“early pregnancy”) and specific birth defects using data from two multi‐site case–control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early‐pregnancy antipsychotic, anxiolytic, antidepressant use, early‐pregnancy opioid use, early‐pregnancy smoking, and study as potential covariates. For defects with three–four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score‐adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early‐pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.
Fibroblast Activation Protein Inhibitor–Based Radionuclide Therapies: Current Status and Future Directions

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor–based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor–based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.
Sex-Specific Reliability of Lower-Limb Corticospinal Excitability and Silent Periods

Abstract Pagan, JI, Harmon, KK, Girts, RM, MacLennan, RJ, Beausejour, JP, Hernandez-Sarabia, JA, Coker, NA, Carr, JC, Ye, X, DeFreitas, JM, and Stock, MS. Sex-specific reliability of lower-limb corticospinal excitability and silent periods. J Strength Cond Res 37(9): 1882–1887, 2023—Transcranial magnetic stimulation (TMS) is a research tool that has potential to provide new insights into strength training–induced adaptations. However, using TMS to study the lower limbs is challenging, and sex-specific reliability has yet to be reported. We examined the reliability of corticospinal excitability and silent periods for the rectus femoris, vastus lateralis, and biceps femoris in both sexes. Thirteen males and 14 females reported to the laboratory twice. During both trials, a double cone coil was used to deliver 20 pulses to the rectus femoris hotspot with a stimulator output of 130% of active motor threshold. Motor-evoked potential peak-to-peak amplitude, which reflects corticospinal excitability, and silent period duration were quantified. Our results offer 4 novel findings. First, corticospinal excitability and silent period demonstrated higher reliability for the females. Second, regardless of sex and muscle, the silent period was more reliable than corticospinal excitability. Third, reliability was highest for our target muscle (rectus femoris), with lower reliability for the vastus lateralis and biceps femoris, suggesting that these methods cannot be used to study coactivation. Fourth, active motor threshold showed less variability than corticospinal excitability and silent period but increased at trial 2 in females. Many of the intraclass correlation coefficients were excellent (≥0.90), although we attribute this finding to variability between subjects. Reliability of lower-limb TMS measures may be sex, muscle, and variable dependent. Our findings suggest that both males and females should be included in lower-limb TMS research, although combining data between sexes should be approached cautiously.