Miracle-dz/UniFAR-FTUs huggingface dataset:
Practical tips for managing FLT3 mutated acute myeloid leukemia with midostaurin

ABSTRACT Introduction FLT3 inhibitors have been recently introduced as novel treatment targets in patients with FLT3-mutated acute myeloid leukemia (AML). Midostaurin is an oral multikinase inhibitor that targets multiple receptor tyrosine kinases including FLT3 and has been approved for the treatment of AML with FLT3 mutations in patients candidates for intensive chemotherapy. This article presents an updated overall overview of the use of midostaurin in clinical practice. Areas covered Tests and examinations to be performed before the use of midostaurin, antifungal and antimicrobial treatment, as well as antifungal and antimicrobial prophylaxis are discussed. Practical tips for the treatment of QTc interval prolongation and heart failure are also presented. Expert opinion Midostaurin is the first agent showing significant survival benefit when combined with chemotherapy in FLT3-mutated AML patients. Optimal use of midostaurin should be a priority, being essential to know the interactions with other drugs like strong CYP3A4 inhibitors or inducers, which are particularly used in the concomitant treatment of AML patients and may increase toxicity or decrease therapeutic benefit. The active role of hematologists and nursing teams is crucial to ensure patient adherence to midostaurin treatment and to minimize adverse effects by administrating the optimal dose for each situation.
GAMMA: Graph Attention Model for Multiple Agents to Solve Team Orienteering Problem With Multiple Depots

In this work, we present an attention-based encoder–decoder model to approximately solve the team orienteering problem with multiple depots (TOPMD). The TOPMD instance is an NP-hard combinatorial optimization problem that involves multiple agents (or autonomous vehicles) and not purely Euclidean (straight line distance) graph edge weights. In addition, to avoid tedious computations on dataset creation, we provide an approach to generate synthetic data on the fly for effectively training the model. Furthermore, to evaluate our proposed model, we conduct two experimental studies on the multi-agent reconnaissance mission planning problem formulated as TOPMD. First, we characterize the model based on the training configurations to understand the scalability of the proposed approach to unseen configurations. Second, we evaluate the solution quality of the model against several baselines—heuristics, competing machine learning (ML), and exact approaches, on several reconnaissance scenarios. The experimental results indicate that training the model with a maximum number of agents, a moderate number of targets (or nodes to visit), and moderate travel length, performs well across a variety of conditions. Furthermore, the results also reveal that the proposed approach offers a more tractable and higher quality (or competitive) solution in comparison with existing attention-based models, stochastic heuristic approach, and standard mixed-integer programming solver under the given experimental conditions. Finally, the different experimental evaluations reveal that the proposed data generation approach for training the model is highly effective.
Ból pooperacyjny na oddziale chirurgicznym w ocenie ankietowego badania z zastosowaniem kwestionariusza McGilla-Melzacka - doniesienie wstępne

Wstep. W toku rozwoju nauk medycznych bol odczuwany przez chorych po zabiegu operacyjnym jest postrzegany jako podstawowy problem pacjentow. Z informacji, jaką pacjent uzyska, powinno wynikac, ze latwiej jest zapobiegac bolowi niz zwalczac juz zaistnialy, a umiejetnośc poslugiwania sie prostymi skalami oceny bolu powinna byc wykorzystana w tym procesie. Leczenie przeciwbolowe powinno byc zroznicowane, zindywidualizowane i zawierac komponent przeciwlekowy. Cel pracy. Celem pracy byla analiza rodzaju i stopnia odczuwanego bolu w bezpośrednim okresie pooperacyjnym na podstawie przekrojowego badania epidemiologicznego z wykorzystaniem kwestionariusza McGilla-Melzacka oraz ocena jego przydatności w praktyce postepowania pooperacyjnego w chirurgii. Material i metody. Badanie przeprowadzono u 132 chorych operowanych w określonym czasie w dwoch wybranych szpitalach na terenie wojewodztwa śląskiego. Badanie bolu pooperacyjnego u operowanych chorych przeprowadzono za pomocą kwestionariusza McGilla-Melzacka (MPQ). Wyniki i wnioski. Kwestionariusz McGilla-Melzacka stanowi przydatne, choc trudne narzedzie badania bolu w okresie pooperacyjnym. Pozwala roznicowac bol odczuwany w sferze sensorycznej i emocjonalnej. Roznica poziomu bolu w T2 w stosunku do T1 zawiera sie w przedziale 1 punktu na skali bolu. Kobiety silniej odczuwają bol. W zwalczaniu bolu stosuje sie metody tradycyjne.
Cortical control of striatal fast‐spiking interneuron synchrony

Inhibitory fast‐spiking interneurons in the dorsal striatum regulate actions and action strategies, including habits. Fast‐spiking interneurons are widely believed to synchronize their firing due to the electrical synapses formed between these neurons. However, neuronal modelling data suggest convergent cortical input may also drive synchrony in fast‐spiking interneuron networks. To better understand how fast‐spiking interneuron synchrony arises, we performed dual whole‐cell patch clamp electrophysiology experiments to inform a simple Bayesian network modelling cortico‐fast‐spiking interneuron circuitry. Dual whole‐cell patch clamp electrophysiology revealed that while responsivity to corticostriatal input activation was high in fast‐spiking interneurons, few of these neurons exhibited electrical coupling in adult mice. In simulations of a cortico‐fast‐spiking interneuron network informed by these data, the degree of glutamatergic cortical convergence onto fast‐spiking interneurons significantly increased fast‐spiking interneuron synchronization while manipulations of electrical coupling between these neurons exerted relatively little impact. These results suggest that the primary source of functional coordination of fast‐spiking interneuron activity in adulthood arises from convergent corticostriatal input activation.
Constant‐ductility response spectra for sequential earthquake and tsunami loading

Simplified approaches for examining structural system response under sequential earthquake and tsunami loading are helpful for understanding response trends. To aid understanding, nonlinear (constant‐ductility) response spectra are developed for elastoplastic single degree of freedom systems subjected to seismic loads followed by hydrodynamic tsunami loads. The forcing function is composed of long‐duration earthquake motion concatenated with a range of tsunami hydrodynamic forces that are proportional to the pseudo‐spectral acceleration produced by the earthquake motion. The constant‐ductility spectra are thus constructed for scenarios where the loading imposed by one hazard is not dominant over the other. The spectra and basic intensity measures indicate that the amplification of response for sequential earthquake and tsunami loading over the earthquake only case is most significant for systems with long natural periods and high‐ductility capacity under seismic loading. Copyright © 2017 John Wiley & Sons, Ltd.
Linear Growth Spurts are Preceded by Higher Weight Gain Velocity and Followed by Weight Slowdowns Among Rural Children in Burkina Faso: A Longitudinal Study

ABSTRACT Background The temporal relationship between length (linear) and weight (ponderal) growth in early life is important to support optimal nutrition program design. Studies based on measures of attained size have established that wasting often precedes stunting, but such studies do not capture responsiveness of growth to previous compared with current conditions. As a result, the temporality of linear and ponderal growth relationships remain unclear. Objectives We used growth velocity indicators to assess the temporal bidirectional relationships between linear and ponderal growth in children. Methods Using monthly anthropometric measurements from 5039 Burkinabè children enrolled at 6 months of age and followed until 28 months from August 2014 to December 2016, we employed multilevel mixed-effects models to investigate concurrent and lagged associations between linear and ponderal growth velocity, controlling for time trends, seasonality, and morbidity. Results Faster ponderal growth is associated with faster concurrent and subsequent linear growth (0.21–0.72 increase in length velocity z-score per unit increase in weight velocity z-score), while faster linear growth is associated with slower future weight gain (0.009–0.02 decrease in weight velocity z-score per unit increase in length velocity z-score), especially among children 9–14 months. Ponderal growth slows around the same time as peaks in morbidity, followed roughly a month later by slower linear growth. Conclusions Use of velocity measures to assess temporal dependencies between linear and ponderal growth demonstrate that the same growth-limiting conditions likely affect both length and weight velocity, that slow ponderal growth likely limits subsequent linear growth, and that linear growth spurts may not be accompanied by sufficient increases in dietary intake to avoid slowdowns in weight gain.
Repeat measures of DNA methylation in an inception cohort of firefighters

Objectives Firefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs). Methods We profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20–37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control. Results We report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures. Conclusions Overall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.
Compressive properties and failure behavior of photocast hydroxyapatite gyroid scaffolds vary with porosity

Hydroxyapatite is commonly used in tissue engineered scaffolds for bone regeneration due to its excellent bioactivity and slow degradation rate in the human body. A method of layer-wise, photopolymerized viscous extrusion, a type of additive manufacturing, was developed to fabricate hydroxyapatite gyroid scaffolds with 60%, 70%, and 80% porosities. This study uses this method to produce and evaluate calcium phosphate–based scaffolds. Gyroid topology was selected due to its interconnected porosity and superior, isotropic mechanical properties compared to typical rectilinear lattice structures. These 3D printed scaffolds were mechanically tested in compression and examined to determine the relationship between porosity, ultimate compressive strength, and fracture behavior. Compressive strength increased with decreasing porosity. Ultimate compressive strengths of the 60% and 70% porous gyroids are comparable to that of human cancellous bone, and higher than previously reported for hydroxyapatite rectilinear scaffolds. These gyroid scaffolds exhibited ultimate compressive strength increases between 1.5 and 6.5 times greater than expected, based on volume of material, as porosity is decreased. The Weibull moduli, a measure of failure predictability, were predictive of failure mode and found to be in the accepted range for engineering ceramics. The gyroid scaffolds were also found to be self-reinforcing such that initial failures due to minor manufacturing inconsistencies did not appear to be the primary cause of early failure of the scaffold. The porous gyroids exhibited scaffold failure characteristics that varied with porosity, ranging from monolithic failure to layer-by-layer failure, and demonstrated self-reinforcement in each porosity tested.
Mental health burden of empty nose syndrome compared to chronic rhinosinusitis and chronic rhinitis

Empty nose syndrome (ENS) is characterized by the paradoxical perception of nasal obstruction despite patent sinonasal anatomy after surgery. We investigated the relationship between ENS, and anxiety, depression, obsessive‐compulsive disorder, and somatic symptom disorder (SSD) compared to individuals with chronic rhinitis (CR) and chronic rhinosinusitis (CRS).
Distribution Patterns of Degeneration of the Lumbar Spine in a Cohort of 200 Patients with an Indication for Lumbar MRI

Lower back pain is one of the most common causes of a reduced quality of life. Magnetic resonance imaging (MRI) is the best suited imaging technique to detect causes of that pain. We retrospectively evaluated the MRIs of the lumbar spine for 200 patients in order to describe the distribution of signs of degeneration with regard to age, sex, and position of the disc affected. The number of spinal segments affected by degeneration increased with age, as did the number of signs of degeneration per segment. In patients aged between 21 and 30, 38.8% of discs were affected, while for patients aged between 51 and 60, 91.6% of discs were affected. There was no statistically significant gender difference. The lower two segments were most commonly affected by degeneration. The most common were structural changes to the discs, which affected 88.4% of patients over 50. Spondylosis was the most common bone-related change, found in 60.4% of patients over the age of 50. A reduction in disc height increases the likelihood of structural changes to the disc and bone-related changes. When investigating risk factors for developing disc-related diseases, the complex disc degeneration patterns described here should be taken into account.
A Graphical Robust PID Controller Design for Time-Varying Uncertain Systems with Applications to Trajectory Tracking of a Load-Varying Rigid SCARA

We proposed in this paper a robust graphical PID controller design technique for trajectory tracking of rigid SCARAs carrying loads with time-varying mass and mass moment of inertia. Because of the time-varying loads and coupled nonlinearities in error dynamics of the tracking control system, the system matrix and the input matrix of the corresponding linearized model about the equilibrium point at the origin were time-varying. Existing robust PID controller design techniques formulated without handling this difficulty were then theoretically lacking. Our controller design technique yielded a 3D graph that could be employed to generate a PID control law that guaranteed input-to-state stability of the resulting control system by using the Lyapunov stability theorem. Simulation results were provided to confirm this. We compared our results with those obtained from using an existing sliding-mode control technique, and constructively drew out relevant characteristics that could be useful for the application of interest.
Impact on Health Care Utilization and Costs of a Medicaid Community Health Worker Program in Detroit, 2018-2020: A Randomized Program Evaluation.

Objectives. To compare health care utilization and costs between beneficiaries randomly assigned to usual services versus a community health worker (CHW) program implemented by 3 Medicaid health plans. Methods. From February 2018 to June 2019, beneficiaries residing in Detroit, Michigan's Cody Rouge neighborhood with more than 3 emergency department (ED) visits or at least 1 ambulatory care‒sensitive hospitalization in the previous 12 months were randomized. CHWs reached out to eligible beneficiaries to assess their needs and link them to services. We compared ED and ambulatory care visits, hospitalizations, and related costs over 12 months. Results. In intention-to-treat analyses among 2457 beneficiaries, the 1389 randomized to the CHW program had lower adjusted ratios of ED visits (adjusted rate ratio [ARR] = 0.96; P < .01) and ED visit costs (ARR = 0.96; P < .01), but higher adjusted ratios of ambulatory care costs (ARR = 1.15; P < .01) and no differences in inpatient or total costs compared with the usual-care group. Conclusions. Initial increases in ambulatory care use from effective programs for underserved communities may mitigate savings from decreased acute care use. Longer-term outcomes should be followed to assess potential cost savings from improved health. Trial Registration: ClinicalTrials.gov identifier: NCT03924713. (Am J Public Health. Published online ahead of print March 24, 2022: e1-e10. https://doi.org/10.2105/AJPH.2021.306700).
Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss

Abstract Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable because of old age or the advanced stage of the disease; thus radio- and chemotherapy are believed as the standard treatments for these patients. However, due to the radio-resistance of tumor cells that may develop during radiotherapy, results remain unsatisfactory. In this article, the possible relationship between the expression of lysine demethylase 5B (KDM5B) and ESCC radio-resistance is clarified, and the underlying mechanism is evaluated. Using the GSE75241 microarray, we identified KDM5B as a potential oncogene in ESCC. KDM5B was overexpressed in ESCC patients and cells. Inhibition of KDM5B enhanced the H3K4me3 methylation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) promoter and induced the expression of PIK3C3. Knockdown of KDM5B or overexpression of PIK3C3 in KYSE-150 and TE-10 cells promoted apoptosis, cell cycle arrest, autophagy, and increased sensitivity to radiotherapy. Silencing of PIK3C3 attenuated the promoting effect of sh-KDM5B on the sensitivity of ESCC cells to radiotherapy. The inhibition of sh-KDM5B in radio-resistance of ESCC cells was also reproduced in vivo. Taken together, our findings provide evidence that reduced expression of KDM5B has a critical role in promoting ESCC radio-sensitivity by upregulating PIK3C3, suggesting KDM5B may function as an oncogene in ESCC.
Feasibility and Acceptability of Ecological Momentary Assessment With Young Adults Who Are Currently or Were Formerly Homeless: Mixed Methods Study

Background Ecological momentary assessment (EMA) has been used with young people experiencing homelessness to gather information on contexts associated with homelessness and risk behavior in real time and has proven feasible in this population. However, the extent to which EMA may affect the attitudes or behaviors of young adults who are currently or were formerly homeless and are residing in supportive housing has not been well investigated. Objective This study aims to describe the feedback regarding EMA study participation from young adults who are currently or were formerly homeless and examine the reactivity to EMA participation and compliance. Methods This mixed methods study used cross-sectional data collected before and after EMA, intensive longitudinal data from a 7-day EMA prompting period, and focus groups of young adults who are currently or were formerly homeless in Los Angeles, California, between 2017 and 2019. Results Qualitative data confirmed the quantitative findings. Differences in the experience of EMA between young adults who are currently or were formerly homeless were found to be related to stress or anxiety, interference with daily life, difficulty charging, behavior change, and honesty in responses. Anxiety and depression symptomatology decreased from before to after EMA; however, compliance was not significantly associated with this decrease. Conclusions The results point to special considerations when administering EMA to young adults who are currently or were formerly homeless. EMA appears to be slightly more burdensome for young adults who are currently homeless than for those residing in supportive housing, which are nuances to consider in the study design. The lack of a relationship between study compliance and symptomatology suggests low levels of reactivity.
Hold that pose: capturing cervical dystonia's head deviation severity from video

Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system—the Computational Motor Objective Rater (CMOR)—to quantify multi‐axis directionality and severity of head posture in CD using only conventional video camera recordings.
Understanding T cell responses to COVID-19 is essential for informing public health strategies

Durable T cell responses to SARS-CoV-2 antigens after infection or vaccination improve immune-mediated viral clearance. To date, population-based surveys of COVID-19 adaptive immunity have focused on testing for IgG antibodies that bind spike protein and/or neutralize the virus. Deployment of existing methods for measuring T cell immunity could provide a more complete profile of immune status, informing public health policies and interventions. Description Deployment of broad-based strategies to measure vaccine-induced T cell immunity can significantly inform public health policies and interventions.