Miracle-dz/UniFAR-FTUs huggingface dataset:
Transposable element insertions in 1000 Swedish individuals

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at >1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though ~0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (<0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.
1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1

A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC50 values in the submicromolar–micromolar range, associated with a significant reduction in cell migration. Moreover, flow cytometric analysis after propidium iodide staining revealed an increase in the G2-M and a decrease in G1-phase, indicating cell cycle arrest, while a specific ELISA demonstrated the inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.
Beyond Valence and Arousal: The Role of Age of Acquisition in Emotion Word Recognition

Although the age of acquisition (AoA) effect has been established in numerous studies, how emotion word processing is modulated by AoA, along with affective factors, such as valence and arousal, is not well understood. Hence, the influence of age of acquisition (AoA), valence, and arousal on Chinese emotion word recognition was investigated through two experiments. Experiment 1 (N = 30) adopted a valence judgment task to explore the roles of valence and AoA in emotion word recognition, whereas Experiment 2 (N = 30) used a lexical decision task to examine AoA and arousal effects. A mixed linear effects model was used to examine the fixed effects of AoA, arousal, and valence and random effects of participants and items. The findings provided confirmation of the effects of AoA, valence, and arousal. Notably, AoA and valence had independent influences on emotion word recognition, as evidenced by longer reaction times for later-acquired words and negative words compared to early-acquired words and positive words (all ps < 0.05). On the other hand, AoA and arousal demonstrated interdependent effects on emotion word recognition. Specifically, a larger AoA effect was observed for low-arousing words (all ps < 0.05), whereas the influence of AoA on high-arousing words was insignificant. These results underscored the significance of AoA in processing emotion words and highlighted the interplay between AoA and arousal. Additionally, it is plausible to suggest that the AoA effect was primarily perceptual rather than semantic in nature.
PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells

An experimentally validated protein abundance structured population dynamic model for CAR T cells (PASCAR) that integrates processes from molecules to single cells to cell populations and systematically explores the design space of constitutive and tunable CAR T cells. CAR T cells are engineered to bind and destroy tumor cells by targeting overexpressed surface antigens. However, healthy cells expressing lower abundances of these antigens can also be lysed by CAR T cells. Various CAR T cell designs increase tumor cell elimination, whereas reducing damage to healthy cells. However, these efforts are costly and labor-intensive, constraining systematic exploration of potential hypotheses. We develop a protein abundance structured population dynamic model for CAR T cells (PASCAR), a framework that combines multiscale population dynamic models and multi-objective optimization approaches with data from cytometry and cytotoxicity assays to systematically explore the design space of constitutive and tunable CAR T cells. PASCAR can quantitatively describe in vitro and in vivo results for constitutive and inducible CAR T cells and can successfully predict experiments outside the training data. Our exploration of the CAR design space reveals that optimal CAR affinities in the intermediate range of dissociation constants effectively reduce healthy cell lysis, whereas maintaining high tumor cell-killing rates. Furthermore, our modeling offers guidance for optimizing CAR expressions in synthetic notch CAR T cells. PASCAR can be extended to other CAR immune cells.
Estimation of Treatment Effects in Repeated Public Goods Experiments

This paper provides a new statistical model for repeated voluntary contribution mechanism games. In a repeated public goods experiment, contributions in the first round are cross-sectionally independent simply because subjects are randomly selected. Meanwhile, contributions to a public account over rounds are serially and cross-sectionally correlated. Furthermore, the cross-sectional average of the contributions across subjects usually decreases over rounds. By considering this non-stationary initial condition—the initial contribution has a different distribution from the rest of the contributions—we model statistically the time varying patterns of the average contribution in repeated public goods experiments and then propose a simple but efficient method to test for treatment effects. The suggested method has good finite sample performance and works well in practice.
Effect of Forearm and Elbow Joint Positions on Ulnar Nerve Conduction Velocity: A Study of Throwers, Archers, and Non-Athletes

ABSTRACT Background: The intensive physical regimen followed by throwers and archers can impose stress on the elbow and hand in particular positions, which may increase the risk of developing peripheral nerve disorders and symptoms like pain and numbness. Purpose: The purpose of the study is to investigate the effect of forearm and elbow joint positions on ulnar nerve conduction velocity in throwers, archers, and non-athletes. Method: Total 34 subjects both males and females were included with body mass index (BMI) between 18.5 and 24.9 kg/m2. Nerve conduction study (NeuroStim NS2 EMG/NCV/EP System) was used for measuring ulnar nerve conduction velocity (NCV) across elbow joint at different angles (0° elbow extension, 45°, 90°, and 120° elbow flexion) with different forearm positions. Result: Repeated Measure Analysis of Variance (RMANOVA) revealed that there was a statistically significant difference in mean values of ulnar NCV at different angles, forearm positions & groups (p < .05). Conclusion: The forearm and elbow positions can have a significant impact on ulnar NCV, especially in athletes who perform repetitive upper limb motions. Results showed that the archers had significantly slower NCV than throwers and non-athletes at 90° of elbow flexion and forearm pronation.
Low-energy backscattering quantum orbits in above-threshold ionization

Using the quantum–orbit formalism we consider the influence of the backward-scattering quantum orbits on the low-energy above-threshold ionization spectra. It is shown that the corresponding ionization rate exhibits sharp peaks for electron energies ≲ 0.1 U P ( U P is the electron ponderomotive energy) at the same places where the forward-scattering-induced low-energy structures appear. The corresponding incident rescattering electron velocities are very small. Semiclassical expressions for the positions of these peaks as functions of U P and the ionization potential are derived.
The Effect of the Peristimulus α Phase on Visual Perception through Real-Time Phase-Locked Stimulus Presentation

Abstract The α phase has been theorized to reflect fluctuations in cortical excitability and thereby impose a cyclic influence on visual perception. Despite its appeal, this notion is not fully substantiated, as both supporting and opposing evidence has been recently reported. In contrast to previous research, this study examined the effect of the peristimulus instead of prestimulus phase on visual detection through a real-time phase-locked stimulus presentation (PLSP) approach. Specifically, we monitored phase data from magnetoencephalography (MEG) recordings over time, with a newly developed algorithm based on adaptive Kalman filtering (AKF). This information guided online presentations of masked stimuli that were phased-locked to different stages of the α cycle while healthy humans concurrently performed detection tasks. Behavioral evidence showed that the overall detection rate did not significantly vary according to the four predetermined peristimulus α phases. Nevertheless, the follow-up analyses highlighted that the phase at 90° relative to 180° likely enhanced detection. Corroborating neural parietal activity showed that early interaction between α phases and incoming stimuli orchestrated the neural representation of the hits and misses of the stimuli. This neural representation varied according to the phase and in turn shaped the behavioral outcomes. In addition to directly investigating to what extent fluctuations in perception can be ascribed to the α phases, this study suggests that phase-dependent perception is not as robust as previously presumed, and might also depend on how the stimuli are differentially processed as a result of a stimulus-phase interaction, in addition to reflecting alternations of the perceptual states between phases.
Possible impact of HLA class I and class II on malignancies driven by a single germ‐line BRCA1 mutation

This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c. 5263_5264insC driven oncogenesis. Observed HLA associations might have practical implications for establishment of predictive markers for the response to immunotherapies in malignancies driven by this germ‐line mutation.
Detecting Epileptic Seizures Using Hand-Crafted and Automatically Constructed EEG Features

Epileptic seizure detection aims to replace unreliable seizure diaries by a model that automatically detects seizures based on electroencephalography (EEG) sensors. However, developing such a model is difficult and time consuming as it requires manually searching for relevant features from complex EEG data. Domain experts may have a partial understanding of the EEG characteristics that indicate seizures, but this knowledge is often not sufficient to exhaustively enumerate all relevant features. To address this challenge, we investigate how automated feature construction may complement hand-crafted features for epileptic seizure detection. By means of an empirical comparison on a real-world seizure detection dataset, we evaluate the ability of automated feature construction to come up with new relevant features. We show that combining hand-crafted and automated features results in more accurate models compared to using hand-crafted features alone. Our findings suggest that future studies on developing EEG-based seizure detection models may benefit from features constructed using a combination of hand-crafted and automated feature engineering.
Magnetic field sensors using VO2/Fe3O4 nanoparticle devices

We combined the metal-insulator transition (MIT) properties of VO2 and the magnetic properties of Fe3O4 to realize a magnetometer with very large nonlinearity and switching characteristics. VO2, Fe3O4 nanoparticles, and a conductive binder (silver paint) were mixed and drop-casted onto two-terminal gap junction devices. The device’s current–voltage characteristics exhibited current-switching behavior related to MIT in VO2 which changed with the external magnetic field. The magnetoresistance and magnetostriction in Fe3O4 both contributed to the field sensitivity of the sensor. Sensitivities as high as 1 A nT−1 (or 50.8 V T−1 with a current bias) were observed near the MIT voltage. The resulting minimum detectable signal was 20 pT/SQRT(Hz).
Breastfeeding Disparities During the COVID-19 Pandemic: Race/Ethnicity, Age, Education, and Insurance Payor

Background: There are well-documented disparities in rates of continued breastfeeding. Existing research regarding breastfeeding during COVID-19 has raised concerns that the pandemic may have exacerbated these disparities. Research Aims: The aim of this research was first to quantify disparities in any breastfeeding associated with the maternal factors of race/ethnicity, age, insurance payor, and zip code rates of education in North Carolina. Second, we aimed to investigate any changes in these disparities before and during the COVID-19 pandemic. Method: This was an observational study, with a retrospective, longitudinal design. Participants included infants who were born in one of eight medical centers across North Carolina from either September 1, 2019 to October 31, 2019 (pre-COVID: n = 1,104) or from April 1, 2020 to May 31, 2020, (during COVID: n = 1,157), and whose caregivers reported whether they were breastfeeding at either a 3-month or 6-month postnatal follow-up (N = 2,261). Mixed effects logistic models, including random effects of zip code, assessed predictors associated with probability of breastfeeding cessation at 3- and 6-month child well-check. Results: Overall, younger maternal age, being non-Hispanic Black, not having commercial insurance, and residing in a zip code with lower rates of higher education, were all independently associated with earlier breastfeeding cessation across both cohorts. Disparities did not significantly change during the COVID-19 pandemic. Conclusion: We did not find support for the hypothesis that the COVID-19 pandemic might have exacerbated breastfeeding disparities. Nevertheless, there is a continued need to eliminate existing disparities.
Application of Information Theory to Spectral Estimation

The need for spectral estimation in some areas of science and engineering is discussed. Some early developments in this area, with an emphasis on the problems in different methods of spectrum estimation are briefly described. Parametric and non-parametric methods are briefly discussed. The maximum entropy method which provides an unbiased method to select unknown data values, that are not determined by the prior information, is given at the end.
Effectiveness and Safety of P2Y12 Inhibitor Pretreatment for Primary PCI in STEMI: Systematic Review and Meta-analysis

Supplemental Digital Content is Available in the Text. Abstract: Dual antiplatelet therapy with aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We performed a systematic search of electronic databases PubMed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration with downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available. Of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79,300 patients (66.1% pretreated, 66.0% treated with clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (odds ratio [OR] 0.61 [0.38–0.98]), all-cause death (OR 0.77 [0.60–0.97]), and cardiogenic shock (OR 0.60 [0.48–0.75]). It was also associated with a lower incidence of thrombolysis in myocardial infarction flow <3 pre-PCI (OR 0.78 [0.67–0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57–1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75–0.92]). Pretreatment with dual antiplatelet therapy, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.
Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients

Abstract Background This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders). Methods Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27. Results At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n = 1) and UL97 F342Y (n = 3). Posttreatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 nonresponders and 25 (86%) of the 29 nonresponders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n = 34), H411Y (n = 26), and C480F (n = 21), first detected 26 to 130 (median 56) days after starting maribavir. Conclusions Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. Clinical Trials Registration NCT02931539.
Russell Viper Venom: A Journey from the Bedside to the Bench and Back to the Bedside

Abstract Russell Viper Venom (RVV) is widely used as a diagnostic test for antiphospholipid syndrome (APS). But the history of how this venom came to be discovered is well known. Dr Patrick Russell is responsible for the identification of the venom during his work on snake bites in India while Dr Robert Macfarlane used it to staunch bleeding in persons with haemophilia. The ability to directly activate factor X led RVV to the laboratory diagnosis of APS. More recently, it has come back to clinical world with a potential for an engineered factor X activator from RVV to be used in the treatment of haemophilia.
Plasmonic Nanopore with Nanopattern and Nanoparticles for Single Molecule Analysis

In this report, the nano‐hole on the electron beam induced membrane surrounded by periodic groove patterns are fabricated by focused ion beam technique (FIB), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM). Initially, a ≈200 nm thick Au films was deposited on the microfabricated pyramid, or on the flat plate by using a sputter‐deposition technique. Nano‐pore formation inside the FIB drilled Au aperture was controlled down to a few nanometer by using electron beam irradiations. Periodic patterns would enhance the optical intensity through the nano‐aperture. Au particles were formed on the membrane several months after electron beam irradiations. In addition, surface plasmon‐enhanced Raman spectroscopy measurements were performed and the greatest optical intensity from on the pyramidal aperture surrounded with the nanopattern was measured. Fabricated plasmonic pore‐device can be utilized as a next generation optical sensor for single molecule analysis. TEM images of the fabricated nanopore surrounded by periodic patterns on the plate are presented with electron beam profile on the detector.
Photography in dermatology ‐ a scoping review: Practices, skin of color, patient preferences, and medical‐legal considerations

Clinical photography is essential in dermatology. However, a comprehensive literature review of photography in dermatology is lacking. This scoping review aims to summarize the literature regarding photography practices in dermatology, photography of skin of color, patient preferences, and medical‐legal considerations. A search was conducted utilizing Embase, MEDLINE, PubMed, and Evidence Based Medicine databases in accordance with the PRISMA extension for Scoping Reviews. In total, 33 studies were summarized. Clinical photography is commonly used in biopsy site marking, assessment, diagnosis, disease monitoring, evaluation of treatment response, medical education, research, seeking advice from colleagues, and teledermatology. Although dermatologic photography remains devoid of skin of color representation, photographic considerations for darker skin are available. Most patients support medical photography, with a preference for clinical photographs to be taken by their own physicians, and for use of clinic/hospital‐owned cameras over personal devices. Pertinent medical‐legal issues include concerns around privacy, personal device use, and documentation of consent. Photography in dermatology is continuously evolving with broader applications. Improved practices and innovations will benefit individuals of various skin tones. Management of consent and privacy must be upheld to sustain the increasing ease of image capture and sharing.
A MODIFIED PARTICLE SWARM OPTIMIZATION ALGORITHM FOR GENERAL INVERSE ORDERED p-MEDIAN LOCATION PROBLEM ON NETWORKS

This paper is concerned with a general inverse ordered p-median location problem on network where the task is to change (increase or decrease) the edge lengths and vertex weights at minimum cost subject to given modification bounds such that a given set of p vertices becomes an optimal solution of the location problem, i.e., an ordered p-median under the new edge lengths and vertex weights. A modified particle swarm optimization algorithm is designed to solve the problem under the cost functions related to the sum-type Hamming, bottleneck-type Hamming distances and the recti-linear and Chebyshev norms. By computational experiments, the high efficiency of the proposed algorithm is illustrated.
SECONDARY FLOW LOSS REDUCTION IN AXIAL TURBINE BLADES BY ENDWALL FENCE APPLICATION

In this study, it is investigated the effects of secondary flows and corresponding aerodynamic loss in axial turbine rotor numerically. To this sense, it is overviewed available literature and presented secondary flow models given by different authors. The rotor blades in which fluid flows is modeled and aerodynamic structure of tip leakage flow and horseshoe vortex are obtained. Loss mechanisms related to secondary flow and methods to reduce these losses are outlined. For same working conditions, total pressure loss is computed for three different fence height via ANSYS Fluent software. It is obtained that there is reduction of total pressure loss coefficient at blade outlet cross-section.