Miracle-dz/UniFAR-FTUs huggingface dataset:
Intraindividual Tumor Heterogeneity of Mismatch Repair Status in Metastatic Colorectal Cancer

Heterogeneous mismatch repair (MMR) status in metastatic colorectal cancer (mCRC) may associate with refractoriness to immunotherapy. We aimed here to study the concordance in MMR status between primary and paired metastasis in mCRC. Our study included 84 patients diagnosed with mCRC with primary and matched metastatic cancers. Immunohistochemistry was used to determine the MMR status of primary lesions and matched metastases. Pooled analysis of 913 cases was used to evaluate the prevalence and organ specificity of MMR status heterogeneity. The correlations between MMR pattern heterogeneity and clinical outcomes were analyzed. MMR status heterogeneity between primary and corresponding metastatic sites was exhibited by 10 (11.9%) patients. The prevalence of the heterogeneous MMR phenotype was significantly higher in primary tumors with deficient MMR (dMMR) than with proficient MMR (pMMR), which was verified in the pooled analysis (P<0.001). Among patients with a dMMR primary tumor, the discrepancy was detected in liver, lung, ovary, peritoneum, and distant lymph node metastases. However, the discrepancy was confined to liver (26/440) or peritoneum (7/112) (P=0.02) in patients with a pMMR primary tumor. Patients with or without MMR status heterogeneity experienced comparable overall survival (P=0.452). Heterogeneous MMR patterns generally existed in a subset of patients with mCRC, particularly those with dMMR primary tumors. Testing the metastatic site may be valuable because the discordance of MMR status may potentially affect immune surveillance and immunotherapy.
Galois representations, embedding problems and modular forms

To an odd irreducible 2-dimensional complex linear representation of the absolute Galois group of the field $\mathbb{Q}$ of rational numbers, a modular form of weight 1 is associated (modulo Artin's conjecture on the L-series of the representation in the icosahedral case). In addition, linear liftings of 2-dimensional projective Galois representations are related to solutions of certain Galois embedding problems. \newline In this paper we present some recent results on the existence of liftings of projective representations and on the explicit resolution of embedding problems associated to orthogonal Galois representations, and explain how these results can be used to construct modular forms.
Simulating the Galaxy Cluster “El Gordo”: Gas Motion, Kinetic Sunyaev–Zel’dovich Signal, and X-Ray Line Features

The massive galaxy cluster “El Gordo” (ACT-CL J0102–4915) is a rare merging system with a high collision speed suggested by multi-wavelength observations and theoretical modeling. Zhang et al. propose two types of mergers, a nearly head-on merger and an off-axis merger with a large impact parameter, to reproduce most of the observational features of the cluster using numerical simulations. The different merger configurations of the two models result in different gas motion in the simulated clusters. In this paper, we predict the kinetic Sunyaev–Zel’dovich (kSZ) effect, the relativistic correction of the thermal Sunyaev–Zel’dovich (tSZ) effect, and the X-ray spectrum of this cluster, based on the two proposed models. We find that (1) the amplitudes of the kSZ effect resulting from the two models are both on the order of ΔT/T ∼ 10−5; but their morphologies are different, which trace the different line-of-sight velocity distributions of the systems; (2) the relativistic correction of the tSZ effect around 240 GHz can be possibly used to constrain the temperature of the hot electrons heated by the shocks; and (3) the shift between the X-ray spectral lines emitted from different regions of the cluster can be significantly different in the two models. The shift and the line broadening can be up to ∼25 eV and 50 eV, respectively. We expect that future observations of the kSZ effect and the X-ray spectral lines (e.g., by ALMA, XARM) will provide a strong constraint on the gas motion and the merger configuration of ACT-CL J0102–4915.
One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines

Abstract Background Although modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed. Methods Participants naive to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, n = 181), 2 doses MVA-BN (2×MVA, n = 183), or placebo (n = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX, n = 200). Subsets of the formerly naive groups (approximately 75 each) received an MVA-BN booster 2 years later. Results Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naive groups) to 7.2 and 7.5 (week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (week 6, 2×MVA after second vaccination). In HSPX, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naive groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified. Conclusions Anamnestic responses to boosting without sustained high nAb titers support presence of durable immunological memory following primary MVA-BN immunization. Clinical Trials Registration. NCT00316524 and NCT00686582.
Inductive Effect of Lewis Acidic Dopants on the Band Levels of Perovskite for a Photocatalytic Reaction.

Band-edge modulation of halide perovskites as photoabsorbers plays significant roles in the application of photovoltaic and photochemical systems. Here, Lewis acidity of dopants (M) as the new descriptor of engineering the band-edge position of the perovskite is investigated in the gradiently doped perovskite along the core-to-surface (CsPbBr3-CsPb1-xMxBr3). Reducing M-bromide bond strength with an increase in hardness of acidic M increases the electron ability of basic Br, thus strengthening the Pb-Br orbital coupling in M-Pb-Br, noted as the inductive effect of dopants. Especially, the highly hard Lewis acidic Mg localized in the outer position of the perovskite induces the increase of work function and then shifts band edge upward along the core-to-surface of the perovskite. Thus, charge separation driven by the dopant-induced internal electric field induces the slow annihilation of the excited holes, improving the slow aromatic Csp3-H dissociation in the photocatalytic oxidation process by ∼211% (491.39 μmol g-1 h-1) enhancements, compared with undoped nanocrystals.
Model-based estimation of the impact on rotavirus disease of RV3-BB vaccine administered in a neonatal or infant schedule

ABSTRACT Rotavirus infection is a common cause of severe diarrheal disease and a major cause of deaths and hospitalizations among young children. Incidence of rotavirus has declined globally with increasing vaccine coverage. However, it remains a significant cause of morbidity and mortality in low-income countries where vaccine access is limited and efficacy is lower. The oral human neonatal vaccine RV3-BB can be safely administered earlier than other vaccines, and recent trials in Indonesia have demonstrated high efficacy. In this study, we use a stochastic individual-based model of rotavirus transmission and disease to estimate the anticipated population-level impact of RV3-BB following delivery according to either an infant (2, 4, 6 months) and neonatal (0, 2, 4 months) schedule. Using our model, which incorporated an age- and household-structured population and estimates of vaccine efficacy derived from trial data, we found both delivery schedules to be effective at reducing infection and disease. We estimated 95–96% reductions in infection and disease in children under 12 months of age when vaccine coverage is 85%. We also estimate high levels of indirect protection from vaccination, including 78% reductions in infection in adults over 17 years of age. Even for lower vaccine coverage of 55%, we estimate reductions of 84% in infection and disease in children under 12 months of age. While open questions remain about the drivers of observed lower efficacy in low-income settings, our model suggests RV3-BB could be effective at reducing infection and preventing disease in young infants at the population level.
Disrupted T‐tubular network accounts for asynchronous calcium release in MTM1‐deficient skeletal muscle

In mammalian skeletal muscle, the propagation of surface membrane depolarization into the interior of the muscle fibre along the transverse (T) tubular network is essential for the synchronized release of calcium from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) in response to the conformational change in the voltage‐sensor dihydropyridine receptors. Deficiency in 3‐phosphoinositide phosphatase myotubularin (MTM1) has been reported to disrupt T‐tubules, resulting in impaired SR calcium release. Here confocal calcium transients recorded in muscle fibres of MTM1‐deficient mice were compared with the results from a model where propagation of the depolarization along the T‐tubules was modelled mathematically with disruptions in the network assumed to modify the access and transmembrane resistance as well as the capacitance. If, in simulations, T‐tubules were assumed to be partially or completely inaccessible to the depolarization and RyRs at these points to be prime for calcium‐induced calcium release, all the features of measured SR calcium release could be reproduced. We conclude that the inappropriate propagation of the depolarization into the fibre interior is the initial critical cause of severely impaired SR calcium release in MTM1 deficiency, while the Ca2+‐triggered opening of RyRs provides an alleviating support to the diseased process.
The transport of polarized synchrotron radiation in a turbulent medium

We have developed a model to describe the transport of polarized synchrotron radiation in an optically thin source possessing small amplitude fluctuations in thermal electron density, energetic electron density, and vector magnetic field. The analysis employs an approximation termed the small phase approximation, which is similar to the first order Rytov approximation in the theory of wave propagation in a random medium. Expressions are derived relating the (observable) autocorreltions and cross-correlations of the Stokes parameters Q and U to the correlation functions of the aforementioned physical quantities. The last section of the paper is intended for observers, and describes how data from polarization maps may be used to determine the intensity and spectral characteristics of turbulence in a synchrotron source, such as a radio galaxy.
Neural bases of motivated forgetting of autobiographical memories

ABSTRACT It is important for mental health to be able to control unwanted intrusive memories. Previous studies suggest that middle frontal gyrus (MFG) down regulates pathways underlie the suppression of retrieval of general memories. However, the neural basis of motivated forgetting of autobiographical memories is unclear. Therefore, this study used two samples to explore the neural mechanisms of motivated forgetting of self-referential memories. Every participant provided 40 life events (20 negative and 20 neutral) from their past personal experience, and then completed the Think/No-Think task while undergoing functional magnetic resonance imaging (fMRI). The first sample showed a significant reduction in recall in the No-Think condition relative to the Think condition. Attempting to exclude negative autobiographical memories from awareness was associated with increased activity in the right MFG, superior frontal gyrus (SFG), and inferior frontal gyrus (IFG), while reduced activity was observed in the bilateral Brodmann areas BA18 and BA19, bilateral medial prefrontal cortex (mPFC), bilateral precuneus, bilateral post cingulate cortex (PCC), the left parahippocampus, and the left hippocampus. Functional connectivity analyses showed that the right MFG projected into the bilateral mPFC, bilateral precuneus, and bilateral middle occipital gyrus (MOG) for negative autobiographical memories. The second sample replicated the results of the first sample at both the behavioral and brain levels. These results suggest that retrieval suppression of autobiographical memories involve the pathway between the MFG and the mPFC and precuneus to exclude self-referential memories. These results reveal how people engage in motivated forgetting of negative events in their daily lives.
Transient Coupled Radiation -Conduction in Semitransparent Spherical Particle

Amethod toanalyzetransientcoupled radiation ‐conductionina semitransparentsphericalparticlesurrounded by isothermal black walls was developed. The radiative transfer coefe cients were deduced using the ray tracing method in combination with Hottel and Saroe m’ s zonal method. The radiative heat source term was calculated by the radiative transfer coefe cients, and the transient energy equation was solved by an implicit e nite difference method. The effects of the related parameters on the transient radiative heat source and temperature distribution wereanalyzed.Theresultsshowthatthepeakofdimensionlessradialradiativeheatsourcecanlocateintheinterior shell of the particleordropletwith small optical thickness when heated by surrounding radiation. Treating volume radiation as surface radiation results in large transient temperature distribution errors for the particle with small optical thickness.
Social distancing with chronic pain during COVID-19: A cross-sectional correlational analysis

Background Understanding of the role social factors play in chronic pain is growing, with more adaptive and satisfying social relationships helping pain management. During the COVID-19 pandemic, social distancing measures facilitated a naturalistic study of how changes to social interaction affected chronic pain intensity. Methods In a cross-sectional correlational design, questionnaire data was collected over a 38-day period during the March 2020 COVID-19 lockdown, individuals with chronic pain were asked about their current pain experience as well as notable social factors which might relate to pain. Results Multiple regression analysis revealed social satisfaction significantly predicted pain experience, with a reduction in social participation during COVID-19 lockdowns increasing pain disability, and increased social satisfaction associated with decreasing pain intensity. Conclusions While pain management often focuses on the functional aspects of pain alleviation, these findings suggest psychological aspects of socialising satisfaction also impact pain experience. Pain management strategies should consider ways to increase social satisfaction in individuals with chronic pain, perhaps by facilitating socialisation in the home using remote communication methods similar to those which became popular during the COVID-19 lockdown.
Distinct inflammation-related proteins associated with T cell immune recovery during chronic HIV-1 infection

ABSTRACT Chronic inflammation and T cell dysregulation persist in individuals infected with human immunodeficiency virus type 1 (HIV-1), even after successful antiretroviral treatment. The mechanism involved is not fully understood. Here, we used Olink proteomics to comprehensively analyze the aberrant inflammation-related proteins (IRPs) in chronic HIV-1-infected individuals, including in 24 treatment-naïve individuals, 33 immunological responders, and 38 immunological non-responders. T cell dysfunction was evaluated as T cell exhaustion, activation, and differentiation using flow cytometry. We identified a cluster of IRPs (cluster 7), including CXCL11, CXCL9, TNF, CXCL10, and IL18, which was closely associated with T cell dysregulation during chronic HIV-1 infection. Interestingly, IRPs in cluster 5, including ST1A1, CASP8, SIRT2, AXIN1, STAMBP, CD40, and IL7, were negatively correlated with the HIV-1 reservoir size. We also identified a combination of CDCP1, CXCL11, CST5, SLAMF1, TRANCE, and CD5, which may be useful for distinguishing immunological responders and immunological non-responders. In conclusion, the distinct inflammatory milieu is closely associated with immune restoration of T cells, and our results provide insight into immune dysregulation during chronic HIV-1 infection.
Comparison of Urinary Tract Infection Incidence Following Intradetrusor OnabotulinumtoxinA in Office Versus Operating Room Settings

Importance Urinary tract infection (UTI) is a known complication of intradetrusor onabotulinumtoxinA (BTX) injection. However, whether administering intradetrusor BTX in different clinical settings affects the risk of postprocedural UTI has not been investigated. Objectives The objective of this study was to assess differences in the incidence of postprocedural UTI in women who received intradetrusor BTX in an outpatient office versus an operating room (OR). Study Design We performed a retrospective chart review of intradetrusor BTX procedures at a single institution between 2013 and 2020. Demographic data, comorbidities, and perioperative data were abstracted. The primary outcome was UTI defined as initiation of antibiotics within 30 days following BTX administration based on clinician assessment of symptoms and/or urine culture results. Univariate analysis of patients with and without UTI was performed. Results A total of 446 intradetrusor BTX procedures performed on female patients either in an outpatient office (n = 160 [35.9%]) or in an OR (n = 286 [64.1%]) were included in the analysis. Within 30 days of BTX administration, UTI was diagnosed after 14 BTX procedures (8.8%) in the office group and 29 BTX procedures (10.1%) in the OR group (P = 0.633). De novo postprocedural urinary retention occurred in more women who were treated in the office than in the OR (13 [9.6%] vs 3 [1.3%], P < 0.001). Conclusions Selecting the appropriate setting for BTX administration is dependent on multiple factors. However, the clinical setting in which intradetrusor BTX is administered may not be an important factor in the development of postprocedural UTI, and further research is warranted.
Effects analysis of reward functions on reinforcement learning for traffic signal control

The increasing traffic demand in urban areas frequently causes traffic congestion, which can be managed only through intelligent traffic signal controls. Although many recent studies have focused on reinforcement learning for traffic signal control (RL-TSC), most have focused on improving performance from an intersection perspective, targeting virtual simulation. The performance indexes from intersection perspectives are averaged by the weighted traffic flow; therefore, if the balance of each movement is not considered, the green time may be overly concentrated on the movements of heavy flow rates. Furthermore, as the ultimate purpose of traffic signal control research is to apply these controls to the real-world intersections, it is necessary to consider the real-world constraints. Hence, this study aims to design RL-TSC considering real-world applicability and confirm the appropriate design of the reward function. The limitations of the detector in the real world and the dual-ring traffic signal system are taken into account in the model design to facilitate real-world application. To design the reward for balancing traffic movements, we define the average delay weighted by traffic volume per lane and entropy of delay in the reward function. Model training is performed at the prototype intersection for ensuring scalability to multiple intersections. The model after prototype pre-training is evaluated by applying it to a network with two intersections without additional training. As a result, the reward function considering the equality of traffic movements shows the best performance. The proposed model reduces the average delay by more than 7.4% and 15.0% compared to the existing real-time adaptive signal control at two intersections, respectively.
Assessing the Utility of Mental Health First Aid Training for Physician Assistant Students

Introduction Physician assistant (PA) students are at increased risk for anxiety and depression compared with the general population. The demands of studying medicine can contribute to a decline in mental health, which may impede a student’s ability to progress in his or her PA program. Mental Health First Aid (MHFA) is one strategy that can be used to increase mental health literacy, promote help-seeking behavior, reduce stigma, and improve confidence in providing help to individuals showing signs of a mental health disorder. The aim of this outcomes assessment was to assess PA students’ satisfaction with the MHFA course and their posttraining confidence in using the skills learned. Methods Participants were PA students (N = 435) across 9 PA programs in their didactic year of training who had completed an MHFA course through the PA Foundation’s Mental Health Outreach Fellowship. MHFA postcourse evaluations, completed by the PA students, were analyzed to determine PA students’ satisfaction with the course and their posttraining confidence in using the skills learned to help both themselves as well as the general population. Results The mean of the MHFA course evaluation items corresponding to satisfaction with the course was 4.82 (maximum score of 5), and the mean of the items corresponding to posttraining confidence in using the skills learned was 4.74 (maximum score of 5). When asked, “Would you recommend this course to others? ” 99.3% of the PA students trained in MHFA answered “yes,” indicating a high level of satisfaction with the training they had received. DIscussion PA students who received MHFA training from the PA Foundation’s Mental Health Outreach fellows showed high levels of satisfaction with the MHFA course and posttraining confidence in using the skills learned.
Does IFITM3 link inflammation to tumorigenesis?

Uncontrolled chronic inflammation, in most cases due to excessive cytokine signaling through their receptors, is known to contribute to the development of tumorigenesis. Recently, it has been reported that the antiviral membrane protein interferon-induced transmembrane protein 3 (IFITM3), induced by interferon signaling as part of the inflammatory response after viral infection, contributes to the development of B-cell malignancy. The unexpected oncogenic signaling of IFITM3 upon malignant B cell activation elucidated the mechanism by which the uncontrolled expression of inflammatory proteins contributes to leukemogenesis. In this review, the potential effects of inflammatory cytokines on upregulation of IFITM3 and its contribution to tumorigenesis are discussed.