Miracle-dz/UniFAR-FTUs huggingface dataset:
The Development of a Multi-physics Simulation Tool to Estimate the Background Dose by Systemic Targeted Alpha Therapy.

PURPOSE To predict biological effects of Targeted Alpha Therapy (TAT) in pre-clinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha-immuno-conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly non-uniform and unsteady distributions of irradiation sources. Since the micro level distribution of emitters cannot be measured and obtained in patients with current technology, a modelling toolset to give more insight of the internal dose could be an alternative. METHODS A multi-physics model based on a Monte Carlo microdosimetry technique and Computational Fluid Dynamics (CFD) modelling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time-dependent absorbed dose to the target. RESULTS The conceptual model is capable of handling complex non-uniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. CONCLUSION Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.
Interferon-Induced IDO1 Mediates Radiation Resistance and Is a Therapeutic Target in Colorectal Cancer

Inhibition of the immune-metabolic enzyme IDO1 enhances radiation sensitivity in colorectal cancer and is radioprotective to the normal small intestine in mice. IDO1 inhibitors may increase radiation therapy effectiveness in humans with colorectal cancer while reducing intestinal toxicity. Colorectal cancer is a major cause of mortality worldwide. Chemotherapy and radiation remain standard treatment for locally advanced disease, with current immune-targeting therapies applying to only a small subset of patients. Expression of the immuno-oncology target indoleamine 2,3 dioxygenase 1 (IDO1) is associated with poor colorectal cancer clinical outcomes but is understudied as a potential treatment target. In this study, we examined the interaction between the IDO1 pathway and radiotherapy in colorectal cancer. We used human and mouse colorectal cancer cell lines, organoids, mouse syngeneic colorectal cancer tumor graft models, and colorectal cancer tissues from patients who received radiotherapy. IDO1 activity was blocked using the clinical IDO1 inhibitor epacadostat and by genetic disruption. We found that radiation induced IDO1 overexpression in colorectal cancer through type I and II IFN signaling. IDO1 enzymatic activity directly influenced colorectal cancer radiation sensitivity. IDO1 inhibition sensitized colorectal cancer to radiation-induced cell death, whereas the IDO1 metabolite kynurenine promoted radioprotection. IDO1 inhibition also potentiated Th1 cytokines and myeloid cell–modulating factors in the tumor microenvironment and promoted an abscopal effect on tumors outside the radiation field. Conversely, IDO1 blockade protected the normal small intestinal epithelium from radiation toxicity and accelerated recovery from radiation-induced weight loss, indicating a role in limiting side effects. These data demonstrated that IDO1 inhibition potentiates radiotherapy effectiveness in colorectal cancer. The findings also provide rationale and mechanistic insight for the study of IDO1 inhibitors as adjuvant therapy to radiation in patients with locally advanced sporadic and colitis-associated colorectal cancer.
Effect of ageing on verbal and visuo-spatial working memory: Evidence from 880 individuals

Abstract It is well-known that ageing is associated with a decrease in working memory abilities. It is not so clear at what age the decline begins and if there are differences in the decline of verbal and visuo-spatial working memory. This study investigates the effect of ageing on verbal and visuo-spatial working memory by comparing the performance of 880 subjects aged between 15- and 80-year old who were subdivided into five groups. The results show that age is negatively correlated with performance on both verbal and visuo-spatial working memory tasks. Specifically, we observed a gradual deterioration in performance with increasing age starting at 36-year old. Comparing the performance of the five groups, it is possible to observe a clear decline in both verbal and visuo-spatial working memory domains in subjects over 66-year old. However, in the next youngest age group, it is possible to notice differences in performance depending on the type of material being processed and the cognitive load required. This variability is discussed by analyzing the factors that may have influenced test performance.
Rotator Cuff Tendon Assessment in Symptomatic and Control Groups Using Quantitative MRI.

BACKGROUND Relatively weak correlations between patient symptoms and rotator cuff tendon (RCT) tearing have been reported; however, the relationship between symptoms and tendinosis has been less well-studied. PURPOSE/HYPOTHESIS To use quantitative MRI to assess the bilateral RCTs in shoulders of both patients with unilateral symptomatic tendinopathy and control subjects. We hypothesized that quantitative MRI measures would differ between symptomatic patients and controls. STUDY TYPE Prospective imaging study. POPULATION/SUBJECTS In all, 48 shoulders from 24 subjects (mean age, 32.8 years), including 14 patients with unilateral symptomatic tendinopathy and 10 asymptomatic controls. FIELD STRENGTH/SEQUENCE 3T/3D ultrashort echo time Cones sequence with magnetization transfer preparation (UTE-Cones-MT) and Carr-Purcell-Meiboom-Gill. ASSESSMENT Macromolecular fraction (MMF) and T2 relaxation were measured in four regions of the superior RCT, including all-segments, and lateral-third, bursal-sided, and articular-sided segments. The Western Ontario Rotator Cuff (WORC) index and visual analog scale were assessed. STATISTICAL TESTS Three shoulder groups were evaluated, including symptomatic shoulders, contralateral asymptomatic shoulders in patients, and asymptomatic controls. MMF and T2 values were compared between groups using a bootstrap-based comparison of means. RESULTS Significant differences were found in both MMF and T2 values between symptomatic and control RCTs when analyzing all-segments (P = 0.027 and P = 0.006, respectively) and articular-sided segments (both P = 0.001). Significant differences between asymptomatic RCTs in patients and control RCTs were also found, including MMF in all four anatomic regions analyzed (P = 0.024-0.044), as well as T2 in all-segments (P = 0.003), bursal-sided segments (P = 0.021), and articular-sided segments (P = 0.002). No significant differences in MMF (P = 0.420-0.950) or T2 (P = 0.380-0.910) were seen between ipsilateral symptomatic and contralateral asymptomatic RCTs in patients. DATA CONCLUSION Symptomatic RCTs showed significantly lower MMF values and higher T2 values compared with control RCTs. In patients with unilateral symptomatic tendinopathy, the contralateral shoulder can demonstrate asymptomatic tendinopathy, which can be quantified using MMF or T2 . EVIDENCE LEVEL 2 TECHNICAL EFFICACY: Stage 2.
Daisy-Chained Systolic Array and Reconfigurable Memory Space for Narrow Memory Bandwidth

SUMMARY A paradigm shift toward edge computing infrastructures that prioritize small footprint and scalable / easy-to-estimate performance is increasing. In this paper, we propose the following to improve the footprint and the scalability of systolic arrays: (1) column multithreading for reducing the number of physical units and maintaining the performance even for back-to-back ﬂoating-point accumulations; (2) a cascaded peer-to-peer AXI bus for a scalable multichip structure and an intra-chip parallel local memory bus for low latency; (3) multilevel loop control in any unit for reducing the startup overhead and adaptive operation shifting for e ﬃ cient reuse of local memories. We designed a systolic array with a single column × 64 row conﬁguration with Verilog HDL, evaluated the frequency and the performance on an FPGA attached to a ZYNQ system as an AXI slave device, and evaluated the area with a TSMC 28nm library and memory generator and identiﬁed the following: (1) the execution speed of a matrix multiplication / a convolution operation / a light-ﬁeld depth extraction, whose size larger than the capacity of the local memory, is 6.3 × / 9.2 × / 6.6 × compared with a similar systolic array (EMAX); (2) the estimated speed with a 4-chip conﬁguration is 19.6 × / 16.0 × / 8.5 × ; (3) the size of a single-chip is 8.4 mm 2 (0.31 × of EMAX) and the basic performance per area is 2.4 × .
Exercise and inflammation in coronary artery disease: A systematic review and meta-analysis of randomised trials

ABSTRACT Current evidence suggests that chronic inflammation contributes to the development of coronary artery disease (CAD). Interestingly, exercise may constitute a method of reducing inflammation in this patient population. As such, this systematic review and meta-analysis examined the evidence generated by randomised studies that investigated the effect of exercise on inflammatory biomarkers in CAD. Literature was sought from various sources. Outcomes were pooled in a random-effects model to calculate standardised mean differences (SMD) with 95% confidence intervals (CI). Twenty-five studies were reviewed; post-intervention C-reactive protein (SMD: −0.55 (95% CI: −0.93, −0.16), P = 0.005), fibrinogen (SMD: −0.52 (95% CI: −0.74, −0.29, P = <0.00001)), and von Willebrand factor (SMD: −1.57 (95% CI: −2.23, −0.92), P = <0.00001) values were significantly lower in exercise groups compared to controls. In addition, qualitative analyses identified evidence that supports a beneficial effect of exercise on these acute-phase reactants. However, the impact of exercise on anti–inflammatory cytokines, adhesion molecules, and chemokines is equivocal, which may be attributed to a paucity of research. Nevertheless, the findings of this review suggest that exercise induces an anti–inflammatory effect in CAD patients. Although, the quality of evidence needs to be improved by further randomised studies with high methodological qualities and large sample sizes.
Year 9 students's views towards their careers and technology education

Technology education is compulsory for all New Zealand students until the end of Year 10. After this time the students have the option to undertake further studies although it is no longer compulsory. Year 9 is usually the first year of secondary schooling and is often seen as the time when students start thinking about future directions. This research aims to ascertain Year 9 students’ views of technology education and its relevance to themselves and their careers.
Effect of Developmental Milestones on Patterns of Teeth Eruption

Introduction: Developmental milestones are a set of functional skills or age-specific tasks that most children can do at a certain age range. The milestones help to check how a child is developing. Keeping in mind the importance of the developmental milestones and the teeth eruption patterns in a child’s life, a study was designed. Materials and Methods: The study was cross-sectional in nature and conducted among four to thirty 6 months old children selected from the government and private hospitals of Bhopal city, Madhya Pradesh, India. This study comprises a total of 1601 subjects from both sexes. The cases were taken from the outpatient departments of government and private hospitals in Bhopal city. The questionnaire collected information on demographic details and milestones of children were examined as per the American Academy of Pediatric Dentistry development chart of milestones. Statistical analysis was done using Statistical Package for Social Science. Result: It was observed that teeth eruption was delayed in children irrespective of the milestones whether it was delayed or normal.
Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

Background Chagas disease has spread beyond its original borders on the American continent with migration. It can be transmitted from mother to child, through organ transplantation and transfusion of blood and blood products. It is necessary to determine when to screen for this infection. Aim Our objective was to evaluate the appropriateness of screening for Trypanosoma cruzi infection in Latin American migrants and their descendants. Methods We reviewed the literature using rigorous criteria. The quality of evidence was ranked according to the GRADE classification. An evidence to decision framework was adopted to provide information on the most relevant aspects necessary to formulate recommendations. Results The 33 studies evaluated revealed a prevalence of T. cruzi infection among Latin American migrants in Europe of 6.08% (95% confidence interval (CI): 3.24–9.69; 28 studies). Vertical transmission occurred in three of 100 live births (95% CI: 1–6; 13 studies). The prevalence of cardiovascular disease was 19% (95% CI: 13–27; nine studies), including only 1% severe cardiac events (95% CI: 0–2; 11 studies). The overall quality of evidence was low because of risk of bias in the studies and considerable heterogeneity of the evaluated populations. The recommendations took into account economic studies on the value of screening strategies and studies on acceptability of screening and knowledge of the disease in the affected population. Conclusions We identified five situations in which screening for T. cruzi infection is indicated. We recommend screening persons from endemic areas and children of mothers from these areas.
Physiologically‐Based Pharmacokinetic Model of Sertraline in Human to Predict Clinical Relevance of Concentrations at Target Tissues

Significant in vitro and in vivo evidence supports the potential use of sertraline as an anticancer and antimicrobial agent. Yet, it is unknown whether effective sertraline concentrations are clinically achieved at therapeutic doses. The study objectives were to develop a physiologically‐based pharmacokinetic (PBPK) model of sertraline and estimate the probability of achieving effective concentrations in various human tissues. A generic PBPK model consisting of perfusion‐limited compartments representing the body organs linked together by blood flows and incorporated with clearance, tissue distribution, and absorption models was implemented in R using the mrgsolve package. Sertraline clearance and volume of distribution were first optimized from i.v. plasma concentration data then absorption and bioavailability were optimized from oral data. Predicted unbound sertraline concentrations at steady‐state in human tissues did not reach concentrations determined in vitro, indicating therapeutic doses of sertraline are unlikely to produce concentrations required for anticancer and antimicrobial activities in humans.
Effect of a Home Pregnancy Test Intervention on Cohort Retention and Pregnancy Detection: A Randomized Trial.

We conducted a parallel non-blinded randomized trial to assess whether offering home pregnancy tests (HPT) to preconception cohort study participants influenced cohort retention or pregnancy detection. Pregnancy Study Online (PRESTO) participants were female, aged 21-45 years, attempting pregnancy, and not using fertility treatment. At enrollment (2017-2018), 1,493 participants with ≤6 cycles of attempt time were randomized with 50% probability to receive Clearblue visual HPTs plus the standard protocol (N=720) or the standard protocol (N=773). Women completed bimonthly questionnaires for 12 months or until conception, whichever came first. In intent-to-treat analyses, retention (≥1 follow-ups) was higher in the HPT arm (N=598; 83%) than the standard protocol arm (N=535; 69%) (mean difference=15%, 95% CI: 10%, 19%). Mean time at first pregnancy testing was identical in both arms (2 days before expected menses), as was mean gestational weeks at first positive pregnancy test (4 weeks). Conception was reported by 78% in the HPT arm and 75% in the standard protocol arm. Spontaneous abortion was reported by 21% in the HPT arm (mean gestational weeks=7) and 21% in the standard protocol arm (mean gestational weeks=6). Randomization of HPTs was associated with greater cohort retention, but had little impact on incidence or timing of pregnancy detection.
A Non-Intrusive Speech Intelligibility Estimation Method Based on Deep Learning Using Autoencoder Features

SUMMARY This paper presents a deep learning-based non-intrusive speech intelligibility estimation method using bottleneck features of au-toencoder. The conventional standard non-intrusive speech intelligibility estimation method, P.563, lacks intelligibility estimation performance in various noise environments. We propose a more accurate speech intelligibility estimation method based on long-short term memory (LSTM) neural network whose input and output are an autoencoder bottleneck features and a short-time objective intelligence (STOI) score, respectively, where STOI is a standard tool for measuring intrusive speech intelligibility with reference speech signals. We showed that the proposed method has a superior performance by comparing with the conventional standard P.563 and mel-frequency cepstral coe ﬃ cient (MFCC) feature-based intelligibility estimation methods for speech signals in various noise environments.
Acute alcohol exposure in early gestation programmes sex‐specific insulin resistance in offspring: a shifting tide in prenatal alcohol exposure models

The maternal environment plays an important role in programming health and disease in offspring. This is known as the developmental origins of health and disease (DOHaD) hypothesis, which states that prenatal and perinatal perturbations (e.g. maternal malnutrition, obesity, drug use, stress, smoking) can impair fetal development and programme the offspring for chronic disease in adulthood. Clinical and preclinical data suggest that the timing of these perturbations is important and can affect different organ systems. Organs that slowly (e.g. and are particularly susceptible to perturbations at multiple points, and thus many maternal insults (e.g. obesity, drug use and alcohol use) programme for metabolic
Impact of Social Support on Colorectal Cancer Screening among Adult Hispanics/Latinos: A Randomized Community-based Study in Central Pennsylvania

In the United States, the five-year survival rate of colorectal cancer for Latinos is lower than it is for White, non-Latinos. Differences in survival are due, in part, to Latinos being diagnosed at a later stage. An ethnic gap in the use of colorectal cancer screening contributes to the difference in survival. We developed, implemented, and evaluated a targeted colorectal cancer screening intervention to increase colorectal cancer screening uptake by sex, ethnicity, and geography. We measured actual colorectal cancer screening uptake in both arms as a method to determine completion rates. We used a randomized, community-based, participatory design to test the impact of social support (intervention) on completion of a provider-recommended, take-home fecal immunochemical test (FIT) kit screening test among average-risk, urban, and rural Pennsylvania Latino adults age 50 and older not currently adherent to national colorectal cancer screening guidelines (n = 264). Participants in each arm attended a community-based educational program offered at eight sites. Among the 264 participants, 154 (58%) returned a completed usable FIT kit screening test. A higher return rate was observed among participants in the social support arm (66.0%) compared with the control (47.2%). Participants in the social support arm were statistically significant 2.67 times as likely to return a completed FIT kit. Of these, 27 (17.5%) had a positive FIT kit screening test result. The results of this study suggest that social support is an effective method to increase colorectal cancer screening rates among Latinos. Future studies should examine dissemination and implementation of community-based strategies among Latinos that include social support.
Material properties of the skull layers of the primate parietal bone: A single-subject study

The outer cortical table of the parietal bone has been commonly used as a calvarial bone graft site for the craniofacial reconstruction. However, little is known about how removing the outer table may affect the function and structure of the inner table, and how the knowledge of the biomechanics and material properties of cortical bones will help the calvarial graft to better integrate into the biological and mechanical functions of its surrounding native tissues. In this study, it was hypothesized that there were significant differences in both density and material properties between inner and outer cortical plates in cranial bones. Twelve cylindrical specimens, including inner-outer layers, of cortical parietal bone of a female baboon were collected. Cortical thicknesses and densities were measured, and elastic properties were assessed using an ultrasonic technique. Results demonstrated remarkable difference in both thickness (t = 8.248, p ≤0.05) and density (t = 4.926, p≤0.05) between inner and outer cortical paired samples. Orthotropic characteristics of the cortical plates were detected as well, these findings suggest that there are differences in biomechanical properties between two surfaces of cranial bones at both tissue and organ levels. How these differences are linked to the stress environments of the inner and outer cranial cortical layers awaits further studies. Further study will greatly enhance our ability to address questions derived from both morphological and craniofacial medicine fields about the development and biomechanics of craniofacial skeletons.