Miracle-dz/UniFAR-FTUs huggingface dataset:
Modest agreement between magnetic resonance and pathological tumor regression after neoadjuvant therapy for rectal cancer in the real world

Magnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high‐volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five‐tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0‐3 vs pTRG 4; mrTRG 2‐5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73‐0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that “T3 greater than 5 mm extent” was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15‐0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI.
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage

The repair of DNA damage caused by chemotherapy in cancer cells occurs mainly at two cell cycle checkpoints (G1 and G2) and is a factor contributing to chemoresistance. Most colorectal cancers harbor mutations in p53, the main pathway involved in the G1 checkpoint, and thus, are particularly dependent on the G2 checkpoint for DNA repair. The present study examined the effect of AZD6738, a specific inhibitor of ataxia telangiectasia mutated and rad3-related (ATR) involved in the G2 checkpoint, combined with 5-fluorouracil (5-FU), a central chemotherapeutic agent, on colorectal cancer cells. Since 5-FU has a DNA-damaging effect, its combination with AZD6738 is likely to enhance the therapeutic effect. The effects of the AZD6738/5-FU combination were evaluated in various colorectal cancer cells (HT29, SW480, HCT116 and DLD-1 cells) by flow cytometry (HT29 cells), western blotting (HT29 cells) and water-soluble tetrazolium 1 assays (HT29, SW480, HCT116 and DLD-1 cells), as well as in an experimental animal model (HT29 cells). In vitro, the AZD6738/5-FU combination increased the number of mitotic cells according to flow cytometry, decreased the checkpoint kinase 1 phosphorylation levels and increased cleaved caspase-3 and phosphorylated form of H2A.X variant histone levels according to western blotting, and decreased the proliferation rate of four colon cancer cell lines according to cell viability experiments. In vivo, xenografted colorectal cancer cells treated with the AZD6738/5-FU combination exhibited a marked decrease in proliferation compared with the 5-FU alone group. The present results suggested that AZD6738 enhanced the effect of 5-FU in p53-mutated colorectal cancer.
Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies

Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synthetic insecticides and is considered less harmful to beneficial insects, yet its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad antagonize its neuronal target, the nicotinic acetylcholine receptor subunit alpha 6 (nAChRα6), reducing the cholinergic response. We show that the nAChRα6 receptors are transported to lysosomes that become enlarged and increase in number upon low doses of spinosad treatment. Lysosomal dysfunction is associated with mitochondrial stress and elevated levels of reactive oxygen species (ROS) in the central nervous system where nAChRα6 is broadly expressed. ROS disturb lipid storage in metabolic tissues in an nAChRα6-dependent manner. Spinosad toxicity is ameliorated with the antioxidant N-acetylcysteine amide. Chronic exposure of adult virgin females to low doses of spinosad leads to mitochondrial defects, severe neurodegeneration, and blindness. These deleterious effects of low-dose exposures warrant rigorous investigation of its impacts on beneficial insects.
Reinventing the Library

Libraries are no longer the hushed, imposing, monolithic repositories of all things printed that they once were. In cities and on campuses, the modern library has become an open, inviting, and dynamic community resource, offering residents and students a place to learn from a variety of sources, engage their peers, and interact with their surroundings. The grand new library at Grand Valley State University, in western Michigan, is a case in point.
Behavioural intention to use 3G mobile multimedia services in Indonesia

The mobile multimedia services (MMS) of third generation (3G) mobile communication networks have been commercially available in Indonesia since 2006. Despite the large amount of investments that 3G operators have rolled out for this technology, the number of subscribers for 3G MMS is still low, comprising only 9% of the total population. The key adoption and moderating factors that affect the behavioural intention of users in Indonesia toward 3G MMS have not been thoroughly investigated. This paper examines issues pertaining to the low acceptance rate of 3G MMS in the Indonesian context using feedback before technology adoption to understand this phenomenon. Specifically, the unified theory of acceptance and use of technology (UTAUT) forms the basis of this study.
Small-Group, Emergent Literacy Intervention Under Two Implementation Models: Intent-to-Treat and Dosage Effects for Preschoolers at Risk for Reading Difficulties

Preschool-age children identified as at risk for later reading difficulties can benefit from supplemental, small-group emergent literacy intervention. As such interventions become commercially available and marketed to preschool programs, it is important to understand their impacts when implemented by intended end users under routine conditions. In this study, we examined the effects of the Nemours BrightStart! (NBS! ) intervention on children’s emergent literacy skills when implemented by teachers and community aides in authentic preschool classrooms. We randomly assigned 98 classrooms to one of three conditions (NBS! teacher-implemented, NBS! community aide-implemented, or control). Children enrolled in these classrooms who met eligibility criteria and were identified as at risk via an early literacy screener (n = 281) completed pretest and posttest emergent literacy assessments; those assigned to NBS! conditions received intervention from their classroom teacher or a community aide affiliated with a local kindergarten-readiness initiative. Intent-to-treat analyses showed no significant impacts of NBS! on any outcome, and an instrumental variable, as-treated approach showed one significant intervention effect on letter writing. Consequently, we did not replicate results of prior highly controlled efficacy trials. Findings have implications for revising the NBS! theory of change, conducting dosage and as-treated analyses, and moving research-based interventions toward scale-up.
Flu vaccination in multiple sclerosis patients: a monocentric prospective vaccine-vigilance study

ABSTRACT Background In 2020, the Italian Medicines Agency recommended to bring forward the flu vaccination campaign, whose importance was also emphasized for patients with Multiple Sclerosis (MS). We aimed to assess the safety profile of flu vaccines in terms of occurrence of short-term and long-term Adverse Events Following Immunization (AEFIs). Methods This is an observational study that enrolled MS patients who were eligible for any of the flu vaccines recommended by the Italian medicines Agency. Results 194 patients were enrolled. Out of 133 patients who accepted to be vaccinated, 45 experienced not serious short-term AEFIs (pain at the injection site, headache, flu-like symptoms, fatigue). Long-term AEs were detected in 12 vaccinated patients (flu-like symptoms, COVID-19 and MS relapse). No statistically significant differences in terms of infections or MS relapse were found between vaccinated and unvaccinated groups. Using Kaplan–Meier analysis we observed no differences in the cumulative survival rate in both groups. Conclusion Flu vaccines were well tolerated in MS patients, who mainly experienced not serious short term AEFIs. Considering that COVID-19 vaccines campaign is still ongoing among MS patients, our results might bring new knowledge concerning the safety profile of vaccines in this frail population.
Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and "silent hypoxemia" at admission: a severity-matched analysis.

BACKGROUND An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS Overall 28-day mortality in 1,316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, p=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (p=0.21). CONCLUSIONS Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.
Nonsingular Practical Fixed-Time Adaptive Output Feedback Control of MIMO Nonlinear Systems

This article studies the nonsingular fixed-time control problem of multiple-input multiple-output (MIMO) nonlinear systems with unmeasured states for the first time. A state observer is designed to solve the problem that system states cannot be measured. Due to the existence of the unknown system nonlinear dynamics, neural networks (NNs) are introduced to approximate them. Then, through the combination of adaptive backstepping recursive technology and adding power integration technology, a nonsingular fixed-time adaptive output feedback control algorithm is proposed, which introduces a filter to avoid the complicated derivation process of the virtual control function. According to the fixed-time Lyapunov stability theory, the practical fixed-time stability of the closed-loop system is proven, which means that all signals of the closed-loop system remain bounded in a fixed time under the proposed algorithm. Finally, the effectiveness of the proposed algorithm is verified by the numerical simulation and practical simulation.
Simulated confluence on micropatterned substrates correlates responses regulating cellular differentiation

While cells are known to behave differently based on the size of micropatterned islands, and this behavior is thought to be related to cell size and cell−cell contacts, the exact threshold for this difference between small and large islands is unknown. Furthermore, while cell size and cell−cell contacts can be easily manipulated on small islands, they are harder to measure and continually monitor on larger islands. To investigate this size threshold, and to explore cell size, cell−cell contacts, and differentiation, we use a previously established simulation to plan experiments and explain results that we could not explain from experiments alone. We use five seeding densities covering three orders of magnitude over 25−500 µm diameter islands to examine markers of proliferation and differentiation in bone marrow‐derived mesenchymal cells (cell line). We show that osteogenic markers are most accurately described as a function of confluence for larger islands, but a function of time for smaller islands. We further show, using results of the simulation, that cell size and cell‐cell contacts are also related to confluence on larger islands, but only cell−cell contacts are related to confluence on small islands. This study uses simulations to explain experimental results that could not be explained from experiments alone. Together, the simulations and experiments in this study show different differentiation patterns on large and small islands, and this simulation may be useful in planning future studies related to this study.
A phase III multicenter randomized clinical trial of 60 Gy vs 50 Gy radiation dose in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma.

PURPOSE In this multicenter, phase 3 trial, the efficacy and safety of 60 Gy and 50 Gy doses delivered with modern radiation technology for definitive concurrent chemoradiation (CCRT) in patients with inoperable esophageal squamous cell carcinoma (ESCC) were evaluated. PATIENTS AND METHODS Patients with pathologically confirmed stage IIA‒IVA ESCC were randomized 1:1 to receive conventional fractionated 60 Gy or 50 Gy to the tumor and regional lymph nodes. Concurrent weekly chemotherapy (docetaxel 25 mg/m2; cisplatin 25 mg/m2) and two cycles of consolidation chemotherapy (docetaxel 70 mg/m2; cisplatin 25 mg/m2 d1‒3) were administered. RESULTS A total of 319 patients were finally analyzed for survival, and the median follow-up was 34.0 months. The 1-, and 3-year locoregional progression-free survival rates for the 60 Gy group were 75.6% and 49.5% vs 72.1% and 48.4%, respectively, for the 50 Gy group (HR, 1.00; 95%CI, 0.75‒1.35; P = 0.98). The overall survival rates were 83.7% and 53.1% vs 84.8% and 52.7%, respectively (HR, 0.99; 95%CI, 0.73‒1.35; P = 0.96), while the progression-free survival rates were 71.2% and 46.4% vs 65.2% and 46.1%, respectively (HR, 0.97; 95%CI, 0.73‒1.30; P = 0.86). The incidence of grade 3+ radiation pneumonitis was higher in the 60 Gy group (nominal P = 0.03) than in the 50 Gy group. CONCLUSIONS The 60 Gy arm had similar survival endpoints but a higher severe pneumonitis rate compared with the 50 Gy arm. 50 Gy should be considered as the recommended dose in CCRT for ESCC.
Missing Stories: Women with Physical Disabilities' Navigation and Responses to Domestic and Family Violence

There is significant global evidence that highlights both the high rates of domestic and family violence (DFV) for women with disabilities and the challenges they can face when navigating and responding to DFV. The purpose of this study was to understand women with physical disabilities’ experiences of help-seeking when they did not access generalist DFV services. Presented are the participants’ lived experiences of navigating and responding to DFV. Key findings include how participants resisted ableism, challenged assumptions about passivity, and the impacts of this resistance on their navigation of DFV.
Prevention and treatment of burn wound infections: the role of topical antimicrobials

ABSTRACT Introduction Skin-related infections are drivers of complications following severe burn, therefore a diverse armamentarium of topical antimicrobial agents have been developed. The last 30 years witnessed dramatic changes in surgical intervention and utilization of topical therapies. Areas Covered We explore well-known topical antimicrobial products used in burn care. First, we investigate how changes in the practice of burn surgery influenced choice of topical therapies used. Then, we examine antimicrobial creams and ointments commonly recognized due to their long use in burn care. Next, we dive into antimicrobial solutions commonly used as adjuncts to surgical intervention. Finally, we explore representative antimicrobial dressings, an ever-advancing roster of products in the next era in burn care. We describe how these new agents relate to already established tools in present-day burn care. Expert Opinion In the current day, though the wisdom of early excision and wound closure remains valid, efforts continue to minimize aggressive wound excision and disfiguring donor tissue collection while securing rapid wound closure. To this end, antimicrobial therapies are titrated to optimize operative outcomes and provide non-operative wound care when appropriate. Antimicrobial agents bridge the gap with the next generation of skin substitute and skin replacement therapies.
Nimotuzumab as Additional Therapy for GLIOMA in Pediatric and Adolescent: A Systematic Review

Introduction Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic modalities are reported to be insufficient to achieve satisfactory result, with follow-up treatment such as adjuvant radiotherapy and chemotherapy recommended to increase survival and hinder tumor progression. Nimotuzumab is a monoclonal antibody that acts as an inhibitor of epidermal growth factor receptor found on the surface of glioma cells and had been studied for its usage in pediatric gliomas in recent years. Methods A systematic review is performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A through literature search was conducted on PubMed, Scopus, Cochrane, and clinicaltrials.gov database. Articles were selected systematically based on the PRISMA protocol and reviewed completely. The relevant data were summarized and discussed. We measured overall survival, progression-free survival, and adverse Events (AE) for nimotuzumab usage as an adjunct therapy in pediatric glioma population. Result From 5 studies included for qualitative analysis, 151 patients are included with overall survival (OS) that vary from 3.2–22.8 mo, progression-free survival (PFS) from 1.7–21.6 mo, and relatively low serious adverse events (0–21) are recorded. Follow-up ranged from 2.4–66 mo with four studies reporting diffuse intrinsic pontine glioma (DIPG) patients and only one study reporting nimotuzumab usage in pediatric high-grade glioma (HGG) patients with better outcome in HGG patients than DIPG. Conclusion There are no significant differences in the PFS and OS of nimotuzumab as adjunct therapy for pediatric compared to result of standard therapy in majority of previous studies. There were also no differences in the AE of nimotuzumab for pediatric glioma between studies, and low event of serious adverse events indicating its safety. But still there is an evidence of possible benefit of nimotuzumab as adjuvant therapy in pediatric glioma. We recommend further studies with larger number of patients that may lead to possibly different results. There should also be more studies with better level of evidence to further validate the effect of nimozutumab on pediatric glioma.
Towards single-trial classification of invasively recorded auditory evoked potentials in cochlear implant users

Objective. One promising approach towards further improving cochlear implants (CI) is to use brain signals controlling the device in order to close the auditory loop. Initial electroencephalography (EEG) studies have already shown promising results. However, they are based on noninvasive measurements, whereas implanted electrodes are expected to be more convenient in terms of everyday-life usability. If additional measurement electrodes were implanted during CI surgery, then invasive recordings should be possible. Furthermore, implantation will provide better signal quality, higher robustness to artefacts, and thus enhanced classification accuracy. Approach. In an initial project, three additional epidural electrodes were temporarily implanted during the surgical procedure. After surgery, different auditory evoked potentials (AEPs) were recorded both invasively (epidural) and using surface electrodes, with invasively recorded signals demonstrated as being markedly superior. In this present analysis, cortical evoked response audiometry (CERA) signals recorded in seven patients were used for single-trial classification of sounds with different intensities. For classification purposes, we used shrinkage-regularized linear discriminant analysis (sLDA). Clinical speech perception scores were also investigated. Main results. Analysis of CERA data from different subjects showed single-trial classification accuracies of up to 99.2% for perceived vs. non-perceived sounds. Accuracies of up to 89.1% were achieved in classification of sounds perceived at different intensities. Highest classification accuracies were achieved by means of epidural recordings. Required loudness differences seemed to correspond to speech perception in noise. Significance. The proposed epidural recording approach showed good classification accuracy into sound perceived and not perceived when the best-performing electrodes were selected. Classifying different levels of sound stimulation accurately proved more challenging. At present, the methods explored in this study would not be sufficiently reliable to allow automated closed-loop control of CI parameters. However, our findings are an important initial contribution towards improving applicability of closed auditory loops and for next-generation automatic fitting approaches.