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Abstract The breadth and depth at which cancer models are interrogated contribute to the successful clinical translation of drug discovery efforts. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, where experimental therapies are typically tested. Here we introduce XENTURION, an open-science resource offering a platform of 128 PDX models from patients with metastatic CRC, along with matched PDX-derived tumoroids. Multidimensional omics analyses indicate that tumoroids retain extensive molecular fidelity with parental PDXs. A tumoroid-based trial with the anti-EGFR antibody cetuximab reveals variable sensitivities that are consistent with clinical response biomarkers, mirror tumor growth changes in matched PDXs, and recapitulate EGFR genetic deletion outcomes. Inhibition of adaptive signals upregulated by EGFR blockade increases the magnitude of cetuximab response. These findings illustrate the potential of large living biobanks, providing avenues for molecularly informed preclinical research in oncology.

Abstract Background The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. The existence of long-COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless of initial infection severity. The mechanisms behind long-COVID are unclear, but virus-induced epigenetic changes could play a role. Methods and results Our study explores the lasting epigenetic impacts of SARS-CoV-2 infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort of 96 patients 6 months after COVID-19 exposure, comparing them to 191 healthy controls. We identified 42 CpG sites with significant methylation differences (FDR

Italian olive oil companies play a significant role in this nation's economy, which is among the top in the world for its geomorphological and meteorological characteristics. This research analyzed the performance of three profitability ratios (return on equity (R.O.E.), return on investment (R.O.I.), and return on sales (R.O.S.)) of 3184 companies from 2013 to 2022. Average ratios for each year and critical descriptive statistics were calculated. Broken lines and interpolating curves, obtained from sixth-degree polynomial equations maximizing R2, represent the trends. One-way ANOVA and Tukey-Kramer methods facilitated statistical comparisons between macro-regions. Despite the regular consumption of olive oil, the profitability of businesses has been erratic and fluctuating, probably due to the varying productivity of raw material crops. The pandemic seems to have had no impact. There are no statistically significant differences between macro-areas. The results are helpful to Italian and foreign entrepreneurs who can relate their situation to the average situation in context, highlighting possible gaps that, if negative, must be bridged with a timely management review. National and supranational political authorities can also use this study to orient the frequent support policies in the agricultural and agro-industrial sectors. So too can the bodies in charge of food education, especially for young people, can encourage the use of olive oil where it is lacking. The main limitation of this study was its focus on a small set of profitability ratios. In the future, the study should consider other profitability and asset ratios and investigate investments in sustainability, keeping in mind that all enterprises should contribute to developing eco-friendly production systems.

Abstract Ion transport in non-aqueous electrolytes is crucial for high performance lithium-ion battery (LIB) development. The design of superior electrolytes requires extensive experimentation across the compositional space. To support data driven accelerated electrolyte discovery efforts, we curated and analyzed a large dataset covering a wide range of experimentally recorded ionic conductivities for various combinations of lithium salts, solvents, concentrations, and temperatures. The dataset is named as ’Conductivity Atlas for Lithium salts and Solvents’ (CALiSol-23). Comprehensive datasets are lacking but are critical to building chemistry agnostic machine learning models for conductivity as well as data driven electrolyte optimization tasks. CALiSol-23 was derived from an exhaustive review of literature concerning experimental non-aqueous electrolyte conductivity measurement. The final dataset consists of 13,825 individual data points from 27 different experimental articles, in total covering 38 solvents, a broad temperature range, and 14 lithium salts. CALiSol-23 can help expedite machine learning model development that can help in understanding the complexities of ion transport and streamlining the optimization of non-aqueous electrolyte mixtures.

Abstract Background Severe obesity is characterized by excessive accumulation of fat generating a general health decline. Multidisciplinary treatment of obesity leads to significant weight loss in a few patients; therefore, many incur bariatric surgery. The main purpose of the study is to evaluate changes in functional capacity of people with obesity undergoing bariatric surgery and, in parallel, to correlate pre-surgery functional capacity with weight loss to improve exercise prescription during pre-operatory stage. Methods sixty women with diagnosed obesity were included. Maximal oxygen consumption, upper and lower limb strength and level of physical activity were recorded 1 month before and 6 months after sleeve gastrectomy. Results significant reduction on body weight (-30.1 kg) and Body Mass Index (-11.4 kg/m2) were highlighted after surgery. Absolute grip strength decreased significantly (-1.1 kg), while body weight normalized grip and lower limb strength increased significantly. The level of physical activity increased especially in leisure time (+ 593 METs/week) and active transport (+ 189.3 METs/week). Pre-surgery BMI and age predicted the amount of weight loss after surgery. Conclusions Sleeve gastrectomy induces a reduction of muscle strength despite the increase of time spent in physical activity. Further research is necessary to integrate these results with data on body composition, and objective evaluation of physical activity level to define useful information for exercise prescription in terms of surgery pre-habilitation. Trial registration Padova University Hospital Board (protocol n. 2027 dated January 12, 2017).

Abstract Background During the COVID-19 pandemic, many countries adopted social distance measures and lockdowns of varying strictness. Social contact patterns are essential in driving the spread of respiratory infections, and country-specific measurements are needed. This study aimed to gain insights into changes in social contacts and behaviour during the early pandemic phase in Norway. Methods We conducted an online panel study among a nationally representative sample of Norwegian adults by age and gender. The panel study included six data collections waves between April and September 2020, and 2017 survey data from a random sample of the Norwegian population (including children

Abstract Background Self-assessment (SA) is an interactive course that endorses the accomplishment of learning objectives through learners’ identification of insufficiencies in their didactic knowledge and pre-clinical skills. This study was planned to determine whether there is any improvement in the faculty assessment (FA) score following the implementation of SA in the Pre-clinical Conservative Dentistry Course. Methods Fifty-four first-semester dental students were given an introductory lecture followed by a demonstration for Class I Cavity Preparation in typhodont mandibular first molar. At the end of the demonstration, the Scoring Rubric (SR) was explained point-wise in the prepared cavities. During the next session, all students performed Class I cavity preparation and they were given an assessment sheet to enter their scores (SA1). All teeth were evaluated by the Grading Faculties in a blinded manner (FA1). Each participant was explained the difference in their respective SA1 from FA1 and their queries were resolved individually. During the next sessions, Students and Grading Faculties followed the same protocol and scores were recorded as SA2, FA2, SA3 and FA3. Results The mean score of SA1 was significantly higher than that of FA1 (p

Several research initiatives across the European Union investigated the application of off-site prefabrication strategies for energy refurbishment of buildings. Although the results obtained, none of these projects offer a solution for reducing the overall cost.This paper presents the results of the ‘LegnAttivo’ project, an applied research initiative that investigates applications of Mass Customization and Design for Manufacturability to reduce the cost of prefabricated timber-based façades for energy refurbishment. Applying a Design Science Research approach, the research develops a design prototype of timber-based façade elements for the energy refurbishment of the Italian building stock. Relying on a single case study which is a starting point for future generalizations and extensions of the method, results highlight that applications of Design for Manufacturability combined with Computational Design techniques provide effective and efficient solutions, even under extremely customized requirements, and bring to considerable saves, aligned with the ones measured by the scientific community.

Background The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. Methods and Results This is a prespecified propensity score‐matched analysis from a prospective multicentric real‐world study (READAPT [Real‐Life Study on Short‐Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90‐day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90‐day risk of stroke and other vascular events and 24‐hour early neurological improvement or deterioration (≥2‐point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI −2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98–1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41–0.79]; P

Obstructive sleep apnoea syndrome is a respiratory sleep disorder that affects 1–5% of children. It occurs equally in males and females, with higher incidence in school age and adolescence. OSAS may be caused by several factors, but in children, adenotonsillar hypertrophy, obesity, and maxillo-mandibular deficits are the most common. In general, there is a reduction in the diameter of the airway with reduced airflow. This condition worsens during sleep due to the muscular hypotonia, resulting in apnoeas or hypoventilation. While snoring is the primary symptom, OSAS-related manifestations have a wide spectrum. Some of these symptoms relate to the nocturnal phase, including disturbed sleep, frequent changes of position, apnoeas and oral respiration. Other symptoms concern the daytime hours, such as drowsiness, irritability, inattention, difficulties with learning and memorisation, and poor school performance, especially in patient suffering from overlapping syndromes (e.g., Down syndrome). In some cases, the child’s general growth may also be affected. Early diagnosis of this condition is crucial in limiting associated symptoms that can significantly impact a paediatric patient’s quality of life, with the potential for the condition to persist into adulthood. Diagnosis involves evaluating several aspects, beginning with a comprehensive anamnesis that includes specific questionnaires, followed by an objective examination. This is followed by instrumental diagnosis, for which polysomnography is considered the gold standard, assessing several parameters, including the apnoea-hypopnoea index (AHI) and oxygen saturation. However, it is not the sole tool for assessing the characteristics of this condition. Other possibilities, such as night-time video recording, nocturnal oximetry, can be chosen when polysomnography is not available and even tested at home, even though with a lower diagnostic accuracy. The treatment of OSAS varies depending on the cause. In children, the most frequent therapies are adenotonsillectomy or orthodontic therapies, specifically maxillary expansion.