Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances and Therapeutic Perspectives in Extended-Stage Small-Cell Lung Cancer

Simple Summary Extended small cell lung cancer (ED-SCLC) remains an aggressive disease without major advances in the last 20 years. Recently, new therapies have eventually improved the outcomes of these patients, completely overturning their management. The objective of this review is to describe the most recent advances in ED-SCLC treatment, starting from immunotherapy as monotherapy or in combination with chemotherapy. Despite the proved clinical activity of this strategy, few patients achieve a long-term benefit and further studies are needed to find useful biomarkers. Furthermore, we review the most promising target agents and chemotherapies currently under investigation. Therefore, this proposal provides a comprehensive overview of available treatment strategies for ED-SCLC patients, highlighting their strengths and weaknesses. Abstract Extended small cell lung cancer (ED-SCLC) is a very aggressive disease, characterized by rapid growth and an early tendency to relapse. In contrast to non-small cell lung cancer, no therapeutic innovation has improved survival in patients with ED-SCLC over the past 20 years. Recently, immunotherapy has shown an important role in the management of these patients, emerging as the treatment of first choice in combination with chemotherapy and completely changing the therapeutic paradigm. However, patients’ selection for this strategy is still challenging due to a lack of reliable predictive biomarkers. Conversely, the immunotherapy efficacy beyond the first line is pretty disappointing and innovative chemotherapies or target agents seem to be more promising in this setting. Some of them are also under evaluation as an upfront strategy and they will probably change the treatment algorithm in the next future. This proposal provides a comprehensive overview of available treatment strategies for ED-SCLC patients, highlighting their strengths and weaknesses.
Repetitive blast promotes chronic aversion to neutral cues encountered in the peri-blast environment

Repetitive mild traumatic brain injury (mTBI) has been called the “signature injury” of military Servicemembers in the Iraq and Afghanistan wars and is highly comorbid with posttraumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Preclinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction—but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD, here we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing upon well-established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that, even while anesthetized during blast exposure, environmental cues encountered in the peri-blast environment could be conditioned to evoke aversion/dysphoria and reexperiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, while both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure.
Silane-Functionalized Sheep Wool Fibers from Dairy Industry Waste for the Development of Plasticized PLA Composites with Maleinized Linseed Oil for Injection-Molded Parts

Poly(lactic acid) (PLA) was plasticized with maleinized linseed oil (MLO) and further reinforced with sheep wool fibers recovered from the dairy industry. The wool fibers were firstly functionalized with 1 and 2.5 phr of tris(2-methoxyethoxy)(vinyl) (TVS) silane coupling agent and were further used in 1, 5, and 10 phr to reinforce the PLA/MLO matrix. Then, the composite materials were processed by extrusion, followed by injection-molding processes. The mechanical, thermal, microstructural, and surface properties were assessed. While the addition of untreated wool fibers to the plasticized PLA/MLO matrix caused a general decrease in the mechanical properties, the TVS treatment was able to slightly compensate for such mechanical losses. Additionally, a shift in cold crystallization and a decrease in the degree of crystallization were observed due to the fiber silane modification. The microstructural analysis confirmed enhanced interaction between silane-modified fibers and the polymeric matrix. The inclusion of the fiber into the PLA/MLO matrix made the obtained material more hydrophobic, while the yellowish color of the material increased with the fiber content.
Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.
Platinum-Quality Mitogenome Haplotypes from United States Populations

A total of 1327 platinum-quality mitochondrial DNA haplotypes from United States (U.S.) populations were generated using a robust, semi-automated next-generation sequencing (NGS) workflow with rigorous quality control (QC). The laboratory workflow involved long-range PCR to minimize the co-amplification of nuclear mitochondrial DNA segments (NUMTs), PCR-free library preparation to reduce amplification bias, and high-coverage Illumina MiSeq sequencing to produce an average per-sample read depth of 1000 × for low-frequency (5%) variant detection. Point heteroplasmies below 10% frequency were confirmed through replicate amplification, and length heteroplasmy was quantitatively assessed using a custom read count analysis tool. Data analysis involved a redundant, dual-analyst review to minimize errors in haplotype reporting with additional QC checks performed by EMPOP. Applying these methods, eight sample sets were processed from five U.S. metapopulations (African American, Caucasian, Hispanic, Asian American, and Native American) corresponding to self-reported identity at the time of sample collection. Population analyses (e.g., haplotype frequencies, random match probabilities, and genetic distance estimates) were performed to evaluate the eight datasets, with over 95% of haplotypes unique per dataset. The platinum-quality mitogenome haplotypes presented in this study will enable forensic statistical calculations and thereby support the usage of mitogenome sequencing in forensic laboratories.
Age Dependence of Antimicrobial Resistance Among Fecal Bacteria in Animals: A Scoping Review

Introduction: A phenomenon of decreasing antimicrobial resistance (AMR) among fecal bacteria as food animals age has been noted in multiple field studies. We conducted a scoping review to summarize the extent, range, and nature of research activity and the data for the following question: “does AMR among enteric/fecal bacteria predictably shift as animals get older? ”. Methods: This review followed a scoping review methodology framework. Pertinent literature published up until November 2018 for all animals (except humans) was retrieved using keyword searches in two online databases, namely, PubMed® and the Web of Science™ Core Collection, without filtering publication date, geographic location, or language. Data were extracted from the included studies, summarized, and plotted. Study quality was also assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines for all included papers. Results: The publications with detailed relevant data (n = 62) in food animals, poultry, and dogs were identified. These included longitudinal studies (n = 32), cross-sectional studies of different age groups within one food animal production system or small-animal catchment area (n = 16), and experimental or diet trials (n = 14). A decline in host-level prevalence and/or within-host abundance of AMR among fecal bacteria in production beef, dairy cattle, and swine was reported in nearly two-thirds (65%) of the identified studies in different geographic locations from the 1970's to 2018. Mixed results, with AMR abundance among fecal bacteria either increasing or decreasing with age, have been reported in poultry (broiler chicken, layer, and grow-out turkey) and dogs. Conclusions: Quantitative synthesis of the data suggests that the age-dependent AMR phenomenon in cattle and swine is observed irrespective of geographic location and specific production practices. It is unclear whether the phenomenon predates or is related to antimicrobial drug use. However, almost 50% of the identified studies predate recent changes in antimicrobial drug use policy and regulations in food animals in the United States and elsewhere.
Ultrathin Single-crystalline MgO (111) Nanosheets.

Synthesizing high-quality two-dimensional nanomaterials of non-layered metal oxide is a grand challenge, especially when long range single-crystallinity and clean high-energy surfaces are required. Here, we report the synthesis of single-crystalline MgO(111) nanosheets via a two-step process involving the formation of ultrathin Mg(OH) 2 nanosheets as precursor and their selective topotactic conversion upon heating under dynamic vacuum. The defect-rich surface displays terminal -OH groups, 3-coordinated O 2- sites, low-coordinated Mg 2+ sites as well as single electrons trapped at oxygen vacancies, that render MgO nanosheets highly reactive as evidenced by the activation of CO molecules at low temperatures and pressures, with formation of strongly adsorbed red-shifted CO and coupling of CO molecules into C 2 species.
Loss of TREM2 Confers Resilience to Synaptic and Cognitive Impairment in Aged Mice

Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor exclusively expressed by microglia in the brain, modulates microglial immune homeostasis. Human genetic studies have shown that the loss-of-function mutations in TREM2 signaling are strongly associated with an elevated risk of age-related neurodegenerative diseases including Alzheimer's disease (AD). Numerous studies have investigated the impact of TREM2 deficiency in the pathogenic process of AD. However, the role of TREM2 in shaping neuronal and cognitive function during normal aging is underexplored. In the present study, we employed behavioral, electrophysiological, and biochemical approaches to assess cognitive and synaptic function in male and female young and aged TREM2-deficient (Trem2−/−) mice compared with age-matched, sex-matched, and genetic background-matched wild-type (WT) C57BL/6J controls. Young Trem2−/− mice exhibited normal cognitive function and synaptic plasticity but had increased dendritic spine density compared with young WT. Unexpectedly, aged Trem2−/− mice showed superior cognitive performance compared with aged WT controls. Consistent with the behavioral data, aged Trem2−/− mice displayed significantly enhanced hippocampal long-term potentiation (LTP) and increased dendritic spine density and synaptic markers compared with aged WT mice. Taken together, these findings suggest that loss of TREM2 affects the neuronal structure and confers resilience to age-related synaptic and cognitive impairment during non-pathogenic aging. SIGNIFICANCE STATEMENT Microglia are innate immune cells of the brain that orchestrates neurodevelopment, synaptic function, and immune response to environmental stimuli. Microglial triggering receptor expressed on myeloid cells 2 (TREM2) signaling plays pivotal roles in regulating these functions and loss of TREM2 signaling leads to increased risk of developing age-related neurologic disorders. However, the neurologic role of TREM2 in normal aging is poorly understood. The results of the present study unveil the positive impacts of TREM2 deficiency on cognitive and synaptic function during aging and suggest that TREM2 may exert detrimental effects on neuronal function. The possibility of age-related negative impacts from TREM2 is critically important since TREM2 has emerged as a major therapeutic target for Alzheimer's dementia.
Tracking Lagrangian transport in Lake Geneva: A 3D numerical modeling investigation

Lake Geneva, the largest freshwater lake in Western Europe, is subject to important environmental pressures from its densely populated shores and watershed. To maintain and improve water quality in this lake, as well as in other enclosed or semi‐enclosed basins, it is essential to understand and be able to predict how nutrients and pollutants are transported within it. A 3D numerical modeling study of Lagrangian transport in Lake Geneva is presented, showing the dispersion of water (based on tracking inert water particles) inflowing from the lake's main tributary, the Rhône River. The relation between dominant winds, circulation patterns, and transport was analyzed. The results demonstrated that transport within the lake is highly inhomogeneous in space and intermittent in time, because water mass movements are controlled by the wind‐induced formation of large‐scale gyres and their subsequent breakdown into smaller ones. Particle spreading was shown to be sensitive to the depth of the initial particle release, and to the mean depth of the particles’ trajectory. However, several preferential pathways could be identified. Some water particles rapidly (days) traveled across the entire lake, through the near‐shore region in the upper layer, while others remained trapped for months, particularly in the central region of the lake at depth. Deeper particles tended to remain longer in the lake, due to the insulating effect of stratification, bathymetry obstacles, and slower currents at greater depth.
Cell types and neuronal circuitry underlying female aggression in Drosophila

Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism’s internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we identify a population of sexually dimorphic aIPg neurons in the adult Drosophila melanogaster central brain whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated aIPg and pC1d neurons as core nodes regulating female aggression. Connectomic analysis demonstrated that aIPg neurons and pC1d are interconnected and suggest that aIPg neurons may exert part of their effect by gating the flow of visual information to descending neurons. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.
Downregulated microRNA-129-5p by Long Non-coding RNA NEAT1 Upregulates PEG3 Expression to Aggravate Non-alcoholic Steatohepatitis

Long non-coding RNAs (lncRNAs) have recently emerged as inflammation-associated biological molecules with a specific role in the progression of liver fibrosis conditions including non-alcoholic steatohepatitis (NASH). The aim of this study was to elucidate the effects of lncRNA nuclear enriched abundant transcript 1 (NEAT1), microRNA-129-5p (miR-129-5p), and paternally expressed gene 3 (PEG3) on the biological activities of hepatic stellate cells (HSCs) subjected to NASH. First, microarray-based analysis revealed upregulated PEG3 in NASH. Liver tissues from mice fed a methionine–choline-deficient (MCD) diet exhibited increased expression of NEAT1 and PEG3 along with lower miR-129-5p expression. A series of in vitro and in vivo assays were then performed on HSCs after transfection with shPEG3, miR-129-5p mimic, or treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of the nuclear factor-kappa B (NF-κB) signaling pathway. Results confirmed the alleviated fibrosis by restoring miR-129-5p, while depleting PEG3 or NEAT1, as evidenced by the inactivation of HSCs. To sum up, NEAT1 can bind specifically to miR-129-5p and consequently regulate miR-129-5p and PEG3 expression in relation to the HSC activation occurring in NASH. Thus, NEAT1-targeted inhibition against miR-129-5p presents a promising therapeutic strategy for the treatment of NASH.
The Relation between Domain-Specific Physical Behaviour and Cardiorespiratory Fitness: A Cross-Sectional Compositional Data Analysis on the Physical Activity Health Paradox Using Accelerometer-Assessed Data

In contrast to leisure time physical activity (LTPA), occupational physical activity (OPA) does not have similar beneficial health effects. These differential health effects might be explained by dissimilar effects of LTPA and OPA on cardiorespiratory fitness (CRF). This study investigated cross-sectional associations between different physical behaviours during both work and leisure time and CRF by using a Compositional Data Analysis approach. Physical behaviours were assessed by two accelerometers among 309 workers with various manual jobs. During work time, more sedentary behaviour (SB) was associated with higher CRF when compared relatively to time spent on other work behaviours, while more SB during leisure time was associated with lower CRF when compared to other leisure time behaviours. Reallocating more time to moderate-to-vigorous physical activity (MVPA) from the other behaviours within leisure time was positively associated with CRF, which was not the case for MVPA during work. The results of our study are in line with the physical activity health paradox and we call for further study on the interaction between LTPA and OPA by implementing device-worn measures in a longitudinal design. Our results highlight the need for recommendations to take into account the different effects of OPA and LTPA on CRF.
Understanding Vietnamese Urban Consumers’ Nutrition Label Use, Health Concerns, and Consumption of Food and Beverages with Added Sugars

Vietnam is experiencing a diet and nutrition transition. Increasing consumption of food and beverages with added sugars is a significant public health concern. Policies and interventions, such as mandatory nutrition labelling, are being considered to improve consumers’ awareness and understanding of diet and health implications of added sugars in food and beverages. The effectiveness of various policy approaches relies on an improved understanding of the interrelationships between urban Vietnamese consumers’ health concerns, nutrition label use, and intake of sugars. We empirically disentangle these relationships for urban Vietnamese households using novel intra-household data covering 4047 adults and 737 adolescents from 1590 households in Hanoi and Ho Chi Minh City. The data are from comprehensive household surveys and 24-hour food diaries. Simultaneous equation regression models are estimated using three-stage least squares (3SLS) to account for possible endogeneity. Nutrition label use is significantly associated with a lower share of calories from foods and beverages with added sugars. These findings suggest that nutrition labelling programs may be an effective policy mechanism to reduce the negative health implications of increasing availability and consumption of food and beverages with added sugars in urban Vietnam.
Bone Mineral Density Quantification from Localizer Radiographs: Accuracy and Precision of Energy-integrating Detector CT and Photon-counting Detector CT.

Background Bone mineral density (BMD) could be derived from CT localizer radiographs and could potentially enable opportunistic osteoporosis screening. Purpose To assess the accuracy and precision of BMD measurement using two localizer radiographs obtained with energy-integrating detector CT and a single localizer radiograph obtained with photon-counting detector CT. Materials and Methods A calibration phantom and a porcine phantom with lumbar vertebrae were imaged with a dual-energy x-ray absorptiometry (DXA) scanner, a clinical energy-integrating detector CT scanner, and a prototype photon-counting detector CT scanner. Two localizer radiographs at different combinations of tube voltages were obtained with energy-integrating detector CT, and one localizer radiograph was obtained with photon-counting detector CT using different energy thresholds. BMD was calculated for all three approaches and compared with the known specifications in the calibration phantom. In the animal phantom, BMDs from both CT systems were compared with those from the DXA scanner (the reference standard). Accuracy was defined as the measurement error of BMD (ΔBMD), and precision was defined as the coefficient of variation (in percentage). Radiation doses were estimated. Nonparametric tests were applied. Results In the calibration phantom, ΔBMD was smaller with both CT systems compared with the DXA scanner (both P < .05). ΔBMD ranged from -5% to -1.8% for DXA, from -2.3% to -1.7% for energy-integrating detector CT, and from -1.6% to 1.6% for photon-counting detector CT. Precision (range, 0.3%-2.8%) was high for both CT systems. In the animal phantom, ΔBMD ranged from -0.6% to 0.1% for energy-integrating detector CT and from -0.1% to 0.6% for photon-counting detector CT, with no significant differences between CT systems (P = .65). The dose-area product in the animal phantom was 4.6 cGy ∙ cm2 for DXA, 3.5-11.5 cGy ∙ cm2 for energy-integrating detector CT, and 7.2-11.2 cGy ∙ cm2 for photon-counting detector CT, depending on tube voltage and energy threshold combination. Conclusion Experimental evidence suggests that bone mineral density measurements are accurate and precise using two localizer radiographs at different tube voltages from energy-integrating detector CT and a single localizer radiograph with different energy thresholds from photon-counting detector CT. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pourmorteza in this issue.