Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative Chemotherapy for Liver Metastasis of Colorectal Cancer

Simple Summary Survival outcomes for resectable metastatic colorectal cancer have improved over the past decade. This is due in part to improvements made in imaging technology, locoregional treatment, and systemic treatment. The focus of this review is to summarize and analyze the existing information available on systemic therapy in the setting of colorectal cancer with liver metastases. It is written with structured viewpoints including patient selection, sequencing of treatment, choice of systemic therapy for upfront resectable disease and conversion chemotherapy for unresectable colorectal cancer. Post-treatment surveillance and future research directions are also discussed. This review will help treating physicians make decisions for the treatment of liver metastases of colorectal cancer. Abstract The liver is the dominant site of metastasis for patients with colorectal cancer. For those with isolated liver metastases, surgical resection with systemic therapy has led to long-term remission in as high as 80% of patients in well-selected cohorts. This review will focus on how systemic therapy should be integrated with resection of liver metastases; in particular, the use of clinical risk scores based on clinicopathological features that help with patient selection, various approaches to the treatment of micro-metastatic disease (peri-operative versus post-operative chemotherapy), as well as conversion chemotherapy for those with initially upfront unresectable disease will be discussed.
Untargeted Lipidomics Analysis of the Cyanobacterium Synechocystis sp. PCC 6803: Lipid Composition Variation in Response to Alternative Cultivation Setups and to Gene Deletion

Cyanobacteria play an important role in several ecological environments, and they are widely accepted to be the ancestors of chloroplasts in modern plants and green algae. Cyanobacteria have become attractive models for metabolic engineering, with the goal of exploring them as microbial cell factories. However, the study of cyanobacterial lipids’ composition and variation, and the assessment of the lipids’ functional and structural roles have been largely overlooked. Here, we aimed at expanding the cyanobacterial lipidomic analytical pipeline by using an untargeted lipidomics approach. Thus, the lipid composition variation of the model cyanobacterium Synechocystis sp. PCC 6803 was investigated in response to both alternative cultivation setups and gene deletion. This approach allowed for detecting differences in total lipid content, alterations in fatty-acid unsaturation level, and adjustments of specific lipid species among the identified lipid classes. The employed method also revealed that the cultivation setup tested in this work induced a deeper alteration of the cyanobacterial cell lipidome than the deletion of a gene that results in a dramatic increase in the release of lipid-rich outer membrane vesicles. This study further highlights how growth conditions must be carefully selected when cyanobacteria are to be engineered and/or scaled-up for lipid or fatty acids production.
PROSPECTIVE COMPARATIVE STUDY OF THE TREATMENT OF HELICOBACTER PYLORI WITH ANTIBIOTIC SUSCEPTIBILITY TESTING-GUIDED TRIPLE THERAPY COMPARED TO QUADRUPLE THERAPY WITH PYLERA®.

INTRODUCTION The current treatment indicated as first-line in the infection due to Helicobacter pylori is the quadruple therapy with bismuth (Pylera®), or the quadruple concomitant therapy without bismuth, with the triple therapy being abandoned due to its low eradication rates, partly due to an increase in antibiotic resistance. The aim of this study is to compare the Helicobacter pylori eradication rates guided by antibiotic susceptibility testing (AST) versus Pylera®. METHODS A specimen was taken prospectively for culture and antibiotic susceptibility testing (AST) from all patients diagnosed with Helicobacter pylori infection using gastroscopy, and they were randomised to receive triple therapy depending on the result of the AST, or quadruple therapy with Pylera®. The eradication rates of both groups were analysed using faecal antigen. The adherence and side effects of the treatment were also analysed. RESULTS Of the 108 patients with Helicobacter pylori infection, 55 received Pylera® and 53 AST-guided triple therapy. The eradication rates were 92.7% with Pylera® and 90.6% in the AST-guided group, with there being no statistically significant differences. There were also no differences found in adherence or side effects. CONCLUSIONS The treatment of Helicobacter pylori with AST-guided triple therapy is effective, especially in regions with high rates of antibiotic resistance.
Predictors of Mortality in Patients with Interstitial Lung Disease-Associated Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is a well-established complication in interstitial lung disease (ILD) patients. The aim of this study is to investigate the physiological and hemodynamic parameters that predict mortality in patients with ILD-PH. Methods: Consecutive ILD patients who underwent right heart catheterization (n = 340) were included. The information analyzed included demographics and physiological and hemodynamic parameters. Cox regression models were used to identify independent predictors of survival. Results: In total, 96 patients had PH and an additional 56 patients had severe PH. The overall survival of idiopathic pulmonary fibrosis (IPF) patients with PH was significantly worse than the survival of patients with other types of ILD with PH (p < 0.0001 by log-rank analysis). Patients with a reduced diffusing capacity of the lung for carbon monoxide (DLco) (<35% predicted), six-minute walk test final oxygen saturation by pulse oximetry (SpO2) < 88% and pulmonary vascular resistance ≥4.5 Wood units in the ILD-PH cohort had significantly worse survival. IPF diagnosis, forced vital capacity, DLco, systolic pulmonary artery pressure and cardiac index were identified as independent predictors of survival among the ILD-PH cohort. Conclusions: Patients with ILD-PH have poor prognosis. Physiological and hemodynamic parameters were important factors independently associated with outcome.
Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.
Neural evidence for cognitive reappraisal as a strategy to alleviate the effects of math anxiety

Abstract Math anxiety (MA) describes feelings of tension, apprehension and fear that interfere with math performance. High MA (HMA) is correlated with negative consequences, including lower math grades, and ultimately an avoidance of quantitative careers. Given these adverse consequences, it is essential to explore effective intervention strategies to reduce MA. In the present functional magnetic resonance imaging (fMRI) study, we investigated the efficacy of cognitive reappraisal as a strategy to alleviate the effects of MA. Cognitive reappraisal, an emotion regulation strategy, has been shown to decrease negative affect and amygdala responsivity to stimuli that elicit negative emotion. We compared a reappraisal strategy to participants’ natural strategy for solving math problems and analogies. We found that HMA individuals showed an increase in accuracy and a decrease in negative affect during the reappraisal condition as compared to the control condition. During math reappraise trials, increased activity in a network of regions associated with arithmetic correlated with improved performance for HMA individuals. These results suggest that increased engagement of arithmetic regions underlies the performance increases we identify in HMA students when they use reappraisal to augment their math performance. Overall, cognitive reappraisal is a promising strategy for enhancing math performance and reducing anxiety in math anxious individuals.
Induced Pluripotency: A Powerful Tool for In Vitro Modeling

One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly acquired the developmental capacity of self-renewal and differentiation into any cells of three germ layers. Before iPSCs can be used routinely in clinical practice, their efficacy and safety need to be rigorously tested; however, iPSCs have already become effective and fully-fledged tools for application under in vitro conditions. They are currently routinely used for disease modeling, preparation of difficult-to-access cell lines, monitoring of cellular mechanisms in micro- or macroscopic scales, drug testing and screening, genetic engineering, and many other applications. This review is a brief summary of the reprogramming process and subsequent differentiation and culture of reprogrammed cells into neural precursor cells (NPCs) in two-dimensional (2D) and three-dimensional (3D) conditions. NPCs can be used as biomedical models for neurodegenerative diseases (NDs), which are currently considered to be one of the major health problems in the human population.
YEARS Algorithm Versus Wells' Score: Incomplete Reporting Undermines Study Quality Assessment-Part 2.

Critical Care Medicine www.ccmjournal. org e1377 2. Cooke K, Sharvill R, Sondergaard S, et al: Volume responsiveness assessed by passive leg raising and a fluid challenge: A critical review focused on mean systemic filling pressure. Anaesthesia 2018; 73:313–322 3. De Backer D, Vincent JL: Should we measure the central venous pressure to guide fluid management? Ten answers to 10 questions. Crit Care 2018; 22:43 4. Mahmood SS, Pinsky MR: Heart-lung interactions during mechanical ventilation: The basics. Ann Transl Med 2018; 6:349 5. Minini A, Abraham P, Malbrain MLNG: Predicting fluid responsiveness with the passive leg raising test: Don’t be fooled by intra-abdominal hypertension! Ann Transl Med 2020; 8:799 DOI: 10.1097/CCM.0000000000004607
68Ga-PSMA-11 PET/CT-Guided Stereotactic Body Radiation Therapy Retreatment in Prostate Cancer Patients with PSA Failure after Salvage Radiotherapy

(1) Purpose: To investigate the role of 68Ga-PSMA-11 PET/CT in guiding retreatment stereotactic body radiation therapy (SBRT) in prostate cancer (PCa) patients in biochemical recurrence (BCR) after salvage radiotherapy (S-RT). (2) Methods: We retrospectively evaluated PCa patients previously treated with S-RT on the prostate bed and with proven serum prostate antigen (PSA) failure after S-RT. In all patients (pts), 68Ga-PSMA-11 PET/CT was positive in the prostate bed only and guided retreatment SBRT. All retreatments were performed by applying the same radiotherapy protocol (median dose of 18 Gy/3 fractions; IQR 18–21 Gy). The median follow-up was 27 months (range 4–35 months). (3) Results: 38 consecutive patients were considered in this analysis. The overall median PSA level before RT was 1.10 ng/mL (IQR 0.82–2.59). PSA decreased at 3 and 6 months after treatment, with a median value of 0.60 ng/mL (IQR 0.31–0.96; p < 0.001) and 0.51 ng/mL (IQR 0.29–1.17; p < 0.001), respectively. Overall, biochemical recurrence-free survival (b-RFS) was 15.0 months (95% CI 13–23). Grade-1 toxicity was reported in 31.6% of patients (12/38). (4) Conclusion: These results confirm that 68Ga-PSMA-11-PET/CT is able to identify the site of recurrence in patients who have failed S-RT, thus supporting the use of metastases-directed radiotherapy as a safe and effective treatment.
Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?

Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients’ quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.
Iron Ion Particle Radiation Resistance of Dried Colonies of Cryomyces antarcticus Embedded in Martian Regolith Analogues

Among the celestial bodies in the Solar System, Mars currently represents the main target for the search for life beyond Earth. However, its surface is constantly exposed to high doses of cosmic rays (CRs) that may pose a threat to any biological system. For this reason, investigations into the limits of resistance of life to space relevant radiation is fundamental to speculate on the chance of finding extraterrestrial organisms on Mars. In the present work, as part of the STARLIFE project, the responses of dried colonies of the black fungus Cryomyces antarcticus Culture Collection of Fungi from Extreme Environments (CCFEE) 515 to the exposure to accelerated iron (LET: 200 keV/μm) ions, which mimic part of CRs spectrum, were investigated. Samples were exposed to the iron ions up to 1000 Gy in the presence of Martian regolith analogues. Our results showed an extraordinary resistance of the fungus in terms of survival, recovery of metabolic activity and DNA integrity. These experiments give new insights into the survival probability of possible terrestrial-like life forms on the present or past Martian surface and shallow subsurface environments.
Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.
Physical and Sensory Properties of Japanese Quince Chips Obtained by Osmotic Dehydration in Fruit Juice Concentrates and Hybrid Drying

Japanese quince has high health value, but due to its taste and texture, it is difficult to eat raw. The use of innovative drying methods to produce dried snack foods from these fruits may be of interest to producers and consumers. The physicochemical and sensory properties of 3 mm slices of Japanese quince fruit (with skin, without seeds) obtained by osmotic pre-treatment in chokeberry and apple juice concentrates, and with the use of convection (convective drying, C-D), freeze-drying (F-D), and convection-microwave-vacuum drying (hybrid) are assessed. The methods of drying osmo-dehydrated slices do not affect the dry matter content. In most dried quince, the water activity is 0.40 or lower. Pre-osmotic dehydration and drying have a significant impact on the mechanical and acoustic properties of quince chips. Sensory attractive chips emit loud acoustic emission (AE) during the breaking test. Chips that are osmo-dehydrated in a mixture of chokeberry juice concentrate and sucrose and dried by a hybrid method are attractive. They have a dark red color given by chokeberry concentrate and a slight sweet (with a slight sour-bitter) taste. The sensory evaluation was useful for determining the quality of the chips in terms of their texture (crispness) tested by mechanical methods. Their sensory ratings (overall desirability as weight of color, taste, crispness, and flavor) are high and similar (from 3.8 to 4.1). The use of innovative drying methods with pre-osmotic treatment allows obtaining dried material with properties comparable to those obtained by the F-D method, but in a much shorter time, i.e., with lower energy and using a simple method.
High Glycemic Load Is Associated with Cognitive Decline in Apolipoprotein E ε4 Allele Carriers

Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their APOE4 carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In APOE4 carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with APOE4 non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research.
Clinical Characteristics of Suicidal Youths and Adults: A One-Year Retrospective Study

Suicide is a major mental health problem, particularly during youth, when it is the second leading cause of death. Since young people at risk of suicide are often cared for by the adult health system, we sought to identify the specificities and similarities between suicidal youths and adults in order to further inform the potential need for adaptations in taking care of suicidal youths. For this study, we used the following data: mental disorders, treatments, previous hospitalization, and reasons for current hospitalization, that were collected from November 2016 to October 2017 among people hospitalized for a suicidal crisis in a specialized psychiatric unit. First, we compared the data from the youth group with those from the adult group, and then we tried to determine if there were any associations between variables. Analyses showed that youths were more similar to adults than expected. In particular, we found comparable rates of personality disorders (especially borderline) and relapse, and similar profiles of reasons for hospitalization in suicidal crisis. Remarkably, among youth, neuroleptics appeared to be associated with fewer hospitalizations for behavioral than ideational reasons, but with more relapses. Results of this study suggest that young people could benefit from brief psychotherapeutic interventions implemented for adults.
Risk factors for delayed negative conversion of SARS-CoV-2 in patients with COVID-19 pneumonia: a retrospective cohort study

Abstract The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11–25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.