Miracle-dz/UniFAR-FTUs huggingface dataset:
Excitation Functions of 3He-Particle Induced Nuclear Reactions on Natural Chromium: Possibilities of Production of 52Fe, 53Fe and 52Mn for Medical Use

Excitation functions were measured by the stacked-foil technique for ""Cr(He, xn) -Fe and ""Cr (He, pxn) '^Mn reactions from threshold to 36 MeV. Thin foils of a Cr/Ni-alloy (20% Cr, 73% Ni) were used as targets. Additionally, thin samples were prepared by electrolytic deposition of Cr on Aubacking. Thick target yields of -Fe and Mn were calculated from the measured excitation functions. The optimum Heenergy ranges for the production of Fe, Fe and Mn were found to be = 36 -> 17 MeV, E ^ = 17 -> 7 MeV and EiHc = 36 —> 15 MeV, respectively, with the expected thick target yields of 1.3 MBq (35 μα)/μΑ1ι for Fe, 78 MBq (2.1 mCi)/ μΑΙι for Fe and 5.6 MBq (150 μα)/μΑ1ι for Mn. For a small scale production of -Fe and Mn 1 mm thick chromium foils were irradiated at beam currents between 1 and 12 μΑ. The radioiron was separated by anion-exchange chromatography and the radiomanganese via adsorption on Fe(OH)3 followed by purification with anion-exchange chromatography. In 1 h irradiations the experimental yields at 1 μΑ amounted to about 70% of the calculated values and at 12 μΑ to about 45%. For routine production at a nominal beam current of 5 μΑ experimental yields of about 3.7 MBq (0.1 mCi)/h Fe, 220 MBq (5.8 mCi)/30 min Fe and 14.8 MBq (0.4 mCi)/h Mn can be expected.
Genome-Wide B Cell, CD4+, and CD8+ T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines

Key Points Highly conserved B and T cell epitopes are identified in human and animal coronaviruses. Cross-reactive coronavirus epitopes are recognized by COVID-19 and healthy patients. Conserved SARS-CoV-2 epitopes are immunogenic in humanized HLA-transgenic mice. Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other global COVID pandemics will emerge in the coming years caused by yet another spillover of a bat-derived SARS-like coronavirus (SL-CoV) into humans. Determining the Ag and the human B cells, CD4+ and CD8+ T cell epitope landscapes that are conserved among human and animal coronaviruses should inform in the development of future pan-coronavirus vaccines. In the current study, using several immunoinformatics and sequence alignment approaches, we identified several human B cell and CD4+ and CD8+ T cell epitopes that are highly conserved in 1) greater than 81,000 SARS-CoV-2 genome sequences identified in 190 countries on six continents; 2) six circulating CoVs that caused previous human outbreaks of the common cold; 3) nine SL-CoVs isolated from bats; 4) nine SL-CoV isolated from pangolins; 5) three SL-CoVs isolated from civet cats; and 6) four MERS strains isolated from camels. Furthermore, the identified epitopes: 1) recalled B cells and CD4+ and CD8+ T cells from both COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2, and 2) induced strong B cell and T cell responses in humanized HLA-DR1/HLA-A*02:01 double-transgenic mice. The findings pave the way to develop a preemptive multiepitope pan-coronavirus vaccine to protect against past, current, and future outbreaks.
Cerium oxide nanomaterial with dual antioxidative scavenging potential: Synthesis and characterization

Many studies have linked reactive oxygen species (ROS) to various diseases. Biomedical research has therefore sought a way to control and regulate ROS produced in biological systems. In recent years, cerium oxide nanoparticles (nanoceria, CNPs) have been pursued due to their ability to act as regenerative ROS scavengers. In particular, they are shown to have either superoxide dismutase (SOD) or catalase mimetic (CAT) potential depending on the ratio of Ce3+/Ce4+ valence states. Moreover, it has been demonstrated that SOD mimetic activity can be diminished by the presence of phosphate, which can be a problem given that many biological systems operate in a phosphate-rich environment. Herein, we report a CNP formulation with both SOD and catalase mimetic activity that is preserved in a phosphate-rich media. Characterization demonstrated a highly dispersed, stable solution of uniform-sized, spherical-elliptical shaped CNP of 12 ± 2 nm, as determined through dynamic light scattering, zeta potential, and transmission electron microscopy. Mixed valence states of Ce ions were observed via UV/Visible spectroscopy and XPS (Ce3+/Ce4+ > 1) (Ce3+∼ 62%). X-ray diffraction and XPS confirmed the presence of oxygen-deficient cerium oxide (CeO2-x) particles. Finally, the CNP demonstrated very good biocompatibility and efficient reduction of hydrogen peroxide under in-vitro conditions.
Triple negative phenomenon in endometrial cancer: recognition criteria and impact on survival.

OBJECTIVES Endometrial cancer is the most common malignant cancer of female reproductive organs. The number of diagnosed cases of endometrial cancer is increasing from year to year. Endometrial cancer is a neoplasm with a good survival rate. However, there are also cases with a fast, aggressive course. In recent years, the triple negative phenomenon (TNP) has been identified as one of the factors determining shorter survival in patients with endometrial cancer. MATERIAL AND METHODS The study covered 265 patients with histopathologically confirmed endometrial cancer. Patients were divided into two groups: 1) patients with endometrial cancer with TNP; 2) patients with endometrial cancer without TNP. Tissue microarrays (TMA) were examined with immunohistochemistry to evaluate the expression of estrogen, progesterone and HER2 receptors. In several cases FISH method was used to assess HER2. The expression was evaluated by computer image analysis using the Nuclear Image Analysis virtual microscopy system. The evaluation of HER2 expression was performed manually. The criterion for TNC diagnosis was H-Score < 50 or < 75 and Allred score < 4. RESULTS Depending on the scoring system used, TNP was found in from 10.19% to 15.09% of cases. Regardless of the criteria employed in endometrial cancer, the presence of TNP was neither a factor increasing the risk of death nor it affected the patients' survival. CONCLUSIONS The proportion of TNP diagnosed in endometrial cancer depends on the examined population and the diagnostic criteria. The incidence of TNP did not affect the survival of patients.
Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with non‐Hodgkin lymphoma treated with B‐cell depleting immunotherapy

Prolonged Covid‐19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in‐hospital stay (LOS) due to Covid‐19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid‐19 to 16 French hospitals in March and April, 2020 were included. Length of in‐hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety‐four patients (85%) had B‐cell non‐Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid‐19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti‐CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow‐up of 191 days (3–260), the 6‐month overall survival was 69%. In multivariable analyses, recent administration of anti‐CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti‐CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid‐19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Strain-driven autonomous control of cation distribution for artificial ferroelectrics

Strain provides autonomous control of atomic building blocks for the synthesis of functional materials. In past few decades, there have been substantial advances in theoretical material design and experimental synthesis, which play a key role in the steep ascent of developing functional materials with unprecedented properties useful for next-generation technologies. However, the ultimate goal of synthesis science, i.e., how to locate atoms in a specific position of matter, has not been achieved. Here, we demonstrate a unique way to inject elements in a specific crystallographic position in a composite material by strain engineering. While the use of strain so far has been limited for only mechanical deformation of structures or creation of elemental defects, we show another powerful way of using strain to autonomously control the atomic position for the synthesis of new materials and structures. We believe that our synthesis methodology can be applied to wide ranges of systems, thereby providing a new route to functional materials.
Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis

Abstract Aims Hepatic capillaries are lined with specialized liver sinusoidal endothelial cells (LSECs) which support macromolecule passage to hepatocytes and prevent fibrosis by keeping hepatic stellate cells (HSCs) quiescent. LSEC specialization is co-determined by transcription factors. The zinc-finger E-box-binding homeobox (Zeb)2 transcription factor is enriched in LSECs. Here, we aimed to elucidate the endothelium-specific role of Zeb2 during maintenance of the liver and in liver fibrosis. Methods and results To study the role of Zeb2 in liver endothelium we generated EC-specific Zeb2 knock-out (ECKO) mice. Sequencing of liver EC RNA revealed that deficiency of Zeb2 results in prominent expression changes in angiogenesis-related genes. Accordingly, the vascular area was expanded and the presence of pillars inside ECKO liver vessels indicated that this was likely due to increased intussusceptive angiogenesis. LSEC marker expression was not profoundly affected and fenestrations were preserved upon Zeb2 deficiency. However, an increase in continuous EC markers suggested that Zeb2-deficient LSECs are more prone to dedifferentiation, a process called ‘capillarization’. Changes in the endothelial expression of ligands that may be involved in HSC quiescence together with significant changes in the expression profile of HSCs showed that Zeb2 regulates LSEC–HSC communication and HSC activation. Accordingly, upon exposure to the hepatotoxin carbon tetrachloride (CCl4), livers of ECKO mice showed increased capillarization, HSC activation, and fibrosis compared to livers from wild-type littermates. The vascular maintenance and anti-fibrotic role of endothelial Zeb2 was confirmed in mice with EC-specific overexpression of Zeb2, as the latter resulted in reduced vascularity and attenuated CCl4-induced liver fibrosis. Conclusion Endothelial Zeb2 preserves liver angioarchitecture and protects against liver fibrosis. Zeb2 and Zeb2-dependent genes in liver ECs may be exploited to design novel therapeutic strategies to attenuate hepatic fibrosis.
Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19

Supplemental Digital Content is available in the text. Objective: Patients with coronary artery disease (CAD) are at increased risk for cardiac death and respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Platelets are crucially involved in pathogenesis of CAD and might also contribute to pathophysiology of SARS-CoV-2 infection. Approach and Results: We enrolled a cohort of 122 participants from February 2020 to July 2020 including 55 patients with preexisting CAD and acute SARS-CoV-2 infection (CAD-SARS-CoV-2positive), 28 patients with CAD and without SARS-CoV-2 (CAD-SARS-CoV-2negative), and 39 healthy controls. Clinical and cardiac examination of the CAD-SARS-CoV-2positive group included blood sampling, echocardiography, and electrocardiography within 24 hours after hospital admission. Phenotyping of platelets was performed by flow cytometry; plasma levels of chemokines were analyzed by ELISA. Respiratory failure of patients was stratified by the Horovitz index as moderately/severely impaired when Horovitz index <200 mm Hg. The clinical end point was defined as Horovitz index <200 mm Hg with subsequent mechanical ventilation within a follow-up of 60 days. CAD-SARS-CoV-2positive patients display a significant enhanced platelet activation and hyper-inflammation early at time of hospital admission. Circulating platelet/leukocyte co-aggregates correlate with plasma levels of cytokines/chemokines like IL (interleukin)-6, CCL2, and CXCL10 (chemokine [C-X-C motif] ligand) as well as activation of platelets is associated with CCL5 and elevation of pulmonary artery pressure. Furthermore, furin is stored and released from activated platelets. High furin plasma levels are associated with poor clinical prognosis in CAD-SARS-CoV-2positive patients. Conclusions: Patients with CAD and SARS-CoV-2 infection exhibit elevated systemic platelet activation and enhanced plasma levels of the subtilisin-like proprotein convertase furin, which may contribute to an unfavorable clinical prognosis.
Effectiveness of Electroacupuncture for Management of Young Patients with Overactive Bladder at 1-Year Follow-Up.

Background: Overactive bladder (OAB) is defined as urgency (a sudden compelling desire to pass urine with or without urge incontinence) usually associated with frequency and nocturia. OAB is a chronic condition that affects quality of life (QoL) significantly in patients. Acupuncture can help in the treatment of OAB for patients who cannot take certain medications. Case: A 32-year-old a female patient was diagnosed with OAB. She came to the department of medical acupuncture with a chief complaint of frequent urination for 15 years. Urinalysis test results were normal. Before acupuncture, a bladder ultrasound (US) showed a postvoid residual volume (PVR) of 53 mL, and a uroflowmetry test showed a maximum flow rate of 20.6 mL/s, with an average flow rate of 12.1 mL/s and a voided volume of 71 mL. Her OAB Symptom Score (OABSS) was 13 and the King's Health Questionnaire result was (KHQ) was 87. She was treated with electroacupuncture (EA). Results: After 12 EA sessions, 3 times per week, this patient's bladder US showed a PVR of 3 mL; a uroflowmetry test showed a maximum flow rate of 30.5 mL/s, with an average flow rate of 15.3 mL/s and a voided volume of 120 mL. Her OABSS score was 7. Her KHQ score was 0. Conclusions: OAB can be treated with EA to improve QoL, as seen by this patient's decreasing OABSS and KHQ scores, reduced PVR, and increase the voided volume.
Multilevel Regulation of β-Catenin Activity by SETD2 Suppresses the Transition from Polycystic Kidney Disease to Clear Cell Renal Cell Carcinoma

These findings characterize multiple mechanisms by which SETD2 inhibits β-catenin activity during the transition of polycystic kidney disease to renal cell carcinoma, providing a potential therapeutic strategy for high risk patients. Patients with polycystic kidney disease (PKD) are at a high risk of developing renal cell carcinoma (RCC). However, little is known about genetic alterations or changes in signaling pathways during the transition from PKD to RCC. SET domain–containing 2 (SETD2) is a histone methyltransferase, which catalyzes tri-methylation of H3K36 (H3K36me3) and has been identified as a tumor suppressor in clear cell renal cell carcinoma (ccRCC), but the underlying mechanism remains largely unexplored. Here we report that knockout of SETD2 in a c-MYC–driven PKD mouse model drove the transition to ccRCC. SETD2 inhibited β-catenin activity at transcriptional and posttranscriptional levels by competing with β-catenin for binding promoters of target genes and maintaining transcript levels of members of the β-catenin destruction complex. Thus, SETD2 deficiency enhanced the epithelial-to-mesenchymal transition and tumorigenesis through the hyperactivation of Wnt/β-catenin signaling. Our findings reveal previously unrecognized roles of SETD2-mediated competitive DNA binding and H3K36me3 modification in regulating Wnt/β-catenin signaling during the transition from PKD to ccRCC. The novel autochthonous mouse models of PKD and ccRCC will be useful for preclinical research into disease progression. Significance: These findings characterize multiple mechanisms by which SETD2 inhibits β-catenin activity during the transition of polycystic kidney disease to renal cell carcinoma, providing a potential therapeutic strategy for high-risk patients. Graphical Abstract: http://cancerres.aacrjournals. org/content/canres/81/13/3554/F1.large. jpg. Graphical Abstract:
A Quality Improvement Pilot of Pharmacist-Led Identification of an Inpatient Population for Opioid Stewardship and Pain Management

Abstract The Joint Commission standards now include identification and monitoring patients at high-risk for adverse outcomes of opioid use. Our institution does not have a method to identify at-risk patients. This pilot aimed to assess feasibility of pharmacist-led identification of a population for pain management and opioid stewardship. All patients admitted to the hospital were screened; electronic health record reports identified all opioid, antidepressant, and benzodiazepine administrations within the previous 24 hours, and pertinent family and social history risk factors for Opioid Use Disorder (OUD) and opioid-induced respiratory depression (OIRD). Data were exported to spreadsheets and calculated risk scores for OUD and OIRD, and opioid utilization and morphine milligram equivalents (MME) were tabulated. Chart reviews were completed on patients identified as high risk for OUD or OIRD, if MME was 90 or greater, or those receiving four or more “as needed” opioid doses in the previous 24 hours. Potential regimen adjustments based on the primary investigator’s judgment were categorized. Mean number of patients identified per day to receive stewardship was 13, and 18.6 potential interventions per day were identified. Based on results of this pilot, pharmacist-led identification of inpatients warranting pain and opioid stewardship is feasible at our institution.
Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma

PURPOSE Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias. PATIENTS AND METHODS We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome. RESULTS Short DTI was associated with advanced-stage disease (P < .001) and higher IPI (P < .001). We also found an inverse correlation between DTI and TMTV (RS = −0.37; P < .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all P < .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels (P < .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI (P < .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; −DTI: 1.1 [1.0 to 1.2]). CONCLUSION Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.
Short-term effects of particulate matter on cardiovascular morbidity in Italy: a national analysis.

AIMS We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy. METHODS AND RESULTS Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013-2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0-5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines. CONCLUSION PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.