Miracle-dz/UniFAR-FTUs huggingface dataset:
Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1

Anaplastic large cell lymphoma (ALCL) is a distinct form of T-cell non-Hodgkin lymphoma which accounts for 10% to 15% of all childhood lymphomas. Lowe and colleagues report on the addition of brentuximab vedotin to standard chemotherapy in unselected stage II to IV newly diagnosed patients, finding minimal additional toxicity and favorable event-free survival without any on-therapy relapse. These data suggest an advance in the management of ALCL.
Multiphysics Flow Modeling and in Vitro Toxicity of Iron Oxide Nanoparticles Coated with Poly(vinyl alcohol)

This study investigated the behavior of ferrofluids containing superparamagnetic iron oxide nanoparticles (SPION) of various compositions for potential applications in drug delivery and imaging. To ensure biocompatibility, the interaction of these SPION with two cell lines (adhesive and suspended) was also investigated using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cell lines studied were primary mouse connective tissue cells (adhesive) and human leukemia cells (suspended). SPION were synthesized with a co-precipitation method under different stirring rates and NaOH molarities. The SPION demonstrated a range of magnetic saturations due to their different shapes, which included magnetite colloidal nanocrystal clusters (CNC’s), magnetic beads, and single-coated nanoparticles. All synthesized SPION maintained reasonable cell viability following exposure to cells. Flow cytometer tests showed that no apoptosis took place in cells exposed to SPION. A multiphysics numerica.
Deuterium-depletion has no significant impact on the mutation rate of Escherichia coli, deuterium abundance therefore has a probabilistic, not deterministic effect on spontaneous mutagenesis

Deuterium (D), the second most abundant isotope of hydrogen is present in natural waters at an approximate concentration of 145–155 ppm (ca. 1.5E-4 atom/atom). D is known to influence various biological processes due to its physical and chemical properties, which significantly differ from those of hydrogen. For example, increasing D-concentration to >1000-fold above its natural abundance has been shown to increase the frequency of genetic mutations in several species. An interesting deterministic hypothesis, formulated with the intent of explaining the mechanism of D-mutagenicity is based on the calculation that the theoretical probability of base pairs to comprise two adjacent D-bridges instead of H-bridges is 2.3E-8, which is equal to the mutation rate of certain species. To experimentally challenge this hypothesis, and to infer the mutagenicity of D present at natural concentrations, we investigated the effect of a nearly 100-fold reduction of D concentration on the bacterial mutation rate. Using fluctuation tests, we measured the mutation rate of three Escherichia coli genes (cycA, ackA and galK) in media containing D at either <2 ppm or 150 ppm concentrations. Out of 15 pair-wise fluctuation analyses, nine indicated a significant decrease, while three marked the significant increase of the mutation/culture value upon D-depletion. Overall, growth in D-depleted minimal medium led to a geometric mean of 0.663-fold (95% confidence interval: 0.483–0.911) change in the mutation rate. This falls nowhere near the expected 10,000-fold reduction, indicating that in our bacterial systems, the effect of D abundance on the formation of point mutations is not deterministic. In addition, the combined results did not display a statistically significant change in the mutation/culture value, the mutation rate or the mutant frequency upon D-depletion. The potential mutagenic effect of D present at natural concentrations on E. coli is therefore below the limit of detection using the indicated methods.
Between two storms, vasoactive peptides or bradykinin underlie severity of COVID‐19?

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to be a world‐wide pandemic with overwhelming socioeconomic impact. Since inflammation is one of the major causes of COVID‐19 complications, the associated molecular mechanisms have been the focus of many studies to better understand this disease and develop improved treatments for patients contracting SARS‐CoV‐2. Among these, strong emphasis has been placed on pro‐inflammatory cytokines, associating severity of COVID‐19 with so‐called “cytokine storm. ” More recently, peptide bradykinin, its dysregulated signaling or “bradykinin storm,” has emerged as a primary mechanism to explain COVID‐19‐related complications. Unfortunately, this important development may not fully capture the main molecular players that underlie the disease severity. To this end, in this focused review, several lines of evidence are provided to suggest that in addition to bradykinin, two closely related vasoactive peptides, substance P and neurotensin, are also likely to drive microvascular permeability and inflammation, and be responsible for development of COVID‐19 pathology. Furthermore, based on published experimental observations, it is postulated that in addition to ACE and neprilysin, peptidase neurolysin (Nln) is also likely to contribute to accumulation of bradykinin, substance P and neurotensin, and progression of the disease. In conclusion, it is proposed that “vasoactive peptide storm” may underlie severity of COVID‐19 and that simultaneous inhibition of all three peptidergic systems could be therapeutically more advantageous rather than modulation of any single mechanism alone.
Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Background Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. Results Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain (p ≥ 1.858 × 10−7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10−7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. Conclusions These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.
Regression models for the determination of the absorbed dose rate with an extrapolation chamber for flat ophthalmic applicators.

Abstract The average surface absorbed dose rate, given by flat ophthalmic applicators 90Sr/90Y/ 925 MBq) is determined in equivalent soft tissue using an extrapolation chamber with two flat parallel electrodes of variable separation; the input electrode is fixed in relation to the collector electrode of constant area. When estimating the extrapolation curve slope using a linear regression model, it has been observed that average surface dose rate values were underestimated by up to 19%, as compared to estimations of these values by means of a second degree polynomial regression model, while an improvement of up to 37% is observed in the standard error of the slope in the quadratic model, as compared to that of the linear model. With the aim of validating the results of these models, goodness of fit tests to a Normal (the ShapiroWilk test) as well as homogeneity tests on treatment variance (the Bartlett test) were applied. The analysis of variance (ANOVA) tables of fit and residual error breakdown are given: table 3a and 3b for linear fit; 7a and 7b for quadratic fit, and table 10 to error breakdown. Also presented is the global uncertainty of the average dose rate, taking into account the reproducibility of the experimental set-up. It may be inferred that by using this type of measurement for the extrapolation curve slope, quadratic regression models allow for a greater degree of accuracy and precision in determining surface dose rate values. The effective area of the collector electrode and the effective electrode separation in the chamber are also determined by measuring the chamber's electric capacity. Finally, there is an attempt to relate the use of the regression models to the experimental conditions during the measurement of ionization currents (diameter of collector electrode, electrical field gradient, radiation field uniformity, radiation field intensity, etc.). In this particular case, deviations in the distance inverse square law and the “screening” effects during the collection of negative charges (both for primary radiation and the ionization generated by it), are presented as necessary, but insufficient, conditions to explain thoroughly the quadratic behavior of ionizing currents.
Brain Activity Foreshadows Stock Price Dynamics

Successful investing is challenging since stock prices are difficult to consistently forecast. Recent neuroimaging evidence suggests, however, that activity in brain regions associated with anticipatory affect may not only predict individual choice, but also forecast aggregate behavior out-of-sample. Thus, in two experiments, we specifically tested whether anticipatory affective brain activity in healthy humans could forecast aggregate changes in stock prices. Using functional magnetic resonance imaging, we found in a first experiment (n = 34, 6 females; 140 trials/subject) that nucleus accumbens activity forecast stock price direction, whereas anterior insula (AIns) activity forecast stock price inflections. In a second preregistered replication experiment (n = 39, 7 females) that included different subjects and stocks, AIns activity still forecast stock price inflections. Importantly, AIns activity forecast stock price movement even when choice behavior and conventional stock indicators did not (e.g., previous stock price movements), and classifier analysis indicated that forecasts based on brain activity should generalize to other markets. By demonstrating that AIns activity might serve as a leading indicator of stock price inflections, these findings imply that neural activity associated with anticipatory affect may extend to forecasting aggregate choice in dynamic and competitive environments such as stock markets. SIGNIFICANCE STATEMENT Many try but fail to consistently forecast changes in stock prices. New evidence, however, suggests that anticipatory affective brain activity may not only predict individual choice, but also may forecast aggregate choice. Assuming that stock prices index collective choice, we tested whether brain activity sampled during the assessment of stock prices could forecast subsequent changes in the prices of those stocks. In two neuroimaging experiments, a combination of previous stock price movements and brain activity in a region implicated in processing uncertainty and arousal forecast next-day stock price changes—even when behavior did not. These findings challenge traditional assumptions of market efficiency by implying that neuroimaging data might reveal “hidden information” capable of foreshadowing stock price dynamics.
Genetically proxied growth‐differentiation factor 15 levels and body mass index

Growth‐differentiation factor 15 (GDF15) is an inflammatory cytokine involved in energy homeostasis that is being pursued as a drug target for obesity. Its circulating levels are acutely increased by the type 2 diabetes medication metformin, resulting in reduced appetite and weight loss. We identified a genetic variant at the GDF15 gene to proxy a small, lifelong increase in circulating GDF15 levels, and leveraged it in colocalization and Mendelian randomization analyses to investigate the effects of chronically elevated GDF15 levels on body mass index (BMI) and type 2 diabetes liability. The results provide human genetic evidence supporting that chronically elevated GDF15 levels increase BMI. There was no genetic evidence to support bi‐directional effects, or that chronically elevated GDF15 levels directly affect liability to type 2 diabetes. Our results contrast the BMI‐lowering effects of an acute increase in GDF15 levels observed after metformin use. These findings have direct implications for informing pharmacological strategies aimed at targeting GDF15 levels for weight loss.
Diagnosis of Epidermolysis Bullosa Acquisita: Multicentre Comparison of Different Assays for Serum Anti-type VII Collagen Reactivity

Epidermolysis bullosa acquisita is a pemphigoid disease characterized by autoantibodies against type VII collagen. This study compared the sensitivity and specificity of 6 diagnostic assays: type VII collagen non-collagenous domains enzyme-linked immunoassay (NC1/2 ELISA) (MBL, Nagoya, Japan); type VII collagen NC1 ELISA (Euroimmun, Lübeck, Germany); indirect immunofluorescence (IF) microscopy test based on the expression of recombinant NC1 in a human cell line (NC1 BIOCHIP®; Euroimmun); full-length recombinant type VII collagen ELISA; immunoblotting with full-length type VII collagen in the extract of human dermis; and immunoblotting with recombinant NC1. Immunoblotting with recombinant NC1 showed a sensitivity of 93.1% and specificity of 100%, followed by NC1 BIOCHIP® (sensitivity, 89.1%; specificity, 100%), immunoblotting with human dermis (sensitivity, 87.1%; specificity 100%), NC1-ELISA (sensitivity 82.2%; specificity 98.6%), NC1/NC2 ELISA (sensitivity 88.1%; specificity 93.3%), and full-length type VII collagen ELISA (sensitivity 80.2%; specificity 93.8%).
Precision Medicine and cardiac channelopathies: when dreams meet reality

Abstract Precision Medicine (PM) is an innovative approach that, by relying on large populations’ datasets, patients’ genetics and characteristics, and advanced technologies, aims at improving risk stratification and at identifying patient-specific management through targeted diagnostic and therapeutic strategies. Cardiac channelopathies are being progressively involved in the evolution brought by PM and some of them are benefiting from these novel approaches, especially the long QT syndrome. Here, we have explored the main layers that should be considered when developing a PM approach for cardiac channelopathies, with a focus on modern in vitro strategies based on patient-specific human-induced pluripotent stem cells and on in silico models. PM is where scientists and clinicians must meet and integrate their expertise to improve medical care in an innovative way but without losing common sense. We have indeed tried to provide the cardiologist’s point of view by comparing state-of-the-art techniques and approaches, including revolutionary discoveries, to current practice. This point matters because the new approaches may, or may not, exceed the efficacy and safety of established therapies. Thus, our own eagerness to implement the most recent translational strategies for cardiac channelopathies must be tempered by an objective assessment to verify whether the PM approaches are indeed making a difference for the patients. We believe that PM may shape the diagnosis and treatment of cardiac channelopathies for years to come. Nonetheless, its potential superiority over standard therapies should be constantly monitored and assessed before translating intellectually rewarding new discoveries into clinical practice.
Development of a new multiplex PCR to detect prevalent species of house dust mites in house dust

ABSTRACT Dermatophagoides pteronyssinus and Dermatophagoides farinae are the most common House Dust Mite (HDM) species in home environments worldwide and responsible for HDM allergy. Since the prevalence of HDM-related clinical conditions is linked to exposure to the mite itself, the detection of HDM in the human households gains importance. We aimed to develop a fast and accessible multiplex PCR to detect and distinguish two relevant HDM species in house dust. New primers were designed, and sensitivity analysis was performed. Sequencing of PCR products was also performed to confirm the method’s specificity. The limit of detection of the multiplex PCR for both species was as low as 30 pg µL−1. The application of the multiplex PCR to dust samples also resulted in the identification of both species with high sensitivity. The protocol required small amount of template, reagents and a short reaction time thus presenting an alternative to classically used techniques for HDM identification.
Theoretical and experimental studies on the adsorption behavior of thiophenol on gold nanoparticles

FT-Raman spectra were obtained for thiophenol (TP) and TP on gold nanoparticles. All vibrational fundamentals for the TP molecule are assigned on the basis of the scaled quantum force field procedure. Three model systems are studied and compared for the interactions of TP with the Au atom: (1) TP with a Au atom, C6H5SHAu; (2) TP anion with a Au atom, C6H5S−Au; and (3) TP with a Au atom and subsequent formation of thiophenylate, C6H5SAu. The equilibrium structures and Raman spectra were calculated for the model systems using density functional theory (DFT) with the B3LYP functionals and the mixed basis set 6-311 + G** (for C, S, H) and LANL2DZ (for Au), and theoretical Raman wavenumbers of C6H5SAu and C6H5S−Au were assigned according to potential energy distributions. The third model system is shown to be preferred over the other two. The calculated binding energies are also shown to support the third model system. It is suggested that a simple model, such as the one used in the present study, is reasonable to describe surface-enhanced Raman spectroscopy of thiophenol adsorbed on gold nanoparticles. Copyright © 2007 John Wiley & Sons, Ltd.
How Diverse Task Experience Affects Both Group and Subsequent Individual Performance

Task demonstrability defines the criteria that, when met, facilitate the effective exchange of knowledge within a problem-solving group. The extent to which those criteria are met should vary as a consequence of the relevant experiences that members have prior to entering the group. We investigate whether group members’ ability to coordinate with one another is facilitated by their prior task-related experiences. Participants worked individually, then in groups, and then individually again to complete a series of circuit board assembly tasks. Groups in which all members had pre-task experience performed significantly better than groups with even a single member lacking task experience, or individuals. Mediation analysis showed that prior task experience helps group members coordinate by improving task demonstrability. Group experience composition also affected post-group individual performance. Groups with diverse task experience produced individuals who performed better solo but only after working on an unstructured task that allowed for greater exploration.
Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer

Purpose: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368). Materials and Methods: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored. Results: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI −11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. Conclusions: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.
Insulin Use and Poor COVID-19 Outcomes among Diabetes Patients: Association Not Necessarily Causation

ABSTRACT Our study looked at the relationship between insulin use and clinical outcomes in COVID-19. A response to our article, written by Dr. Chia Sing Kow and Dr. Syed Shahzad Hasan raised a few questions. They mentioned our use of hemoglobin A1c may be inaccurate as the patients in our study had high rates of CKD or ESRD which could alter the hemoglobin A1c levels. However due to the limitations of our patient population and perhaps in a lot of other sample populations in the real-world setting, it was the most feasible way to represent glucose control.The writers also suggested that the use of metformin, a potential confounder, was also not adjusted for. This should be considered in future research but addition of too many variables in a regression model may lead to less reliability of results for our study.The letter writers also suggested that the results of our paper may lead to misinterpretation by readers and may influence providers to not use insulin therapy for their patients when necessary due to fear of worse outcomes in the setting of COVID-19. We reiterated that it is very important that the data not be misinterpreted, and that nowhere in our paper did we imply or suggest that patients who need insulin therapy to treat their diabetes should not receive proper therapy due to the association we delineated in our paper. Instead, more careful surveillance of patients with advanced diabetes is needed especially when admitted with COVID-19.