Miracle-dz/UniFAR-FTUs huggingface dataset:
Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402).

PURPOSE This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
A Computer Vision Platform to Automatically Locate Critical Events in Surgical Videos

Supplemental Digital Content is available in the text Objective: The aim of this study was to develop a computer vision platform to automatically locate critical events in surgical videos and provide short video clips documenting the critical view of safety (CVS) in laparoscopic cholecystectomy (LC). Background: Intraoperative events are typically documented through operator-dictated reports that do not always translate the operative reality. Surgical videos provide complete information on surgical procedures, but the burden associated with storing and manually analyzing full-length videos has so far limited their effective use. Methods: A computer vision platform named EndoDigest was developed and used to analyze LC videos. The mean absolute error (MAE) of the platform in automatically locating the manually annotated time of the cystic duct division in full-length videos was assessed. The relevance of the automatically extracted short video clips was evaluated by calculating the percentage of video clips in which the CVS was assessable by surgeons. Results: A total of 155 LC videos were analyzed: 55 of these videos were used to develop EndoDigest, whereas the remaining 100 were used to test it. The time of the cystic duct division was automatically located with a MAE of 62.8 ± 130.4 seconds (1.95% of full-length video duration). CVS was assessable in 91% of the 2.5 minutes long video clips automatically extracted from the considered test procedures. Conclusions: Deep learning models for workflow analysis can be used to reliably locate critical events in surgical videos and document CVS in LC. Further studies are needed to assess the clinical impact of surgical data science solutions for safer laparoscopic cholecystectomy.
Comparison of Oncologic Outcomes between Carbon Ion Radiotherapy and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

Simple Summary Lung cancer is a leading cause of cancer-related death. Stereotactic body radiotherapy (SBRT) is the standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC). Carbon ion radiotherapy (CIRT) is a safe and effective treatment for early-stage NSCLC. However, there is no direct comparison study between these treatments. The present study aimed to compare oncologic outcomes after CIRT and SBRT for early-stage NSCLC in a single-institutional and contemporaneous cohort. We demonstrated favorable overall survival and local control in the CIRT group compared to those in the SBRT group using log-rank tests and Cox regression analyses for 89 patients. In addition, these results were validated in propensity score-adjusted analyses. The present retrospective comparison study showed a positive efficacy profile of CIRT, which is beneficial in the management of early-stage NSCLC. Abstract Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.
The Production of Anthocyanins and Anthocyanidins

The idea that the anthocyan pigments are closely related to the flavone and flavonol glucosides is by no means new. Attempts to solve the problem of their relationship have come chiefly from botanists, and, as a result of their researches, a number of hypotheses have sprung up around which quite considerable controversy has been centred. Miss Wheldale puts forward the suggestion that anthocyan pigments are the oxidation products of colourless or faintly coloured chromogens; and that these chromogens are products of hydrolysis of glucosides present in the tissues of the plant (probably glucosides of flavone or flavonol derivatives). The hydrolysis of the glucoside she considers as essential to the production of the anthocyan pigment. She represents the changes taking place by means of the following equations :— Glucoside + water ⇆ chromogen + sugar. Then— Oxidation of chromogen → anthocyan pigment.
Species-Specific and Distance-Dependent Dispersive Behaviour of Forisomes in Different Legume Species

Forisomes are giant fusiform protein complexes composed of sieve element occlusion (SEO) protein monomers, exclusively found in sieve elements (SEs) of legumes. Forisomes block the phloem mass flow by a Ca2+-induced conformational change (swelling and rounding). We studied the forisome reactivity in four different legume species—Medicago sativa, Pisum sativum, Trifolium pratense and Vicia faba. Depending on the species, we found direct relationships between SE diameter, forisome surface area and distance from the leaf tip, all indicative of a developmentally tuned regulation of SE diameter and forisome size. Heat-induced forisome dispersion occurred later with increasing distance from the stimulus site. T. pratense and V. faba dispersion occurred faster for forisomes with a smaller surface area. Near the stimulus site, electro potential waves (EPWs)—overlapping action (APs), and variation potentials (VPs)—were linked with high full-dispersion rates of forisomes. Distance-associated reduction of forisome reactivity was assigned to the disintegration of EPWs into APs, VPs and system potentials (SPs). Overall, APs and SPs alone were unable to induce forisome dispersion and only VPs above a critical threshold were capable of inducing forisome reactions.
Electrochemical Characterization of Catalytic Activities of Manganese Oxides to Oxygen Reduction in Alkaline Aqueous Solution

The catalytic function and activity of manganese oxides (MnOx: Mn 2 O 3 , Mn 3 O 4 , Mn 5 O 8 , and MnOOH) to the electrochemical reduction of O 2 in 0.10 M KOH aqueous solution have been investigated by cyclic voltammetry at MnOx/Nafion-modified gold electrodes. Two successive reduction current peaks were observed at Nafion-modified electrodes in the cyclic voltammograms, i p,1 for a two-electron reduction of O 2 to hydrogen peroxide (HO 2 ) and i p,2 for a two-electron reduction of HO 2 to OH - . The peak current heights of i p,1 and i p,2 changed greatly depending on the kind of MnOx species incorporated into the MnOx/Nafion-modified gold electrodes; i p,1 increased and i p,2 decreased. On the assumption that HO 2 produced in the first reduction step is chemically decomposed into O 2 and OH with a catalytic action of MnOx and that this regenerated O 2 is reduced again in the same first reduction step, we evaluated the catalytic activity of MnOx using the values of i p,1 and i p,2 . MnOOH provided the highest catalytic activity to the electrochemical reduction of O 2 . This result was supported by another experiment by using a chemical method where catalytic decomposition of HO 2 with MnOx was estimated by measuring the O 2 concentration directly with a commercial oxygen sensor.
A Neuromorphic CMOS Circuit With Self-Repairing Capability

Neurophysiological observations confirm that the brain not only is able to detect the impaired synapses (in brain damage) but also it is relatively capable of repairing faulty synapses. It has been shown that retrograde signaling by astrocytes leads to the modulation of synaptic transmission and thus bidirectional collaboration of astrocyte with nearby neurons is an important aspect of self-repairing mechanism. Specifically, the retrograde signaling via astrocyte can increase the transmission probability of the healthy synapses linked to the neuron. Motivated by these findings, in the present research, a CMOS neuromorphic circuit with self-repairing capabilities is proposed based on astrocyte signaling. In this way, the computational model of self-repairing process is hired as a basis for designing a novel analog integrated circuit in the 180-nm CMOS technology. It is illustrated that the proposed analog circuit is able to successfully recompense the damaged synapses by appropriately modifying the voltage signals of the remaining healthy synapses in the wide range of frequency. The proposed circuit occupies 7500- $\mu \text{m}^{2}$ silicon area and its power consumption is about $65.4~\mu \text{W}$ . This neuromorphic fault-tolerant circuit can be considered as a key candidate for future silicon neuronal systems and implementation of neurorobotic and neuro-inspired circuits.
Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation

Asthma and obesity are two epidemics affecting the developed world. The relationship between obesity and both asthma and severe asthma appears to be weight-dependent, causal, partly genetic, and probably bidirectional. There are two distinct phenotypes: 1. Allergic asthma in children with obesity, which worsens a pre-existing asthma, and 2. An often non allergic, late-onset asthma developing as a consequence of obesity. In obesity, infiltration of adipose tissue by macrophages M1, together with an increased expression of multiple mediators that amplify and propagate inflammation, is considered as the culprit of obesity-related inflammation. Adipose tissue is an important source of adipokines, such as pro-inflammatory leptin, produced in excess in obesity, and adiponectin with anti-inflammatory effects with reduced synthesis. The inflammatory process also involves the synthesis of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and TGFβ, which also contribute to asthma pathogenesis. In contrast, asthma pro-inflammatory cytokines such as IL-4, IL-5, IL-13, and IL-33 contribute to maintain the lean state. The resulting regulatory effects of the immunomodulatory pathways underlying both diseases have been hypothesized to be one of the mechanisms by which obesity increases asthma risk and severity. Reduction of weight by diet, exercise, or bariatric surgery reduces inflammatory activity and improves asthma and lung function.
CRISPR/Cas9-Mediated Knockout of HOS1 Reveals Its Role in the Regulation of Secondary Metabolism in Arabidopsis thaliana

In Arabidopsis, the RING finger-containing E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) functions as a main regulator of the cold signaling. In this study, CRISPR/Cas9-mediated targeted mutagenesis of the HOS1 gene in the first exon was performed. DNA sequencing showed that frameshift indels introduced by genome editing of HOS1 resulted in the appearance of premature stop codons, disrupting the open reading frame. Obtained hos1Cas9 mutant plants were compared with the SALK T-DNA insertion mutant, line hos1-3, in terms of their tolerance to abiotic stresses, accumulation of secondary metabolites and expression levels of genes participating in these processes. Upon exposure to cold stress, enhanced tolerance and expression of cold-responsive genes were observed in both hos1-3 and hos1Cas9 plants. The hos1 mutation caused changes in the synthesis of phytoalexins in transformed cells. The content of glucosinolates (GSLs) was down-regulated by 1.5-times, while flavonol glycosides were up-regulated by 1.2 to 4.2 times in transgenic plants. The transcript abundance of the corresponding MYB and bHLH transcription factors, which are responsible for the regulation of secondary metabolism in Arabidopsis, were also altered. Our data suggest a relationship between HOS1-regulated downstream signaling and phytoalexin biosynthesis.
Drug-Induced Acute Kidney Injury: A Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method

Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to provide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture-recapture method was performed to estimate the total number of DIAKIs. Results: The estimated total number of DIAKIs was 521 (95%CI 480; 563), representing 20.0% of all AKIs. The notification was at a rate of 12.9% (95%CI 10.0; 15.8). According to the KDIGO classification, 50.2% of the DIAKI cases were stage 1 and 49.8% stage 2 and 3. The mortality rate was 11.1% and 9.6% required hemodialysis. Conclusion: This study showed that drugs are involved in a significant proportion of patients developing AKI during a hospital stay and emphasizes the severity of DIAKI cases.
Determination of mobile heavy metal fraction in soil: Results of a pot experiment with sewage sludge

Abstract The development of a method using a chelating resin to assess heavy metal mobility in soil and the first results obtained from a pot experiment with sewage sludge additions were studied. The resin was Chelex 100 with the calcium (Ca)‐form of the resin proving to be best suited for the extraction. The efficiency of recovery of the heavy metals from an aqueous solution ranged from 81.2% for cadmium (Cd) to 102% for copper (Cu) within 24 hours. For heavy metal extractions from a soil sample, a 96 hour extraction period was found to be optimum. The extracted heavy metal portion was comparable with the results obtained with an ammonium acetate (NH4AOc) extraction. Total heavy metal contents in the substrate of the pot experiment did not show a significant influence due to the sewage sludge treatments, although considerable amounts of heavy metals were added by the sewage sludge. This effect can be both due to the incomplete recovery of heavy metals by an aqua regia extraction and leaching losses of th.
Evaluation of a bioslurry remediation of petroleum hydrocarbons contaminated sediments using chemical, mathematical and microscopic analysis

This paper concerns the bioremediation of three petroleum hydrocarbon polluted sediment samples collected from the Gulf of Suez, Egypt. The study used a bioslurry system inoculated with Staphylococcus gallinarum NK1, which showed good bioremediation capability regardless of the type of pollutant hydrocarbon and its concentration.
Water Sorption and Water Vapour Permeability Properties of Polysaccharide (Locust Bean Gum) Based Edible Films

Abstract Water sorption data of edible films containing locust bean gum (LBG) and polyethylene glycol (PEG) 200 as plasticizer determined at different water activities showed that equilibrium water content increases sharply above a w =0.65. The effects of the amount and molecular weight of PEG on water vapour transfer properties of these edible films were also examined. Generally, permeance and permeability values of edible films were found to increase with both quantity and molecular weight of PEG up to PEG 600. With increasing amounts of plasticizers (PEG 200, PEG 400, PEG 600), which are liquid at room temperature, a diluting effect in the film solution occured and permeance and permeability values of edible films increased. This situation was reversed for the edible films containing PEG 1000, which is solid at room temperature.
In Situ and Reversible Control of the Surface Activity of Ferrocenyl Surfactants in Aqueous Solutions

The redox-active surfactant (11-ferrocenylundecyl)trimethylammonium bromide (Fc(CH 2 ) 11 N + (CH 3 ) 3 Br - ; Fc = [η 5 -C 5 H 5 ]Fe [η 5 -C 5 H 5 ]), in combination with electrochemical methods, permits reversible control over the surface tension of an aqueous solution. The change in surface activity of the surfactant was caused by oxidation of the electrically neutral ferrocenyl moiety to the polar ferrocenium cation. Oxidation of 0.1 mM Fc(CH 2 ) 11 N + (CH 3 ) 3 dissolved in aqueous 0.1 M Li 2 SO 4 caused the surface tension of the solution to increase from 49 to 72 mN/m. The change in surface tension was reversible ; reduction of the dicationic Fc + (CH 2 ) 11 N + (CH 3 ) 3 to Fc(CH 2 ) 11 N + (CH 3 ) 3 recovered the initial surface tension of the solution (49 mN/m). Surface tensions of aqueous solutions were cycled repeatedly (> 14 cycles) between these limits. Surprisingly, oxidation of Fc(CH 2 ) 11 N + (CH 3 ) 3 at concentrations greater than 10 mM caused a decrease in the equilibrium surface tension. The limiting area per molecule at the surface ofthe aqueous solution (0.1 M Li 2 SO 4 , pH 2) was unexpectedly similar for both Fc(CH 2 ) 11 N + (CH 3 ) 3 (85 ± 4 A 2 ) and Fc + (CH 2 ) 11 N + (CH 3 ) 3 (75 ± 4 A 2 ).
Polypyrrole nanofiber-carbon nanotube electrodes for supercapacitors with high mass loading obtained using an organic dye as a co-dispersant†

Polypyrrole (PPy) nanofibers and composites, containing PPy and multiwalled carbon nanotubes (MWCNTs), were used for the fabrication of electrodes of electrochemical supercapacitors (ES). It was found that cationic malachite green (MG) dye adsorbed on PPy and MWCNTs and allowed their efficient electrosteric dispersion in water. Sedimentation tests, electrophoretic deposition (EPD) experiments, Fourier transform infrared spectroscopy and UV-Vis spectroscopy data showed strong adsorption of MG on PPy and MWCNTs. The important finding was the possibility of efficient dispersion of PPy and MWCNTs using MG dye as a co-dispersant. The new approach allowed colloidal processing of individual materials and composites. This method is suitable for the cathodic EPD of electrically neutral PPy and MWCNTs. The ES electrodes with high material loading in the range of 10–30 mg cm−2 were prepared from colloidal suspensions of PPy nanofibers and MWCNTs using Ni foam current collectors. The composite PPy–MWCNT electrodes, prepared using MG, showed superior electrochemical performance compared to pure PPy and composite electrodes prepared without MG. The composite PPy–MWCNT electrodes with high mass loadings showed excellent capacitance retention at high scan rates and over a wide range of frequencies, and excellent cycling stability. The highest capacitance of 4.62 F cm−2 was obtained at a material loading of 30 mg cm−2. The PPy nanofiber–MWCNT composites, prepared using MG as a dispersant, are promising electrodes for ES.
Cell DistensionInduced Increase of the Delayed Rectifier K+ Current in Guinea Pig Ventricular Myocytes

Abstract Single ventricular myocytes of guinea pig heart were distended by applying a positive pressure of 5 to 20 mm Hg in the pipette during the whole-cell voltage clamp. The amplitude of delayed rectifier K + current (I K ) was increased by ≈1.5 times, whereas the inward rectifier K + current was scarcely affected. The increase of I K was reversible by applying a negative pressure of −10 to −30 mm Hg accompanied by shrinkage of the inflated cell. This response of I K was largely attributed to the E-4031–insensitive component of I K . The fully activated current amplitude, measured using long-lasting depolarizing pulses (>30 seconds) to +60 mV, was increased by the cell distension. The activation time course of I K during the long pulse consisted of more than three exponential components, and the slowest time constant was decreased by the distension from control 20.2±7.7 seconds (n=4) to 7.6±1.6 seconds (n=5). We failed to detect an involvement of microtubules or microfilaments, protein kinase C, and Ca 2+ in the inflation-mediated increase of I K .