Miracle-dz/UniFAR-FTUs huggingface dataset:
Pegilodecakin as monotherapy or in combination with anti‐PD‐1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma: Final results of cohorts A, G, H and I of IVY Phase I study

Interleukin (IL)‐10 has anti‐inflammatory and CD8+ T‐cell‐stimulating properties. Pegilodecakin (pegylated recombinant human IL‐10) induces intratumoral antigen‐specific CD8 + T‐cells and upregulates IFNγ and major histocompatibility complexes (MHC) I and II. Pegilodecakin has single‐agent activity with manageable toxicity in advanced renal cell carcinama (aRCC) (data cutoff 24 March 2016). Pegilodecakin with pembrolizumab or nivolumab revealed clinical activity in aRCC (data cutoff 1 July 2018). Here, we report for the first time the results of pegilodecakin+ pazopanib, and final results for monotherapy and long‐term follow‐up with pegilodecakin + anti‐programmed cell death 1 (anti‐PD‐1) inhibitors (data cutoff 19 February 2019). Phase 1/1b multi‐cohort dose escalation IVY study enrolled 353 patients. Sixty‐six patients with aRCC were treated with pegilodecakin alone or with pazopanib or anti‐PD‐1 inhibitor in cohorts A, G, H and I (data cutoff 19 February 2019). Primary endpoints included safety and tolerability. Secondary endpoint was tumor response by immune‐related response criteria (irRC). Pegilodecakin plus nivolumab or pembrolizumab yielded median progression‐free survival (mPFS) of 13.9 months and 6‐month PFS probability of 60%, 76% 1‐year overall survival (OS) probability and 61% 2‐year OS probability. Pegilodecakin monotherapy produced mPFS of 1.8 months, 6‐month PFS probability 25%, 1‐year OS 50%, and 2‐year OS 17%. Median OS was not reached in both combinations. Objective response rates (ORRs) were 33% with pazopanib and 43% with anti‐PD‐1. Most common Grade 3/4 treatment‐related adverse events included anemia, thrombocytopenia and hypertriglyceridemia. In these heavily pretreated renal cell carcinama cohorts of IVY, pegilodecakin+anti‐PD‐1 inhibitor showed promising clinical activity. Safety profile of pegilodecakin alone and with anti‐PD‐1 inhibitors was consistent as previously reported.
Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma

PURPOSE Uterine serous carcinoma (USC) is a distinct histologic subtype of endometrial cancer, with molecular characteristics suggesting frequent cell-cycle dysregulation paired with a high level of oncogene-driven replication stress. Adavosertib is a potent and selective oral inhibitor of the WEE1 kinase, a key regulator of the G2/M and S phase cell-cycle checkpoints. Because cells with impaired cell-cycle regulation and high replication stress may be vulnerable to WEE1 inhibition, we conducted this study to assess the activity of adavosertib monotherapy in women with recurrent USC. PATIENTS AND METHODS This was a single-arm two-stage phase II study with coprimary end points of objective response rate (ORR) and rate of progression-free survival at 6 months (PFS6). Women with recurrent USC were treated with adavosertib monotherapy at a starting dose of 300 mg orally once daily days 1 through 5 and 8 through 12 of a 21-day cycle until disease progression. RESULTS In 34 evaluable patients, 10 total responses (one confirmed complete response, eight confirmed partial responses, and one unconfirmed partial response) were observed with adavosertib monotherapy, for an ORR of 29.4% (95% CI, 15.1 to 47.5). Sixteen patients were progression-free at 6 months, for a PFS6 rate of 47.1% (95% CI, 29.8 to 64.9). Median PFS was 6.1 months, and median duration of response was 9.0 months. Frequent treatment-related adverse events (AEs) included diarrhea (76.5%), fatigue (64.7%), nausea (61.8%), and hematologic AEs. No clear correlation of clinical activity with specific molecular alterations was observed in an exploratory biomarker analysis. CONCLUSION Adavosertib monotherapy demonstrated encouraging and durable evidence of activity in women with USC, and further investigation of this agent in this cancer and biomarkers of activity are indicated.
Coaxial electrospun biomimetic copolymer fibres for application in diffusion magnetic resonance imaging

Objective. The use of diffusion magnetic resonance imaging (dMRI) opens the door to characterizing brain microstructure because water diffusion is anisotropic in axonal fibres in brain white matter and is sensitive to tissue microstructural changes. As dMRI becomes more sophisticated and microstructurally informative, it has become increasingly important to use a reference object (usually called an imaging phantom) for validation of dMRI. This study aims to develop axon-mimicking physical phantoms from biocopolymers and assess their feasibility for validating dMRI measurements. Approach. We employed a simple and one-step method—coaxial electrospinning—to prepare axon-mimicking hollow microfibres from polycaprolactone-b-polyethylene glycol (PCL-b-PEG) and poly(D, L-lactide-co-glycolic) acid (PLGA), and used them as building elements to create axon-mimicking phantoms. Electrospinning was firstly conducted using two types of PCL-b-PEG and two types of PLGA with different molecular weights in various solvents, with different polymer concentrations, for determining their spinnability. Polymer/solvent concentration combinations with good fibre spinnability were used as the shell material in the following co-electrospinning process in which the polyethylene oxide polymer was used as the core material. Following the microstructural characterization of both electrospun and co-electrospun fibres using optical and electron microscopy, two prototype phantoms were constructed from co-electrospun anisotropic hollow microfibres after inserting them into water-filled test tubes. Main results. Hollow microfibres that mimic the axon microstructure were successfully prepared from the appropriate core and shell material combinations. dMRI measurements of two phantoms on a 7 tesla (T) pre-clinical scanner revealed that diffusivity and anisotropy measurements are in the range of brain white matter. Significance. This feasibility study showed that co-electrospun PCL-b-PEG and PLGA microfibre-based axon-mimicking phantoms could be used in the validation of dMRI methods which seek to characterize white matter microstructure.
The relationship between premature ejaculation and the timing of pre‐adult circumcision

We aimed to investigate the relationship between premature ejaculation and the age when men had been circumcised before adulthood. A total of 2,768 sexually active male patients aged between 18 and 65 years were included in this study. A multicentre study was conducted prospectively with the participation of 20 centres. A survey consisting of 12 questions prepared by the researchers, as well as the validated Turkish versions of the five‐item Premature Ejaculation Diagnostic Tool, was administered to all participants. The study included 1,603 participants who met the inclusion criteria. There was no significant difference in the Premature Ejaculation Diagnostic Tool and self‐reported ejaculation time between the participants who had been circumcised at different ages during childhood. Remembering circumcision experience with fear or anxiety did not increase the risk of sexual dysfunction compared to the participants who described their experience with happiness or with no particular emotion. There was no significant difference in Premature Ejaculation Diagnostic Tool scores or the self‐reported ejaculation time of the participants circumcised at different ages. The age of childhood circumcision, having a fearful or anxious circumcision experience, does not affect the risk of premature ejaculation in adult life.
Louse-borne relapsing fever—A systematic review and analysis of the literature: Part 2—Mortality, Jarisch–Herxheimer reaction, impact on pregnancy

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch–Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.
Estudo da estabilidade térmica de óleos e gorduras vegetais por TG/DTG e DTA

Óleos e gorduras vegetais são muito ultilizados pela indústria alimentícia e farmacêutica, tem exigido de pesquisadores e técnicos métodos analíticos capazes de avaliar as condições de processamento e estocagem. A estabilidade térmica de óleos vegetais é um fator determinante na sua qualidade. Neste trabalho avaliou-se a estabilidade térmica de óleos e gorduras vegetais extraídos de semente de plantas do cerrado ( araticum, babaçu, buriti, guariroba e murici) usando os resultados de TG, DTG e DTA, numa faixa de temperatura entre 30 e 650ºC, em atmosfera de nitrogênio, com razão de aquecimento de 10ºC min-1. As técnicas termoanalíticas utilizadas mostraram–se eficientes e rápidas na determinação da estabilidade térmica dos óleos e gorduras estudados.
Clustering approach for the analysis of the fluorescent bioaerosol collected by an automatic detector

Automatically operating particle detection devices generate valuable data, but their use in routine aerobiology needs to be harmonized. The growing network of researchers using automatic pollen detectors has the challenge to develop new data processing systems, best suited for identification of pollen or spore from bioaerosol data obtained near-real-time. It is challenging to recognise all the particles in the atmospheric bioaerosol due to their diversity. In this study, we aimed to find the natural groupings of pollen data by using cluster analysis, with the intent to use these groupings for further interpretation of real-time bioaerosol measurements. The scattering and fluorescence data belonging to 29 types of pollen and spores were first acquired in the laboratory using Rapid-E automatic particle detector. Neural networks were used for primary data processing, and the resulting feature vectors were clustered for scattering and fluorescence modality. Scattering clusters results showed that pollen of the same plant taxa associates with the different clusters corresponding to particle shape and size properties. According to fluorescence clusters, pollen grouping highlighted the possibility to differentiate Dactylis and Secale genera in the Poaceae family. Fluorescent clusters played a more important role than scattering for separating unidentified fluorescent particles from tested pollen. The proposed clustering method aids in reducing the number of false-positive errors.
Comparison of Ultrasound‐Guided Type‐II Pectoral Nerve Block and Rhomboid Intercostal Block for Pain Management Following Breast Cancer Surgery: A Randomized, Controlled Trial

Although breast‐conserving surgery‐axillary dissection (BCS‐AD) is a minimally invasive surgery, patients may suffer from moderate‐to‐severe pain. Several regional techniques can be used for pain control. The type II pectoral nerve block (PECS II) and the rhomboid intercostal block (RIB) are interfascial plane blocks that have been reported to provide effective analgesia after breast surgery. This study aims to compare the analgesic efficacy of the PECS II block and the RIB after breast surgery.
Utility of fluoroscopy alone for monitoring of intrathoracic bleeding complications during transvenous lead extraction

Transvenous lead extraction (TLE) carries a significant risk of major complications, namely bleeding into the pericardial sac or thoracic cavity. While echocardiographic imaging has been recommended for intraprocedural monitoring for those complications, no studies had examined the potential benefits of fluoroscopy alone as an alternative to echocardiography. The aim of this study was to evaluate the utility of fluoroscopy for monitoring intrathoracic bleeding complications during TLE.
Case studies of ozone transport between North America and Europe in summer 2000

This paper reports on Long Range Transport (LRT) of ozone and related species over the North Atlantic ocean and its impact on Europe. Measurements of NO 2 and O 3 columns from the GOME and MOPITT satellite instruments are first used in conjunction with the GEOS-CHEM global model of transport and tropospheric chemistry to identify the major events of LRT that reach Europe over the course of the summer 2000. Model simulations are then used to examine surface O 3 observations at a European mountain site and O 3 vertical profiles over several European cities to quantify the impact of the LRT events on the European ozone distributions. Over the course of summer 2000, we identified nine major episodes of pollution transport between North America and Europe, which are in majority associated with WCB/post-frontal outflow (7 events) and zonal transport (2 events). We find that on average three episodes occur per month with the strongest ones being in June. The number and frequency of LRT events that reach Europe after leaving North America is strongly driven by the position and strength of the Azores anticyclone. After leaving North America, the plumes can either i) travel in the North American cyclones, mostly in the Warm Conveyor Belt (WCB), tracking poleward and thus reach Europe at high latitudes; ii) be transported zonally between 40° and 55° N directly to Europe; iii) be incorporated into the Azores anticyclone and reach Europe at mid-latitudes. Based on model sensitivity simulation it can be concluded that on average the North American sources of ozone contribute between 2–8 ppb in PBL and 10–13 ppb in FT. During particular episodes the North American sources resulted in O 3 enhancement up to 25–28 ppb in the layer between 800–600 hPa and 10–12 ppb in PBL. For some episodes a substantial North American contribution (30% or higher) does not translate into a well marked enhancement of the total O 3 .
Beyond Isolated and Associated: A Novel Fetal MR Imaging–Based Scoring System Helps in the Prenatal Prognostication of Callosal Agenesis

BACKGROUND AND PURPOSE: Although “corpus callosum agenesis” is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. MATERIALS AND METHODS: We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. RESULTS: We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P < .0001) without a significant score difference between complete and partial corpus callosum agenesis (P = .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. CONCLUSIONS: The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group.
Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials

Background: The aging process has great impact on body composition, such as the increase of adipose tissue in abdominal region, and the decrease of lean body mass, due to skeletal muscle loss. A reduction in muscle mass is associated to high risk of fractures and falls, loss of mobility, and increased number of hospitalizations. Beta-hydroxy-beta-methylbutyrate (HMB) is a biological substance derived from leucine metabolism, with anabolic and anticatabolic properties. Some HMB effects are tissue repair stimulation and protein anabolism. Aims: We aimed to evaluate the effects of HMB supplementation on body composition and muscle strength in elderly, as well as to identify the efficient dosages to reach these effects. Methods: This review included studies that evaluated muscle mass and muscle strength, associated or not with physical exercise and diet in elderly people. Only studies published from 2008 to 2019 were selected for analysis. Results: Six articles were included in the review. The used doses varied from 1.5 to 3 g. In 5 studies, HMB supplementation was associated with calcium; only 1 study did not use the oral administration route. Two studies used 4 g of maltodextrin as a vehicle; 1 used HMB with a hypercaloric and hyperproteic supplement; 1 associated HMB with lysine and arginine; and 1 with arginine and glutamine. Supplementation of 3 g of HMB has shown to be most beneficial in improving strength and body composition in people over 65 years, especially in bed rest and untrained conditions. Conclusion: Our findings suggest that HMB has a positive effect on body composition and strength, especially in bedridden or sedentary elderly, due to its anticatabolic properties.
Social organization in ungulates: Revisiting Jarman’s hypotheses

Ungulates (antelopes, deer and relatives) have some of the most diverse social systems among mammals. To understand the evolution of ungulate social organization, Jarman (1974) proposed an ecological scenario of how distribution of resources, habitat and feeding style may have influenced social organization. Although Jarman's scenario makes intuitive sense and remains a textbook example of social evolution, it has not been scrutinized using modern phylogenetic comparative methods. Here we use 230 ungulate species from ten families to test Jarman's hypotheses using phylogenetic analyses. Consistent with Jarman's proposition, both habitat and feeding style predict group size, since grazing ungulates typically live in open habitats and form large herds. Group size, in turn, has a knock‐on effect on mating systems and sexual size dimorphism, since ungulates that live in large herds exhibit polygamy and extensive sexual size dimorphism. Phylogenetic confirmatory path analyses suggest that evolutionary changes in habitat type, feeding style and body size directly (or indirectly) induce shifts in social organization. Taken together, these phylogenetic comparative analyses confirm Jarman's conjectures, although they also uncover novel relationships between ecology and social organization. Further studies are needed to explore the relevance of Jarman (1974) scenario for mammals beyond ungulates.
Interleukin (IL)-1 family cytokines could differentiate primary immune thrombocytopenia from systemic lupus erythematosus-associated thrombocytopenia

Background Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by a decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease in which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP. Methods Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP), and 10 healthy controls. Results The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 were decreased significantly in ITP patients compared with SLE-TP patients, SLE-NTP patients, and healthy controls (P<0.05). While there was no significant difference in the serum level of IL-37 between ITP and SLE-TP patients, there was a positive correlation between the platelet count and IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33, and IL-37 could be considered biomarkers in the diagnosis of ITP. Conclusions Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.