Miracle-dz/UniFAR-FTUs huggingface dataset:
The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients

Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37–62). The median duration of VEX treatment after the first year was 14 months (min–max range 0.3–81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7–36.2) and at 4 years was 18.5% (95% CI, 10.1–28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.
Graspability Modulates the Stronger Neural Signature of Motor Preparation for Real Objects vs. Pictures

Abstract The cognitive and neural bases of visual perception are typically studied using pictures rather than real-world stimuli. Unlike pictures, real objects are actionable solids that can be manipulated with the hands. Recent evidence from human brain imaging suggests that neural responses to real objects differ from responses to pictures; however, little is known about the neural mechanisms that drive these differences. Here, we tested whether brain responses to real objects versus pictures are differentially modulated by the “in-the-moment” graspability of the stimulus. In human dorsal cortex, electroencephalographic responses show a “real object advantage” in the strength and duration of mu (μ) and low beta (β) rhythm desynchronization—well-known neural signatures of visuomotor action planning. We compared desynchronization for real tools versus closely matched pictures of the same objects, when the stimuli were positioned unoccluded versus behind a large transparent barrier that prevented immediate access to the stimuli. We found that, without the barrier in place, real objects elicited stronger μ and β desynchronization compared to pictures, both during stimulus presentation and after stimulus offset, replicating previous findings. Critically, however, with the barrier in place, this real object advantage was attenuated during the period of stimulus presentation, whereas the amplification in later periods remained. These results suggest that the “real object advantage” is driven initially by immediate actionability, whereas later differences perhaps reflect other, more inherent properties of real objects. The findings showcase how the use of richer multidimensional stimuli can provide a more complete and ecologically valid understanding of object vision.
Mortality and Exacerbation Risk by Body Mass Index in Patients with COPD in TIOSPIR and UPLIFT

Rationale There is an association between body mass index (BMI) and mortality in chronic obstructive pulmonary disease (COPD), with underweight individuals having higher mortality risk. Mortality and exacerbation risks among individuals with higher BMI are unclear. Objectives To examine the relationship between BMI and adverse outcomes in COPD. Methods This post hoc analysis included data from TIOSPIR (Tiotropium Safety and Performance in Respimat) (N = 17,116) and tiotropium-treated patients in UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) (N = 2,986). BMI classes (underweight [BMI < 20 kg/m2], normal weight [BMI 20 to <25 kg/m2], overweight [BMI 25 to <30 kg/m2], obesity class I [BMI 30 to <35 kg/m2], obesity class II [BMI 35 to <40 kg/m2], and obesity class III [BMI ⩾ 40 kg/m2]) were examined for adjusted associations with mortality, exacerbation, and nonfatal cardiovascular event risk using over 50,000 patient-years of cumulative follow-up data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. Results In TIOSPIR, obesity prevalence was 22%, overweight 32%, and underweight 12%. The proportion of females was highest in obesity classes II and III. Overweight and obese participants had better baseline lung function versus other BMI classes; underweight participants were more likely to be current smokers. Underweight participants had a significantly higher risk of death (HR, 1.88; 95% CI, 1.62–2.20; P < 0.0001) and severe exacerbations (HR, 1.31; 95% CI, 1.16–1.47; P < 0.0001) versus normal-weight participants; however, overweight and obese participants were at lower to no additional risk. Results from UPLIFT were similar to TIOSPIR. Conclusions These results suggest that there is a strong association between body weight, COPD events, and risk of death. A holistic management approach taking into account respiratory and cardiovascular risk factors and nutritional status is needed to improve the general well-being of patients with COPD.
Comptabilization of PMMA/PS blends by nanoparticles and block copolymers : effect on morphology and interfacial relaxation phenomena

In this thesis, the compatibilization mechanism induced by clay nanoparticles in polymer blends was investigated using rheology. To do so, montmorillonite, laponite and halloysite, modified or not, were added to PMMA/PS blends. Linear shear rheology showed that the compatibilization mechanism, especially the coalescence phenomenon, was greatly influenced by the localization of clay nanoparticles. Modified montmorillonite, which was located at the interface, was shown to be the most efficient at inhibiting coalescence among clays and as efficient as a block copolymer with a high molecular mass. The latter is particularly interesting as nanoparticles are cheaper than block copolymers. In this work, special attention was given to relaxations happening in blends. Using linear shear rheology, Marangoni stresses due to a gradient in compatibilizer concentration at the interface was evidenced for the first time in the case of organically modified clay nanoparticles when located at the interface. Finally, submitting blends to elongational flow and subsequent relaxation showed that the relaxation of the droplets after high deformations was faster in the case of clays dispersed in the matrix and slowed down by the interfacial tension in the case of a better dispersion of clays at the interface or in the whole blend.
Association of Multifocality With Prognosis of Papillary Thyroid Carcinoma: A Systematic Review and Meta-analysis.

Importance Multifocality is common in papillary thyroid carcinoma (PTC), but it is unclear whether multifocal tumors are associated with tumor recurrence or cancer-specific survival. Objective To compare tumor recurrence rates in patients with multifocal vs unifocal PTCs. Data Sources We searched PubMed, SCOPUS, Web of Science Core Collection, and Cochrane Database of Systematic Reviews for pertinent studies published in English from inception to June 30, 2020. Study Selection The search strategy yielded 26 studies that compared tumor recurrence in patients with multifocal vs unifocal PTC. Data Extraction and Synthesis Data was extracted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Characteristics of study populations and hazard ratio (HR) of multifocality were independently extracted by 2 investigators. Main Outcomes and Measures The primary outcome was tumor recurrence and the secondary outcome was cancer-specific survival. Subgroup analysis of the primary outcome was based on primary tumor size, number of tumor foci, and patient age. Results Among 26 studies with a total of 33 976 patients, recurrence rates were significantly higher in patients with multifocal PTC than in those with unifocal PTC (pooled HR, 1.81; 95% CI, 1.52-2.14). Cancer-specific survival was comparable between the groups (HR, 1.19; 95% CI, 0.85-1.68). In subgroup analyses, the HRs of multifocality for recurrence were associated with primary tumor size (HRs for PTC ≤1 cm and >1 cm were 1.81 and 1.90, respectively), number of tumor foci (HRs for 2 foci and ≥3 foci were 1.45 and 1.95, respectively), and patient age (HRs for pediatric and adult patients were 3.19 and 1.89, respectively). Conclusions and Relevance This systematic review with meta-analysis found that multifocality was significantly associated with an increased risk of recurrence in patients with PTC, while cancer-specific survival showed no difference. Differences in tumor size, number of tumor foci, and patient age should be considered when interpreting the multifocality and the risk of recurrence.
Genome Typing and Epidemiology of Human Listeriosis in New Zealand, 1999 to 2018

This study describes the epidemiology of listeriosis in New Zealand between 1999 and 2018 as well as the retrospective whole-genome sequencing (WGS) of 453 Listeria monocytogenes isolates corresponding to 95% of the human cases within this period. The average notified rate of listeriosis was 0.5 cases per 100,000 population, and non-pregnancy-associated cases were more prevalent than pregnancy-associated cases (averages of 19 and 5 cases per annum, respectively). ABSTRACT This study describes the epidemiology of listeriosis in New Zealand between 1999 and 2018 as well as the retrospective whole-genome sequencing (WGS) of 453 Listeria monocytogenes isolates corresponding to 95% of the human cases within this period. The average notified rate of listeriosis was 0.5 cases per 100,000 population, and non-pregnancy-associated cases were more prevalent than pregnancy-associated cases (averages of 19 and 5 cases per annum, respectively). WGS data was assessed using multilocus sequencing typing (MLST), including core-genome and whole-genome MLST (cgMLST and wgMLST, respectively) and single-nucleotide polymorphism (SNP) analysis. Thirty-nine sequence types (STs) were identified, with the most common being ST1 (21.9%), ST4 (13.2%), ST2 (11.3%), ST120 (6.1%), and ST155 (6.4%). A total of 291 different cgMLST types were identified, with the majority (n = 243) of types observed as a single isolate, consistent with the observation that listeriosis is predominately sporadic. Among the 49 cgMLST types containing two or more isolates, 18 cgMLST types were found with 2 to 4 isolates each (50 isolates in total, including three outbreak-associated isolates) that shared low genetic diversity (0 to 2 whole-genome alleles), some of which were dispersed in time or geographical regions. SNP analysis also produced results comparable to those from wgMLST. The low genetic diversity within these clusters suggests a potential common source, but incomplete epidemiological data impaired retrospective epidemiological investigations. Prospective use of WGS analysis together with thorough exposure information from cases could potentially identify future outbreaks more rapidly, including those that may have been undetected for some time over different geographical regions.
Effect of Flexibility, Lipophilicity, and the Location of Polar Residues on the Passive Membrane Permeability of a Series of Cyclic Decapeptides.

Cyclic peptides have received increasing attention over the recent years as potential therapeutics for "undruggable" targets. One major obstacle is, however, their often relatively poor bioavailability. Here, we investigate the structure-permeability relationship of 24 cyclic decapeptides that share the same backbone N-methylation pattern but differ in their side chains. The peptides cover a large range of values for passive membrane permeability as well as lipophilicity and solubility. To rationalize the observed differences in permeability, we extracted for each peptide the population of the membrane-permeable conformation in water from extensive explicit-solvent molecular dynamics simulations and used this as a metric for conformational rigidity or "prefolding. " The insights from the simulations together with lipophilicity measurements highlight the intricate interplay between polarity/lipophilicity and flexibility/rigidity and the possible compensating effects on permeability. The findings allow us to better understand the structure-permeability relationship of cyclic peptides and extract general guiding principles.
The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation

Visual Abstract Background and objectives Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin. Design, setting, participants, & measurements Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. Results Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%. Conclusions Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.
Differential Patterns of Delayed Emotion Circuit Maturation in Abused Girls With and Without Internalizing Psychopathology.

OBJECTIVE Childhood abuse represents one of the most potent risk factors for developing psychopathology, especially in females. Evidence suggests that exposure to early-life adversity may be related to advanced maturation of emotion processing neural circuits. However, it remains unknown whether abuse is related to early circuit maturation and whether maturation patterns depend on the presence of psychopathology. METHODS A multisite sample of 234 girls (ages 8-18 years) completed clinical assessment, maltreatment histories, and high-resolution T1-weighted structural MRI. Girls were stratified by abuse history and internalizing disorder diagnosis into typically developing (no abuse/no diagnosis), resilient (abuse/no diagnosis), and susceptible (abuse/current diagnosis) groups. Machine learning models of normative brain development were aggregated in a stacked generalization framework trained to predict chronological age using gray matter volume in whole-brain, emotion, and language circuit parcellations. Brain age gap estimations (BrainAGEs; predicted age minus true chronological age) were calculated as indices of relative circuit maturation. RESULTS Childhood abuse was related to reduced BrainAGE (delayed maturation) specific to emotion circuits. Delayed emotion circuit BrainAGE was further related to increased hyperarousal symptoms. Childhood physical neglect was associated with increased whole-brain BrainAGE (advanced maturation). Neural contributors to emotion circuit BrainAGE differed in girls with and without an internalizing diagnosis, especially in the lateral prefrontal, parietal, and insular cortices and the hippocampus. CONCLUSIONS Abuse exposure in girls is associated with a delayed structural maturation pattern specific to emotion circuitry, a potentially adaptive mechanism enhancing threat generalization. Physical neglect, on the other hand, is associated with a broader brain-wide pattern of advanced structural maturation. The differential influence of fronto-parietal cortices and the hippocampus on emotion circuit maturity in resilient girls may represent neurodevelopmental markers of reduced psychiatric risk following abuse.
Proteorhodopsin Phototrophy in Antarctic Coastal Waters

Proteorhodopsin-bearing microorganisms in the Southern Ocean have been overlooked since their discovery in 2000. The present study identify taxonomy and quantify the relative abundance of proteorhodopsin-bearing bacteria and proteorhodopsin gene transcription in the West Antarctic Peninsula’s coastal waters. ABSTRACT Microbial proton-pumping rhodopsins are considered the simplest strategy among phototrophs to conserve energy from light. Proteorhodopsins are the most studied rhodopsins thus far because of their ubiquitous presence in the ocean, except in Antarctica, where they remain understudied. We analyzed proteorhodopsin abundance and transcriptional activity in the Western Antarctic coastal seawaters. Combining quantitative PCR (qPCR) and metagenomics, the relative abundance of proteorhodopsin-bearing bacteria accounted on average for 17, 3.5, and 29.7% of the bacterial community in Chile Bay (South Shetland Islands) during 2014, 2016, and 2017 summer-autumn, respectively. The abundance of proteorhodopsin-bearing bacteria changed in relation to environmental conditions such as chlorophyll a and temperature. Alphaproteobacteria, Gammaproteobacteria, and Flavobacteriia were the main bacteria that transcribed the proteorhodopsin gene during day and night. Although green light-absorbing proteorhodopsin genes were more abundant than blue-absorbing ones, the latter were transcribed more intensely, resulting in >50% of the proteorhodopsin transcripts during the day and night. Flavobacteriia were the most abundant proteorhodopsin-bearing bacteria in the metagenomes; however, Alphaproteobacteria and Gammaproteobacteria were more represented in the metatranscriptomes, with qPCR quantification suggesting the dominance of the active SAR11 clade. Our results show that proteorhodopsin-bearing bacteria are prevalent in Antarctic coastal waters in late austral summer and early autumn, and their ecological relevance needs to be elucidated to better understand how sunlight energy is used in this marine ecosystem. IMPORTANCE Proteorhodopsin-bearing microorganisms in the Southern Ocean have been overlooked since their discovery in 2000. The present study identify taxonomy and quantify the relative abundance of proteorhodopsin-bearing bacteria and proteorhodopsin gene transcription in the West Antarctic Peninsula’s coastal waters. This information is crucial to understand better how sunlight enters this marine environment through alternative ways unrelated to chlorophyll-based strategies. The relative abundance of proteorhodopsin-bearing bacteria seems to be related to environmental parameters (e.g., chlorophyll a, temperature) that change yearly at the coastal water of the West Antarctic Peninsula during the austral late summers and early autumns. Proteorhodopsin-bearing bacteria from Antarctic coastal waters are potentially able to exploit both the green and blue spectrum of sunlight and are a prevalent group during the summer in this polar environment.
Simultaneous removal of lead and cadmium ions from simulant and industrial waste water: using Calophyllum Inophyllum plant materials as sorbents

Abstract Simple effective sorbents derived from stem powders of Calophyllum inophyllum (CISP) and its active carbon (CISAC) are investigated to remove simultaneously lead and cadmium ions from wastewater with respect to various extraction conditions. Sorbents are characterized by conventional and surface morphological techniques. Maximum removal of Lead and Cadmium with CISP are: 85.8 and 82.8%; with CISAC are: 95.0 and 92.0%, respectively. The optimum conditions of extraction are: pH: 6.5, 7.0; dosage: 2.25, 2.0 g/L; agitation time: 75, 120 min for CISP and for CISAC respectively. The sorption capacities for Pb2+ and Cd2+, respectively are: 14.9 and 17.0 mg/g with CISP; 16.2, 18.5 mg/g with CISAC. The sorption nature is analyzed thermodynamically and by adopting kinetic and isothermal models. High ΔH values of: 32.789& 45.869 kJ/mole for Pb2+ &Cd2+ for sorption on CISP; 26.682 and 33.15 kJ/mole for Pb2+ and Cd2+ for sorption on CISAC, indicate a sort of ‘complex formation and/or ion-exchange’ mechanism between the metal ions and functional groups of sorbents. Positive ΔS and negative ΔG values show disorder in the vicinity of solid–liquid interface and spontaneity of sorption process, respectively. Spent bio-adsorbents can be regenerated-cum-reused. The real effluent samples from industries are successfully treated with these simple bio-sorbents developed. Novelty statement The merit of this investigation is that simple and effective bio-sorbents based on Calophyllum inophyllum plant materials with high sorption capacities, are developed for the simultaneous removal of the toxic Pb2+ and Cd2+ at neutral or nearly neutral pHs. These sorbents are successful in water remediation of Pb2+ and Cd2+ ions from real effluents from industries. These findings have great significance as the identified bio-sorbents are simple, effective and renewable in extracting highly toxic lead and cadmium ions from the effluents from industries or polluted water.