Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluctuations in frailty among older adults.

BACKGROUND frailty fluctuations, that is, within-person up and down deviations from individual long-term frailty index trajectories represent a hitherto both conceptually and empirically untapped facet of frailty among older adults. OBJECTIVE to assess the size of frailty fluctuations in old age and their association with frailty levels, frailty growth as well as sex and socio-economic position. METHODS a total of 18,704 biannual observations from 4,514 community-dwelling older adults (65+) in 10 European countries over 12 years from the Survey of Health, Ageing and Retirement in Europe (SHARE) were analysed. A frailty index was constructed based on 50 items. Long-term frailty trajectories and fluctuations were modelled simultaneously using Bayesian mixed-effects location-scale regression models. RESULTS frailty index fluctuations were non-negligible among older adults, amounting to 0.04/0.05 FI or 2.0/2.5 health deficits on average. 30% of fluctuations were between 0.04 and 0.1 FI (2 and 5 health deficits) and 8% were larger than 0.1 FI (5 health deficits). Fluctuations increased with age and frailty levels, and were higher among women, those with low socio-economic position (education) and individuals who died during follow-up. CONCLUSIONS frailty index fluctuations refer to instabilities in an older person's health status and represent a hitherto untapped but relevant aspect of vulnerability in old age. Future analysis of frailty fluctuations should be based on a larger number of repeated observations with shorter time intervals.
Managing Skew in Hadoop

Challenges in Big Data analytics stem not only from volume, but also variety: extreme diversity in both data types (e.g., text, images, and graphs) and in operations beyond relational algebra (e.g., machine learning, natural language processing, image processing, and graph analysis). As a result, any competitive Big Data system must support some form of parallel user-defined operations (UDOs) that can capture complex data processing tasks over complex data types without changing the core of the parallel data processing engine. Hadoop and other popular systems have been shown to provide a convenient programming model for implementing parallel UDOs, but the “black-box” nature of UDOs complicates the automatic load balancing required to achieve parallel scalability. In this paper, we present an overview of some of our recent work that tackles the problem of load imbalance (a.k.a. skew) in parallel UDO evaluation. We first discuss the prevalence of skew in today’s applications and clusters. We then discuss our experience with static and dynamic methods for mitigating it.
PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer

Significance PD-1 blockade is a cancer immunotherapy effective in various types of cancer. However, we observed rapid cancer progression, called hyperprogressive disease (HPD), in ∼10% of advanced gastric cancer patients treated with anti–PD-1 monoclonal antibody. Tumors of HPD patients possessed highly proliferating FoxP3+ Treg cells after treatment, contrasting with their reduction in non-HPD tumors. In vitro PD-1 blockade augmented proliferation and suppressive activity of human Treg cells. Likewise, murine Treg cells that were deficient in PD-1 signaling were more proliferative and immunosuppressive. Thus, HPD may occur when PD-1 blockade activates and expands tumor-infiltrating PD-1+ Treg cells to overwhelm tumor-reactive PD-1+ effector T cells. Depletion of the former may therefore help treat and prevent HPD. PD-1 blockade is a cancer immunotherapy effective in various types of cancer. In a fraction of treated patients, however, it causes rapid cancer progression called hyperprogressive disease (HPD). With our observation of HPD in ∼10% of anti–PD-1 monoclonal antibody (mAb)-treated advanced gastric cancer (GC) patients, we explored how anti–PD-1 mAb caused HPD in these patients and how HPD could be treated and prevented. In the majority of GC patients, tumor-infiltrating FoxP3highCD45RA−CD4+ T cells [effector Treg (eTreg) cells], which were abundant and highly suppressive in tumors, expressed PD-1 at equivalent levels as tumor-infiltrating CD4+ or CD8+ effector/memory T cells and at much higher levels than circulating eTreg cells. Comparison of GC tissue samples before and after anti–PD-1 mAb therapy revealed that the treatment markedly increased tumor-infiltrating proliferative (Ki67+) eTreg cells in HPD patients, contrasting with their reduction in non-HPD patients. Functionally, circulating and tumor-infiltrating PD-1+ eTreg cells were highly activated, showing higher expression of CTLA-4 than PD-1− eTreg cells. PD-1 blockade significantly enhanced in vitro Treg cell suppressive activity. Similarly, in mice, genetic ablation or antibody-mediated blockade of PD-1 in Treg cells increased their proliferation and suppression of antitumor immune responses. Taken together, PD-1 blockade may facilitate the proliferation of highly suppressive PD-1+ eTreg cells in HPDs, resulting in inhibition of antitumor immunity. The presence of actively proliferating PD-1+ eTreg cells in tumors is therefore a reliable marker for HPD. Depletion of eTreg cells in tumor tissues would be effective in treating and preventing HPD in PD-1 blockade cancer immunotherapy.
Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations

The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60 is proved to effectively inhibit Aβ fibrillation while the poor water-solubility restricts its use as a biomedicine agent. In this work, we examined the interaction of fullerene C60 and water-soluble fullerenol C60(OH)6/C60(OH)12 (C60 carrying 6/12 hydroxyl groups) with preformed Aβ40/42 protofibrils by multiple molecular dynamics simulations. We found that when binding to the Aβ42 protofibril, C60, C60(OH)6 and C60(OH)12 exhibit distinct binding dynamics, binding sites and peptide interaction. The increased number of hydroxyl groups C60 carries leads to slower binding dynamics and weaker binding strength. Binding free energy analysis demonstrates that the C60/C60(OH)6 molecule primarily binds to the C-terminal residues 31–41, whereas C60(OH)12 favors to bind to N-terminal residues 4–14. The hydrophobic interaction plays a critical role in the interplay between Aβ and all the three nanoparticles, and the π-stacking interaction gets weakened as C60 carries more hydroxyls. In addition, the C60(OH)6 molecule has high affinity to form hydrogen bonds with protein backbones. The binding behaviors of C60/C60(OH)6/C60(OH)12 to the Aβ40 protofibril resemble with those to Aβ42. Our work provides a detailed picture of fullerene/fullerenols binding to Aβ protofibril, and is helpful to understand the underlying inhibitory mechanism.
Endoscopic staging of low-grade gastric MALT lymphoma.

INTRODUCTION Endoscopic ultrasonography (EUS) has already proven useful in the assessment of submucosal lesions, and the staging of gastrointestinal cancer, particularly gastric MALT-type lymphoma. The goal of this paper was EUS staging. PATIENTS AND METHOD 24 patients (10 females, 14 males) with a median age of 56 years and possibly gastric MALT lymphoma (25 cases) were studied using videoendoscopy, biopsies, and echoendoscopy with 7.5- and 20-MHz radial EUS, and also with 12- and 20-MHz miniprobes (MPs). Nineteen patients were definitely evaluated (7 females, 12 males) as having 20 MALT-type lymphomas, as five patients were post-hoc disregarded when an invasive, high-grade gastric lymphoma (3c) or plasmocytoma (2c) was subsequently demonstrated. Of these 19 patients, all had T1 lesions except for two with T2 lesions; one patient had a gastroduodenal T1 lymphoma. Echographic findings with MPs were compared to EUS (gold standard) and histology both before and after eradication. Then, patients were followed up every 1-3-6 months using videoendoscopy and MPs. RESULTS Echoendoscopy correctly identified T stages in 90% of cases. MPs identified T stages in 88% of cases, and N stages in 33% of cases, with results being slightly inferior to those obtained with conventional EUS (91 vs. 45%); they were consequently used for follow-up. After eradication, all but two patients are in complete remission and have been followed every 1-3-6 months using MPs without echographic abnormalities, except for a patient who relapsed.
Biliary Excretion of Ximelagatran and Its Metabolites and the Influence of Erythromycin Following Intraintestinal Administration to Healthy Volunteers

The biliary excretion of the oral thrombin inhibitor ximelagatran and its metabolites was investigated by using duodenal aspiration in healthy volunteers following intraintestinal dosing. In the first investigation, radiolabeled [14C]ximelagatran was administered, enabling quantification of the biliary excretion and identification of metabolites in the bile. In the second study, the effect of erythromycin on the biliary clearance of ximelagatran and its metabolites was investigated to clarify the reported ximelagatran‐erythromycin interaction. Approximately 4% of the intraintestinal dose was excreted into bile with ximelagatran and its active form, melagatran, being the most abundant compounds. Four novel ximelagatran metabolites were identified in bile (<0.1% of dose). Erythromycin changed the pharmacokinetics of ximelagatran and its metabolites, with an elevated ximelagatran (78% increase), OH‐melagatran (89% increase), and melagatran (86% increase) plasma exposure and higher peak plasma concentrations of the compounds being measured. In parallel, the biliary clearance was moderately reduced. The results suggest that inhibition of hepatobiliary transport is a likely mechanism for the interaction between erythromycin and ximelagatran. Furthermore, the study demonstrated the value of direct bile sampling in humans for the identification of primary biliary metabolites.
Laparoscopic resections of colorectal cancer and synchronous liver metastases: a case controlled study

Abstract Purpose: To investigate the efficacy and safety of laparoscopic simultaneous resections of colorectal cancer and synchronous colorectal liver metastases (SCRLM), relative to open surgery. Methods: Between 1 January 2009 and 20 April 2014, 20 of 25 patients who underwent laparoscopic simultaneous colorectal cancer and SCRLM resections were matched with 20 of 29 patients who underwent an open approach, based on prognostic propensity scores. Perioperative results and survival outcomes were compared. Results: The laparoscopic and open groups were comparable in demographics, cancer characteristics, surgery characteristics, and chemotherapy treatment. No postoperative mortality occurred in either group. The estimated blood loss and postoperative stay were significantly greater in the open group than in the laparoscopic group (all, p < .05). All other perioperative results and postoperative complications were similar between the two groups, as well as three-year overall and disease-free survival rates. Conclusions: The postoperative complications and survival rates of patients given laparoscopic simultaneous colorectal cancer and SCRLM resections were similar to those treated with an open approach, but with greater short-term benefits. Laparoscopy in this setting by an experienced surgical team appears safe and effective, and is a feasible alternative to an open approach for selected patients.
TRIAS--An Algorithm for Mining Iceberg Tri-Lattices

In this paper, we present the foundations for mining frequent tri-concepts, which extend the notion of closed item-sets to three-dimensional data to allow for mining folk-sonomies. We provide a formal definition of the problem, and present an efficient algorithm for its solution as well as experimental results on a large real-world example.
Gene Transfer Targeting Mouse Vestibule Using Adenovirus and Adeno-Associated Virus Vectors

Hypothesis The present study assessed how to inject a gene into the mouse vestibule and which is the optimum gene to the mouse vestibule adenovirus (AdV) vector or adeno-associated virus (AAV) vector. Background Loss of vestibular hair cell is seen in various balance disorder diseases. There have been some reports concerning gene delivery to the mouse vestibule in recent years. To effectively induce transgene expression at the vestibule, we assessed the efficiency of inoculating the mouse inner ear using various methods. Methods We employed an AdV- and AAV-carrying green fluorescent protein using a semicircular canal approach (via a canalostomy) and round window approach. Results AAV injection via canalostomy induced gene expression at the hair cells, supporting cells, and fibrocytes at the vestibular organs without auditory or balance dysfunction, suggesting it was the most suitable transfection method. This method is thus considered to be a promising strategy to prevent balance dysfunction. Conclusion AAV injection via canalostomy to the vestibule is the noninvasive and highly efficient transfection method, and this study may have the potential to repair balance disorders in human in the future.
Transposable elements are important contributors to standing variation in gene expression in Capsella grandiflora

Transposable elements (TEs) make up a significant portion of eukaryotic genomes, and thus are important drivers of genome evolution. However, the evolutionary forces controlling TE copy number and the extent to which TEs affect phenotypic variation on a genome-wide scale are still unclear. We characterised TE insertion polymorphism and its effects on gene expression in 124 whole genome sequences from a single population of Capsella grandiflora. The frequency of insertions was negatively correlated with distance to genes, as well as density of conserved non-coding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare single nucleotide polymorphisms (SNPs) contribute equally to up- and down-regulation, but have a weaker effect. Taken together, these results imply that TEs are a significant contributor to gene expression variation and can be more likely than rare SNPs to cause extreme changes in gene expression. Author Summary Transposable elements (TEs), mobile DNA elements with the ability to excise from the genome and reinsert in new locations, are important components of genomic diversity. Due to their abundance and mobility, TEs play an influential role in genomic evolution, often deleterious. Here we show that TEs in a population of the plant Capsella grandiflora are most deleterious when they insert in genic and regulatory regions. We find that TEs indeed are associated with unusual levels of gene expression, predominantly decreased expression. Furthermore, this effect is stronger than the association of single nucleotide polymorphisms with gene expression variation, highlighting the importance of TE contribution to the maintenance of expression variation.
Optimal Cross-Layer Scheduling of Transmissions Over a Fading Multiaccess Channel

We consider the problem of several users transmitting packets to a base station, and study an optimal scheduling formulation involving three communication layers, namely, the medium access control, link, and physical layers. We assume Markov models for the packet arrival processes and the channel gain processes. Perfect channel state information is assumed to be available at the transmitter and the receiver. The transmissions are subject to a long-run average transmitter power constraint. The control problem is to assign power and rate dynamically as a function of the fading and the queue lengths so as to minimize a weighted sum of long run average packet transmission delays.
Prostate Artery Embolization for Lower Urinary Tract Symptoms in Men Unfit for Surgery

Nearly one in three men develop lower urinary tract symptoms (LUTS) and 10% clinically progress despite medication. Transurethral resection of the prostate (TURP) is the reference standard for symptoms refractory to medical treatment. However, some patients cannot tolerate TURP for medical (e.g., comorbidity) or technical (e.g., large prostate) reasons. This study estimated the safety and effect of prostate artery embolization (PAE) in men unfit for surgery. A prospective, single-centre trial including men with LUTS or urinary retention secondary to benign prostatic hyperplasia (BPH) who were unfit for surgery. The primary objective was to treat urinary retention and LUTS. Outcome measures included International Prostate Symptom Score (IPSS), quality of life (IPSS-QoL), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate-specific antigen (PSA), peak void flow (Qmax), post-void residual (PVR), and complications. A p-value < 0.05 was considered statistically significant. Eleven consecutive patients with a mean age of 75.2 (SD ± 8.2) underwent PAE. Catheter removal was successful in 60%. IPSS-QoL improved 4.5 points (95% CI: −5.6; −3.4), and PV was reduced by 26.2 cm3 (95% CI: −50.9; −2.3). None of the remaining outcomes changed. No major complications occurred. PAE was effective and safe for LUTS and urinary retention associated with BPH in men unfit for surgery.
Reasons to leave: the motives of first-line nurse managers' for leaving their posts.

OBJECTIVE To study the reasons for first-line nurse managers to resign, their perceptions of difficult situations, experience of support and satisfaction with work. BACKGROUND The intentions of first-line nurse managers' to stay at their posts varied between 45% and 75% in different studies. METHODS Data were collected by questionnaire and letters from 32 first-line nurse managers who had left their posts. Qualitative content analysis was used to analyse the letters. RESULTS Eleven first-line nurse managers resigned due to reorganization or other changes and 19 due to their own accord. Reasons to leave were personal, organizational, as well as lack of support from and relations to the head of department. Difficult situations were unclear conditions, lack of support from supervisors and, implementation of changes, staff matters and economy. Important support was personal, organizational, practical and to have opportunities for development and education. The perception of work satisfaction was higher after resignation. CONCLUSIONS The dominant reason to leave was reorganization and other changes. The relation to the head of department influenced the first-line nurse managers' overall work situation.
Impact of Density, Load, and Mobility on the Performance of Routing Protocols in Vehicular Networks

Designing routing protocols in vehicular network is a challenging task due to the high mobility of nodes, the instability of wireless links, and the diversity of deployment scenarios. Several routing protocols have been designed with the goal of solving one or more specific problems of each scenario. In this paper, we present a performance evaluation of routing protocols in vehicular networks addressing the impact of density, load, and mobility pattern. Four protocols are evaluated in urban and highway scenarios. The results presented in this paper provide guidelines for network designers in planning efficient routing protocols for vehicular network, able to adapt to different scenarios.
Life history predicts risk of species decline in a stochastic world

Understanding what traits determine the extinction risk of species has been a long-standing challenge. Natural populations increasingly experience reductions in habitat and population size concurrent with increasing novel environmental variation owing to anthropogenic disturbance and climate change. Recent studies show that a species risk of decline towards extinction is often non-random across species with different life histories. We propose that species with life histories in which all stage-specific vital rates are more evenly important to population growth rate may be less likely to decline towards extinction under these pressures. To test our prediction, we modelled declines in population growth rates under simulated stochastic disturbance to the vital rates of 105 species taken from the literature. Populations with more equally important vital rates, determined using elasticity analysis, declined more slowly across a gradient of increasing simulated environmental variation. Furthermore, higher evenness of elasticity was significantly correlated with a reduced chance of listing as Threatened on the International Union for Conservation of Nature Red List. The relative importance of life-history traits of diverse species can help us infer how natural assemblages will be affected by novel anthropogenic and climatic disturbances.
A General Strategy for the Stereoselective Synthesis of the Furanosesquiterpenes Structurally Related to Pallescensins 1–2

Here, we describe a general stereoselective synthesis of the marine furanosesquiterpenes structurally related to pallescensins 1–2. The stereoisomeric forms of the pallescensin 1, pallescensin 2, and dihydropallescensin 2 were obtained in high chemical and isomeric purity, whereas isomicrocionin-3 was synthesized for the first time. The sesquiterpene framework was built up by means of the coupling of the C10 cyclogeranyl moiety with the C5 3-(methylene)furan moiety. The key steps of our synthetic procedure are the stereoselective synthesis of four cyclogeraniol isomers, their conversion into the corresponding cyclogeranylsulfonylbenzene derivatives, their alkylation with 3-(chloromethyl)furan, and the final reductive cleavage of the phenylsulfonyl functional group to afford the whole sesquiterpene framework. The enantioselective synthesis of the α-, 3,4-dehydro-γ- and γ-cyclogeraniol isomers was performed using both a lipase-mediated resolution procedure and different regioselective chemical transformations.
Wavelet-Based Texture Retrieval Using a Mixture of Generalized Gaussian Distributions

In this paper, we address the texture retrieval problem using wavelet distribution. We propose a new statistical scheme to represent the marginal distribution of the wavelet coefficients using a mixture of generalized Gaussian distributions (MoGG). The MoGG allows to capture a wide range of histogram shapes, which provides a better description of texture and enhances texture discrimination. We propose a similarity measurement based on Kullback-Leibler distance (KLD), which is calculated using MCMC Metropolis-Hastings sampling algorithm. We show that our approach yields better texture retrieval results than previous methods using only a single probability density function (pdf) for wavelet representation, or texture energy distribution.