Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Patient Safety And Ease Of Use Of A Novel Connection-Assist Device For Peritoneal Dialysis

Introduction It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study. Methods Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects’ subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews. Results Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback. Discussion Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment.
Weekly alternate intensive regimen FirB/FOx in metastatic colorectal cancer patients: an update from clinical practice

Background: Several trials evaluated the role of intensive regimens, made of triplet chemotherapies plus bevacizumab, as first-line treatment for patients with metastatic colorectal cancer (mCRC). We previously reported, in a Phase II prospective study, the efficacy and the tolerability of FIrB/ FOx regimen, reporting interesting results in terms of received dose intensities (rDIs) and safety. Methods: We reported a retrospective update of 85 patients treated with FIrB/FOx, an intensive regimen of 5-fluorouracil, bevacizumab, and weekly alternate irinotecan and oxaliplatin, to confirm its feasibility in “real life”. Subgroup analyses were performed, particularly among patients treated with standard and modified FIrB/FOx (based on age, performance status, and/or comorbidities). Results: Overall, 3-month objective response rate (ORR) and 6-month ORR were 75.9% and 55.3%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 14.4 and 34.9 months, respectively. Among the patients treated with standard and modified regimens, 3-month ORR, PFS, and OS were 75.8% and 76% ( P = 1.0000), 14.4 and 14.4 months ( P =0. 8589), and 37.8 and 26.6 months ( P = 0.7746), respectively. Among the K/NRAS wild-type and K/NRAS mutant patients, 3-month ORR, PFS, and OS were 95.2% and 74.5% ( P = 0.0526), 15.3 and 14.4 months ( P = 0.8753), and 37.8 and 51.4 months ( P = 0.8527), respectively. The rDIs were $ 80% of full doses both in the standard and in the modified regimens subgroups. Cumulative G3/4 toxicities were neutropenia (14.1%), diarrhea (17.6%), asthenia (9.4%), vomiting (5.6%), and hypertension (16.5%). Conclusion: This update shows that intensive regimens such as FIrB/FOx are also feasible options for first-line treatment of mCRC patients in the “real-life” setting.
A new feather mite species of the genus Proctophyllodes Robin , 1877 ( Astigmata : Proctophyllodidae ) from the Long-tailed Tit Aegithalos caudatus ( Passeriformes : Aegithalidae ) — morphological description with DNA barcode data

A new feather mites species, Proctophyllodes valchukae sp. n. , is described from the Long-tailed Tit, Aegithalos caudatus (Linnaeus, 1758) (Passeriformes: Aegithalidae), captured in the Primoriye (Russian Far East). The new species belongs to the tricetratus species group and is most closely related to P. stachyris Atyeo et Braasch, 1966. For the first time for feather mites the standard morphological description is supplemented by sequence data of the mitochondrial cytochrome c oxidase subunit I gene fragment (COI) and nuclear D2 region of 28S rDNA.
A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen®) in the Clinical Management of Acute Viral Diarrhea in Children

This randomized, open-label study evaluated the additional benefits of the synbiotic Prodefen® in the clinical management of acute diarrhea of suspected viral origin in children between 6 months and 12 years of age. Study outcomes included the duration of diarrhea, the recovery from diarrhea, and the tolerability and acceptance of the treatment. The proportion of patients without diarrhea over the study period was greater in the synbiotic group than in the control group at all study time points, showing a statistically significant difference on the fifth day (95% vs 79%, p < 0.001). The duration of diarrhea (median and interquartile range) was reduced by 1 day in the synbiotic-treated patients (3 [2-5] vs 4 [3-5], p = 0.377). The tolerability of the treatment regimen, as evaluated by the parents, was significantly better in those receiving the synbiotic than in the control group. Overall, 96% of the parents of children receiving the synbiotic reported being satisfied to very satisfied with the treatment regimen. The results of this study indicate that the addition of the synbiotic Prodefen® is a well-tolerated and well-accepted approach that provides an additional benefit to the standard supportive therapy in the management of acute viral diarrhea in children.
KDM4B-regulated unfolded protein response as a therapeutic vulnerability in PTEN-deficient breast cancer

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Single-Molecule Dynamics and Discrimination between Hydrophilic and Hydrophobic Amino Acids in Peptides, through Controllable, Stepwise Translocation across Nanopores

In this work, we demonstrate the proof-of-concept of real-time discrimination between patches of hydrophilic and hydrophobic monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when serine or isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent “molecular brake” on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.
DNA methylation directs polycomb-dependent 3D genome reorganisation in naïve pluripotency

The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naïve pluripotency by culturing in 2i conditions results in redistribution of polycomb (H3K27me3) away from its target loci. Here we demonstrate that 3D genome organisation is also altered in 2i. We found chromatin decompaction at polycomb target loci as well as loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground-state, we are able to restore the H3K27me3 distribution, and polycomb-mediated 3D genome organisation that is characteristic of primed ESCs grown in serum, to ESCs in 2i. However, these cells retain the functional characteristics of 2i ground state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organisation but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs.
Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

Human brain transcriptomes can highlight biological pathways associated with Alzheimer’s disease (AD); however, challenges remain to link expression changes with causal triggers. We have examined 30 AD-associated, gene coexpression modules from human brains for overlap with 251 differentially-expressed gene sets from mouse brain RNA-sequencing experiments, including from models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus neurofibrillary tangle pathology and further reveal age- and sex-dependent expression signatures for AD progression. Human coexpression modules enriched for neuronal and/or microglial genes overlap broadly with signatures from mouse models of AD, Huntington’s disease, Amyotrophic Lateral Sclerosis, and also aging. Several human AD coexpression modules, including those implicated in the unfolded protein response and oxidative phosphorylation, were not activated in AD models, but instead were detected following other, unexpected mouse genetic manipulations. Our results comprise a powerful, cross-species resource and pinpoint experimental models for diverse features of AD pathophysiology from human brain transcriptomes.
Mitochondrial Membrane Potential in Human Neutrophils Is Maintained by Complex III Activity in the Absence of Supercomplex Organisation

Background Neutrophils depend mainly on glycolysis for their energy provision. Their mitochondria maintain a membrane potential (Δψm), which is usually generated by the respiratory chain complexes. We investigated the source of Δψm in neutrophils, as compared to peripheral blood mononuclear leukocytes and HL-60 cells, and whether neutrophils can still utilise this Δψm for the generation of ATP. Methods and Principal Findings Individual activity of the oxidative phosphorylation complexes was significantly reduced in neutrophils, except for complex II and V, but Δψm was still decreased by inhibition of complex III, confirming the role of the respiratory chain in maintaining Δψm. Complex V did not maintain Δψm by consumption of ATP, as has previously been suggested for eosinophils. We show that complex III in neutrophil mitochondria can receive electrons from glycolysis via the glycerol-3-phosphate shuttle. Furthermore, respiratory supercomplexes, which contribute to efficient coupling of the respiratory chain to ATP synthesis, were lacking in neutrophil mitochondria. When HL-60 cells were differentiated to neutrophil-like cells, they lost mitochondrial supercomplex organisation while gaining increased aerobic glycolysis, just like neutrophils. Conclusions We show that neutrophils can maintain Δψm via the glycerol-3-phosphate shuttle, whereby their mitochondria play an important role in the regulation of aerobic glycolysis, rather than producing energy themselves. This peculiar mitochondrial phenotype is acquired during differentiation from myeloid precursors.
External validation of the PUMA COPD diagnostic questionnaire in a general practice sample and the PLATINO study population

Background A seven-item prescreening questionnaire (gender, age, pack-years smoking, dyspnea, sputum, cough, previous spirometry data) was developed for COPD detection in the primary care setting (PUMA Study) of four Latin America countries. Objectives To validate the PUMA prescreening COPD questionnaire externally in two different populations (primary care and general). Methods The PUMA prescreening COPD questionnaire score was applied to subjects from the Hospital Maciel, Montevideo (primary care), case-ﬁnding program and the PLATINO population (general) using PUMA study inclusion criteria. Post-bronchodilator FEV1/FVC <0.70 and lower limit of normal (LLN) criteria were used to define COPD. Area under the received operator curve (ROCAUC), sensitivity, specificity, predictive positive and negative values (PNV), number needed to treat (NNT), and best cut-points of the score were calculated. Results 974 individuals from Hospital Maciel and 2512 from the PLATINO population were eligible, using post-bronchodilator FEV1/FVC <0.70, 45.1% and 18.7% had COPD, respectively, and using LLN 38.4% and 15.4% had COPD, respectively. From Hospital Maciel (post-bronchodilator FEV1/FVC <0.70), the best cut-point of ≥6 had moderate discriminatory power (ROCAUC 0.70), sensitivity 69.9%, specificity 62.1%, PNV 70.9%, and NNT of 3. The discriminatory power was 0.73 (ROCAUC) in the PLATINO population with three potential cut-points (Youden’s index): ≥3 (sensitivity 85.4%, specificity 46.9%), ≥4 (sensitivity 66.7%, specificity 66.5%), and ≥5 (sensitivity 51.5%, specificity 81.6%); the PNV at each cut-point was 93.3%, 89.9%, and 88.0%, respectively. The NNT was 5 for scores ≥3 and ≥4, and 4 for ≥5. The mean accuracy using the LLN for Hospital Maciel and PLATINO was 0.67 and 0.70, respectively. Conclusion External validation of the PUMA prescreening questionnaire in two Latin American populations (general and primary care) suggests moderate accuracy, similar to the original study in which the questionnaire was developed.
Homozygous hypomorphic HNF1A alleles are a novel cause of young-onset diabetes and result in sulphonylurea sensitive diabetes

Introduction: Heterozygous loss-of-function mutations in HNF1A cause MODY and affected individuals can be treated with low-dose sulphonylureas. Homozygous MODY-causing mutations are unreported. Methods: We phenotyped a kindred with young-onset diabetes, undertaking molecular genetic testing, a mixed meal tolerance test, a sulphonylurea challenge and in vitro assays to assess variant protein function. Results: A homozygous HNF1A variant (p.A251T) was identified in three inuslin-treated family members diagnosed with diabetes <20 years-of-age. Homozygous variant carriers had low hsCRP levels (0.2-0.8 mg/L) and, those tested, demonstrated sulphonylurea sensitivity at low-dose, with complete transition off insulin. In silico modelling predicted a variant of unknown significance, however in vitro studies supported a modest reduction (79% of wildtype p<0.05) in transactivation potential in the absence of endogenous HNF1A . Conclusion: Homozygous hypomorphic HNF1A variants are a cause of HNF1A-MODY. We expand the allelic spectrum of variants causing diabetes in dominant genes.
Isolation and Characterization of Actinomycete Antagonists of a Fungal Root Pathogen

By use of selective media, 267 actinomycete strains were isolated from four rhizosphere-associated and four non-rhizosphere-associated British soils. Organic media with low nutrient concentrations were found to be best for isolating diverse actinomycetes while avoiding contamination and overgrowth of isolation media by eubacteria and fungi. While all isolates grew well at pHs 6.5 to 8.0, a few were unable to grow at pH 6.0 and a significant number failed to grow at pH 5.5. Eighty-two selected isolates were screened for in vitro antagonism towards Pythium ultimum by use of a Difco cornmeal agar assay procedure. Five isolates were very strong antagonists of the fungus, four were strong antagonists, and ten others were weakly antagonistic. The remaining isolates showed no antagonism by this assay. Additional studies showed that several of the P. ultimum antagonists also strongly inhibited growth of other root-pathogenic fungi. Twelve isolates showing antifungal activity in the in vitro assay were also tested for their effects on the germination and short-term growth of lettuce plants in glasshouse pot studies in the absence of pathogens. None of the actinomycetes prevented seed germination, although half of the isolates retarded seed germination and outgrowth of the plants by 1 to 3 days. During 18-day growth experiments, biomass yields of some actinomycete-inoculated plants were reduced in comparison with untreated control plants, although all plants appeared healthy and well rooted. None of the actinomycetes significantly enhanced plant growth over these short-term experiments. For some, but not all, actinomycetes, some correlations between delayed seed germination and reduced 18-day plant biomass yields were seen. For others, plant biomass yields were not reduced despite an actinomycete-associated delay in seed germination and plant outgrowth. Preliminary glasshouse experiments indicated that some of the actinomycetes protect germinating lettuce seeds against damping-off caused by P. ultimum.
Effectiveness of Interventions to Promote Sustainable Employability: A Systematic Review

Background: Despite growing interest in sustainable employability (SE), studies on the effectiveness of interventions aimed at employees’ SE are scarce. In this review, SE is defined by four core components: health, productivity, valuable work, and long-term perspective. The aim of this review is to summarize the effectiveness of employer-initiated SE interventions and to analyze whether their content and outcome measures addressed these SE components. Methods: A systematic search was performed in six databases for the period January 1997 to June 2018. The methodological quality of each included study was assessed. A customized form was used to extract data and categorize interventions according to SE components. Results: The initial search identified 596 articles and 7 studies were included. Methodological quality ranged from moderate to weak. All interventions addressed the components ‘health’ and ‘valuable work’. Positive effects were found for ‘valuable work’ outcomes. Conclusions: The quality of evidence was moderate to weak. The ‘valuable work’ component appeared essential for the effectiveness of SE interventions. Higher-quality evaluation studies are needed, as are interventions that effectively integrate all SE core components in their content.
Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections—A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.
CIA_A_222948 1829..1840

1Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, University of SouthChina,Hengyang,Hunan, People’s Republic of China; 2Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 3School of Biomedical Sciences, TheChinese University of Hong Kong, Sha Tin, Hong Kong, People’s Republic of China; 4Guangdong Provincial People's Hospital affiliated to South China University of Technology, Guangzhou, Guangdong, People's Republic of China; 5School of Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; 6Department of Cardiovascular Surgery, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China
Dual cognitive pathways to voice quality: Frequent voicers improvise, infrequent voicers elaborate

We investigate the involvement of Working Memory Capacity (WMC, the cognitive resource necessary for controlled elaborate thinking) in voice behavior (speaking up with suggestions, problems, and opinions to change the organization). While scholars assume voice requires elaborate thinking, some empirical evidence suggests voice might be more automatic. To explain this discrepancy, we distinguish between voice quantity (frequency of voice) and voice quality (novelty and value of voiced information) and propose that WMC is important for voice quality, but less for voice quantity. Furthermore, we propose that frequent voicers rely less on WMC to reach high voice quality than people who voice rarely. To test our ideas, we conducted three studies: a between-participant lab-study, a within-participant experiment, and a multi-source field-study. All studies supported our expectation that voice quantity is unrelated to WMC, and that voice quality is positively related to WMC, but only for those who rarely voice. This indicates that the decision to voice (quantity) might be more automatic and intuitive than often assumed, whereas its value to the organization (quality), relies more on the degree of cognitive elaboration of the voicer. It also suggests that frequent and infrequent voicers use distinct cognitive pathways to voice high-quality information: frequent voicers improvise, while infrequent voicers elaborate.