Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Fc fusion protein misfolding: A three-phasic cultivation experimental design

Cell culture process optimization is a critical solution to most of the challenges faced by the pharmaceutical manufacturing. One of the major problems encountered in large-scale production of therapeutic proteins is misfolded protein production. The accumulation of misfolded therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity of the final product. The aim of this study was the statistical optimization of three-phasic temperature shift and timing for enhanced production of correctly folded Fc-fusion protein. The effect of culture temperatures were investigated using the biphasic culture system. Box–Behnken design was then used to compute temperature and time of shifting optimum. Response surface methodology revealed that maximum production with low level of misfolded protein was achieved at two-step temperature shift from 37°C to 30°C during the late logarithmic phase and 30°C to 28°C in the mid-stationary phase. The optimized condition gave the best results of 1860 mg L−1 protein titer with 24.5% misfolding level. The validation experiments were carried out under optimal conditions with three replicates and the protein misfolding level was decreased by two times while productivity increased by ~ 1.3-fold. Large-scale production in 250 L bioreactor under the optimum conditions was also verified the effectiveness and the accuracy of the model. The results showed that by utilizing two-step temperature shift, productivity and the quality of target protein have been improved simultaneously. This model could be successfully applied to other products.
Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.
Core Competencies in Evidence-Based Practice for Health Professionals: Consensus Statement Based on a Systematic Review and Delphi Survey.

Importance Evidence-based practice (EBP) is necessary for improving the quality of health care as well as patient outcomes. Evidence-based practice is commonly integrated into the curricula of undergraduate, postgraduate, and continuing professional development health programs. There is, however, inconsistency in the curriculum content of EBP teaching and learning programs. A standardized set of minimum core competencies in EBP that health professionals should meet has the potential to standardize and improve education in EBP. Objective To develop a consensus set of core competencies for health professionals in EBP. Evidence Review For this modified Delphi survey study, a set of EBP core competencies that should be covered in EBP teaching and learning programs was developed in 4 stages: (1) generation of an initial set of relevant EBP competencies derived from a systematic review of EBP education studies for health professionals; (2) a 2-round, web-based Delphi survey of health professionals, selected using purposive sampling, to prioritize and gain consensus on the most essential EBP core competencies; (3) consensus meetings, both face-to-face and via video conference, to finalize the consensus on the most essential core competencies; and (4) feedback and endorsement from EBP experts. Findings From an earlier systematic review of 83 EBP educational intervention studies, 86 unique EBP competencies were identified. In a Delphi survey of 234 participants representing a range of health professionals (physicians, nurses, and allied health professionals) who registered interest (88 [61.1%] women; mean [SD] age, 45.2 [10.2] years), 184 (78.6%) participated in round 1 and 144 (61.5%) in round 2. Consensus was reached on 68 EBP core competencies. The final set of EBP core competencies were grouped into the main EBP domains. For each key competency, a description of the level of detail or delivery was identified. Conclusions and Relevance A consensus-based, contemporary set of EBP core competencies has been identified that may inform curriculum development of entry-level EBP teaching and learning programs for health professionals and benchmark standards for EBP teaching.
Outpatient Parenteral Antibiotic Treatment (OPAT) for Infective Endocarditis: a Prospective Cohort Study From the GAMES Cohort.

Background Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious and safe for treating infective endocarditis (IE). However, the 2001 IDSA criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). Methods Retrospective analysis of data from a multicenter prospective cohort study of 2,000 consecutive IE patients in 25 Spanish hospitals from 2008 to 2012. Results A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (IQR 56-76), 57% had native-valve IE, 27% had prosthetic-valve IE, and 19% had pacemaker/defibrillator IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). The median length of antibiotic treatment was 42 days (IQR 32-54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P<0.001), 1.4% of patients relapsed, and 10.9% were readmitted during the first three months after discharge (no significant differences compared with HBAT). Charlson score (OR 1.21, 95%CI 1.04-1.42; P=0.01) and cardiac surgery (OR 0.24, 95%CI 0.09-0.63; P=0.04) were associated with one-year mortality, whereas aortic valve involvement (OR 0.47, 95%CI 0.22-0.98; P=0.007) was the only predictor of readmission at one year. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. Conclusions OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA; OPAT criteria should therefore be expanded.
Identification of several cell cycle relevant genes highly correlated with the progression and prognosis of human bladder urothelial tumor

The incidence of bladder cancer (BCa) in China is the highest among genitourinary system tumors, and its progression is affected by multitudinous pathways, of which cell cycle progress plays an important role. This study screened and enriched differentially expressed genes (DEGs) from four gene expression profiles using bioinformatics analysis methods. The enrichment and analysis of gene function showed that these genes were highly correlated with cell cycle regulation. Identification of candidate small molecules was conducted to evaluate the application of clinical transformation in these DEGs. Prognostic and stage‐related expression analysis further sorted five highly expressed genes associated with worse prognosis and higher stages in patients with BCa. Further analysis revealed their interaction in cell cycle regulation and genetical alteration. Meanwhile, we validated the elevated expression of these genes through transcription and translation levels. Taking the results together, we could infer that these five genes are valuable in diagnosis, prediction, and providing candidate therapeutic targets for patients with BCa in different stages.
Microbiological assessment of a contaminated library : implications for book preservation and users health

The use of Compactus shelves by libraries and archives is a good solution to optimize the storage space and prevent dust deposits on books. However, they are probably the cause of severe cases of fungal colonization in historical library materials. A typical phenomenon occurs as a spread of white mycelial growth forming scattered spots, mainly on volumes with leather or fabric bindings. Recent studies have identified the xerophilic fungus Eurotium halophilicum (anamorph Aspergillus halophilicus) as responsible for this kind of contamination. A similar situation was found inside the Library of Humanities (BAUM), at Ca' Foscari University, Venice (Italy). Various sampling methods, including cotton swabs and adhesive tape, were adopted to isolate fungi from books and a set of aerobiological analyses was performed to characterize the environment of the repository. The presence of E. halophilicum on both books and in the indoor air was confirmed by direct observation of adhesive tape samples, microscopic observations and molecular methods. Moreover, Aspergillus creber and Aspergillus protuberus belonging to the revised group Aspergillus section Versicolores, were also isolated for the first time in Italian conservation environments. © 2014 Elsevier Ltd. All rights reserved.
Acute Liver Failure due to Wilson Disease: Eight Years of the National Liver Transplant Program in Uruguay.

INTRODUCTION AND AIM Wilson's disease (WD) is an uncommon cause of acute liver failure (ALF). Our aim was to describe clinical features, diagnostic findings, treatments, and outcomes of patients with ALF due to WD. MATERIAL AND METHODS Retrospective medical record reviews of all patients with ALF due to WD in eight years in Uruguay. RESULTS WD was the cause of six (15%) of thirty-nine ALF cases. All patients were females, with a mean age of 18 years. Four patients presented with hyperacute liver failure and two with acute failure. Jaundice was the main complaint of all patients. Mean total bilirubin (TB), alkaline phosphatase (AP), AST, and ALT were 27.5 mg/dL, 45.5 IU/l, 156 IU/L, and 51 IU/L, respectively. Ceruloplasmin levels were low in four patients, urinary cooper was high in four, and two had Kayser-Fleischer rings. All patients had Coombs-negative hemolytic anemia, acute kidney injury, histochemical identifiable copper, and advanced fibrosis on liver histology. The average MELD score was 36. All patients were treated with d-penicillamine and listed for urgent liver transplantation (LT). Prometheus® was performed in one patient. Three patients died: two without LT and one after LT. Three patients survived: one without LT (New Wilson Index < 11) and two with LT. The referral time to the program and the total time (referral plus waiting list time) were longer for non-survivors than for survivors (14 vs. 3 days and 23 vs. 8 respectively). CONCLUSION All cases had typical clinical, analytical and histopathology characteristics. Early referral was determinant of prognosis.
Transform domain model-based wideband speech enhancement with hearing aid applications

This thesis studies transform-domain model-based algorithms to improve the feedback and noise control performance of hearing aids processing wideband speech in non-stationary environments. Subband adaptive filter structures are investigated for continuous and non-continuous adaptation feedback compensation, and the particle filter framework is used to develop state-space model-based speech enhancement algorithms. Subband feedback compensation is shown to offer several advantages. The flexibility offered by the frequency division allows subband systems to offer faster and more stable convergence for wideband signals, and better tracking of changing acoustic feedback paths. Robustness is also improved, as divergence caused by path changes or input signal correlation is confined to individual frequency bands. A Rao-Blackwellized particle filter (RBPF) algorithm is proposed for enhancement of speech discrete cosine transform (DCT) coefficients, and is evaluated in comparison to the standard fullband RBPF. The DCT subband decomposition is shown to enable improved modeling of wideband speech signals, especially in spectral troughs, thereby decreasing intra-speech noise in both best-case and real-world conditions. A novel particle filter algorithm is also proposed for short-time spectral amplitude (STSA) speech enhancement. A dynamic model of spectral amplitude evolution is used to allow for speech signal correlation in the frequency domain. Two variants of the basic algorithm are presented: the first incorporates phase information to improve the spectral amplitude estimates; the second uses interacting multiple models to account for speech presence uncertainty. The monaural algorithm is extended to the binaural case with a filter based speech and noise parameter estimator. The estimator exploits knowledge of the diffuse noise field coherence to separate the clean speech and noise power spectra without external noise or voice-activity estimation. In both feedback and noise control, the transform domain allows for processing strategies that take into account the diverse frequency-dependent characteristics of the wideband signals. Incorporating models of speech, noise and the acoustic environment allows the addition of time-domain constraints and a-priori knowledge to address signal non-stationarity. The developed algorithms are evaluated using real speech and noise signals recorded with a commercial hearing aid.
The Effect of Core Stabilization Exercises on Trunk-Pelvis Three-Dimensional Kinematics During Gait in Non-Specific Chronic Low Back Pain.

MINI: We evaluate the effect of core training program (CTP) on the trunk-pelvis kinematics during gait between chronic low back pain (CLBP) and healthy. CTP increased the frontal and transverse planes pattern variability in CLBP. However, there was a significant higher the sagittal plane pattern variability in healthy participants compared with CLBP after the intervention. STUDY DESIGN Controlled clinical trial study. OBJECTIVE This study aimed to evaluate the effect of core stabilization exercise program (CSEP) on trunk-pelvis kinematics during gait in non-specific chronic low back pain (NCLBP). SUMMARY OF BACKGROUND DATA NCLBP is a major public burden with variety of dysfunction including gait variability. METHODS Thirty participants (15 NCLBP and 15 healthy) were included in this study via the convenience sampling method. NCLBP group were intervened via the 16 sessions CSEP 3 days for 6 weeks and trunk-pelvis kinematics (angular displacement, waveform pattern [CVp], and offset variability [CVo]) during gait, pain, disability were evaluated before and after the intervention. RESULTS No significant differences in displacement and CVo in three planes were found between NCLBP and healthy groups. Independent t test was revealed that significant differences in CVp in the sagittal, frontal, and transverse planes were found between healthy and NCLBP in pre intervention. No significant changes in displacement and CVo were found as the result of intervention in NCLBP. Pain and disability decreased significantly after intervention. Paired t test revealed that the CSEP increased the frontal (P = 0.04) and transverse planes (P = 0.02) pattern variability significantly. However, there was a significant difference between groups in the sagittal plane CVp after intervention (sagittal plane CVp in healthy vs. NCLBP in post-CSE: mean difference = 14.1; P = 0.04). CONCLUSION Considering the role of the deep trunk muscles in gait, and their common deconditioning in CLBP, a CSEP intervention may increase trunk-pelvis kinematic pattern variability. These results suggest CSEP may specifically increase transverse and frontal plane variability, indicating improved motor pattern replication through this movement planes. LEVEL OF EVIDENCE 2.
Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD

Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−. Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.
Prognostic value of pretreatment lymphocyte-to-monocyte ratio in patients with urologic tumors

Background: The prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in patients with urologic tumors remains controversial. Therefore, we herein conducted a meta-analysis to systematically assess the prognostic value of LMR in patients with urologic tumors. Methods: We comprehensively searched PubMed, EMBASE and Web of Science to identify eligible studies. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the prognostic value of LMR in patients with urologic tumors. This meta-analysis was registered in PROSPERO (CRD42018108959). Results: A total of 20 studies were included in this meta-analysis. Our synthesized analysis showed that low LMR was significantly correlated with poor overall survival (OS) and progression-free survival (PFS) in patients with upper tract urothelial cancer (UTUC). We also found that renal cell cancer (RCC) patients with low LMR had poor OS, PFS and cancer-specific survival (CSS). Besides, it was observed that low LMR predicted poor OS, RFS and CSS in patients with bladder cancer (BC). Conclusion: This meta-analysis demonstrated that pretreatment LMR is associated with survival, and may be a useful prognostic parameter in urologic tumors. Nevertheless, more prospective and heterogeneous studies with large samples are required to further confirm our findings before it is applied for daily clinical decision making.
Triglyceride glucose index for predicting cardiovascular outcomes in patients with coronary artery disease.

Background Triglyceride glucose (TyG) index is a novel marker for metabolic disorders and recently it has been reported to be associated with cardiovascular disease (CVD) risk in apparently healthy individuals. However, the prognostic value of TyG index in patients with stable coronary artery disease (CAD) is not determined. Methods We conducted a nested case-control study among 3,745 patients with stable CAD. Patients were followed up for 11,235 person-years. The cardiovascular events (CVEs) were defined as all-cause death, non-fatal myocardial infarction (MI), stroke and post-discharge revascularization [percutaneous coronary intervention (PCI) coronary artery bypass grafting (CABG)]. In total, 290 (7.7%) patients with CVEs and 1,450 controls were matched according to age, gender, previous history of PCI or CABG and the duration of follow-up. TyG index was calculated as formula: ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Multivariable Cox proportional hazards models revealed that TyG index was positively associated with CVEs risk (hazard ratio: 1.364, 95% confidence interval: 1.100-1.691, P=0.005). The Kaplan-Meier analysis indicated that patients within the highest quartile of TyG index presented the lowest event-free survival (P=0.029). Moreover, a 1-standard deviation (SD) increment in TyG index was associated with 23.2% [hazard ratio (HR): 1.232, 95% confidence interval (95% CI): 1.084-1.401] higher risk of CVEs, which was superior to other triglyceride or glycemic related markers. Conclusions The present study, firstly, showed that TyG index was positively associated with future CVEs, suggesting that TyG may be a useful marker for predicting clinical outcomes in patients with CAD.
Gait velocity and joint power generation after stroke: contribution of strength and balance.

OBJECTIVE To assess the degree to which isometric strength of multiple lower limb muscle groups and balance is associated with gait velocity and joint power generation during gait after stroke. DESIGN Sixty-three participants in a multi-site, multi-national cross-sectional, observational study underwent assessment of gait velocity (10m walk test), standing balance (computerised posturography), and isometric strength (hand-held dynamometry). Twenty-seven participants had joint power generation assessed (three-dimensional gait analysis). Bivariate associations were examined using Spearman's correlations. Regression models with partial F-tests were used to compare the contribution to gait between measures. RESULTS While all muscle groups demonstrated significant associations with gait velocity (rho = 0.40-0.72), partial F-tests identified that ankle plantarflexor and hip flexor strength made the largest contribution to gait velocity. Ankle plantarflexor strength also had strong associations with habitual and fast paced ankle power generation (rho = 0.65 and 0.75). Balance had significant associations with habitual and fast gait velocity (rho = -0.57 and -0.53), with partial F-tests showing the contribution was independent of strength. CONCLUSION Ankle plantarflexor and hip flexor strength had the largest contribution to gait velocity. Future research may wish to refocus strength assessment and treatment to target the ankle plantarflexors and hip flexors.