Miracle-dz/UniFAR-FTUs huggingface dataset:
Viral Suppression Following Switch to Second-line Antiretroviral Therapy: Associations With Nucleoside Reverse Transcriptase Inhibitor Resistance and Subtherapeutic Drug Concentrations Prior to Switch

Background. High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification. Methods. Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression. Results. One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77–263) and 4.3 log10 copies/mL (IQR, 3.8–4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥1 thymidine analogue mutations (47% vs 18%), all P = . 01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL. Conclusions. Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.
Novel ceramic bone replacement material Osbone® in a comparative in vitro study with osteoblasts.

OBJECTIVE Hydroxyapatite (HA) is a very common ceramic material for bone replacement due to its similarity in composition to the mineral phase of natural bone. A recently developed bone graft material is Osbone(®), a synthetic HA ceramic available as porous granules with different sizes and block forms. The goal of this study was to characterise Osbone(®) in vitro in comparison to the already established calcium phosphate-based bone grafts Cerasorb M(®) and Bio-Oss(®). MATERIALS AND METHODS Adhesion and proliferation of SaOS-2 osteoblasts were evaluated quantitatively by determining DNA content and lactate dehydrogenase (LDH) activity and qualitatively by scanning electron microscopy (SEM). In addition, MTT cell vitality staining was performed to confirm the attachment of viable cells to the different materials. Osteogenic differentiation of the cells was evaluated by means of alkaline phosphatase (ALP) activity quantification as well as by gene expression analysis of osteogenic markers using reverse transcriptase PCR. RESULTS MTT staining after 1 day of adhesion showed viable cells on all examined materials. DNA content and LDH activity revealed proliferation of osteoblasts on Osbone(®) and Cerasorb M(®), but not on Bio-Oss(®) during cultivation over 28 days. SEM showed a well-spread morphology of cells attached to both Osbone(®) and Cerasorb M(®). We detected an increase of specific ALP activity during cultivation of osteoblasts on Osbone(®) and Cerasorb M(®) as well as expression of the bone-related genes ALP, osteonectin, osteopontin and bone sialoprotein II on both materials. CONCLUSIONS Osbone(®) granules support proliferation and osteogenic differentiation in vitro and are therefore promising candidates for in vivo applications.
Structure and strategy in the associative false memory paradigm

List-learning experiments can have several levels of structure: individual words, the gist (if any) of each list, and the task in which those lists are embedded. The usual presentation of the DRM associative paradigm (Deese, 1959; Roediger & McDermott, 1995) strongly encourages a focus on gist and produces a high rate of false recall of key words (FRK). The experiments reported here were designed to invite the use of memory strategies based on structures other than the gist and thus reduce FRK. The crucial condition of Experiment 1, short lists followed by rehearsal, encouraged a focus on individual words and produced a low rate of FRK. In Experiment 2, the lists were embedded in a guessing game, which virtually eliminated FRK. FRK was also low in Experiments 3a and 3b when participants engaged in a complex task involving the first letters of list words. The relevance of these findings to false memories in the DRM and the connection of false autobiographical memories is discussed.
Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†

OBJECTIVES The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status. METHODS We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known. RESULTS A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001]. CONCLUSION Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.
Handbook of Pharmaceutical Granulation Technology

Theory of granulation drug substance and excipient characterization binders and solvents spray drying as an alternative granulation technique roller compaction technology high shear mixer granulators low shear granulators batch fluid bedgranulation single-pot processing extrusion-spheronization as a granulation technique continuous granulation sizing of granulation granulation characterization - methods and significance bioavailability and granule properties regulatory issues ingranulation processes.
Archives of Inequalities and Applications xx (200x)xxx-xxx LOWER BOUNDS FOR NATURAL PSEUDODISTANCES VIA SIZE FUNCTIONS

Let us consider two C closed homeomorphic manifolds M, N and two C functions φ : M → R, ψ : N → R, called measuring functions. The natural pseudodistance d between the pairs (M, φ), (N , ψ) is defined as the infimum of Θ(f) def = maxP∈M |φ(P ) − ψ(f(P ))|, as f varies in the set of all homeomorphisms from M onto N . In this paper we show that size functions allow us to get a lower bound for d. Furthermore, we prove that this lower bound can be assumed equal either to |c′ − c′′| or to 12 |c′ − c′′|, where c′, c′′ are two suitable critical values of the measuring functions. AMS (MOS) Subject Classification.Primary 58C05; Secondary 53C15.
Netherlands An Energy-Based Excess Pore Pressure Generation Model for Cohesionless Soils

ABSTRACT: In 1976, J.R. Booker, M.S. Rahman, and H.B. Seed developed a computer program for the analysis of pore pressure generation and dissipation during cyclic or earthquake loading. The pore pressure generation model used by Booker et al. (1976) is a two-parameter stress-based model. Their study marked one of the first attempts to model effective stresses in cohesionless soils during earthquakes. The authors have developed a single parameter, energy-based pore pressure generation model, denoted as the GMP model. The motivation for the development of an energy-based model is for application to projects and problems involving liquefaction for soil densification and ground improvement purposes. The GMP model is an empirical relation between dissipated shear energy and the residual excess pore pressure ratio, ru. The model has accurately approximated ru in samples of sand and silt-sand mixtures at various densities tested in cyclic triaxial, cyclic torsional shear, and in large-scale shake table tests. A comparison of ru values measured in cyclic triaxial samples with those computed using both the energy-based GMP model and the stress-based model used by Booker et al. (1976), shows that both models give good results. Because the GMP model has a simple mathematical form and a single calibration parameter, it is easy to implement and calibrate. A preliminary correlation between the GMP model’s single calibration parameter and relative density is presented for fine sand.
Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii

Pathogenic microbes confront a constant evolutionary conflict between the pressure to maintain genome stability and the need to adapt to mounting external stresses. Prokaryotes often respond with elevated mutation rates, but to date little evidence exists of stable eukaryotic hypermutators in nature. Whole genome resequencing of the human fungal pathogen Cryptococcus deuterogattii identified an outbreak lineage characterized by a nonsense mutation in MSH2. This defect in mismatch repair results in a moderate mutation rate increase in typical genes, and a larger increase in genes containing homopolymer runs. This allows facile inactivation of genes with coding homopolymer runs including FRR1, which encodes the target of the immunosuppresive antifungal drugs FK506 and rapamycin. Our study identifies a eukaryotic hypermutator lineage spread over two continents and suggests that pathogenic eukaryotic microbes may experience similar selection pressures on mutation rate as bacterial pathogens, particularly during long periods of clonal growth or while expanding into new environments.
Torque control based sensorless hand guiding for direct robot teaching

In recent years, much research has been done to develop various direct teaching schemes, in which an operator directly teaches a robot by hand guiding instead of using a teach pendant. However, conventional direct teaching methods are usually sensor based, thus leading to an expensive solution. To deal with this problem, this study proposes a sensorless hand guiding method based on torque control. The dynamic model of a robot along with the motor current and friction model is used to determine the user's intention to move the end-effector of a robot instead of directly sensing the external force by the user. A friction torque observer is employed for the friction model identification. The proposed method was experimentally verified using a 6 DOF robot. The experimental results show that the proposed sensorless hand guiding scheme is quite useful for practical direct teaching although the sensitivity is slightly lower than the sensor-based approach.
A Basic Study of Heat Transfer Through Foam Insulation

the development of improved foam insulations has been an evolutionary process. Current research efforts to develop higher R value foams are handicapped by the fact that the mechanisms of heat transfer through foam are not well understood and a basic model is not available. It is the goal of this paper to help develop a better understanding of the mechanisms controlling heat transfer through foams. This will aid future foam developments and form the basis of a fundamental model for the R value of foam. This work also applies to understanding the aging of foams. In a review of the foam literature, Valenzuela [1] showed that published heat transfer models underestimate the effective conductivity of foams, even when upper limits are used for the contribution of solid and gas conduction. Gas convection within the cells was shown to be negligible and hence could not account for the discrepancy. It was hypothesized that thermal radiation accounted for the balance of
Co-Evolutionary Fitness Landscapes for Sequence Design.

Efficient and accurate models to predict the fitness of a sequence would be extremely valuable in protein design. We have explored the use of statistical potentials for the coevolutionary fitness landscape, extracted from known protein sequences, in conjunction with Monte Carlo simulations, as a tool for design. As proof of principle, we created a series of predicted high-fitness sequences for three different protein folds, representative of different structural classes: the GA (all-α) and GB (α/β) binding domains of streptococcal protein G, and an SH3 (all-β) domain. We found that most of the designed proteins can fold stably to the target structure, and a structure for a representative of each for GA, GB and SH3 was determined. Several of our designed proteins were also able to bind to native ligands, in some cases with higher affinity than wild-type. Thus, a search using a statistical fitness landscape is a remarkably effective tool for finding novel stable protein sequences.
On the Probabilistic Model Checking of Cognitive Radio Networks and Cognitive Infocommunication Systems

We report on the usage of the probabilistic model checker PRISM to validate respectively falsify previously published results on the performance of cognitive radio networks and other cognitive infocommunication systems. For this purpose, we construct formal system models in the PRISM modeling language as Continuous Time Markov Chains (CTMCs) that are analyzed with the help of queries formulated in a variant of continuous stochastic logic (CSL). It is shown that many results can be accurately reproduced but also that a few previously reported results are clearly erroneous. Furthermore, we report several deviations from previously reported results where the reasons are unclear and need further investigation. Here a major problem is that the systems that have been analyzed in literature are usually just described in informal language which leaves ample room for interpretation. This makes the reconstruction of corresponding formal system models and the reproduction of performance measures a difficult task and limits the long-term scientific value of the reported results. ∗Supported by the Stiftung Aktion Österreich-Ungarn project 96öu8 “Engineering Information Technology Modelling and Design of Cognitive Radio Networks”.
Verifiable Public Key Encryption Scheme With Equality Test in 5G Networks

The emergence of 5G networks will allow cloud computing providers to offer more convenient services. However, security and privacy issues of cloud services in 5G networks represent huge challenges. Recently, to improve security and privacy, a novel primitive was proposed by Ma et al. in TIFS 2015, called public key encryption with equality test supporting flexible authorization (PKEET-FA). However, the PKEET scheme lacks verification for equality test results to check whether the cloud performed honestly. In this paper, we expand the study of PKEET-FA and propose a verifiable PKEET (V-PKEET) scheme, which, to the best of our knowledge, is the first work that achieves verification in PKEET. Moreover, V-PKEET has been designed for three types of authorization to dynamically protect the privacy of data owners. Therefore, it further strengthens security and privacy in 5G networks.
Changes in the Profile of Endovascular Procedures Performed in Freestanding Dialysis Access Centers over 15 Years.

BACKGROUND AND OBJECTIVES Marked changes occurred in the vascular access profile of patients receiving hemodialysis in the United States over the 15-year period of 2001-2015. This study was undertaken to evaluate how these changes have affected dialysis access maintenance and salvage procedures performed in freestanding dialysis access centers and to examine the effectiveness, efficiency, and safety of these procedures in this setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data were collected from freestanding, dedicated dialysis access centers operating under a common system of management. Data were available on 689,676 dialysis access procedures. Data relating to case mix, procedure outcome, procedural time, and intraprocedural and immediate postprocedural complications were analyzed. RESULTS The arteriovenous procedure profile changed from one characterized by approximately equal numbers of angioplasties and thrombectomies performed on arteriovenous grafts (AVGs) to one characterized primarily by angioplasties performed on arteriovenous fistulas. The percentage of angioplasties performed throughout the study was significantly greater than thrombectomies, with a mean of 67.9% versus 32.1% (P<0.001). Interventional procedures did not decrease with increasing arteriovenous fistula utilization in prevalent patients receiving dialysis. The incidence roughly paralleled the increasing prevalence of this type of access. A decreasing percentage of AVG utilization resulted in a progressive, roughly parallel, but disproportionately higher, decrease in the percentage of AVG procedures (P<0.001). A progressive improvement in procedure outcomes and a decrease in complication rates and procedure times were observed (P<0.001 for each). A progressive decrease in tunneled dialysis catheter placement was also observed. CONCLUSIONS The procedure profile treated in freestanding, dedicated dialysis access centers changed significantly over 15 years, reflecting the changes that have occurred in the vascular access profile of the dialysis population.
The particulars on parechovirus

HISTORICAL BACKGROUND HPeV are nonenveloped, positive-sense, single-stranded RNA picornoviruses that were first detected in 1956 in children with diarrhea. HPeV-1 and HPeV-2 were originally believed to belong to the genus Enterovirus (EV) and were named echoviruses 22 and 23 (1). In 1999, HPeV were assigned their genus name when genomic sequencing proved that they were not EV. At least 14 other HPeV types have been identified (Table 1) (2-34), starting with HPeV-3, which was initially reported in Japan in 2004 (21) and next reported in Canada in 2005 (35). Recombination between HPeV types may occur (31).
Anti-HER2 scFv-Directed Extracellular Vesicle-Mediated mRNA-Based Gene Delivery Inhibits Growth of HER2-Positive Human Breast Tumor Xenografts by Prodrug Activation

This paper deals with specific targeting of the prodrug/enzyme regimen, CNOB/HChrR6, to treat a serious disease, namely HER2+ human breast cancer with minimal off-target toxicity. HChrR6 is an improved bacterial enzyme that converts CNOB into the cytotoxic drug MCHB. Extracellular vesicles (EV) were used for mRNA-based HchrR6 gene delivery: EVs may cause minimal immune rejection, and mRNA may be superior to DNA for gene delivery. To confine HChrR6 generation and CNOB activation to the cancer, the EVHB chimeric protein was constructed. It contains high-affinity anti-HER2 scFv antibody (ML39) and is capable of latching on to EV surface. Cells transfected with EVHB-encoding plasmid generated EVs displaying this protein (“directed EVs”). Transfection of a separate batch of cells with the new plasmid, XPort/HChrR6, generated EVs containing HChrR6 mRNA; incubation with pure EVHB enabled these to target the HER2 receptor, generating “EXO-DEPT” EVs. EXO-DEPT treatment specifically enabled HER2-overexpressing BT474 cells to convert CNOB into MCHB in actinomycin D–independent manner, showing successful and specific delivery of HChrR6 mRNA. EXO-DEPTs—but not undirected EVs—plus CNOB caused near-complete growth arrest of orthotopic BT474 xenografts in vivo, demonstrating for the first time EV-mediated delivery of functional exogenous mRNA to tumors. EXO-DEPTs may be generated from patients' own dendritic cells to evade immune rejection, and without plasmids and their potentially harmful genetic material, raising the prospect of clinical use of this regimen. This approach can be used to treat any disease overexpressing a specific marker. Mol Cancer Ther; 17(5); 1133–42. ©2018 AACR.
Evaluation of the benefit and use of the new terminology in endometrial cytology reporting system

The introduction and establishment of a new classification system for endometrial cytology, the “New Terminology in Endometrial Cytology (NTEMC) system,” which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies.
Premitotic Assembly of Human CENPs -T and -W Switches Centromeric Chromatin to a Mitotic State

Centromeres are differentiated chromatin domains, present once per chromosome, that direct segregation of the genome in mitosis and meiosis by specifying assembly of the kinetochore. They are distinct genetic loci in that their identity in most organisms is determined not by the DNA sequences they are associated with, but through specific chromatin composition and context. The core nucleosomal protein CENP-A/cenH3 plays a primary role in centromere determination in all species and directs assembly of a large complex of associated proteins in vertebrates. While CENP-A itself is stably transmitted from one generation to the next, the nature of the template for centromere replication and its relationship to kinetochore function are as yet poorly understood. Here, we investigate the assembly and inheritance of a histone fold complex of the centromere, the CENP-T/W complex, which is integrated with centromeric chromatin in association with canonical histone H3 nucleosomes. We have investigated the cell cycle regulation, timing of assembly, generational persistence, and requirement for function of CENPs -T and -W in the cell cycle in human cells. The CENP-T/W complex assembles through a dynamic exchange mechanism in late S-phase and G2, is required for mitosis in each cell cycle and does not persist across cell generations, properties reciprocal to those measured for CENP-A. We propose that the CENP-A and H3-CENP-T/W nucleosome components of the centromere are specialized for centromeric and kinetochore activities, respectively. Segregation of the assembly mechanisms for the two allows the cell to switch between chromatin configurations that reciprocally support the replication of the centromere and its conversion to a mitotic state on postreplicative chromatin.