Miracle-dz/UniFAR-FTUs huggingface dataset:
Baseline features and initial treatment as predictors of remission and relapse in Wegener's granulomatosis.

OBJECTIVE To describe the course of disease activity and determine predictors of remission and relapse in a population based cohort of patients with Wegener's granulomatosis (WG). METHODS Retrospective cohort study of 56 patients (median age 50 yrs) followed for 42.5 months. Disease activity was assessed by Birmingham Vasculitis Activity Score (BVAS-1) and permanent organ damage by Vasculitis Damage Index (VDI). Induction therapy consisted of prednisolone (Pred) 0.5-1 mg/kg and cyclophosphamide (CYC) daily orally 2 mg/kg (19 patients) or intravenous pulses 15 mg/kg every 2nd week (32 patients). Baseline clinical and laboratory features and cumulative treatment during the first 6 months were recorded. Multiple Cox and logistic regression analyses were used to find risk factors for remission and relapse. RESULTS All patients surviving > 1 month achieved either complete (85%) or partial remission (15%). Higher baseline BVAS-1 increased the likelihood of achieving complete remission [BVAS-1 > 23, relative hazard (RH) 2.94, 95% confidence interval (CI) 1.48-5.85]. Relapse occurred in 31 patients (60%) after a median period of 18 months. The risk of relapse was increased in patients having received < 10 g CYC during the first 6 months (RH 2.83, 95% CI 1.33-6.02), in patients having received Pred > 20 mg/day for < 2.75 months (RH 2.41, 95% CI 1.12-5.21), and in patients with initial heart involvement (RH 2.87, 95% CI 1.09-7.58). A higher Pred dose during the first 6 months was associated with severe infections. Therapy resistance (no complete remission) was associated with baseline organ damage (VDI increase by 1, OR 1.53, 95% CI 1.03-2.27). CONCLUSION Initial high disease activity increased and the presence of baseline organ damage reduced the likelihood for complete remission in WG. Relapse was associated with less intensive initial treatment in terms of lower CYC doses and shorter time taking Pred > 20 mg/day.
Generating Nano-Aerosols from TiO2 (5 nm) Nanoparticles Showing Different Agglomeration States. Application to Toxicological Studies

Agglomeration of nanoparticles (NP) is a key factor in the generation of aerosols from nano-powders and may represent an important parameter to consider in toxicological studies. For this reason, the characterization of NP aerosols (e.g., concentration, size, and structure of agglomerates) is a critical step in the determination of the relationship between exposure and effects. The aim of this study was to generate and characterize aerosols composed of TiO2 (5 nm) NP showing different agglomeration states. Two concentrations were tested: 2 and 7 mg/m3. Stable mass concentrations over 6 hr were successfully generated by a wet method using Collison and Delavan nebulizers that resulted in aerosols composed of smaller agglomerates (<100 nm), while aerosols composed of larger agglomerates (>100 nm) were obtained by dry generation techniques using either a Palas dust feeder or a Fluidized Bed. Particle size distributions in the aerosols were determined by an electrical low pressure impactor. Median number aerodynamic diameters corresponding to the aerosol with smaller and larger agglomerates were 30 and 185 nm, respectively, for the 2 mg/m3 concentration, and 31 and 194 nm for the 7 mg/m3 experiment. Image analysis by transmission electron microscopy showed the presence of compact or agglomerates with void spaces in the different nano-aerosols. These characterized nano-aerosols will be used in further experiments to study the influence of agglomerate size on NP toxicity.
Improving recruitment and retention rates in preventive longitudinal research with adolescent mothers.

PROBLEM In order to understand the risks and protective factors associated with poor health outcomes in adolescent mothers and their children, nurses need to design rigorous longitudinal research. Attrition of subjects can contribute to sampling error. Recruitment and retention efforts need to be optimized. METHODS In a 4-year longitudinal study with adolescent mothers and their babies, the design for tracking included frequent phone calls, progressive monetary incentives, gifts, and one phone number of an alternative contact. FINDINGS Of the 97 mother-infant dyads recruited, retention was 54% at 6 months and 38% at final data collection. Successful strategies included persistence in making contacts and utilizing alternative contact numbers. CONCLUSIONS Retention rates for this study were low. With today's technology, many additional strategies need to be employed to improve retention rates with adolescent mothers.
A 43-mW MASH 2-2 CT $\Sigma \Delta$ Modulator Attaining 74.4/75.8/76.8 dB of SNDR/SNR/DR and 50 MHz of BW in 40-nm CMOS

This paper proposes a multistage noise-shaping continuous-time sigma-delta modulator (CT<inline-formula> <tex-math notation="LaTeX">$\Sigma \Delta \text{M}$ </tex-math></inline-formula>) with on-chip <italic>RC</italic> time constant calibration circuits, multiple feedforward interstage paths, and a fully integrated noise-cancellation filter (NCF). The core modulator architecture is a cascade of two single-loop second-order CT<inline-formula> <tex-math notation="LaTeX">$\Sigma \Delta \text{M}$ </tex-math></inline-formula> stages, each of which consists of an integrator-based active- <italic>RC</italic> loop filter, current-steering feedback digital-to-analog converters, and a 4-b flash quantizer. On-chip <italic>RC</italic> time constant calibration circuits and high-gain multistage operational amplifiers are realized to mitigate quantization noise leakage due to process variation. Multiple feedforward interstage paths are introduced to: 1) synthesize a fourth-order noise transfer function with dc zeros; 2) simplify the design of NCF; and 3) reduce signal swings at the second-stage integrator outputs. Fully integrated in 40-nm CMOS, the prototype chip achieves 74.4 dB of signal-to-noise-and-distortion ratio (SNDR), 75.8 dB of signal-to-noise ratio, and 76.8 dB of dynamic range in 50.3 MHz of bandwidth (BW) at 1 GHz of sampling frequency with 43 mW of power consumption (P) from 1.1/1.15/2.5-V power supplies. It does not require external software calibration and possesses minimal out-of-band signal transfer function peaking. The figure-of-merit (FOM), defined as <inline-formula> <tex-math notation="LaTeX">$\text {FOM}=\text {SNDR}+10\times \log _{10}(\text {BW}/\text {P})$ </tex-math></inline-formula>, is 165.1 dB.
Aberrations of the Tissue Factor Pathway in Patients Positive for Lupus Anticoagulant

To evaluate the relationship between the tissue factor (TF) pathway and lupus anticoagulant (LA), in the pres ent study, we measured the plasma levels of TF antigen and TF pathway inhibitor (TFPI) antigen in patients positive for LA. Plasma TF and TFPI levels in LA-positive patients were sig nificantly higher than levels in healthy volunteers (p < 0.01). In LA-positive patients, there were no significant differences in plasma TF and TFPI levels between patients with and without thrombosis. In patients with thrombosis, there was no signifi cant difference in the plasma TF level between LA-positive and LA-negative patients; however, the plasma TFPI level in LA- positive patients was significantly lower than that in LA- negative patients (p < 0.01). We also examined the TF pathway in human umbilical venous endothelial cells (HUVEC) incu bated with plasma of LA-positive patients, LA-negative pa tients, and healthy volunteers. TF activity was significantly higher (p < .05) in HUVECs incubated with the plasma of LA-positive patients than in cells incubated with the plasma of the other two groups (p < .01). However, there was no signifi cant difference in TFPI antigen levels among the media of HUVECs incubated with the plasma of all groups. The viability of HUVEC incubated with the plasma of LA-positive patients with thromboses, LA-positive patients without thromboses, and LA-negative patients with thromboses were significantly lower than that of HUVECs incubated with the plasma of healthy volunteers (p < .01). These findings suggest that abnormalities of the TF pathway plays an important role in the mechanism of hypercoagulability in LA-positive patients. LA may affect vas cular endothelial cells causing thrombogenesis. Key Words: Lupus anticoagulant—Tissue factor—Tissue factor pathway inhibitor—Vascular endothelial cell—MTT assay.
Epidural spinal cord stimulation: calculation of field potentials with special reference to dorsal column nerve fibers

The effect of electrical stimulation with several electrode combinations on nerve fibers with different orientations in the spinal cord was investigated by computing the steady-state field potentials and activating functions. An infinite homogeneous model was used, and the spinal cord and its surrounding tissues where then modeled as an inhomogeneous anisotropic volume conductor. The effect of mediodorsal epidural stimulation was calculated. It was concluded that the cathodal stimulation, mediodorsally in the epidural space, longitudinal fibers are depolarized, but dorsoventral ones are hyperpolarized. With anodal stimulation the opposite will occur. It was found that parameters substantially affecting the potential distribution in the dorsal columns are the conductivity of the white matter and the width and the conductivity of the cerebrospinal fluid layer. <<ETX>>
The expression of depression among Javanese patients with major depressive disorder: A concept mapping study

In this study, we explored the presentation of clinical depression in Java, Indonesia. Interviews were conducted with 20 Javanese patients (male and female) with major depressive disorder from both lower and higher socioeconomic levels. The recruited participants came from provincial and private mental health hospitals in the cities of Solo, Yogykarta (Jogja), Jakarta, and Malang on the island of Java, Indonesia. Concept mapping methodology using multidimensional scaling and hierarchical cluster analysis was used to identify underlying themes in the expression of depressive phenomena in this Indonesian population. The results identified themes that grouped into six clusters: interpersonal relationships, hopelessness, physical/somatic, poverty of thought, discourage, and defeat. Findings give support to the view that culture influences the expression of Indonesian depressive phenomenology, which nevertheless has some common roots with Western clinical pictures of the disorder. Cultural influences may mask symptoms of the disorder to clinicians. Diagnostic and assessment tools must be carefully selected to ensure they address culturally specific expressions of depression.
MUC1 as a Potential Target in Anticancer Therapies

MUC1 is a glycoprotein that is overexpressed in tumor cells. In normal cells it forms a protective layer against microbes and toxic chemicals, besides providing lubrication on ductal surfaces. Oversecretion of MUC1 provide cancer cells with invasiveness, metastasis, and resistance to death induced by reactive oxygen species. MUC1 is made up of 2 heterodimers, MUC1-N and MUC1-C. MUC1-N is heavily glycosylated at 5 regions of the variable N-tandem repeats. MUC1-C is divisible into extracellular, intracellular, and cytoplasmic domain (MUC1-C/CD). The extracellular domain serves as a docking site for epidermal growth factor receptors and other receptor kinases; the transmembrane domain serves to relay messages from extracellular to MUC1-C/CD. The MUC1-C/CD has 5 phosphorylating sites that on interacting with the SH2 domain of specific proteins can stimulate tumor growth. Therapies targeting MUC1 consists of monoclonal antibodies (MAb), vaccines, or small molecules (aptamers). MAb therapies are mainly aimed at MUC1-N with little success, however, new generation of MAb are being developed for MUC1-C. Vaccines (peptide, carbohydrate, glycopeptide, DNA, and dendritic cell) have been developed that recognizes the aberrant glycosylated region of the variable N-tandem repeats in MUC1-N, whereas new generation vaccines are aimed at the cytoplasmic region of MUC1-C. Aptamers (peptides that resemble DNA, RNA) have been used for blocking the dimerization of CQC region and the 5 phosphorylating region of MUC1-C. In addition, aptamers have been used as cytotoxic drug carriers. However, none of the therapies for MUC1 are currently in clinical application, as they need further refinement and evaluation.
Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure

Background Although Plasmodium vivax contributes to almost half of all malaria cases outside Africa, it has been relatively neglected compared to the more deadly P. falciparum. It is known that P. vivax populations possess high genetic diversity, differing geographically potentially due to different vector species, host genetics and environmental factors. Results We analysed the high-quality genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents. Using population genetic methods we identified hotspots of selection pressure, including the previously reported MRP1 and DHPS genes, both putative drug resistance loci. Extra copies and deletions in the promoter region of another drug resistance candidate, MDR1 gene, and duplications in the Duffy binding protein gene (PvDBP) potentially involved in erythrocyte invasion, were also identified. For surveillance applications, continental-informative markers were found in putative drug resistance loci, and we show that organellar polymorphisms could classify P. vivax populations across continents and differentiate between Plasmodia spp. Conclusions This study has shown that genomic diversity that lies within and between P. vivax populations can be used to elucidate potential drug resistance and invasion mechanisms, as well as facilitate the molecular barcoding of the parasite for surveillance applications.
Developing Consensus Criteria for Sarcopenia: An Update

Sarcopenia, the age‐related loss of muscle mass and strength, is a major cause of impaired physical function, which contributes to mobility disability, falls and hospitalizations in older adults. Lower muscle mass and strength are also associated with lower bone mineral density and greater risk for osteoporotic fractures. Thus, identification of sarcopenia could be important for fracture prevention as it may help improve fracture risk assessment, and muscle mass and strength can be improved with exercise, even among the frailest older adults. Unfortunately, there are no consensus diagnostic criteria for sarcopenia. Consequently there is no guidance to help clinicians identify older adults with clinically meaningful low muscle mass or weakness. Further, development of novel sarcopenia therapies is hindered not only due to the difficulty in identifying participants for clinical trials, and but also because there are no validated, clinically appropriate endpoints for assessment of treatment efficacy. There is currently a major push to establish a consensus definition of sarcopenia, and recent work holds promise that this goal may be within reach. This article discusses the evolution of the definition of sarcopenia, and focuses on the latest recommended diagnostic criteria proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. While these empirically‐based cut‐points for clinically important low muscle mass and weakness are a significant step forward for the sarcopenia field, important questions remain to be answered before consensus diagnostic criteria can be definitively established. Ongoing work to refine sarcopenia criteria will further advance the field and bring this important contributor to falls, fractures and disability into the mainstream of clinical care and ultimately lead to better quality of life with aging. © 2015 American Society for Bone and Mineral Research.
Preparation, characterization and in vitro-targeted delivery of novel Apolipoprotein E-based nanoparticles to C6 glioma with controlled size and loading efficiency

Abstract Apolipoprotein E (APOE) with its extraordinary features is readily assembled with hydrophobic compounds via its compact hydrophobic units (CHUs). These assemblies can then be converted to stable particles by protein–protein interactions via coiled coil regions (CCRs) which exist in APOE structure. Applying these features of APOE, we prepared novel nanoparticles called NAPOE, using no cross-linker. Vitamin D3 – a hydrophobic antitumor model – was loaded within the nanoparticles (NPs). The NPs were mostly spherical with the mean diameter and zeta potential of 94.39 ± 5.71 nm and −20 ± 0.3 mV, respectively. The molar ratio of VD3/APOE in NPs was 37.2 ± 0.61. The NPs targeted C6 glioma cells in vitro via over-expressed LDLRs. The efficiency of the NPs uptake to malignant C6 glioma cells was remarkable compared to non-tumor glial cells (p < 0.05). The releasing rate of hydrophobic cargo from the particles was high (p < 0.05) and reached to maximum, 12 h after targeting C6 cells. The size and drug loading of NPs were found to be controlled by the definite numbers of CCRs and CHUs in APOE. In conclusion, it is suggested that NAPOE NPs can facilitate the controlled delivery of hydrophobic drugs to the malignant C6 glioma cells according to the degree of invasiveness.
Effects of oxygen plasma treatment on adipose-derived human mesenchymal stem cell adherence to poly(L-lactic acid) scaffolds

Plasma treatment of substrate surfaces can be utilized to improve adhesion of cells to tissue-engineered scaffolds. The purpose of this study was to enhance cell adhesion to non-woven poly(L-lactic acid) (PLLA) scaffolds using oxygen plasma treatment to increase surface hydroxyl groups and thereby enhance substrate hydrophilicity. It was hypothesized that oxygen plasma treatment would increase the number of adipose-derived human mesenchymal stem cells (hMSCs) that adhered to melt-blown, non-woven PLLA scaffolds without affecting cell viability. The number of cells that adhered to the oxygen plasma-treated (10 min at 100 W) or untreated PLLA scaffolds was assessed at 2, 4, 8, 12, 24 and 48 h post-seeding via DNA analysis. Cell viability and morphology were also assessed at 2, 4, 8, 12 and 24 h post-seeding via a live/dead assay and hematoxylin staining, respectively. Oxygen plasma treatment decreased the contact angle of water from 75.6° to 58.2°, indicating an increase in the surface hydrophilicity of PLLA. The results of the DNA analysis indicated that there was an increased number of hMSCs on oxygen plasma treated scaffolds for two of the three donors. In addition, oxygen plasma treatment promoted a more even distribution of hMSCs throughout the scaffold and enhanced cell spreading at earlier time points without altering cell viability. This early induction of cell spreading and the uniform distribution of cells, in turn, may increase future proliferation and differentiation of hMSCs under conditions that simulate the microenvironment in vivo.
Safety of capecitabine: a review

Importance of the field: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. Areas covered in this review: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. What the reader will gain: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. Take home message: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand–foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.
Motion interactive video games in home training for children with cerebral palsy: parents’ perceptions

Purpose: To explore parents’ perceptions of using low-cost motion interactive video games as home training for their children with mild/moderate cerebral palsy. Method: Semi-structured interviews were carried out with parents from 15 families after participation in an intervention where motion interactive games were used daily in home training for their child. A qualitative content analysis approach was applied. Results: The parents’ perception of the training was very positive. They expressed the view that motion interactive video games may promote positive experiences of physical training in rehabilitation, where the social aspects of gaming were especially valued. Further, the parents experienced less need to take on coaching while gaming stimulated independent training. However, there was a desire for more controlled and individualized games to better challenge the specific rehabilitative need of each child. Conclusions: Low-cost motion interactive games may provide increased motivation and social interaction to home training and promote independent training with reduced coaching efforts for the parents. In future designs of interactive games for rehabilitation purposes, it is important to preserve the motivational and social features of games while optimizing the individualized physical exercise. Implications for Rehabilitation Children with neurodevelopmental disorders like cerebral palsy (CP) are in need of fun and engaging rehabilitation methods to enhance motivation and increase compliance with motor training. There is a rising interest among clinical professionals and parents to use motion interactive games as a rehabilitation device for these children. In this qualitative study parents perceived that motion interactive games can enhance motivation for practice, stimulate the child, and reduce the parental efforts related to home-based rehabilitation of children with CP.
A Chemical Tool for In Vitro and In Vivo Precipitation of Lysine Methyltransferase G9a

Here we report the design, synthesis, and biochemical characterization of a new chemical tool, UNC0965. UNC0965 is a biotinylated version of our previously reported G9a chemical probe, UNC0638. Importantly, UNC0965 maintains high in vitro potency and is cell penetrant. The biotinylated tag of UNC0965 enables “chemiprecipitation” of G9a from whole cell lysates. Further, the cell penetrance of UNC0965 allowed us to explore the localization of G9a on chromatin both in vitro and in vivo through chemical inhibitor‐based chromatin immunoprecipitation (chem‐ChIP).