Miracle-dz/UniFAR-FTUs huggingface dataset:
The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.

OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents. METHODS A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted. RESULTS Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo. CONCLUSION Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.
Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients

The aim of this study was to investigate the efficacy of combined treatment with rituximab and subcutaneous cladribine in patients with newly diagnosed and relapsed chronic lymphocytic leukemia (CLL). Forty-three patients with active CLL or small lymphocytic lymphoma received rituximab 375 mg/m2 on day 1 and cladribine 0.1 mg/kg subcutaneously on days 2–6. The treatment was repeated every 4 weeks for a total of four cycles. Sixteen patients were pretreated. The overall response rate was 88% (50% complete remission and 38% partial remission). The median time to treatment failure was 37.9 months. Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL.
Implementation of the EGFP‐K562 flow cytometric NK test: Determination of NK cytotoxic activity in healthy elderly volunteers before and after feeding

Natural Killer (NK) cells are key actors of innate immunity that supervise the organism's cells, and fight against viral infections and cancer development through their cytotoxic activity. This cytotoxic activity is modulated by cytokines and hormones and could be influenced by physiological or pathological conditions. New techniques for measuring NK cytotoxic activity by flow‐cytometry have recently been developed, and they correlated strongly with the standard chromium (51Cr) release assay. Our aim was to implement a previously published enhanced green fluorescent protein (EGFP)‐K562 flow cytometric method and use it to evaluate NK cytotoxic activity under different nutritional conditions.
PUBLIC CAPITAL AND PRIVATE SECTOR PERFORMANCE: VAR/ECM MODELING

Empirical evidence on the dynamic effects of public capital on real economic growth in the United States is presented in this paper. The sample period covers the years 1971–2001. A five-variable VAR model and a Vector Error Correction (VEC) model are estimated using the following variables: public net capital stock, private net capital stock, the number of employed persons, an energy to all commodities price index ratio, real gross domestic product.
Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors: preliminary data from the prostate, lung, colon, and ovarian cancer screening trial.

OBJECTIVE We assessed whether asymptomatic ovarian abnormalities detected on ultrasonography in postmenopausal women are precursors to ovarian cancer. STUDY DESIGN We compared the transvaginal ultrasonographic findings from the initial examination of 20,000 postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening with data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suggestive characteristic(s) of a septum, a solid component, or an irregular or thick wall ("complex cysts") from simple sonolucent cysts with none of those features. RESULTS High parity, a strong ovarian cancer protective factor, was negatively associated with complex cysts (odds ratio for > or =5 births vs no births, 0.72; 95% confidence interval, 0.53-0.97), but long-term oral contraceptive use, another strong ovarian cancer protective factor, was not associated with complex cysts (odds ratio, 0.96; 95% confidence interval, 0.76-1.20). A family history of ovarian cancer or multiple breast cancers, a strong risk factor for cancer, was not associated with complex cysts (odds ratio, 0.99; 95% confidence interval, 0.68-1.44). Other abnormalities found on ultrasonography (including simple cysts, bilateral cysts, or all abnormalities combined) also did not share the established risk factors for ovarian malignancy. We did not identify any combination of features of abnormalities (septum, echogenicity, size, or papillary projections) that manifested the cancer risk factor profile. CONCLUSIONS Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasonography are determined to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer. The eventual identification of such precursors will yield opportunities for earlier diagnosis, screening of high-risk groups, and better understanding of the cause of this often lethal malignancy.
Sources of Momentum Profits in Emerging Stock Markets: The Case of Dhaka Stock Exchange

This study focuses on sources of momentum strategies for the Dhaka Stock Exchange of Bangladesh. For these purposes, this study applies models based on serial correlation and lead - lag effect suggested by Jegadeesh and Titman (1993) and (1995) respectively. Results of these models find that investors' overreaction to firm- specific information is the source of momentum profits in the Dhaka Stock Exchange. Furthermore, lead- lag pattern in stock returns does not contribute to the expected momentum profits in Dhaka Stock Exchange. However, this study finds a large difference between expected and actual momentum profits for the Dhaka Stock Exchange.
Fourier Transform Infrared Imaging Analysis of Cancellous Bone in Alendronate- and Raloxifene-Treated Osteopenic Sheep

Fourier transform infrared imaging spectroscopy (FTIRI)-assessed bone composition parameters (mineral content, collagen maturity, crystal size and perfection, and carbonate content) describe bone quality and correlate to bone fracture risk. The challenge with studying bone quality in patients treated with antiresorptive drugs such as bisphosphonates (e.g., alendronate) and selective estrogen receptor modulators (SERMs) (e.g. raloxifene) is being able to test bone mechanical performance and material properties pre- and posttreatment. The purpose of this study was to evaluate the FTIRI changes in a large animal model of osteoporosis (female sheep with dietary induced metabolic acidosis; MA). Previous studies have investigated the relationship between bone material properties and bone strength in humans and smaller animals and have shown that changes in compositional properties influence fracture risk. Here we characterize the MA model at 6 and 12 months, demonstrate the loss of bone and changes in compositional properties, and show that 6 months of treatment with both antiresorptives ameliorate the bone loss as assessed by bone mineral density and FTIRI. This preliminary data suggest that the MA sheep model allows investigation of whether drug treatments preserve bone properties that exist at the time of treatment or if they induce further beneficial changes.
Versatile Synthesis and Rational Design of Caged Morpholinos

Embryogenesis is regulated by genetic programs that are dynamically executed in a stereotypic manner, and deciphering these molecular mechanisms requires the ability to control embryonic gene function with similar spatial and temporal precision. Chemical technologies can enable such genetic manipulations, as exemplified by the use of caged morpholino (cMO) oligonucleotides to inactivate genes in zebrafish and other optically transparent organisms with spatiotemporal control. Here we report optimized methods for the design and synthesis of hairpin cMOs incorporating a dimethoxynitrobenzyl (DMNB)-based bifunctional linker that permits cMO assembly in only three steps from commercially available reagents. Using this simplified procedure, we have systematically prepared cMOs with differing structural configurations and investigated how the in vitro thermodynamic properties of these reagents correlate with their in vivo activities. Through these studies, we have established general principles for cMO design and successfully applied them to several developmental genes. Our optimized synthetic and design methodologies have also enabled us to prepare a next-generation cMO that contains a bromohydroxyquinoline (BHQ)-based linker for two-photon uncaging. Collectively, these advances establish the generality of cMO technologies and will facilitate the application of these chemical probes in vivo for functional genomic studies.
The impact of the antivirus on the digital evidence

Digital forensics DF has a significant role in accusing cyber criminals and proving them guilty. A criminal, if possible, may manage to delete the crime evidences in order to deny her responsibility about the crime. As the antivirus AV becomes an essential security component, this paper studies the effect of the AV on the digital evidence. The AV intercepts many system operations to check if the involved data contain malicious contents. This paper studies the effect of the AV on data from forensics perspectives. We design representing experiments and check if the AV affects the RAM artefacts of the involved tasks. We test three common AVs and show that the AV has an obvious effect on the RAM artefacts. To the best of our knowledge, we are the first to study the impact of the AV on the digital evidence.
Placebo Ointment Response in the Blanching Test

REFEREN'CES CREAM, J . J. (1971) Iniiiuinoiluorescent Studios of tho Skin in Cryoglobiilinaemic Va-sciilitis. Br, J. Derm. , S4, 48. HEITMANN, H . J . & KxuKEN, N. (1970) Iinniunofluorescenzserologische Untersuchiingen bei dcr Vasculitis Ruiter. Arch. klin. e-xp. Derm. ,237, 59, LtJDERS, G. (1970) Zur Pathogoncso drogeiiallcrgischer Morphen an Her Haiit. Arrh. H'ii>. foiji. Derm. , 237, 201. MiESCHER, P. A. , PAKONETTO, F . & KoFFLER, I). (1965) Immunofluorescont Studies in Human Vasculitis. In Immunopaihology. IVlh Intel-national Sn-inposiwn. Ed. P. Grabar and P. A. Micscher. Basel: Schwabe. P. 446. BuiTER, M. (1965) Vornehmlich auf die Haut beschrankte altergische Vaskulitiden. Zentbl. Pklebologie, 4, 120.
Randomized clinical trials, developmental theory, and antisocial youth: Guidelines for research

The design of effective interventions for antisocial adolescents has been greatly influenced by research-based developmental theories. However, randomized clinical trials (RCTs) demonstrating effectiveness of these treatments have contributed minimally to alterations and refinements of these theories. In this article, nine guidelines for research that may enhance the contributions of RCTs to developmental theory are proposed: (1) use mediational analyses to test and refine theories of change; (2) use moderator analyses to test differential pathways to change; (3) assess change processes separately for different types of antisocial behavior; (4) use constructive and dismantling designs to isolate effects of intervention components on targeted mediators and outcomes; (5) assess the time-sensitive nature of change mechanisms with theoretically relevant spacing of multiple assessments and long-term follow-ups; (6) expand the nomological net of developmental theories by assessing intervention effects on nontargeted constructs; (7) use RCTs to disentangle direction of effects questions in developmental theories; (8) conduct secondary analyses of RCTs to assess extra-treatment influences on antisocial behavior; and (9) assess the generalizability of mediator and moderator effects. Use of these guidelines may promote a recursive and iterative relationship between RCTs and theory building. Improved developmental theories may yield more effective interventions, and theory-testing interventions may engender more comprehensive and better informed theories.
Shiitake mushrooms and molecular clocks: historical biogeography of Lentinula

Fungi make up a large, ecologically important group of eukaryotes that has been neglected in historical biogeography. In this study, molecular phylogenies and molecular clock dating were used to infer historical biogeography of the shiitake genus, Lentinula Earle, which occurs in both the Old World and New World. The major goals of this study were to determine if the Old World and New World groups are monophyletic, and whether the Old World/New World disjunction is the result of vicariance or long distance dispersal.
CheY‐mediated modulation of Campylobacter jejuni virulence

Four motile, non‐adherent and non‐invasive mutants of Campylobacter jejuni 81‐176 generated by a site‐specific insertional mutagenesis scheme were characterized at the molecular level and all contained a duplication of the same region of the chromosome. When this region was cloned from wild‐type 81‐176 and transferred into 81‐176 on a shuttle plasmid, the same non‐invasive phenotype as the original mutants was observed, suggesting that the region contained a repressor of adherence and invasion. The smallest piece of DNA identified which was capable of repressing adherence and invasion was a 0.8 kb fragment encoding the cheY gene of C. jejuni. To confirm further that CheY was responsible for the observed non‐adherent and non‐invasive phenotypes, the cheY gene was inserted into the arylsulfatase gene of 81‐176 to generate a strain with two chromosomal copies of cheY. This diploid strain displayed the same non‐adherent and non‐invasive phenotype as the original mutants. Insertional inactivation of the cheY gene in 81‐176 resulted in an approx. threefold increase in adherence and invasion in vitro, but this strain was unable to colonize or cause disease in animals. The diploid cheY strain, although able to colonize mice, was attenuated in a ferret disease model.
Community Response of Cladocera to Trophic Stress by Biomanipulation in a Shallow Oxbow Lake

Studying contemporary and subfossil Cladocera (Crustacea) communities, we explored the effect of top-down stressors on the cladoceran communities; we are also interested in the coherence of the contemporary and subfossil communities. The studied Cibakháza oxbow lake is in E Hungary, on the left-floodplain of the River Tisza; it is a large, long, and shallow oxbow lake. Three areas of the oxbow lake were distinguished based on the strength of top-down stress: protected area with low top-down stress, biomanipulated area with high top-down stress, and recreational area with moderate top-down stress. Altogether, we identified 28 taxa in the contemporary and subfossil communities in the oxbow lake. We found that the species number of the contemporary Cladocera communities was lower (protected area: 13; biomanipulated area: 9, and recreational area: 14) than in the subfossil communities (protected area: 20; biomanipulated area: 16, and recreational area: 14). Among the environmental variables, we observed differences between the protected and biomanipulated area, while the recreational area showed a transition. Species number, abundances, and Simpson diversity also showed the effect of the fish introduction. There were no differences in beta-diversity among the contemporary and subfossil Cladocera community. The non-metric multidimensional scaling (NMDS) ordination showed that the biomanipulated area in the case of the contemporary communities was separated from the other areas, while in the case of the subfossil communities, there was no separation according to top-down stress. Our results showed that the number of species of contemporary Cladocera communities was lower in each area (3–10; 3–9; 5–9) compared to the subfossil communities (6–17; 7–12; 8–12). However, the highest abundances were found in the biomanipulated area due to the appearance of small-sized Cladocera species. Our findings suggest that the effect of a short-time fish introduction is restorable when the oxbow lake has a protected part.
Mucins carrying selectin ligands as predictive biomarkers of disseminated intravascular coagulation complication in ARDS.

BACKGROUND ARDS patients present with intrapulmonary and systemic coagulation abnormalities. We previously demonstrated that circulating KL-6/MUC1 could predict complications of disseminated intravascular coagulation (DIC) in ARDS. Recent studies indicate that circulating mucin can induce intravascular coagulation via interactions with selectin. We, therefore, investigated whether circulating mucins carrying selectin ligands are associated with DIC in ARDS. METHODS We evaluated newly diagnosed patients with ARDS (n = 46) or bacterial pneumonia (n = 17), and healthy control subjects (n = 60). Using serum collected at diagnosis, circulating levels of KL-6/MUC1, KL-6/MUC1 carrying sialyl Lewis(a) (SLAK), KL-6/MUC1 carrying sialyl Lewis(x) (SLXK), and P-selectin glycoprotein ligand-1 (PSGL-1) were measured. RESULTS Serum mucins with selectin ligands were significantly elevated in patients with ARDS compared with healthy control subjects. Significantly elevated levels of SLAK and SLXK were found in patients with ARDS subsequently complicated with DIC, as compared with those without DIC. In contrast, serum PSGL-1 levels were significantly decreased in ARDS patients with DIC. Furthermore, SLAK was discovered to be an independent predictor of DIC complication in ARDS. Using cutoff levels obtained by receiver operating characteristic curves, we found that these mucins can be used to distinguish between patients with ARDS with and without subsequently occurring DIC. Among the analyzed mucins, SLAK has the highest sensitivity and specificity for predicting future DIC development. CONCLUSIONS These results suggest that mucins with selectin ligands are novel markers for ARDS with future complications of DIC, and KL-6/MUC1 carrying selectin ligands may be involved in the pathogenesis of DIC in patients with ARDS.
Privacy and Autonomous Systems

We discuss the problem of privacy in autonomous systems, introducing different conceptualizations and perspectives on privacy to assess the threats that autonomous systems may pose to privacy. After this, we outline technical and legal measures that should be put in place to mitigate these threats. Beyond privacy threats and countermeasures, we also argue how autonomous systems may be, at the same time, the key to address some of the most challenging and pressing privacy problems nowadays and in the near future.
The telomere hypothesis of stress and aging

3 The “Telomere Hypothesis of Stress and Aging” 4 Telomeres and Aging—“The Telomere Hypothesis of Cellular Aging” 5 Telomeres in Ecology and Evolutionary Biology 7 Telomere Regulation of Gene Expression 9 Telomere Length and Gene Expression are Dependent on Chromatin State 11 Telomere Recombination (Normal ALT) Facilitates Length Dynamics 13 Telomere Transcription (TERRA) and Normal ALT 15 The Three ‘Telotype’ Model of Telomere Function 16 Telotype-Mediated Stress Resilience 17 Heritability of Telomere Length 20 Mechanisms of Stress and TL Interaction 23 References 24 CHAPTER 3. TELOMERE LOSS AND LIFESPAN RELATIONSHIPS DIFFER BETWEEN BIRDS AND MAMMALS 41 Abstract 4
Complete genomic sequence and recombination analysis of wheat yellow mosaic virus isolate from Zhouzhi in China

Wheat yellow mosaic virus (WYMV) is the causal agent of wheat yellow mosaic disease in China. WYMV was detected in wheat sample collected from Zhouzhi of Shanxi province. The nearly complete genomic sequence of Zhouzhi isolate (WYMV-ZZ) was determined; it was compared with six complete sequences of WYMV isolates (five Chinese isolates and one Japanese isolate). WYMV-ZZ and the other six different WYMV isolates shared 96.6 to 97.7% and 95.1 to 98.2% nucleotide sequence identity for RNA1 and RNA2, respectively; at the amino acid level, WYMV-ZZ had 94.1 to 98.2% identity for RNA1 and 94.1 to 96.7% identity for RNA2, respectively, with the other six isolates. Phylogenetic analysis showed that the NIa-VPg region can separate the Chinese isolates from Japanese isolate. Based on the recombinant analysis, there were three possible recombination events; one event was located in RNA1 CI region of WYMV-ZZ with a RDP P-value of 8.526×10-06. This work advanced our understanding of the WYMV molecular variation and was helpful to study the disease spread. Key words: Sequence comparison, phylogenetic analysis, NIa-VPg, recombinant event.
Vsx‐1 and Vsx‐2: Differential expression of two Paired‐like homeobox genes during zebrafish and goldfish retinogenesis

Vsx‐1 and Vsx‐2 are two homeobox genes that were cloned originally from an adult goldfish retinal library. They are members of the paired‐like:CVC gene family, which is characterized by the presence of a paired homeodomain and an additional conserved region, termed the CVC domain. To analyze the possible roles for Vsx‐1 and Vsx‐2 in eye development, we used in situ hybridization to examine their expression patterns in zebrafish and goldfish embryos. Vsx‐2 is initially expressed by proliferating neuroepithelial cells of the presumptive neural retina, then it is down‐regulated as differentiation begins, and it is finally reexpressed at later stages of differentiation in a subset of cells, presumed to be bipolar cells, in the inner nuclear layer. In contrast, Vsx‐1 is expressed only weakly in undifferentiated, presumptive neural retina and is then up‐regulated selectively in presumptive bipolar cells at early stages of differentiation (when Vsx‐2 is turned off), before decreasing to an intermediate level, which is maintained in the differentiated (adult) retina. The restricted expression patterns of Vsx‐2 correspond to the observed phenotypes in mice with the ocular retardation mutation (orJ), further supporting the notion that Vsx‐2 and Chx10 are homologues. The sequential complimentary and then corresponding expression patterns of Vsx‐1 and Vsx‐2 suggest that these similar transcription factors may be recruited for partially overlapping, but distinct, functions during the development of the retina. J. Comp. Neurol. 388:495–505, 1997. © 1997 Wiley‐Liss, Inc.