Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Results Following Ankle Arthrodesis for Post-Traumatic Arthritis

Background: Ankle arthrodesis is considered by many to be the standard operative treatment for end-stage ankle arthritis; however, the long-term effect of ankle arthrodesis on other lower-extremity joints remains largely unknown. The purpose of this study was to perform a clinical and radiographic review to determine the effect of ankle arthrodesis on the development of osteoarthritis in other lower-extremity joints. Methods: Twenty-three patients who had had an isolated ankle arthrodesis for the treatment of painful post-traumatic arthritis of the ankle were followed for a mean of twenty-two years (range, twelve to forty-four years) after the operation. Each completed standardized, self-reported outcome questionnaires (the Foot Function Index, Western Ontario and McMaster University Osteoarthritis Index [WOMAC], and Short Form-36 [SF-36]), was examined clinically by two of the investigators, and underwent complete radiographic examination of the knee, ankle, and foot bilaterally. The radiographic grade of osteoarthritis was determined for each joint, and the levels of overall activity limitation, pain, and disability were determined for each patient from the clinical findings and questionnaire information. Results: Osteoarthritis of the ipsilateral subtalar (p < 0.0001), talonavicular (p < 0.0001), calcaneocuboid (p < 0.0001), naviculocuneiform (p = 0.0012), tarsometatarsal (p = 0.0009), and first metatarsophalangeal joints (p = 0.0012) was consistently more severe than the osteoarthritis of those joints on the contralateral side. Osteoarthritis did not develop more frequently in the ipsilateral knee or lesser metatarsophalangeal joints than it did on the contralateral side. Significant differences between the two sides were found with regard to overall activity limitation (p < 0.0001), pain (p < 0.0001), and disability (p < 0.0001), with the involved side consistently more symptomatic. Conclusions: To our knowledge, the present series represents the longest follow-up study of ankle arthrodesis to date. Our cohort of patients all had isolated post-traumatic ankle arthritis, and each underwent a successful isolated ankle arthrodesis. At a mean of twenty-two years, the majority of the patients had substantial, and accelerated, arthritic changes in the ipsilateral foot but not the knee. They were often limited functionally by foot pain. Although ankle arthrodesis may provide good early relief of pain, it is associated with premature deterioration of other joints of the foot and eventual arthritis, pain, and dysfunction.
Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.

BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).
Egr-1 Induces the Expression of Its Corepressor Nab2 by Activation of the Nab2 Promoter Thereby Establishing a Negative Feedback Loop*

The transcription factor Egr-1 regulates the expression of numerous genes involved in differentiation, growth, and in response to environmental signals. Egr-1 activity is modulated in part through the binding of corepressors Nab1 and Nab2. Nab2 appears crucial for controlling Egr-1-mediated transactivation because it is a delayed early response gene, induced by the same stimuli that induce the immediate early gene Egr-1. To identify important elements regulating Nab2 expression, we cloned the human Nab2 gene and investigated the 5′-region. The TATA- and initiator-less Nab2 promoter, located from –679 to –74 bp, contains a total of 11 Egr binding sites, including a cluster of multiple overlapping Egr/Sp1 sites between –329 and –260 bp. This region is critical for basal promoter activity as well as for maximum induction by phorbol esters. Electromobility shifts show that Sp1 binds to this region in normal and stimulated cells, whereas stimulation induces binding of Egr-1. In addition Egr-1 activates the Nab2 promoter in a pattern similar to phorbol esters, suggesting that Egr-1 is a major inducer of protein kinase C-mediated Nab2 induction. Depletion of Egr-1 by each of two distinct Egr-1 short-interfering RNAs reduces Nab2 expression and inducibility, confirming that Egr-1 is an important regulator of Nab2 expression. Transfection experiments show that Egr-1-induced Nab2 promoter activity is itself repressed by Nab2. These results indicate that Egr-1 mediates the induction of its own repressor, thereby preventing a permanent transactivation of Egr-1 target genes and a damaging overreaction in response to environmental signals.
The effect of partial sleep deprivation on weight-lifting performance.

This study examined the effects of partial sleep deprivation on submaximal and maximal weight-lifting tasks and on subjective states pre- and post-activity. Eight male subjects (aged 18-24 years) were restricted to a nightly ration of 3 h sleep for 3 successive nights after baseline measures on the first day. A 4 day period where normal sleep was permitted fulfilled a control condition, the normal and sleep-deprived conditions being counterbalanced and separated by 10 days. The weight-lifting tasks consisted of biceps curl, bench press, leg press, and dead lift. For each exercise a submaximal load, corresponding to a fixed value on a category ratio scale of exertion, was determined for 20 repetitions; the maximal lift for that exercise was then obtained. A profile of mood states and subjective sleepiness were determined at each test occasion, tests being conducted in the evening of each day. There was no significant effect of sleep loss on performance of maximal biceps curl (p < 0.05) but a significant effect was noted on maximal bench press, leg press, and dead lift (p < 0.001). Trend analysis indicated decreased performance in submaximal lifts for all the 4 tasks: the deterioration was significant after the second night of sleep loss (p < 0.01). Performing the lifts had little influence on sleepiness ratings which increased linearly with successive days of sleep loss. Mood states of confusion, vigour, and fatigue were affected significantly by the sleep deprivation regimen (p < 0.001), but there was no significant effect of sleep loss or anger, tension, and depression (p > 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Infant feeding practices and attitudes among women with HIV infection in northern Thailand

Knowledge and attitudes towards infant feeding among women in northern Thailand were examined. Face-to-face interviews using structured questionnaires were undertaken in three districts of Chiang Rai province. Subjects included postnatal women with HIV infection (group 1, n=80), antenatal women with HIV infection (group 2, n=36) and antenatal women with unknown HIV status (group 3, n=86). Advantages of breastfeeding and formula feeding according to several characteristics (convenience, cleanliness, cheapness and safety) were rated using a four-point (0-3) scale. Overall, breastfeeding was rated much higher (11.4/12) than formula feeding (6.1/12)(p < 0.0005). Formula feeding rating was highest among postnatal women with HIV infection (6.8/12); however, it was lower than the rating for breastfeeding (11.3/12). The vast majority of women with HIV infection were either formula feeding (group 1, 94%) or intended to formula feed (group 2, 72%) their infants. In contrast, the vast majority of antenatal women of unknown HIV status planned to breastfeed (group 3, 83%). All women, regardless of HIV status, consider breastfeeding to be more advantageous than formula feeding. However, once women with HIV infection are informed of the risk of HIV transmission through breastfeeding, they are able to make their own decision to follow the Thai Ministry of Public Health's recommendation to formula feed.
Outbreaks of salmonellosis associated with eating uncooked tomatoes: implications for public health

Laboratory-based surveillance of salmonella isolates serotyped at four state health departments (Illinois, Michigan, Minnesota and Wisconsin) led to the identification of multistate outbreaks of salmonella infections during 1990 (176 cases of S. javiana) and 1993 (100 cases of S. montevideo). Community-based case-control studies and product traceback implicated consumption of tomatoes from a single South Carolina tomato packer (Packer A) MOR 16·0; 95% CI 2·1, 120·6; P<0·0001 in 1990 and again in 1993 (MOR 5·7; 95% CI 1·5, 21·9; P=0·01) as the likely vehicle. Contamination likely occurred at the packing shed, where field grown tomatoes were dumped into a common water bath. These outbreaks represent part of a growing trend of large geographically dispersed outbreaks caused by sporadic or low-level contamination of widely distributed food items. Controlling contamination of agricultural commodities that are also ready-to-eat foods, particularly fruits and vegetables, presents a major challenge to industry, regulators and public health officials.
Kernel Principal Component Analysis for Fuzzy Point Data Set

Kernel principal component analysis (KPCA) has provided an extremely powerful approach to extracting nonlinear features via kernel trick, and it has been suggested for a number of applications. Whereas the nonlinearity can be allowed by the utilization of Mercer kernels, the standard KPCA could only process exact training samples which be treated uniformly and can't reflect prior information of data. However, in many real-world applications, each training data has different meanings and confidence degrees for population. In this paper, a new concept, called "fuzzy point data" which is defined by giving a fuzzy membership to each training sample, is proposed for helping us handle the confidence of data. We reformulate KPCA for fuzzy point data. Experimental results show our method could embody effects of different samples in constructing principal axes and supply a feasible method to control possible outliers.
Prognosis value of the monoclonal blood plasma cells in multiple myeloma.

To the Editor: We have read with interest the paper of Witzyg et al[1][1] about the prognostic value of peripheral blood clonal plasma cells (PBPC) in patients with multiple myeloma (MM). We have recently evaluated the presence of PBPC at diagnosis in 49 MM patients. Plasma cell leukemia cases were
From User Demand to Software Service: Using Machine Learning to Automate the Requirements Specification Process

Bridging the gap between informal, imprecise, and vague user requirements descriptions and precise formalized specifications is the main task of requirements engineering. Techniques such as interviews or story telling are used when requirements engineers try to identify a user's needs. The requirements specification process is typically done in a dialogue between users, domain experts, and requirements engineers. In our research, we aim at automating the specification of requirements. The idea is to distinguish between untrained users and trained users, and to exploit domain knowledge learned from previous runs of our system. We let untrained users provide unstructured natural language descriptions, while we allow trained users to provide examples of behavioral descriptions. In both cases, our goal is to synthesize formal requirements models similar to statecharts. From requirements specification processes with trained users, behavioral ontologies are learned which are later used to support the requirements specification process for untrained users. Our research method is original in combining natural language processing and search-based techniques for the synthesis of requirements specifications. Our work is embedded in a larger project that aims at automating the whole software development and deployment process in envisioned future software service markets.
The Avian Retrovirus Avian Sarcoma/Leukosis Virus Subtype A Reaches the Lipid Mixing Stage of Fusion at Neutral pH

ABSTRACT We previously showed that the envelope glycoprotein (EnvA) of avian sarcoma/leukosis virus subtype A (ASLV-A) binds to liposomes at neutral pH following incubation with its receptor, Tva, at ≥22°C. We also provided evidence that ASLV-C fuses with cells at neutral pH. These findings suggested that receptor binding at neutral pH and ≥22°C is sufficient to activate Env for fusion. A recent study suggested that two steps are necessary to activate avian retroviral Envs: receptor binding at neutral pH, followed by exposure to low pH (W. Mothes et al., Cell 103:679-689, 2000). Therefore, we evaluated the requirements for intact ASLV-A particles to bind to target bilayers and fuse with cells. We found that ASLV-A particles bind stably to liposomes in a receptor- and temperature-dependent manner at neutral pH. Using ASLV-A particles biosynthetically labeled with pyrene, we found that ASLV-A mixes its lipid envelope with cells within 5 to 10 min at 37°C. Lipid mixing was neither inhibited nor enhanced by incubation at low pH. Lipid mixing of ASLV-A was inhibited by a peptide designed to prevent six-helix bundle formation in EnvA; the same peptide inhibits virus infection and EnvA-mediated cell-cell fusion (at both neutral and low pHs). Bafilomycin and dominant-negative dynamin inhibited lipid mixing of Sindbis virus (which requires low pH for fusion), but not of ASLV-A, with host cells. Finally, we found that, although EnvA-induced cell-cell fusion is enhanced at low pH, a mutant EnvA that is severely compromised in its ability to support infection still induced massive syncytia at low pH. Our results indicate that receptor binding at neutral pH is sufficient to activate EnvA, such that ASLV-A particles bind hydrophobically to and merge their membranes with target cells. Possible roles for low pH at subsequent stages of viral entry are discussed.
Low Temperature Microcrystalline Silicon Solar Cells Prepared by Hot-Wire Chemical Vapor Deposition

Intrinsic hydrogenated microcrystalline silicon (muc-Si:H) films were prepared by hot-wire chemical vapor deposition (HWCVD) using a graphite filament at a substrate temperature of 210degC. Films were characterized by Raman Spectroscopy, FTIR and electrical conductivity measurements with varying silane concentrations on glass substrates. Solar cells were fabricated in a glass/SnO2/pin/Al structure and device efficiency was measured to be 2.8%
Hydrogen sulfide is an endogenous stimulator of angiogenesis

The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H2S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H2S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H2S increased vascular length. Exposure of ECs to H2S resulted in increased phosphorylation of Akt, ERK, and p38. The KATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H2S-induced EC motility. Since glibenclamide inhibited H2S-triggered p38 phosphorylation, we propose that KATP channels lay upstream of p38 in this process. When CAMs were treated with H2S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H2S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H2S release, while pharmacological inhibition of H2S production or KATP channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H2S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H2S enhanced wound healing in a rat model, while wound healing was delayed in CSE−/− mice. We conclude that endogenous and exogenous H2S stimulates EC-related angiogenic properties through a KATP channel/MAPK pathway.
Monoubiquitinated Histone H2A Destabilizes Photolesion-containing Nucleosomes with Concomitant Release of UV-damaged DNA-binding Protein E3 Ligase

Background: The compaction of DNA into nucleosomes interferes with DNA repair. Results: Monoubiquitination of core histone H2A destabilizes nucleosomes containing UV-damaged DNA. Conclusion: Destabilized nucleosomes enable the release of the DNA damage-binding complex DDB1-CUL4BDDB2, which assists in histone ubiquitination. Significance: This mechanism explains how the ubiquitination of histone H2A, in addition to chromatin remodeling, promotes repair and facilitates genome stability. How the nucleotide excision repair (NER) machinery gains access to damaged chromatinized DNA templates and how the chromatin structure is modified to promote efficient repair of the non-transcribed genome remain poorly understood. The UV-damaged DNA-binding protein complex (UV-DDB, consisting of DDB1 and DDB2, the latter of which is mutated in xeroderma pigmentosum group E patients, is a substrate-recruiting module of the cullin 4B-based E3 ligase complex, DDB1-CUL4BDDB2. We previously reported that the deficiency of UV-DDB E3 ligases in ubiquitinating histone H2A at UV-damaged DNA sites in the xeroderma pigmentosum group E cells contributes to the faulty NER in these skin cancer-prone patients. Here, we reveal the mechanism by which monoubiquitination of specific H2A lysine residues alters nucleosomal dynamics and subsequently initiates NER. We show that DDB1-CUL4BDDB2 E3 ligase specifically binds to mononucleosomes assembled with human recombinant histone octamers and nucleosome-positioning DNA containing cyclobutane pyrimidine dimers or 6-4 photoproducts photolesions. We demonstrate functionally that ubiquitination of H2A Lys-119/Lys-120 is necessary for destabilization of nucleosomes and concomitant release of DDB1-CUL4BDDB2 from photolesion-containing DNA. Nucleosomes in which these lysines are replaced with arginines are resistant to such structural changes, and arginine mutants prevent the eviction of H2A and dissociation of polyubiquitinated DDB2 from UV-damaged nucleosomes. The partial eviction of H3 from the nucleosomes is dependent on ubiquitinated H2A Lys-119/Lys-120. Our results provide mechanistic insight into how post-translational modification of H2A at the site of a photolesion initiates the repair process and directly affects the stability of the human genome.
Long‐term safety of biologics in dermatology

The use of biologics in dermatology has increased rapidly. Although most are relatively safe when correctly used and monitored, there are known side effects and adverse events that occur. Selection of patients should be done on a case‐by‐case basis. Severity of disease, comorbidity profile, drug profile, and cost‐effectiveness should be all taken into consideration while deciding to start and/or maintain one of these therapies. Dermatologists should be aware of the benefits and limitations of this class of drugs, as well as the appropriate monitoring. The authors propose a concise overview of the safety profiles of some of the biologics currently used in the dermatologic field.
Is nicotine replacement therapy for smoking cessation effective in the “real world”? Findings from a prospective multinational cohort study

Background: Increasing smoking cessation rates is an important goal in preventing lung cancer and chronic obstructive pulmonary disease. Nicotine replacement therapy (NRT) has been found in clinical trials to improve the chances of success at stopping, but recent cross-sectional survey data have raised doubts as to whether it is effective when used by smokers making quit attempts unsupervised outside clinical trials. Because of biases inherent in cross-sectional surveys, this issue can only be adequately addressed using longitudinal studies. This paper reports the first study of its kind to examine the issue. Methods: The ATTEMPT cohort is a multinational cohort study with data collection by the internet which recruited smokers of ⩾5 cigarettes per day aged 35–65 years who were intending to stop smoking within the next 3 months. Phase 1 began in spring 2003 and involved 2009 smokers from the USA, UK, Canada and France. Phase 2 involved 3645 smokers and included the same countries plus Spain. Follow-up assessments were carried out every 3 months. 492 smokers who made a quit attempt without formal behavioural support or bupropion in the first 3-month follow-up period were identified from phase 1, 357 of whom were followed up for a further 6 months. The phase 2 sample involved 906 smokers making quit attempts, 732 of whom were followed up. At baseline, demographic characteristics, smoking history and nicotine dependence were assessed. Smokers who made quit attempts were questioned on methods used to aid them. The main outcome measure was self-report of complete abstinence throughout both the 3-month periods following the quit date. Results: 35.6% of smokers followed up in phase 1 and 29.6% of those followed up in phase 2 used NRT. The odds ratios comparing abstinence for 6 months in those using and those not using NRT, adjusting for nicotine dependence, were 3.0 (95% CI 1.2 to 7.5) for the phase 1 sample and 2.1 (95% CI 1.0 to 4.1) for the phase 2 sample. The difference in success rates between those using NRT and those not using it, adjusted for the Fagerstrom test for nicotine dependence (FTND) score, was 6% in the phase 1 sample and 3.7% in the phase 2 sample. The improved odds of success were not explicable in terms of motivation to use some form of aid to cessation or differential loss to follow-up. Conclusion: NRT use by smokers making self-initiated quit attempts without formal behavioural support is associated with improved long-term abstinence rates.