Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabis abuse is not a risk factor for treatment outcome in methadone maintenance treatment: a 1-year prospective study in an Israeli clinic.

OBJECTIVE We addressed the following questions. What are the current and lifetime prevalence of cannabis abuse in an Israeli methadone maintenance treatment (MMT) clinic? Does cannabis abuse change over time during MMT? Is cannabis abuse related to treatment outcome measures such as retention rate and the abuse of drugs? Is the abuse of cannabis related to psychopathology, HIV/HCV risk-taking and infectious diseases? Do cannabis abusers (CAs) have a different psychosocial and demographic profile than nonabusers (NCAs)? Is cannabis abuse part of a polydrug abuse tendency or a distinct substance of abuse? METHOD Overlapping samples of either the entire clinic population (n = 283) or all the patients who had completed 1 year of MMT treatment (n = 196 of which 20 were re-entering) underwent random and twice-weekly observed urine analysis for various drugs of abuse, responded to self-report questionnaires (SCL-90-R; HIV/HCV risk-taking behaviours; n = 164), interviews (ASI, n = 176; SCID, n = 151) and hepatitis C and HIV testing (n = 149). RESULTS Lifetime abuse prevalence was found in 75% and current abuse at MMT intake in 25%. Abuse did not increase significantly over a 1-year period. Cannabis abusers were found to be more often polydrug abusers than NCAs. Cannabis abusers did not suffer from more psychological distress, infectious diseases, and did not engage in more HCV/HIV risk-taking behaviour, nor did they leave treatment earlier than NCAs. CONCLUSIONS Cannabis abuse MMT patients should be treated as polydrug abusers, although no specific influences of cannabis abuse on psychological and medical conditions of MMT patients have been observed. Treatment policy should take these results into consideration.
Spinal cord stimulation for patients with failed back surgery syndrome: a systematic review.

BACKGROUND Failed back surgery syndrome is common in the United States. Management of post lumbar surgery syndrome with multiple modalities includes interventional techniques, resulting in moderate improvement, leaving a proportion of patients in intractable pain. The systematic reviews of long-term benefits and risks of spinal cord stimulation (SCS) for patients with failed back surgery syndrome showed limited to moderate evidence and cost effectiveness. However, with the exponential increase in surgery in the United States, spinal cord implants are also increasing. Thus, the discussion continues with claims of lack of evidence on one hand and escalating increases in utilization on the other hand. STUDY DESIGN A systematic review of SCS in patients with failed back surgery syndrome. OBJECTIVES This systematic review is undertaken to examine the evidence from randomized controlled trials (RCTs) and observational studies to evaluate the effectiveness of SCS in post lumbar surgery syndrome and to demonstrate clinical and cost effectiveness. METHODS Review of the literature was performed according to the Cochrane Musculoskeletal Review Group Criteria as utilized for interventional techniques for randomized trials and the Agency for Healthcare Research and Quality (AHRQ) criteria for observational studies. The 5 levels of evidence were classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature of the English language identified through searches of PubMed and EMBASE from 1966 to December 2008, and manual searches of bibliographies of known primary and review articles. OUTCOME MEASURES The primary outcome measure was pain relief (short-term relief < or = one-year and long-term > one-year). Secondary outcome measures of improvement in functional status, psychological status, return to work, and reduction in opioid intake were utilized. RESULTS The indicated evidence is Level II-1 or II-2 for long-term relief in managing patients with failed back surgery syndrome. LIMITATIONS The limitations of this review included the paucity and heterogeneity of the literature. CONCLUSION This systematic review evaluating the effectiveness of SCS in relieving chronic intractable pain of failed back surgery syndrome indicated the evidence to be Level II-1 or II-2 for clinical use on a long-term basis.
The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells

ABSTRACT RNA interference (RNAi) is a process of eukaryotic posttranscriptional gene silencing that functions in antiviral immunity in plants, nematodes, and insects. However, recent studies provided strong supports that RNAi also plays a role in antiviral mechanism in mammalian cells. To combat RNAi-mediated antiviral responses, many viruses encode viral suppressors of RNA silencing (VSR) to facilitate their replication. VSRs have been widely studied for plant and insect viruses, but only a few have been defined for mammalian viruses currently. We identified a novel VSR from coronaviruses, a group of medically important mammalian viruses including Severe acute respiratory syndrome coronavirus (SARS-CoV), and showed that the nucleocapsid protein (N protein) of coronaviruses suppresses RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. Mouse hepatitis virus (MHV) is closely related to SARS-CoV in the family Coronaviridae and was used as a coronavirus replication model. The replication of MHV increased when the N proteins were expressed in trans, while knockdown of Dicer1 or Ago2 transcripts facilitated the MHV replication in mammalian cells. These results support the hypothesis that RNAi is a part of the antiviral immunity responses in mammalian cells. IMPORTANCE RNAi has been well known to play important antiviral roles from plants to invertebrates. However, recent studies provided strong supports that RNAi is also involved in antiviral response in mammalian cells. An important indication for RNAi-mediated antiviral activity in mammals is the fact that a number of mammalian viruses encode potent suppressors of RNA silencing. Our results demonstrate that coronavirus N protein could function as a VSR through its double-stranded RNA binding activity. Mutational analysis of N protein allowed us to find out the critical residues for the VSR activity. Using the MHV-A59 as the coronavirus replication model, we showed that ectopic expression of SARS-CoV N protein could promote MHV replication in RNAi-active cells but not in RNAi-depleted cells. These results indicate that coronaviruses encode a VSR that functions in the replication cycle and provide further evidence to support that RNAi-mediated antiviral response exists in mammalian cells.
Differential evolution for a constrained combinatorial optimisation problem

Differential evolution (DE) has been extensively applied to continuous problems, its mechanics naturally lending themselves to such. While some efforts have been made to adapt it to combinatorial problems, these have largely been problem specific and have not dealt extensively with constraint handling beyond penalty approaches. In this paper, a simple and generic strategy, relying on pre-developed heuristic units, is applied to DE and the generalised assignment problem. In addition, a simple, parameter-free approach to adapting control parameters is used. The results are competitive with other well established meta-heuristics. However, there is still scope for further improvement in the way that DE may be applied to constrained combinatorial optimisation.
Perspectives on Pooled Data Analysis: the Case for an Integrated Approach

In the absence of denitive trials on the safety and ecacy of drugs, a systematic and careful synthesis of available data may provide critical in- formation to help decision making by policy makers, medical professionals, patients and other stakeholders. However, uncritical and unbalanced use of pooled data to inform decision about important healthcare issues may have consequences that adversely impact public health, stie innovation, and con- found medical science. In this paper, we highlight current methodological issues and discuss advantages and disadvantages of alternative meta-analytic techniques. It is argued that results from pooled data analysis would have maximal reliability and usefulness in decision making if used in a holistic framework that includes presentation of data in light of all available knowl- edge and eective collaboration among academia, industry, regulatory bodies and other stakeholders.
Simple Round Compression for Parallel Vertex Cover

Recently, Czumaj et.al. (arXiv 2017) presented a parallel (almost) $2$-approximation algorithm for the maximum matching problem in only $O({(\log\log{n})^2})$ rounds of the massive parallel computation (MPC) framework, when the memory per machine is $O(n)$. The main approach in their work is a way of compressing $O(\log{n})$ rounds of a distributed algorithm for maximum matching into only $O({(\log\log{n})^2})$ MPC rounds. In this note, we present a similar algorithm for the closely related problem of approximating the minimum vertex cover in the MPC framework. We show that one can achieve an $O(\log{n})$ approximation to minimum vertex cover in only $O(\log\log{n})$ MPC rounds when the memory per machine is $O(n)$. Our algorithm for vertex cover is similar to the maximum matching algorithm of Czumaj et.al. but avoids many of the intricacies in their approach and as a result admits a considerably simpler analysis (at a cost of a worse approximation guarantee). We obtain this result by modifying a previous parallel algorithm by Khanna and the author (SPAA 2017) for vertex cover that allowed for compressing $O(\log{n})$ rounds of a distributed algorithm into constant MPC rounds when the memory allowed per machine is $O(n\sqrt{n})$.
Hypoxia inducible factor‐1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor‐1α (HIF‐1α), and HIF‐1α has been associated with an impaired prognosis in breast cancer and down‐regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF‐1α regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF‐1α using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF‐1α was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki‐67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF‐1α expressing tumours. In lymph node‐positive patients as well as NHG 1/2 tumours, high HIF‐1α protein expression was significantly associated with an impaired recurrence‐free survival (p = 0.014, 0.018). When analyzing the subgroup of NHG 1/2 tumours, a high HIF‐1α expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF‐1α might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. © 2005 Wiley‐Liss, Inc.
Longitudinal Changes in Optical Quality, Spatial Vision, and Depth Vision after Laser Refractive Surgery for Myopia.

SIGNIFICANCE Laser refractive surgery procedures are efficacious at correcting myopia, but they result in long-term deterioration of optical quality that affects monocular and binocular visual performance. The study shows that the optical quality of the two eyes needs to be similar to optimize binocular visual performance after surgery. PURPOSE This study aimed to systematically analyze longitudinal changes in optical quality, high- and low-contrast logMAR acuity and random-dot stereoacuity before and after three refractive surgery procedures for correcting myopia. METHODS A total of 106 subjects (laser-assisted in situ keratomileusis, 40; photorefractive keratectomy, 26; small-incision lenticule extraction, 40) with myopia and astigmatism ≤1.5 D participated in this prospective cohort-based study. All aforementioned outcome variables were measured in both eyes pre-operatively and 1 week and 1, 3, and 6 months post-operatively. RESULTS Pre-operative myopic spherical equivalent of refraction (median [25th to 75th interquartile range], -6.4 D [-8.0 to -4.2 D] for laser-assisted in situ keratomileusis, -4.3 D [-5.0 to -3.5 D] for photorefractive keratectomy, -5.5 D [-6.5 to -4.3 D] for small-incision lenticule extraction) was corrected to within ±0.75 D of emmetropia in all cohorts up to 6 months post-operatively (P < .001). Higher-order wavefront aberrations, uncorrected high- and low-contrast logMAR acuity, and stereoacuity all worsened and remained so up to 6 months post-operatively, relative to pre-operative values (P < .001). Stereoacuity worsened with both interocular average and difference in the magnitude of higher-order aberrations, whereas logMAR acuities worsened only with interocular average of these aberrations (r ≥ 0.40; P < .01 for all). CONCLUSIONS Although the refractive surgery procedures tested here correct myopia, they result in a sustained (up to 6 months) loss of optical quality and spatial and depth-related visual functions post-operatively. Both interocular average and difference in the eye's optical quality seem to impair binocular visual functions after refractive surgery for myopia.
Phosphatidylinositol 3‐kinase coordinately activates the MEK/ERK and AKT/NFκB pathways to maintain osteoclast survival

We have examined highly purified osteoclasts that were generated in vitro from murine co‐culture of marrow precursors with stromal support cells and have found evidence of activation of the MEK/ERK and AKT/NFκB survival pathways. Many mature marrow‐derived osteoclasts survived for at least 48 h in culture whether or not they are maintained with stromal cells. Moreover, supplementing purified osteoclasts with RANKL and/or M‐CSF had no impact on their survival pattern. In addition, spleen‐derived osteoclasts generated with RANKL and M‐CSF treatment exhibited a similar survival pattern. Blocking MEK, AKT, or NFκB activity resulted in apoptosis of many, but not all, of the osteoclasts in purified marrow‐derived osteoclasts, marrow‐derived osteoclasts co‐cultured with stromal cells, and spleen‐derived osteoclasts maintained with RANKL and M‐CSF. These data support that both the MEK/ERK and AKT/NFκB pathways contribute to osteoclast survival. Since PI3K has been shown to activate either of these pathways, we have examined its role in osteoclast survival. PI3K inhibition caused apoptosis of nearly all osteoclasts in purified and co‐cultured marrow‐derived osteoclasts and spleen‐derived osteoclasts maintained with RANKL and M‐CSF. Interestingly, in marrow‐derived co‐cultures, the apoptotic response was restricted to osteoclasts as there was no evidence of stromal support cell apoptosis. PI3K inhibition also blocked MEK1/2, ERK1/2, and AKT phosphorylation and NFκB activation in purified osteoclasts. Simultaneous blockage of both AKT and MEK1/2 caused rapid apoptosis of nearly all osteoclasts, mimicking the response to PI3K inhibition. These data reveal that PI3K coordinately activates two distinct survival pathways that are both important in osteoclast survival. J. Cell. Biochem. 89: 165–179, 2003. © 2003 Wiley‐Liss, Inc.
Microevolución En San Pedro De Atacama (Norte De Chile): El Cementerio De Quitor

Resumen Se estudia la diferenciación temporal y la divergencia genética entre los períodos Formativo (300 a.C–400 d.C), Tiwanaku (400 d.C–1000 d.C.) y Desarrollo Regional (1000 d.C–1470 d.C.) del grupo inhumado en el ayllu de Quitor de San Pedro de Atacama (Norte de Chile), con el fin de conocer si existen cambios biológicos asociados con los períodos o fases del desarrollo cultural de la región. La muestra está representada por 326 individuos provenientes de diferentes sitios o sectores del yacimiento. Para evaluar las diferencias fenotípicas entre períodos se emplearon 37 caracteres métricos del cráneo y un conjunto de procedimientos de análisis estadístico uni y multivariado. En el marco de la teoría genética de los caracteres cuantitativos se espera que el parentesco de cada período junto con la varianza fenotípica, fluctúen de acuerdo con el tamaño efectivo y el aporte migratorio desde regiones próximas y más o menos distantes. En efecto, el parentesco promedio estimado para este ayllu (FST) fue de . 03, siendo mayor en mujeres que en hombres. En general, de acuerdo con este valor es posible inferir que los habitantes de Quitor vivieron en una condición de mayor aislamiento que los grupos agroalfareros asentados en el Valle de Azapa (FST = .013). Además en el período Medio (Tiwanaku) se produjo un incremento moderado de la varianza fenotípica producida probablemente por un exceso de flujo gènico proveniente de regiones próximas.
Designing a large prevention trial: statistical issues

Recent research in Alzheimer's disease (AD) is centred about the early detection and prevention of this disease. Several recent moderate size clinical trials targeted at high risk cohorts have been designed along this theme. There have been few attempts to design a large trial to prevent this disease in elderly individuals at low risk for the disease. The purpose of this paper is to suggest a framework for designing a simple, large AD prevention trial. This framework uses a discrete time hazard model for decreasing the incidence of AD when participants are randomly assigned to one or more active prevention agents or placebo. This design allows for differential incidence among participants due to age, family history, genetic disposition, and ethnicity. It takes into account the length of the follow‐up period, participant mortality, drop‐outs, drop‐ins, and loss to follow‐up. This framework is illustrated by PREADVISE, a recently initiated large add‐on prevention trial investigating the use of anti‐oxidants for preventing AD among men enrolled in a even larger prostate cancer prevention study, SELECT. Copyright © 2004 John Wiley & Sons, Ltd.
Thermal acclimation modulates the impacts of temperature and enrichment on trophic interaction strengths and population dynamics

Global change affects individual phenotypes and biotic interactions, which can have cascading effects up to the ecosystem level. However, the role of environmentally induced phenotypic plasticity in species interactions is poorly understood, leaving a substantial gap in our knowledge of the impacts of global change on ecosystems. Using a cladoceran–dragonfly system, we experimentally investigated the effects of thermal acclimation, acute temperature change and enrichment on predator functional response and metabolic rate. Using our experimental data, we next parameterized a population dynamics model to determine the consequences of these effects on trophic interaction strength and food‐chain stability. We found that (1) predation and metabolic rates of the dragonfly larvae increase with acute warming, (2) warm‐acclimated larvae have a higher maximum predation rate than cold‐acclimated ones, and (3) long‐term interaction strength increases with enrichment but decreases with both acclimation and acute temperatures. Overall, our experimental results show that thermal acclimation can buffer negative impacts of environmental change on predators and increase food‐web stability and persistence. We conclude that the effect of acclimation and, more generally, phenotypic plasticity on trophic interactions should not be overlooked if we aim to understand the effects of climate change and enrichment on species interaction strength and food‐web stability.
COMPARISON OF MAGNETIC-GEARED PERMANENT- MAGNET MACHINES

With the advent of magnetic gears, researchers have developed a new breed of permanent-magnet machines. These magnetic-geared permanent-magnet machines artfully incorporate the concept of magnetic gearing into the permanent-magnet machines, leading to achieve low-speed high-torque direct-drive operation. In this paper, a quantitative comparison of three viable magnetic-geared permanent-magnet machines is flrstly performed, hence revealing their key features, merits, demerits and applications. Initially, the development of the magnetic gears, including the converted topologies and fleld-modulated topologies, is reviewed. Then, three viable magnetic-geared permanent-magnet machines are identifled and discussed. Consequently, the corresponding performances are analyzed and quantitatively compared. The results and discussions form an important foundation for research in low-speed high-torque direct-drive systems.
Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography.

CONTEXT Controversy remains as to the optimal management of patients with multiple thyroid nodules. OBJECTIVE The objective of this study was to determine the prevalence, distribution, and sonographic features of thyroid cancer in patients with solitary and multiple thyroid nodules. DESIGN We describe a retrospective observational cohort study that was carried out from 1995 to 2003. SETTING The study was conducted in a tertiary care hospital. PATIENTS Patients with one or more thyroid nodules larger than 10 mm in diameter who had ultrasound-guided fine needle aspiration (FNA) were included in the study. MAIN OUTCOME MEASURES The main outcome measures were prevalence and distribution of thyroid cancer and the predictive value of demographic and sonographic features. RESULTS A total of 1985 patients underwent FNA of 3483 nodules. The prevalence of thyroid cancer was similar between patients with a solitary nodule (175 of 1181 patients, 14.8%) and patients with multiple nodules (120 of 804, 14.9%) (P = 0.95, chi(2)). A solitary nodule had a higher likelihood of malignancy than a nonsolitary nodule (P < 0.01). In patients with multiple nodules larger than 10 mm, cancer was multifocal in 46%, and 72% of cancers occurred in the largest nodule. Multiple logistic regression analysis of statistically significant features demonstrates that the combination of patient gender (P < 0.02), whether a nodule is solitary vs. one of multiple (P < 0.002), nodule composition (P < 0.01), and presence of calcifications (P < 0.001) can be used to assign risk of cancer to each individual nodule. Risk ranges from a 48% likelihood of malignancy in a solitary solid nodule with punctate calcifications in a man to less than 3% in a noncalcified predominantly cystic nodule in a woman. CONCLUSIONS In a patient with one or more thyroid nodules larger than 10 mm in diameter, the likelihood of thyroid cancer per patient is independent of the number of nodules, whereas the likelihood per nodule decreases as the number of nodules increases. For exclusion of cancer in a thyroid with multiple nodules larger than 10 mm, up to four nodules should be considered for FNA. Sonographic characteristics can be used to prioritize nodules for FNA based on their individual risk of cancer.