Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective study of novice smokers

Objective: Case control studies in adults suggest that defective alleles in the gene that codes for the hepatic cytochrome P450 2A6 (CYP2A6) protect against nicotine dependence (ND) and higher levels of cigarette consumption. These two hypotheses were tested in young adolescents. Design: Self reports of tobacco use and ND symptoms were collected every 3–4 months in a prospective study of 1293 grade 7 students from a convenience sample of 10 schools. Subjects: 281 smokers with genetic data were analysed; those who were not already tobacco dependent and who had inhaled (n = 228) were followed 29.9 months on average, until they became dependent or were censored. Main outcome measures: The association between metabolic activity, represented by CYP2A6 genotype, and conversion to dependence was analysed using Cox’s proportional hazards model. Results: During follow up 67 subjects (29.4%) became dependent. Relative to CYP2A6*1/*1, having 1–2 copies of the inactive CYP2A6*2 or *4 variant was a strong risk factor for developing dependence (hazard ratio 2.8, 95% confidence 1.3 to 6.3). Subjects with 1–2 partially inactive CYP2A6*9 or *12 variants were not at increased risk. Mean past-week cigarette consumption at the end of follow up (controlling for age, sex, and number of months since first inhalation) among dependent subjects was 29.1 among normal inactivators, compared to 17.2, and 12.7 among slower (1–2 copies of *9 or *12), and slowest (1–2 copies of *2 or *4) inactivators, respectively (p = 0.09). Conclusion: Adolescents with 1–2 copies of CYP2A6*2 or *4 are at substantially increased risk of becoming dependent but smoke less once dependent. Genetic risk for ND may need to be considered in the conceptualisation of tobacco control programmes for adolescents.
Predictors for the development of post-thrombotic syndrome in patients with primary lower limb deep venous thrombosis: A case–control study

Introduction Post-thrombotic syndrome is a common and debilitating sequelae of lower limb deep venous thrombosis. Very little awareness is present about the risk factors and about the diagnosis, prevention, and treatment of this condition. Objective The objective of this study is to identify the predictors of post-thrombotic syndrome after lower limb deep venous thrombosis. Materials and methods A case–control study was conducted on all adult patients who were admitted with lower limb deep venous thrombosis at our institution from January 2005 to June 2012. These patients were scheduled for a research clinic visit, which included informed consent, data collection, and physical examination. Patients found to have post-thrombotic syndrome served as cases and those without post-thrombotic syndrome served as controls. Villalta scoring system was used to diagnose the post-thrombotic syndrome and then to assess the severity of the condition in both the groups. Cox regression risk factor analysis was performed to identify the predictors of post-thrombotic syndrome. Results Out of the 125 patients examined, 49 were found to have post-thrombotic syndrome. Risk factors found to be significant were body mass index of more than 35 kg/m2 (n = 13, p = 0.003), history of immobilization (n = 19, p = 0.003), one or more hypercoagable disorders (n = 32, p = 0.02), iliofemoral deep venous thrombosis (n = 18, p = 0.001), complete obstruction on ultrasound (n = 26, p = 0.016), unstable range of international normalized ratio (n = 23, p = 0.041) and non-compliance for the use of compressions stockings (n = 14, p = 0.001). On multivariate analysis, one or more hypercoagable disorder, iliofemoral deep venous thrombosis, and non-compliance to the use of compression stockings were found to be independent risk factors for the development of post-thrombotic syndrome. Conclusion One or more hypercoagable disorders, iliofemoral deep venous thrombosis and non-compliance to the use of compression stockings were independent predictors of post-thrombotic syndrome after deep venous thrombosis. These findings will help prognosticate and prevent development of PTS in similar patient populations.
Cross-Resistance to Nitro Drugs and Implications for Treatment of Human African Trypanosomiasis

ABSTRACT The success of nifurtimox-eflornithine combination therapy (NECT) for the treatment of human African trypanosomiasis (HAT) has renewed interest in the potential of nitro drugs as chemotherapeutics. In order to study the implications of the more widespread use of nitro drugs against these parasites, we examined the in vivo and in vitro resistance potentials of nifurtimox and fexinidazole and its metabolites. Following selection in vitro by exposure to increasing concentrations of nifurtimox, Trypanosoma brucei brucei nifurtimox-resistant clones designated NfxR1 and NfxR2 were generated. Both cell lines were found to be 8-fold less sensitive to nifurtimox than parental cells and demonstrated cross-resistance to a number of other nitro drugs, most notably the clinical trial candidate fexinidazole (∼27-fold more resistant than parental cells). Studies of mice confirmed that the generation of nifurtimox resistance in these parasites did not compromise virulence, and NfxR1 remained resistant to both nifurtimox and fexinidazole in vivo. In the case of fexinidazole, drug metabolism and pharmacokinetic studies indicate that the parent drug is rapidly metabolized to the sulfoxide and sulfone form of this compound. These metabolites retained trypanocidal activity but were less effective in nifurtimox-resistant lines. Significantly, trypanosomes selected for resistance to fexinidazole were 10-fold more resistant to nifurtimox than parental cells. This reciprocal cross-resistance has important implications for the therapeutic use of nifurtimox in a clinical setting and highlights a potential danger in the use of fexinidazole as a monotherapy.
Terrane assembly and structural relationships in the eastern Prince Rupert Quadrangle, British Columbia

The eastern part of the Prince Rupert quadrangle, British Columbia, is subdivided into two regions: the western metamorphic belt and the central belt. The western metamorphic belt is underlain by five distinct mappable rock sequences. From west to east these are the Digby, Venn, Delusion Bay, Kaien, and Tsimpsean sequences. Rocks of the Digby sequence seem to correlate with Triassic and upper Paleozoic rocks of the Alexander terrane; the overlying Venn sequence contains rocks of the same age as parts of the Gravina belt. The Tsimpsean sequence is considered to be part of the Yukon-Tanana terrane, a continental margin assemblage. Correlation of the two intervening sequences, Kaien and Delusion Bay, is uncertain; they may belong either to the Taku terrane or to the Yukon-Tanana terrane. We tend to favor the latter interpretation. North- to northwest-striking thrust faults approximately bisect the belt and separate the Digby and Venn sequences on the west from the structurally overlying units to the east. Near Prince Rupert, west-directed, probably mid-Cretaceous, thrusting accompanied emplacement of tonalite and basalt dikes and sills. These thrusts and others to the north juxtapose upper amphibolite facies rocks over greenschist facies schist. The northern thrusts appear to postdate the regional metamorphism. Above and below the thrusts the rocks show intense ductile deformation. The Prince Rupert shear zone, east of the thrusts, records a strong flattening deformation, possibly due to overthrusting by the 91 Ma Ecstall pluton and associated high-grade gneiss. This tectonic emplacement of hot rocks and the associated igneous activity represented by syntectonic tonalite sills emplaced in the shear zone are inferred to be the cause of the 90 Ma amphibolite facies metamorphism that underlies the Prince Rupert shear zone. The western metamorphic belt is bounded on the east by the Coast shear zone, which separates the western belt from the central belt. This shear zone evolved during emplacement of 65-52 Ma plutons of the Paleogene Coast Mountains batholith that underlie much of the central belt. As the Coast Mountains batholith was emplaced, strain within the arc changed from dominantly contractional normal to the batholith and to the orogen, to extensional parallel to the length of the batholith. The latter stages of batholith emplacement apparently accompanied batholith exhumation. The youngest part of the Coast shear zone is a 1-2-km-wide zone of vertical fabric along the western side of the shear zone and is at the westernmost extent of 85-50 Ma plutons. This Work-Behm shear zone formed during the late stages of uplift of the western metamorphic belt by westward tilting about a northwest-trending hinge. After a hiatus with no identified tectonic activity other than gradual exhumation, Miocene and younger felsic and mafic dikes and young brittle faults cut the rocks throughout the eastern part of the quadrangle.
Treatment of interprosthetic fractures of the femur.

BACKGROUND The treatment of interprosthetic femoral fractures is challenging because of several factors. Poor bone stock, advanced age, potential prosthetic instability, and limited fracture fixation options both proximally and distally can complicate standard femur fracture treatment procedures. The purpose of this report was to describe our experience treating interprosthetic femoral fractures, providing an emphasis on treatment principles and specific intraoperative management. METHODS All patients with fractures occurring between ipsilateral hip and knee prostheses between 2004 and 2010 were identified from a comprehensive database and included in this study. Patients had been treated using principles adapted from two isolated periprosthetic fracture classification systems, the Vancouver and Su classifications. The electronic medical record (including inpatient medical records, operative notes, outpatient medical records, and all radiographs) was reviewed for each patient and demographic and treatment-related variables as well as complications and outcomes were recorded. RESULTS Thirteen consecutive patients with interprosthetic fractures were included. Four fractures occurred around a clearly loose prosthesis, which were subsequently treated with long-stemmed revisions. The remaining 12 fractures were treated with a locked-plate construct. Two of nine patients (22.2%) died before fracture union. Follow-up averaged 28 months ± 4 months, with fracture union achieved at an average of 4.7 months ± 0.3 months. All patients returned to their self-reported preoperative ambulatory status except one who developed a loose hip prosthesis at 3-year follow-up after fracture union. CONCLUSIONS The principles for treatment of isolated periprosthetic fractures are useful to guide the fixation of interprosthetic fractures. Locked plating is an effective method for the treatment of interprosthetic femoral fractures. Bypassing the adjacent prosthesis by a minimum of two femoral diameters is a necessary technique to prevent a stress riser.
Simulations of Surfactant Spreading

Thin liquid films driven by surface tension gradients are studied in diverse applications, including the spreading of a droplet and fluid flow in the lung. The nonlinear partial differential equations that govern thin films are difficult to solve analytically, and must be approached through numerical simulations. We describe the development of a numerical solver designed to solve a variety of thin film problems in two dimensions. Validation of the solver includes grid refinement studies and comparison to previous results for thin film problems. In addition, we apply the solver to a model of surfactant spreading and make comparisons with theoretical and experimental results.
A Novel 3D Graphical Password Schema

In this paper, we propose and evaluate our contribution which is a new scheme of authentication. This scheme is based on a virtual three-dimensional environment. Users navigate through the virtual environment and interact with items inside the virtual three-dimensional environment. The combination of all interactions, actions and inputs towards the items and towards the virtual three-dimensional environment constructs the user's 3D password. The 3D password combines most existing authentication schemes such as textual passwords, graphical passwords, and biometrics into one virtual three-dimensional environment. The 3D password's main application is the protection of critical resources and systems
Shifted T Helper Cell Polarization in a Murine Staphylococcus aureus Mastitis Model

Mastitis, one of the most costly diseases in dairy ruminants, is an inflammation of the mammary gland caused by pathogenic infection. The mechanisms of adaptive immunity against pathogens in mastitis have not been fully elucidated. To investigate T helper cell-mediated adaptive immune responses, we established a mastitis model by challenge with an inoculum of 4 × 106 colony-forming units of Staphylococcus aureus in the mammary gland of lactating mice, followed by quantification of bacterial burden and histological analysis. The development of mastitis was accompanied by a significant increase in both Th17 and Th1 cells in the mammary gland. Moreover, the relative expression of genes encoding cytokines and transcription factors involved in the differentiation and function of these T helper cells, including Il17, Rorc, Tgfb, Il1b, Il23, Ifng, Tbx21, and Il12, was greatly elevated in the infected mammary gland. IL-17 is essential for neutrophil recruitment to infected mammary gland via CXC chemokines, whereas the excessive IL-17 production contributes to tissue damage in mastitis. In addition, a shift in T helper cell polarization toward Th2 and Treg cells was observed 5 days post-infection, and the mRNA expression of the anti-inflammatory cytokine Il10 was markedly increased at day 7 post-infection. These results indicate that immune clearance of Staphylococcus aureus in mastitis is facilitated by the enrichment of Th17, Th1 and Th2 cells in the mammary gland mediated by pro-inflammatory cytokine production, which is tightly regulated by Treg cells and the anti-inflammatory cytokine IL-10.
Fitness Impact and Stability of a Transgene Conferring Resistance to Dengue-2 Virus following Introgression into a Genetically Diverse Aedes aegypti Strain

In 2006, we reported a mariner (Mos1)-transformed Aedes aegypti line, Carb77, which was highly resistant to dengue-2 virus (DENV2). Carb77 mosquitoes expressed a DENV2-specific inverted-repeat (IR) RNA in midgut epithelial cells after ingesting an infectious bloodmeal. The IR-RNA formed double-stranded DENV2-derived RNA, initiating an intracellular antiviral RNA interference (RNAi) response. However, Carb77 mosquitoes stopped expressing the IR-RNA after 17 generations in culture and lost their DENV2-refractory phenotype. In the current study, we generated new transgenic lines having the identical transgene as Carb77. One of these lines, Carb109M, has been genetically stable and refractory to DENV2 for >33 generations. Southern blot analysis identified two transgene integration sites in Carb109M. Northern blot analysis detected abundant, transient expression of the IR-RNA 24 h after a bloodmeal. Carb109M mosquitoes were refractory to different DENV2 genotypes but not to other DENV serotypes. To further test fitness and stability, we introgressed the Carb109M transgene into a genetically diverse laboratory strain (GDLS) by backcrossing for five generations and selecting individuals expressing the transgene's EGFP marker in each generation. Comparison of transgene stability in replicate backcross 5 (BC5) lines versus BC1 control lines demonstrated that backcrossing dramatically increased transgene stability. We subjected six BC5 lines to five generations of selection based on EGFP marker expression to increase the frequency of the transgene prior to final family selection. Comparison of the observed transgene frequencies in the six replicate lines relative to expectations from Fisher's selection model demonstrated lingering fitness costs associated with either the transgene or linked deleterious genes. Although minimal fitness loss (relative to GDLS) was manifest in the final family selection stage, we were able to select homozygotes for the transgene in one family, Carb109M/GDLS.BC5. HZ. This family has been genetically stable and DENV2 refractory for multiple generations. Carb109M/GDLS.BC5. HZ represents an important line for testing proof-of-principle vector population replacement.
Deliberation Versus Intuition: Decomposing the Role of Expertise in Judgment and Decision Making

What produces better judgments: deliberating or relying on intuition? Past research is inconclusive. We focus on the role of expertise to increase understanding of the effects of judgment mode. We propose a framework in which expertise depends on a person's experience with and knowledge about a domain. Individuals who are relatively experienced but have modest knowledge about the subject matter ("intermediates") are expected to suffer from deliberation and to benefit from a more intuitive approach, because they lack the formal knowledge to understand the reasons underlying their preferences. Individuals who are high ("experts") or low ("novices") on both experience and knowledge are expected to do well or poorly, respectively, regardless of decision mode. We tested these predictions in the domain of art. Experiments 1 and 2 showed that intermediates performed better when relying on intuition than after deliberation. Judgments of experts and novices were unaffected. In line with previous research relating processing style to judgment mode, Experiment 3 showed that the effect of processing style (global versus local) on judgment quality is similarly moderated by expertise. © 2012 John Wiley & Sons, Ltd.
Battered Woman Syndrome

Abstract: The construct of Battered Woman Syndrome (BWS) has been conceptualized as a subcategory of posttraumatic stress disorder (PTSD). It is composed of the following symptoms: (a) re‐experiencing the battering as if it were reoccurring even when it is not, (b) attempts to avoid the psychological impact of battering by avoiding activities, people, and emotions, (c) hyperarousal or hypervigilance, (d) disrupted interpersonal relationships, (e) body image distortion or other somatic concerns, and (f) sexuality and intimacy issues. This article presents empirical data derived from administering the Battered Woman Syndrome Questionnaire (BWSQ) to women of four countries—United States, Spain, Greece, and Russia. The data support a theory of BWS.
Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs

The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.
Dynamic server allocation to parallel queues with randomly varying connectivity

Consider N parallel queues competing for the attention of a single server. At each time slot each queue may be connected to the server or not depending on the value of a binary random variable, the connectivity variable. Allocation at each slot; is based on the connectivity information and on the lengths of the connected queues only. At the end of each slot, service may be completed with a given fixed probability. Such a queueing model is appropriate for some communication networks with changing topology. In the case of infinite buffers, necessary and sufficient conditions are obtained for stabilizability of the system in terms of the different system parameters. The allocation policy that serves the longest connected queue stabilizes the system when the stabilizability conditions hold. The same policy minimizes the delay for the special case of symmetric queues. In a system with a single buffer per queue, an allocation policy is obtained that maximizes the throughput and minimizes the delay when the arrival and service statistics of different queues are identical. >
Revision of the Patella with Deficient Bone Using a Biconvex Component

Revision surgery on a failed patellar component can be difficult because of deficient residual bone that may compromise the functional outcome of the revision. We reviewed 20 knees in 20 patients in whom the residual patellar bone was less than 10 mm at the time of revision and used the Genesis Biconvex Patella implant to reconstruct the patella. The patients were followed up for an average of 34 months (range, 24-65 months), and were followed up clinically and radiographically by Knee Society criteria. Patellar revisions and complications were noted and standard radiographic studies to ascertain radiolucent lines and patella/patellar component thickness were evaluated. The Knee Society Scores improved from an average of 45 points to 89 points. Function scores improved from an average of 47 points to 65 points. None of the patients has required revision surgery and no patellar fractures have been seen. Radiographs showed complete lucencies at the cement-bone interface in two knees. The mean residual central patella bone thickness was 6.5 mm and the average postoperative composite thickness was 14.5 mm. The data indicate that the use of the Genesis Biconvex Patella implant is a satisfactory method of treating revision of the patella when there is major bone deficiency. Level of Evidence: Retrospective study, Level IV-1 (case study). See the Guidelines for Authors for a complete description of levels of evidence.