Miracle-dz/UniFAR-FTUs huggingface dataset:
Coagulation gene predictors of photodynamic therapy for occult choroidal neovascularization in age-related macular degeneration.

PURPOSE To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.
Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease

Objective There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. Methods We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40–69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. Results Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) −173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. Conclusions Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.
Pediatric Stroke in the United States and the Impact of Risk Factors

One approach to studying pediatric stroke is to analyze a national database that contains data on a significant number of children. We examined an administrative dataset of hospital discharges from the United States, Kids' Inpatient Database 2003 (KID2003), for ICD-9 codes associated with hemorrhagic or ischemic stroke in children aged >30 days to 20 years. 3156 children were discharged with a diagnosis of ischemic stroke and 2022 with hemorrhagic stroke after statistical weighting. The odds for a male discharged with hemorrhagic stroke was 1.5 (CI: 1.35-1.68) and for ischemic stroke was 1.37 (CI: 1.24-1.51) compared with a female. The odds for males discharged with a stroke were greatest for ages 16 to 20 years and least for 4 years. This study confirms a male predominance for stroke. The odds for hospitalization with a stroke diagnosis are greatest in very young and older adolescent males. Hemorrhage is an important stroke subtype in children.
An interaction design for MEL-SindD: A basic reading courseware for Down syndrome children

The design of an early reading courseware (MEL-SindD) for Down syndrome (DS) needs to focus particularly on the students unique learning styles. Thus, this paper reports on DS students' characteristics, shortcomings and strength which need to be integrated in the design of the courseware. Hence, this paper demonstrates how the approaches and learning principles can be translated into guidelines for the interaction design of MEL-SindD that enables to motivate the DS students to learn.
Book Review: Digital piracy: An integrated theoretical approach

stitutes a violation of international human rights protocols. Institutions have attempted to address many issues with the parent–child relationship and even offer parenting courses for incarcerated mothers to learn productive and appropriate parenting techniques. Although these programs have been implemented, Van Gundy and Baumann-Grau contend that alternative diversion-based measures would be better suited to this group of individuals. Chapter 6, in conclusion, applies feminist criminological theory to the idea of gender-specific human rights violations and gives suggestions to policy makers how to effectively change these circumstances. Women, Incarceration, and Human Rights would function as a great supplemental text to any corrections course; chapters could also be helpful in any advanced criminological theory course. Van Gundy and Baumann-Grau’s use of case studies enables readers to not only grasp the larger idea of feminist theory but also ground them in the greater global concept of human rights. The content is often unsettling, and disconcerting, but the text is very readable and engaging as well. The text at a total of 147 pages is short and can be read in one sitting if the reader chooses to do so. This coupled with the topic should also encourage many to include this as a text for use in many courses.
Tolerance of Sexual Nonconformity: City Size as a Situational and Early Learning Determinant

Phillips, David 1974 "The influence of suggestion on suicide: substantive and theoretical implications of the Werther effect. " American Sociological Review 39:340-54. 1977 "Motor vehicle fatalities increase just after publicized suicide stories. " Science 196:1464-65. 1978 "Airplane accident fatalities increase just after newspaper stories about murder and suicide. " Science 201:748-50. 1979 "Suicide, motor vehicle fatalities, and the mass media: evidence toward a theory of suggestion. " American Journal of Sociology 84:1150-74. 1980 "Airplane accidents, murder, and the mass media: towards a theory of imitation and suggestion. " Social Forces 58:1001-24.
Genital HPV Lesions and Molluscum Contagiosum Occurring in Patients Receiving Anti-TNF-α Therapy

Second Case A 29-year-old patient with chronic plaque psoriasis (PASI score of 20.4 at baseline) was treated with efalizumab with an excellent clinical response. Twenty-one months after initiation of efalizumab treatment, a generalized inflammatory flare (PASI score 30.5) was observed, in the absence of infection. Ciclosporin 3.5 mg/kg daily was then given for 1 month in combination with efalizumab, but psoriasis continued to worsen (PASI 34.6). Efalizumab and ciclosporin were discontinued, and infliximab (5 mg/ kg) was introduced, 1 week after the discontinuation of the previous 2 drugs. Laboratory assessment was normal. Two weeks after the first infusion, the patient presented with a significant improvement (PASI 16.5). The blood leukocyte count was 9,300/ mm 3 consisting of 36% neutrophils and 53% lymphocytes, and the patient was HIV negative. However, molluscum contagiosum was observed in the lower abdomen, at sites not recently involved by psoriasis, and preexisting HPV lesions of the genital area (which were not noted on initial examination) were exacerbated. Both viral infections were very pronounced in terms of size and number of lesions. Infliximab was discontinued. The condylomata were treated with 3 sessions of cryotherapy followed by imiquimod cream application, whereas the mollusca were treated by manual expression of the central core. PAP smear was normal. Methotrexate (15 mg/week) was started 1 month after infliximab withdrawal.
Selection of HIV Resistance Associated With Antiretroviral Therapy Initiated Due to Pregnancy and Suspended Postpartum

ObjectiveCompare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. MethodsSpecimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. ResultsSixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. ConclusionsHIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.
Diagnostic accuracy of fused positron emission tomography/magnetic resonance mammography: initial results.

OBJECTIVES The aim of this study was to evaluate the diagnostic accuracy of fused fluoro-deoxy-D-glucose positron emission tomography/magnetic resonance mammography (FDG-PET/MRM) in breast cancer patients and to compare FDG-PET/MRM with MRM. METHODS 27 breast cancer patients (mean age 58.9±9.9 years) underwent MRM and prone FDG-PET. Images were fused software-based to FDG-PET/MRM images. Histopathology served as the reference standard to define the following parameters for both MRM and FDG-PET/MRM: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the detection of breast cancer lesions. Furthermore, the number of patients with correctly determined lesion focality was assessed. Differences between both modalities were assessed by McNemaŕs test (p<0.05). The number of patients in whom FDG-PET/MRM would have changed the surgical approach was determined. RESULTS 58 breast lesions were evaluated. The sensitivity, specificity, PPV, NPV and accuracy were 93%, 60%, 87%, 75% and 85% for MRM, respectively. For FDG-PET/MRM they were 88%, 73%, 90%, 69% and 92%, respectively. FDG-PET/MRM was as accurate for lesion detection (p = 1) and determination of the lesions' focality (p = 0.7722) as MRM. In only 1 patient FDG-PET/MRM would have changed the surgical treatment. CONCLUSION FDG-PET/MRM is as accurate as MRM for the evaluation of local breast cancer. FDG-PET/MRM defines the tumours' focality as accurately as MRM and may have an impact on the surgical treatment in only a small portion of patients. Based on these results, FDG-PET/MRM cannot be recommended as an adjunct or alternative to MRM.
Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects

Background and objectives Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) at the 17q21 locus conferring increased risk for childhood-onset asthma. Little is known about how these SNPs impact adult asthma patients. We sought to examine an adult population for associations between rs7216389 (17q21-associated SNP) and features of asthma including fractional exhaled nitric oxide (FeNO), eosinophil counts, and age of asthma onset. Methods Subjects were genotyped at SNP rs7216389. The geometric mean of FeNO measurements and peripheral blood eosinophil counts from 2008 to 2015 were collected. Demographics and medical history were collected including self-reported allergy diagnoses and age of asthma onset. Eosinophils, monocytes, and peripheral blood mononuclear cells (PBMCs) were isolated for the examination of ORMDL3 expression. Results FeNO levels from 157 genotyped subjects (31CC, 72CT, and 54TT) and peripheral eosinophil counts from 252 genotyped subjects (46CC, 122CT, and 84TT) were analyzed. In a sub-group analysis of asthma subjects, the number of attributable T alleles was associated with significantly lower age of asthma onset (P=0.03) and greater FeNO levels (geometric mean 30.0 ppb TT, 20.0 ppb CT, 20.0 ppb CC, P=0.02). In the total cohort of subjects, the T allele was associated with a higher percentage of individual eosinophil counts >200/mm3 (45% TT, 26% CT, 24% CC, P=0.005). Eosinophils expressed ORMDL3 mRNA and protein. Conclusion In adult subjects, the number of T alleles at SNP rs7216389 corresponds to significantly greater FeNO levels and peripheral eosinophil counts. The expression of ORMDL3 in eosinophils suggests that they may participate in mediating the asthma risk associated with the 17q21 locus.
Pharmacogenomics in pain treatment

Abstract The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter-individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics. However, uptake of this information has been slow due in large part to the lack of robust evidences demonstrating clinical utility. Furthermore, novel therapies, including targeting of epigenetic changes and gene therapy-based approaches are further broadening future options for the treatment of chronic pain. The aim of this article is to review the evidences behind pharmacogenetics (PGx) to individualize therapy (boosting the efficacy and minimizing potential toxicity) and genes implicated in pain medicine, in two parts: (i) genetic variability with pain sensitivity and analgesic response; and (ii) pharmacological concepts applied on PGx.
Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment

Hypoxia is a prominent feature of the microenvironment of solid tumors and may contribute to tumor progression through the oxygen-sensitive transcriptional regulator hypoxia-inducible factor-1 (HIF-1). Chronic inflammation is another typical feature. Inflammatory mediators, including Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB), play an important role in cancer development. Recent studies have revealed extensive cross-talk between hypoxia and inflammation signaling, though the mechanisms remain unclear. Our results confirm that TLR3 and TLR4 are highly expressed in oral squamous cell carcinoma (OSCC). Activation of TLR3 and TLR4 stimulated the expression of HIF-1 through NF-κB. In addition, HIF-1 increased the expression of TLR3 and TLR4 through direct promoter binding. Thus, the TLR/NF-κB pathway forms a positive feedback loop with HIF-1. These results indicate a novel cross-talk between the TLR/NF-κB and HIF-1 signaling, which may contribute to OSCC initiation and progression. With the elucidation of this novel mechanism, it might serve as a basis for future microenvironment targeted cancer therapy.
Aging identity: Do theories match experiences?

Dominant aging identity theories ("mask of ageing", "social mask", M.Foucault's "disembodiment thesis", gerotranscendental theory) as well as the concept of postmodern reflexive self of A.Giddens can hardly be used to explain the old age identity in contemporary Lithuania. More suitable for this purpose is E.Goffman's stigma concept that allows explaining the denial, evasion and marginalization of old age, direct and indirect age discrimination experienced in everyday interactions and institutionalized in private and public structures. These are conclusions of a qualitative research - in-depth interviews with elderly people - that aimed to examine ways, in which old age is created and aging is experienced and made meaningful by older people, as well as ascertain whether the elderly experience stigmatization in everyday interactions. The data were collected in October 2010 - January 2011 in Vilnius (N=24), selection of informants was targeted by gender, age groups (60-74 and 75-89), level of education (primary, secondary, higher), and household type (households of several generations, single-generation and institutional housholds). For interpretation of data, the method of abduction or inference to the best explanation (Harman, 1965) was used.
European approaches to adolescent sexual behavior and responsibility.

This document presents the major findings of the 1998 European Study Tour in which 28 US experts in adolescent health 12 graduate students and 2 teenage journalists participated. The 2-week study tour was sponsored by the Advocates for Youth and the University of North Carolina at Charlotte. It explored how Netherlands Germany and France achieved successful adolescent sexual health indicators. In each country the participants conducted qualitative critical analyses of issues that research demonstrates to have an impact on adolescent reproductive and sexual health attitudes behaviors and outcomes. These issues include 1) access to health care especially reproductive and sexual health services; 2) sexuality education; 3) mass media and social marketing campaigns; and 4) family community and religion. Overall major differences were noted among the four countries when it comes to adolescent reproductive and sexual health attitudes behavior and outcomes. It appears that teen sexual behavior in the US is viewed in many contexts--a moral failing a political issue a private family matter or a public health concern--but seldom as a developmental matter as viewed by the other three countries.
Electromyography Pattern-Recognition-Based Control of Powered Multifunctional Upper-Limb Prostheses

The human history has been accompanied by accidental trauma, war, and congenital anomalies. Consequently, amputation and deformity have been dealt with, one way or another, throughout the ages. More than one million individuals in the United States today are living with limb amputations (Adams et al., 1999), in which there are approximately 100,000 patients with an upper limb amputation. The wars in Iraq and Afghanistan have added to this number. According to the survey results of the Second China National Sample Survey on Disables (SCNSSD 2006) led by the National Statistics Bureau in 2006, approximately 8% of physical disables, or 2.26 million people, live with limb amputations in China alone. Natural disasters and accidents have been making this number increase. The massive earthquakes that occurred in May 2008, Sichuan Province, China, recently increased about 20 thousand of new limb amputees. Expectations for control of upper limb prostheses have always been high because of the standard established by able-bodied dexterity. Most commercially available upper limb prostheses are either body-powered or electrical motor powered. The body-powered prostheses are operated by certain movements of the amputees’ body through a system of cables, harnesses, and sometimes, manual control. In order to operate a body-powered prosthesis, the upper limb amputees have to possess significant strength and control over various body parts, including the shoulders, chest, and residual limb which must have sufficient residual limb length, musculature, and range of motion. Exaggerated movements of the body are captured by harness systems and are transferred through cables to operate the hand, wrist, or elbow movements of a prosthesis. With some advantages such as low cost, high reliability, and some kinesthetic feedback provided by the harness system, body-powered prostheses are still widely accepted by the upper limb amputees worldwide, especially in some developing countries. However, with this inappropriate control approach, body-powered upper limb prostheses are limited in utility, frustratingly slow to operate, awkward to maintain, and can operate only one joint at a time. Myoelectric signals detected with electrodes placed on the skin surface overlying the muscles, well-known as electromyography (EMG), have been used in control of motorized upper-limb prostheses for several decades (Kay & Newman, 1975; Parker & Scott, 1986). The
Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design

While recent research on Brain-Computer Interfaces (BCI) has highlighted their potential for many applications, they remain barely used outside laboratories. The main reason is their lack of robustness. Indeed, with current BCI, mental state recognition is usually slow and often incorrect. Spontaneous BCI (i.e., mental imagery-based BCI) often rely on mutual learning efforts by the user and the machine, with BCI users learning to produce stable ElectroEncephaloGraphy (EEG) patterns (spontaneous BCI control being widely acknowledged as a skill) while the computer learns to automatically recognize these EEG patterns, using signal processing. Most research so far was focused on signal processing, mostly neglecting the human in the loop. However, how well the user masters the BCI skill is also a key element explaining BCI robustness. Indeed, if the user is not able to produce stable and distinct EEG patterns, then no signal processing algorithm would be able to recognize them. Unfortunately, despite the importance of BCI training protocols, they have been scarcely studied so far, and used mostly unchanged for years. In this paper, we advocate that current human training approaches for spontaneous BCI are most likely inappropriate. We notably study instructional design literature in order to identify the key requirements and guidelines for a successful training procedure that promotes a good and efficient skill learning. This literature study highlights that current spontaneous BCI user training procedures satisfy very few of these requirements and hence are likely to be suboptimal. We therefore identify the flaws in BCI training protocols according to instructional design principles, at several levels: in the instructions provided to the user, in the tasks he/she has to perform, and in the feedback provided. For each level, we propose new research directions that are theoretically expected to address some of these flaws and to help users learn the BCI skill more efficiently.