Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid and easy prenatal diagnosis of sickle cell anemia using double‐dye LNA probe technology

Taking advantage of the high specificity of double-dye hydrolysis-locked nucleic acid (LNA) probes (Ugozzoli et al, 2004), we developed a qualitative three-colour real-time polymerase chain reaction (PCR) assay for the genotyping of sickle cell disease (SCD). The term SCD encompasses a group of disorders associated with mutations in the Haemoglobin Beta gene (HBB). The most common forms are defined by the presence, in codon 6, of an E6V mutation (GAG > GTG; Haemoglobin S; Hb S) on both alleles (sickle cell anaemia) and co-inheritance of Hb S and Hb C (E6K mutation; GAG > AAG; Hb SC disease). The highest prevalence of SCD is found in subSaharan Africa (sickle-cell gene carrier prevalence varying between 5% and 40% of the population), and most affected children die in the early years of life without being diagnosed or because of non-adapted treatments (Weatherall & Clegg, 2001). The methodological approach presented here combined the use of a primer pair designed to amplify the region of interest in the HBB gene and three double-dye probes containing LNA nucleotides. Each probe was labelled with a different fluorochrome to enable the different alleles to be discriminated (Fig 1). Primers were designed with the freeware meltcalc, ver. 2.0 (http://www.meltcalc.de). The Tm of each double-dye LNA probe was calculated by using the Exiqon Tm prediction tool (http://lna-tm.com). Samples from patients that were homozygous for each of the three aforementioned alleles were used to demonstrate the specificity of the probes (Fig 1). We used unique PCR conditions on the ABI 7500 Fast machine (Applied Biosystems, Foster City, CA, USA), which generated specific results for each probe in <40 min (see Table SI, Fig S1). A cohort of 37 genomic DNA representing the different possible genotypes was used to compare our new technique with either a PCR followed by restriction endonuclease cleavage to detect the A and S alleles (Saiki et al, 1988), or an allele-specific PCR designed to detect A and C alleles (Fischel-Ghodsian et al, 1990). A 100% concordance was observed between our technology and the two published methods. Moreover, the deduced genotypes matched perfectly with the available phenotypic analysis (Gulbis et al, 2006). To investigate the sensitivity of this analysis, we tested different amounts of genomic DNA per PCR reaction. The results were perfectly interpretable from 100 to 1 ng of starting material (data not shown), and enabled the testing of prenatal diagnosis samples even when there was scarce fetal tissue (demonstrated on 18 gDNA obtained from fetal samples; data not shown). Finally, to demonstrate the robustness of our approach, we tested 10 representative samples on currently available instru-
Oral Contraceptive Tolerance: Does the Type of Pill Matter?

OBJECTIVE: To examine the frequencies of reported symptoms by oral contraceptive pill (OCP) composition among French women. METHODS: A population-based cohort of 2,863 women studied between 2000 and 2004 was used to compare the frequency of reported symptoms (weight gain, nausea, breast tenderness, lower frequency of menstrual periods, breakthrough bleeding, painful and heavy periods, swollen legs) by type of OCPs (classified by estrogen dosage, progestin component, and sequence of administration). RESULTS: Results show little variation in the frequency of symptoms by type of OCPs, with the exception of progestin-only pills being associated with higher frequencies of breakthrough bleeding and lower frequencies of menstrual periods. We found no decrease in the reporting of symptoms with the reduction of estrogen dosage, nor with the use of third-generation OCPs compared with second-generation OCPs. Likewise, we found little variation by sequence of administration of OCPs (monophasic versus triphasic). CONCLUSION: In the absence of sufficient evidence-based data to support the existence of differences in the tolerance profile of low-dose combined OCPs, future well-designed randomized trials are needed to guide providers in their choice of OCPs. However, research should also assess the effectiveness of counseling on the tolerance of OCPs, an intervention that may prove to be more rewarding than basing the choice of OCPs on their theoretical properties. LEVEL OF EVIDENCE: II
Suboptimal ward care of critically ill patients

Editor—McQuillan et al show that most patients receive suboptimal management of oxygen therapy, airway, breathing, circulation, and monitoring before admission to intensive care.1 In an area of medicine renowned for objective measurement it is surprising that this study should rely on the subjective opinions of two assessors about what constituted suboptimal care. Understandably, their opinions often disagreed. The authors accept that there are difficulties in relying on assessors’ opinions, but we must not underestimate these limitations. The assessors knew the outcomes of the patients, which must have biased their opinions, particularly since suboptimal care is not defined. How suboptimal care was defined is crucial to the paper’s message, and more information about the data evaluated by the assessors would have been preferable to the lengthy discussion, much of which was not directly related to the data. Unfortunately, many of the data are self fulfilling. It is unsurprising that the suboptimally managed group scored badly on oxygen therapy and airway, breathing, and circulation and that 67% of this group were late admissions to intensive care since these were presumably the factors used to determine suboptimal management. Nevertheless, a key message is that most of the well managed patients were admitted to intensive care units within the first day of admission, with presumably some going straight from accident and emergency. These acutely ill patients are perhaps more easily identifiable as going to need intensive care. Conversely, those patients who arrived at hospital less ill and who deteriorated while on general wards were those who received suboptimal care. There was a longer time between admission to hospital and admission to intensive care in these patients. We are not told if any of the admissions to intensive care were delayed because of lack of beds. Although there is no excuse for suboptimal care, sometimes admission to intensive care is requested because a ward with overstretched nursing staff and no high dependency beds recognises that it is unable to provide optimal care for an acutely ill patient.
Sufficient Conditions for Some Optimum-Property Facility Designs

A facility design is considered to consist of n mutually nonoverlapping facilities of known areas. Some problems are considered of finding, from the class of all possible facility designs, facility designs with optimum properties; sufficient conditions are given for certain minimum total cost and minimax facility designs, and examples are considered. Possible facility design applications include those of warehouse design and layout, parking lot design and layout, and stadium design.
Household Transmission of Influenza (H1N1-2009) in Japan: Age-Specificity and Reduction of Household Transmission Risk by Zanamivir Treatment

This study investigated household transmission data for influenza (H1N1-2009) in Japan in order to quantify the age-specific risk of infection and estimate the impact of antiviral treatment on the risk of household transmission. Among a total of 1547 households, involving 4609 household contacts, the secondary attack ratio (SAR) was estimated to be 11.4%. School children aged 5 – 18 years dominated the index cases. Age-specific infectiousness and susceptibility were highest among 0 – 4-year olds, with SAR estimated at 19.4% and 29.6%, respectively. Zanamivir treatment within 24 and 24 – 48 h of illness onset in index cases, respectively, reduced the risk of household transmission to 0.57 (95% CI 0.44, 0.73) and 0.58 (95% CI 0.38, 0.86) times that among those receiving the same treatment at > 48 h and those not receiving treatment. The preventive performance of antiviral treatment and prophylaxis should be further examined in randomized controlled trials.
Ideal Parent Figure method in the treatment of complex posttraumatic stress disorder related to childhood trauma: a pilot study

ABSTRACT Background: There is a consensus within the trauma field for the necessity of a three-phase treatment programme for complex posttraumatic stress disorder (CPTSD). This pilot study focuses on the stabilisation phase, the goal of which is the development of psychological resources and the reduction of disabling symptoms. Objective: To test the efficacy of the Ideal Parent Figure (IPF) method as a stabilization treatment for CPTSD patients with a history of childhood trauma. Method: The sample was comprised of 17 adults with a history of childhood trauma concomitant with CPTSD symptoms consulting at a clinic in France. Participants enrolled in a 5-week psychotherapy programme based on the IPF method, a semi-structured visualization programme designed to treat attachment disturbances. Measures of DESNOS symptoms, psychological symptoms, quality of life, and adult attachment were administered pre- and posttreatment as well as at 8-month follow-up. Results: A significant decrease in symptom severity and attachment traumatization and a significant increase in quality of life were found, both with medium-to-large effect sizes. The 8-month follow-up assessment showed outcome stability. Conclusions: These results suggest that treating attachment disturbances directly with an approach akin to the Ideal Parent Figure method may lead to fast and stable improvement for individuals with CPTSD.
Severe menopausal symptoms are widespread among survivors of breast cancer treatment regardless of time since diagnosis.

BACKGROUND The intensity and persistence of treatment-related symptoms among breast cancer survivors is incompletely understood. OBJECTIVE The objective of the study was to estimate prevalence of severe symptoms well after initial treatment for breast cancer, to test whether symptom intensity diminishes with time or varies by treatment received. DESIGN, SETTING, SUBJECTS This was a cross-sectional survey of female survivors of stage I-III invasive breast cancer, seen for routine follow-up a year or more after diagnosis. MEASUREMENTS Data was derived from three validated questionnaires indicating physical and emotional domains. Symptoms rated in the top two levels of four- or five-item Likert scales were "severe. " Associations with symptom intensity were tested using multivariate linear regression. RESULTS Survey response was 68.5% (50/73). Respondents were age 55.4 (±9.1) years, median 2.2 (1.0-13.1) years since diagnosis; 64% were receiving endocrine therapy. Severe levels of hot flashes (42% of respondents), weight gain (32%), low libido (32%), and joint pain (30%) were common; (36%) of respondents rated sleep "fairly poor" or "very bad;" 30% were fatigued at least half the day. For 34%, health typically limited vigorous activities "a lot. " Most (84%) respondents were experiencing at least one severe symptom. Symptom intensity did not vary with time since diagnosis. Of seven symptoms, three (hot flashes, weight gain, low libido) were more intense when systemic treatment had included endocrine therapy. Time in past month feeling down, nervous, or worn out increased with intensity of physical symptoms. CONCLUSIONS Given their severity, persistence, and association with emotional burden, treatment-related symptoms among breast cancer survivors (BCS) merit greater attention toward clinical management, patient education, and longitudinal study.
Mediterranean diet and plasma concentration of inflammatory markers in old and very old subjects in the ZINCAGE population study

Abstract Background: Aging is associated with low-grade elevation of circulating inflammatory markers, leading to increased risk of morbidity and mortality. The Mediterranean diet has been suggested as a determinant of longevity. In the current study, we investigated the impact of the Mediterranean diet on inflammatory status in old subjects. Methods: Within the ZINCAGE study, 957 healthy old subjects (≥60 years old) from five European countries were recruited. Plasma interleukin (IL)-6, IL-8, monocyte chemoattractant protein, tumor necrosis factor-α, high-density lipoprotein cholesterol (HDL-C) and erythrocyte sedimentation rate (ESR) were measured. Dietary data were collected applying a food frequency questionnaire and were used to estimate adherence to the Mediterranean diet. Results: The Italians presented the greatest adherence to the Mediterranean diet, while the Polish the poorest. In females, higher diet score was significantly associated with lower body mass index and ESR and higher HDL-C levels (β=−0.127, p=0.003; β=−0.144, p=0.001; β=0.144, p=0.029, respectively). In males, diet score was negatively associated with IL-8 levels (β=−0.101, p=0.044). The Mediterranean diet was associated with reduced IL-8 concentrations in Greeks (β=−0.213, p=0.007). Conclusions: There were significant effects of the components of the Mediterranean diet on inflammation markers. The Mediterranean diet score is useful in assessing nutritional influence on immune status. Clin Chem Lab Med 2008;46:990–6.
Hypophosphatasia: Enzyme Replacement Therapy Brings New Opportunities and New Challenges

Hypophosphatasia (HPP) is caused by loss‐of‐function mutation(s) of the gene that encodes the tissue‐nonspecific isoenzyme of alkaline phosphatase (TNSALP). Autosomal inheritance (dominant or recessive) from among more than 300 predominantly missense defects of TNSALP (ALPL) explains HPP's broad‐ranging severity, the greatest of all skeletal diseases. In health, TNSALP is linked to cell surfaces and richly expressed in the skeleton and developing teeth. In HPP,TNSALP substrates accumulate extracellularly, including inorganic pyrophosphate (PPi), an inhibitor of mineralization. The PPi excess can cause tooth loss, rickets or osteomalacia, calcific arthropathies, and perhaps muscle weakness. Severely affected infants may seize from insufficient hydrolysis of pyridoxal 5ʹ‐phosphate (PLP), the major extracellular vitamin B6. Now, significant successes are documented for newborns, infants, and children severely affected by HPP given asfotase alfa, a hydroxyapatite‐targeted recombinant TNSALP. Since fall 2015, this biologic is approved by regulatory agencies multinationally typically for pediatric‐onset HPP. Safe and effective treatment is now possible for this last rickets to have a medical therapy, but a number of challenges involving diagnosis, understanding prognosis, and providing this treatment are reviewed herein. © 2017 American Society for Bone and Mineral Research.
Public Information and Breeding Habitat Selection in a Wild Bird Population

According to the “public information” hypothesis, some animal species may monitor the current reproductive success of conspecifics to assess local habitat quality and to choose their own subsequent breeding site. To test this hypothesis experimentally, we manipulated two components of public information, the mean number of offspring raised locally (“quantity”) and their condition (“quality”), in the collared flycatcher Ficedula albicollis. Immigration rate decreased with local offspring quantity but did not depend on local offspring quality, suggesting that immigrants are deprived of information regarding local quality. Conversely, emigration rate increased both when local offspring quantity or quality decreased, suggesting that residents can use both components of public information.
The Relationship Between CAG Repeat Length and Age of Onset Differs for Huntington's Disease Patients with Juvenile Onset or Adult Onset

Age of onset for Huntington's disease (HD) varies inversely with the length of the disease‐causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R‐squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two‐segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log‐transformed age of onset against CAG repeat length reveals this segmental relationship. This two‐segment exponential regression on age of onset data increases the adjusted R‐squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two‐segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 × 10−5] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 × 10−16]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult‐onset range of CAG repeats than in the juvenile‐onset range.
Longitudinal Profile of Immunoglobulin G (IgG), IgM, and IgA Antibodies against the Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein in Patients with Pneumonia Due to the SARS Coronavirus

ABSTRACT By using a recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein-based enzyme-linked immunosorbent assay (ELISA) and serum specimens serially collected (from day 0 to day 240 after symptom onset) from patients with pneumonia due to SARS-CoV, we analyzed the longitudinal profiles of immunoglobulin G (IgG), IgM, and IgA antibodies against the SARS-CoV nucleocapsid protein in patients with pneumonia due to SARS-CoV. For IgG, the median optical density at 450 nm (OD450) turned positive at day 17 and a biphasic response was observed. At day 240, all patients were still positive for anti-nucleocapsid protein IgG antibody. For IgM, the median OD450 turned positive at day 20.5, peaked at about day 80, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgM antibody. For IgA, the median OD450 turned positive at day 17, peaked at about day 50, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgA antibody. The time of seroconversion detected by the recombinant SARS-CoV nucleocapsid protein-based ELISA and that detected by indirect immunofluorescence assay were similar. The median times of seroconversion for IgG, IgM, and IgA detected by the indirect immunofluorescence assay were 17 days (17 days by ELISA), 16.5 days (20.5 days by ELISA), and 17.5 days (17 days by ELISA), respectively, after disease onset. One, four, and one of the six patients who died did not produce any IgG, IgM, and IgA antibodies against the nucleocapsid protein of SARS-CoV, respectively, although these antibodies were detected in all six patients by the indirect immunofluorescence assay. Further studies should be performed to see whether SARS-CoV nucleocapsid protein antibody positivity has any prognostic significance.
Sensitization and lung function in workers occupationally exposed to natural thickening products

Background: Three workers engaged in the manufacture of natural thickener products (Cassia spp., guar, and tamarind flour) were occupationally sensitized to Cassia spp. Therefore, a cross‐sectional study on the prevalence of sensitization among and respiratory health of the employees of this plant was conducted.
Cameras, Coyotes, and the Assumption of Equal Detectability

Abstract Remote cameras are an increasingly important tool in management and wildlife studies. However, we often do not know if they provide an unbiased sample of populations. Using a marked, radiocollared population of coyotes (Canis latrans) of known social status, we evaluated the influence of temporal (daily and seasonal) and spatial (distance between units, habitat, and proximity to human structures) factors on vulnerability to photo-captures. During 8 unbaited camera sessions of 6 weeks each, we obtained 158 coyote photographs at a photo-capture success rate of 1.6%. We were able to identify not only marked individuals, but also a number of uncollared adults through variation in their pelage. Photo-capture of adults peaked 2 weeks after we established camera stations. Annual success for photographing adult coyotes was greatest during March and April, which corresponded with the dispersal season. The majority of photo-captures occurred at night, and adult photo-captures peaked around midnight, with smaller peaks at dawn and dusk. Rather than reflecting a circadian activity pattern, nighttime captures seemed to reflect when adult coyotes were most vulnerable to photo-capture. Characteristics of camera locations, such as amount of human activity, being on roads versus trails, and habitat type, also influenced the number of photo-captures. We conclude that remote cameras do not always provide an unbiased sample of populations and that animal behavior is important to consider when using these systems. Researchers using camera techniques need to carefully consider when, where, and how cameras are placed to reduce this bias.
Multicolor Spectral Analyses of Mitotic and Meiotic Mouse Chromosomes Involved in Multiple Robertsonian Translocations. II. The NMRI/CD and CD/TA Hybrid Strains

Multicolor spectral analyses (spectral karyotyping) were performed on mitotic chromosomes of NMRI, CD, and TA mice and on male meiotic chromosomes (diakineses) of NMRI/CD and CD/TA hybrids. All chromosomes, including the various centric (robertsonian) fusions, could be unequivocally identified. Apart from the robertsonian translocations, which were previously detected by conventional banding analyses, no other interchromosomal rearrangements were found in these mice. In both the CD and TA mice, the autosomes 19 and the XY sex chromosomes are not involved in robertsonian translocations. In diakineses of male meiosis of the NMRI/CD hybrid, the 9 expected trivalents were present, whereas in those of the CD/TA hybrids a stable large meiotic multivalent, formed by 15 robertsonian fusion chromosomes and 2 terminally located normal chromosomes, was observed. The specific sequential order of the robertsonian fusion chromosomes found within this meiotic chain was as theoretically predicted. In the majority of diakineses of the NMRI/CD and CD/TA hybrids, the free autosomal bivalent 19 and the XY sex bivalent formed noticeable tight spatial associations.
Sortilin: The Mechanistic Link Between Genes, Cholesterol, and Coronary Artery Disease

Hyperlipidemia is an important risk factor for cardiovascular disease globally, but there is still much mystery surrounding the topic of lipid regulation. Many studies have attempted to assess the underlying genetic basis of low-density lipoprotein (LDL) metabolism. Recently, multiple genome-wide association studies identified genes that strongly associate with plasma lipid concentration and cardiovascular disease. Compelling evidence linking the SORT1 gene to both LDL cholesterol (LDL-C) levels and the risk of coronary artery disease emerged from the data, prompting the search for the molecules and mechanisms responsible for this association. Three recent studies explored this relation through sortilin, the gene product of SORT1, and an intracellular trafficking molecule. Careful, hypothesis-driven experimental designs elucidated the potential mechanisms of sortilin’s role in LDL-C metabolism. However, each study’s conclusions differed in the details of SORT1’s association to LDL-C and the subcellular mechanisms at work. Nevertheless, these 3 studies demonstrate how a complex disease such as hyperlipidemia can be evaluated from the scope of the genome down through the level of cellular regulation. Their findings serve as a platform for further study of LDL-C metabolism and hyperlipidemia while also providing lessons on how to better study other complex diseases.