Miracle-dz/UniFAR-FTUs huggingface dataset:
Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies

Objectives To investigate the association between long term intake of individual saturated fatty acids (SFAs) and the risk of coronary heart disease, in two large cohort studies. Design Prospective, longitudinal cohort study. Setting Health professionals in the United States. Participants 73 147 women in the Nurses’ Health Study (1984-2012) and 42 635 men in the Health Professionals Follow-up Study (1986-2010), who were free of major chronic diseases at baseline. Main outcome measure Incidence of coronary heart disease (n=7035) was self-reported, and related deaths were identified by searching National Death Index or through report of next of kin or postal authority. Cases were confirmed by medical records review. Results Mean intake of SFAs accounted for 9.0-11.3% energy intake over time, and was mainly composed of lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), and stearic acid (18:0; 8.8-10.7% energy). Intake of 12:0, 14:0, 16:0 and 18:0 were highly correlated, with Spearman correlation coefficients between 0.38 and 0.93 (all P<0.001). Comparing the highest to the lowest groups of individual SFA intakes, hazard ratios of coronary heart disease were 1.07 (95% confidence interval 0.99 to 1.15; Ptrend=0.05) for 12:0, 1.13 (1.05 to 1.22; Ptrend<0.001) for 14:0, 1.18 (1.09 to 1.27; Ptrend<0.001) for 16:0, 1.18 (1.09 to 1.28; Ptrend<0.001) for 18:0, and 1.18 (1.09 to 1.28; Ptrend<0.001) for all four SFAs combined (12:0-18:0), after multivariate adjustment of lifestyle factors and total energy intake. Hazard ratios of coronary heart disease for isocaloric replacement of 1% energy from 12:0-18:0 were 0.92 (95% confidence interval 0.89 to 0.96; P<0.001) for polyunsaturated fat, 0.95 (0.90 to 1.01; P=0.08) for monounsaturated fat, 0.94 (0.91 to 0.97; P<0.001) for whole grain carbohydrates, and 0.93 (0.89 to 0.97; P=0.001) for plant proteins. For individual SFAs, the lowest risk of coronary heart disease was observed when the most abundant SFA, 16:0, was replaced. Hazard ratios of coronary heart disease for replacing 1% energy from 16:0 were 0.88 (95% confidence interval 0.81 to 0.96; P=0.002) for polyunsaturated fat, 0.92 (0.83 to 1.02; P=0.10) for monounsaturated fat, 0.90 (0.83 to 0.97; P=0.01) for whole grain carbohydrates, and 0.89 (0.82 to 0.97; P=0.01) for plant proteins. Conclusions Higher dietary intakes of major SFAs are associated with an increased risk of coronary heart disease. Owing to similar associations and high correlations among individual SFAs, dietary recommendations for the prevention of coronary heart disease should continue to focus on replacing total saturated fat with more healthy sources of energy.
Structure and Regulatory Interactions of the Cytoplasmic Terminal Domains of Serotonin Transporter

Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains.
Accurate Amplitude Estimation of Harmonic Components of Incoherently Sampled Signals in the Frequency Domain

This paper focuses on estimating the amplitude of harmonic components of a harmonically distorted sine wave by the interpolated discrete Fourier transform (IpDFT) method with maximum sidelobe decay windows. The expression of the maximum of the interference error caused by the fundamental sine-wave component on the amplitude estimation of harmonic components is derived. In addition, for a signal corrupted by stationary white noise, the statistical efficiency of the IpDFT method is investigated with respect to the single-tone unbiased Crame¿r-Rao lower bound (CRLB). Based on the derived expressions, a constraint is derived ensuring that interference from the fundamental component could practically be neglected. Finally, the performance of the IpDFT method is compared with that of the energy-based method on the basis of theoretical, simulation, and experimental results and with that of a state-of-the-art method according to simulation and experimental results.
Population Structure and Cryptic Relatedness in Genetic Association Studies

We review the problem of confounding in genetic association studies, which arises principally because of population structure and cryptic relatedness. Many treatments of the problem consider only a simple "island" model of population structure. We take a broader approach, which views population structure and cryptic relatedness as different aspects of a single confounder: the unobserved pedigree defining the (often distant) relationships among the study subjects. Kinship is therefore a central concept, and we review methods of defining and estimating kinship coefficients, both pedigree-based and marker-based. In this unified framework we review solutions to the problem of population structure, including family-based study designs, genomic control, structured association, regression control, principal components adjustment and linear mixed models. The last solution makes the most explicit use of the kinships among the study subjects, and has an established role in the analysis of animal and plant breeding studies. Recent computational developments mean that analyses of human genetic association data are beginning to benefit from its powerful tests for association, which protect against population structure and cryptic kinship, as well as intermediate levels of confounding by the pedigree.
Automated tri-image analysis of stored corneal endothelium

Background: Endothelial examination of organ culture stored corneas is usually done manually and on several mosaic zones. Some banks use an image analyser that takes account of only one zone. This method is restricted by image quality, and may be inaccurate if endothelial cell density (ECD) within the mosaic is not homogeneous. The authors have developed an analyser that has tools for automatic error detection and correction, and can measure ECD and perform morphometry on multiple zones of three images of the endothelial mosaic. Methods: 60 human corneas were divided into two equal groups: group 1 with homogeneous mosaics, group 2 with heterogeneous ones. Three standard microscopy video images of the endothelium, graded by quality, were analysed either in isolation (so called mono-image analysis) or simultaneously (so called tri-image analysis), with 50 or 300 endothelial cells (ECs) counted. The automated analysis was compared with the manual analysis, which concerned 10 non-adjacent zones and about 300 cells. For each analysis method, failures and durations were studied according to image quality. Results: All corneas were able to undergo analysis, in about 2 or 7.5 minutes for 50 and 300 ECs respectively. The tri-image analysis did not increase analysis time and never failed, even with mediocre images. The tri-image analysis of 300 ECs was always most highly correlated with the manual count, particularly in the heterogeneous cornea group (r=0.94, p<0.001) and prevented serious count errors. Conclusions: This analyser allows reliable and rapid analysis of ECD, even for heterogeneous endothelia mosaics and mediocre images.
Donor-Specific Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative treatment for a wide variety of hematological diseases. In 30% of the cases, a geno-identical donor is available. Any other situation displays some level of human leukocyte antigen (HLA) incompatibility between donor and recipient. Deleterious effects of anti-HLA immunization have long been recognized in solid organ transplant recipients. More recently, anti-HLA immunization was shown to increase the risk of primary graft failure (PGF), a severe complication of AHSCT that occurs in 3–4% of matched unrelated donor transplantation and up to 15% in cord blood transplantation and T-cell depleted haplo-identical stem cell transplantation. Rates of PGF in patients with DSA were reported to be between 24 and 83% with the highest rates in haplo-identical and cord blood transplantation recipients. This led to the recommendation of anti-HLA antibody screening to detect donor-specific antibodies (DSA) in recipients prior to AHSCT. In this review, we highlight the role of anti-HLA antibodies in AHSCT and the mechanisms that may lead to PGF in patients with DSA, and discuss current issues in the field.
The Val66Met polymorphism of the brain‐derived neurotrophic factor gene is associated with risk for psychosis: Evidence from a family‐based association study

Schizophrenia (SZ) is a prevalent and severe mental disorder. One of the most favored hypotheses for the etiology of SZ is the neurodevelopmental hypothesis. Brain‐derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, promotes the development, regeneration, and survival of neurons and has been linked to the neuropathology of SZ. The present study tested, in a sample of 94 nuclear families, the hypothesis that the BDNF gene Val66Met polymorphism is associated to SZ and its psychopathologic phenotype using a multidimensional symptom approach. Furthermore, considering a reported reduction of BDNF in the frontal cortex of patients with SZ, we studied the relationship between this polymorphism and prefrontal function. The transmission disequilibrium test (TDT) showed a preferential transmission of allele Val from heterozygous parents to the affected offspring (P = 0.002), suggesting a possible role of this gene in the vulnerability to SZ spectrum disorders. The findings remained essentially unchanged when the analysis was restricted to the subgroup of patients with SZ (P = 0.009) and when a multidimensional approach to the diagnosis was used. Quantitative transmission disequilibrium test (QTDT) analyses did not demonstrate a significant association between the prefrontal tests assessed (Wisconsin Card Sorting Test and Trail Making Test) and the transmission of the BDNF alleles. Our finding suggests that the investigated BDNF polymorphism plays an important role in the phenotype of psychosis, but not in the performance of tests of prefrontal cognitive functions analyzed in these patients. © 2006 Wiley‐Liss, Inc.
Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus

The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus (TuMV) was investigated. To discriminate between primary infections and secondary infections associated with the virus intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent to a TuMV infectious cassette expressing 6K2:mCherry, both within the T-DNA borders of the binary vector pCambia. In this system, both gene cassettes were delivered to the same cell by a single binary vector and primary infection foci emitted green and red fluorescence while secondarily infected cells emitted only red fluorescence. Intercellular movement was measured at 72 hours post infiltration and was estimated to proceed at an average rate of one cell being infected every three hours over an observation period of 17 hours. To determine if the secretory pathway were important for TuMV intercellular movement, chemical and protein inhibitors that blocked both early and late secretory pathways were used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB-E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport, reduced intercellular movement by the virus. These treatments, however, did not inhibit virus replication in primary infected cells. Pharmacological interference assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not important for TuMV intercellular movement. Lack of co-localization by endocytosed FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K2-tagged vesicles further supported this conclusion. Microfilament depolymerizing drugs and silencing expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV intercellular movement. Expression of dominant negative myosin mutants confirmed the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular movement. Using this dual gene cassette expression system and transport inhibitors, components of the secretory and actomyosin machinery were shown to be important for TuMV intercellular spread.
How to Maintain Pregnancy

On some days, “how to maintain pregnancy” seems an elusive goal. In some cases, by the time practitioners recognize that a mare is demonstrating signs of preterm birth, any assistance we can provide is insufficient to allow delivery of a vigorous and healthy foal. Thus, a large component of how to maintain pregnancy is determining when to intervene. Bosh et al (2009) described reproductive performance measures among 1011 Thoroughbred mares in central Kentucky during the 2004 mating and 2005 foaling seasons (Table 1). This study demonstrated a 12.9% pregnancy loss between day 40 of gestation and foaling. This is similar to fetal loss rates between 3 and 10 months gestation found in other studies. In comparison, the human rate of preterm births in the United States in 12.5%. In a review of 3527 aborted fetuses and placentas, stillborn foals or foals that died 24 hours after birth, 34% were due to feto-placental infection or placentitis of unidentified etiology. Bacterial infection caused 628 (17.8%) of these losses. Complications of birth led to the demise of 679 (19%), congenital anomalies including contracted foals counted for 348 (10%), and no diagnosis was identified in 585 (17%) of these cases. Other causes included placental edema, premature placental separation, twins, umbilical cord anomalies, placental villous atrophy, body pregnancy, fetal diarrhea, and neoplasia. This tells us that if we can manage inflammation and infection, we are targeting approximately one-third of the problem. The vast majority of pregnancies will require no intervention. For anxious clients or mares at higher risk for problematic pregnancy, routine monitoring can be instituted. Case selection can be based on the following:
Accuracy of Postoperative End-tidal Pco2 Measurements with Mainstream and Sidestream Capnography in Non-obese Patients and in Obese Patients with and without Obstructive Sleep Apnea

Background:Obtaining accurate end-tidal carbon dioxide pressure measurements via nasal cannula poses difficulties in postanesthesia patients who are mouth breathers, including those who are obese and those with obstructive sleep apnea (OSA); a nasal cannula with an oral guide may improve measurement accuracy in these patients. The authors evaluated the accuracy of a mainstream capnometer with an oral guide nasal cannula and a sidestream capnometer with a nasal cannula that did or did not incorporate an oral guide in spontaneously breathing non-obese patients and obese patients with and without OSA during recovery from general anesthesia. Methods:The study enrolled 20 non-obese patients (body mass index less than 30 kg/m2) without OSA, 20 obese patients (body mass index greater than 35 kg/m2) without OSA, and 20 obese patients with OSA. End-tidal carbon dioxide pressure was measured by using three capnometer/cannula combinations (oxygen at 4 l/min): (1) a mainstream capnometer with oral guide nasal cannula, (2) a sidestream capnometer with a nasal cannula that included an oral guide, and (3) a sidestream capnometer with a standard nasal cannula. Arterial carbon dioxide partial pressure was determined simultaneously. The major outcome was the arterial-to-end-tidal partial pressure difference with each combination. Results:In non-obese patients, arterial-to-end-tidal pressure difference was 3.0 ± 2.6 (mean ± SD) mmHg with the mainstream capnometer, 4.9 ± 2.3 mmHg with the sidestream capnometer and oral guide cannula, and 7.1 ± 3.5 mmHg with the sidestream capnometer and a standard cannula (P < 0.05). In obese non-OSA patients, it was 3.9 ± 2.6 mmHg, 6.4 ± 3.1 mmHg, and 8.1 ± 5.0 mmHg, respectively (P < 0.05). In obese OSA patients, it was 4.0 ± 3.1 mmHg, 6.3 ± 3.2 mmHg, and 8.3 ± 4.6 mmHg, respectively (P < 0.05). Conclusions:Mainstream capnometry performed best, and an oral guide improved the performance of sidestream capnometry. Accuracy in non-obese and obese patients, with and without OSA, was similar.
Cognitive coping skills training in children with sickle cell disease pain

AbrstractThis study was designed to examine whether brief training in cognitive coping skills would enhance pain coping strategies and alter pain perception in children and adolescents with sickle cell disease (SCD). Forty-nine participants with SCD were randomly assigned to either a cognitive coping skills condition or a standard care control condition. At pre- and posttesting, coping strategies and pain sensitivity using laboratory pain stimulation were measured. Results indicated that, in comparison to the randomly assigned control condition, brief training in cognitive coping skills resulted in decreased negative thinking and lower pain ratings during low intensity laboratory pain stimulation.
Smooth Vibrotactile Flow Generation Using Two Piezoelectric Actuators

This paper proposes a method for generating a smooth directional vibrotactile flow on a thin plate. While actuating two piezoelectric actuators spatially across the plate, temporal sweeping of the input excitation frequency from zero to the first mode of the resonance frequency can smooth the perceived directional vibrotactile flow, as compared to a vibrotactile flow generated by conventional apparent tactile movement and phantom sensation methods. In order to ascertain important factors in the excitation pattern, a user study was conducted for three factors (amplitude (constant versus modulated), frequency (constant versus swept), and ending shape (sharp versus smooth)). The results showed that frequency sweeping in addition to amplitude modulation and smooth ending were the most important factors in smoothing vibrotactile flows. Moreover, an excitation signal with a smooth ending shape was important for generating nonspiky flows at the midpoint. In this study, a vibration isolation design is also proposed in order to substantially decrease the transmission of the actuator vibration to the mockup housing. As such, it is expected that the proposed vibrotactile flow generation method and vibration isolation design may be useful in applications including generating directional information in navigation maps or for identifying callers in mobile devices.
Arming the Melanoma Sentinel Lymph Node through Local Administration of CpG-B and GM-CSF: Recruitment and Activation of BDCA3/CD141+ Dendritic Cells and Enhanced Cross-Presentation

Sluijter and colleagues report that intradermal injection of combined CpG/GM-CSF at the primary melanoma excision site prior to removal of sentinel lymph nodes (SLN) led to recruitment of BDCA3+ conventional dendritic cell (cDC) precursors from blood and enhanced DC maturation with selective increase of SLN-resident CLEC9A/BDCA3/CD141+ cDCs. Melanoma-induced suppression of dendritic cells (DC) in the sentinel lymph node (SLN) interferes with the generation of protective antitumor immunity. In an effort to strengthen immune defense against metastatic spread, we performed a three-arm phase II study comprising 28 patients with stage I–II melanoma randomized to receive intradermal injections around the primary tumor excision site of saline or low-dose CpG-B, alone or combined with GM-CSF, before excision of the SLNs. After pathologic examination, 5 patients were diagnosed with stage III melanoma based on the presence of tumor cells in the SLNs. Combined CpG/GM-CSF administration resulted in enhanced maturation of all identifiable conventional (cDC) and plasmacytoid (pDC) DC subsets and selectively induced increased frequencies of SLN-resident BDCA3/CD141+ cDC subsets that also expressed the C-type lectin receptor CLEC9A. Correlative in vivo analyses and in vitro studies provided evidence that these subsets were derived from BDCA3+ cDC precursors in the blood that were recruited to the SLNs in a type I IFN-dependent manner and subsequently matured under the combined influence of CpG and GM-CSF. In line with their reported functional abilities, frequencies of in vivo CpG/GM-CSF–induced BDCA3/CD141+ DCs correlated with increased ex vivo cross-presenting capacity of SLN suspensions. Combined local CpG/GM-CSF delivery thus supports protective antimelanoma immunity through concerted activation of pDC and cDC subsets and recruitment of BDCA3+ cDC subsets with T cell–stimulatory and cross-priming abilities. Cancer Immunol Res; 3(5); 495–505. ©2015 AACR.
The Risk-Adjusted Cost of Financial Distress

In this paper we argue that risk-adjustment matters for the valuation of financial distress costs, since financial distress is more likely to happen in bad times. Systematic distress risk implies that the risk-adjusted probability of financial distress is larger than the historical probability. Alternatively, the correct valuation of distress costs should use a discount rate that is lower than the risk free rate. We derive a formula for the valuation of distress costs, and propose two strategies to implement it. The first strategy uses corporate bond spreads to derive risk-adjusted probabilities of financial distress. The second strategy estimates the risk adjustment directly from historical data on distress probabilities, using several established asset pricing models. In both cases, we find that exposure to systematic risk increases the NPV of financial distress costs. In addition, the magnitude of the risk-adjustment can be very large, suggesting that a valuation of distress costs that ignores systematic risk significantly underestimates their true present value. Finally, we show that marginal distress costs computed using our new formula can be large enough to balance the marginal tax benefits of debt derived by Graham (2000), and we conclude that systematic distress risk can help explain why firms appear rather conservative in their use of debt.