Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of tuberculosis infection among community health agents.

OBJECTIVE To estimate the risk of tuberculosis infection among community health agents involved in disease control. METHODS A prospective cohort was followed up from April 2007 to May 2008 in the municipality of Cachoeiro de Itapemirim, Southeastern Brazil. The cohort was composed of 61 community agents, divided between unexposed individuals (n = 37) and exposed individuals (who were following up tuberculosis patients; n = 24). Over the 12-month follow-up, the tuberculin test was performed, using the tuberculin PPD RT23. The relative risk and 95% confidence interval were calculated, and the correlation between tuberculin response and the agents' occupational history was evaluated by means of Pearson's correlation. RESULTS The incidence of the response was 41.7% in the exposed group and 13.5% in the unexposed group. The annual risk of infection was 52.8% in the exposed group and 14.4% in the unexposed group (p = 0.013). An association between tuberculin response and exposure to patients with tuberculosis was observed (RR = 3.08; 95% CI: 1.201;7.914). CONCLUSIONS The agents who followed up tuberculosis patients during their routine work presented a greater risk of infection than did those who were not following up such patients. Implementation of routine administrative biosafety measures, among which the tuberculin test, should be prioritized, given the high risk of acquiring tuberculous infection among community health agents.
Organochlorine Pesticides and Risk of Endometriosis: Findings from a Population-Based Case–Control Study

Background: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. Objective: We investigated endometriosis risk in relation to environmental exposure to OCPs. Methods: We conducted the present analyses using data from the Women’s Risk of Endometriosis (WREN) study, a population-based case–control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Results: Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). Conclusions: In our case–control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women. Citation: Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, Holt VL. 2013. Organochlorine pesticides and risk of endometriosis: findings from a population-based case–control study. Environ Health Perspect 121:1319–1324; http://dx.doi. org/10.1289/ehp.1306648
A Rising Titan: TTN Review and Mutation Update

The 364 exon TTN gene encodes titin (TTN), the largest known protein, which plays key structural, developmental, mechanical, and regulatory roles in cardiac and skeletal muscles. Prior to next‐generation sequencing (NGS), routine analysis of the whole TTN gene was impossible due to its giant size and complexity. Thus, only a few TTN mutations had been reported and the general incidence and spectrum of titinopathies was significantly underestimated. In the last months, due to the widespread use of NGS, TTN is emerging as a major gene in human‐inherited disease. So far, 127 TTN disease‐causing mutations have been reported in patients with at least 10 different conditions, including isolated cardiomyopathies, purely skeletal muscle phenotypes, or infantile diseases affecting both types of striated muscles. However, the identification of TTN variants in virtually every individual from control populations, as well as the multiplicity of TTN isoforms and reference sequences used, stress the difficulties in assessing the relevance, inheritance, and correlation with the phenotype of TTN sequence changes. In this review, we provide the first comprehensive update of the TTN mutations reported and discuss their distribution, molecular mechanisms, associated phenotypes, transmission pattern, and phenotype–genotype correlations, alongside with their implications for basic research and for human health.
B-cell display-based one-step method to generate chimeric human IgG monoclonal antibodies

The recent development of screening strategies based on the generation and display of large libraries of antibody fragments has allowed considerable advances for the in vitro isolation of monoclonal antibodies (mAbs). We previously developed a technology referred to as the ‘ADLib (Autonomously Diversifying Library) system’, which allows the rapid screening and isolation in vitro of antigen-specific monoclonal antibodies (mAbs) from libraries of immunoglobulin M (IgM) displayed by the chicken B-cell line DT40. Here, we report a novel application of the ADLib system to the production of chimeric human mAbs. We have designed gene knock-in constructs to generate DT40 strains that coexpress chimeric human IgG and chicken IgM via B-cell-specific RNA alternative splicing. We demonstrate that the application of the ADLib system to these strains allows the one-step selection of antigen-specific human chimeric IgG. In addition, the production of chimeric IgG can be selectively increased when we modulate RNA processing by overexpressing the polyadenylation factor CstF-64. This method provides a new way to efficiently design mAbs suitable for a wide range of purposes including antibody therapy.
Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport

Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+-dependent and Na+-independent conditions to determine whether the function of excitatory amino acid transporters (also known as system XAG) or of system Xc– (glial cysteine–glutamate exchanger) was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent) compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+-dependent nor Na+-independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical–striatal pathways underlies the increases in extracellular glutamate found in the ethanol-dependent mice.
Toward Realistic Hands Gesture Interface: Keeping it Simple for Developers and Machines

Development of a rich hand-gesture-based interface is currently a tedious process, requiring expertise in computer vision and/or machine learning. We address this problem by introducing a simple language for pose and gesture description, a set of development tools for using it, and an algorithmic pipeline that recognizes it with high accuracy. The language is based on a small set of basic propositions, obtained by applying four predicate types to the fingers and to palm center: direction, relative location, finger touching and finger folding state. This enables easy development of a gesture-based interface, using coding constructs, gesture definition files or an editing GUI. The language is recognized from 3D camera input with an algorithmic pipeline composed of multiple classification/regression stages, trained on a large annotated dataset. Our experimental results indicate that the pipeline enables successful gesture recognition with a very low computational load, thus enabling a gesture-based interface on low-end processors.
Family history interview of a broad phenotype in specific language impairment and matched controls

The aim was to study a broader phenotype of language‐related diagnoses and problems in three generations of relatives of children with specific language impairment (SLI). Our study is based on a family history interview of the parents of 59 children with SLI and of 100 matched control children, exploring the prevalence of problems related to language, reading, attention, school achievement and social communication as well as diagnoses such as attention‐deficit hyperactivity disorder (ADHD), autism, Asperger syndrome, dyslexia, mental retardation, cleft palate and stuttering. The results show a spectrum of language‐related problems in families of SLI children. In all three generations of SLI relatives, we found significantly higher prevalence rates of language, literacy and social communication problems. The risk of one or both parents having language‐related diagnoses or problems was approximately six times higher for the children with SLI (85%) than for the control children (13%) (odds ratio = 37.2). We did not find a significantly higher prevalence of the diagnoses ADHD, autism or Asperger syndrome in the relatives of the children with SLI. However, significantly more parents of the children with SLI had problems with attention/hyperactivity when compared with the parents of controls. Our findings suggest common underlying mechanisms for problems with language, literacy and social communication, and possibly also for attention/hyperactivity symptoms.
Timing of Gene Expression Responses to Environmental Changes

Cells respond to environmental perturbations with changes in their gene expression that are coordinated in magnitude and time. Timing information about individual genes, rather than clusters, provides a refined way to view and analyze responses, but it is hard to estimate accurately. To analyze response timing of individual genes, we developed a parametric model that captures the typical temporal responses: an abrupt early response followed by a second transition to a steady state. This impulse model explicitly represents natural temporal properties such as the onset and the offset time, and can be estimated robustly, as demonstrated by its superior ability to impute missing values in gene expression data. Using response time of individual genes, we identify relations between gene function and their response timing, showing, for example, how cytosolic ribosomal genes are only repressed after the mitochondrial ribosome is activated. We further demonstrate a strong relation between the binding affinity of a transcription factor and the activation timing of its targets, suggesting that graded binding affinities could be a widely used mechanism for controlling expression timing. See online Supplementary Material at (www.liebertonline.com).
Material Density Hepatic Steatosis Quantification on Intravenous Contrast-Enhanced Rapid Kilovolt (Peak)–Switching Single-Source Dual-Energy Computed Tomography

Purpose The purpose of this study was to evaluate intravenous (IV) contrast-enhanced single-source rapid kilovolt (peak)–switching dual-energy (RSDE) multidetector computed tomography (CT) material density assessment of hepatic steatosis compared to conventional unenhanced (CU) Multidetector computed tomography (MDCT). Materials and Methods This is an institutional review board–approved intrapatient study of 363 consecutive adults (189 men, 174 women; mean age, 59 years) evaluated with multiphasic IV abdominal RSDE. Material density virtual unenhanced water and fat hepatic parenchymal values were measured and correlated to Hounsfield units (HUs) on CU CT using linear regression. Study population was dichotomized into steatotic or nonsteatotic liver parenchyma on the basis of CU liver-spleen (L-S) difference. The RSDE fat(-iodine) values (in milligram per milliliter) were compared (t test), correlated to the L-S difference in HU, and a milligram-per-milliliter fat threshold for clinically significant steatosis was calculated using receiver operator curve (ROC) analysis. Results Regression analysis revealed r value of 0.86 for mg/mL water (P < 0.001) and 0.87 for milligram-per-milliliter fat (P < 0.001). Twenty-seven participants were excluded from the L-S analysis (splenectomy). A total of 107 (32%) had steatosis (mean L-S, − 6.3; mean fat(-iodine) milligram per milliliter, 1018.4); 229 (68%) had no steatosis (mean L-S, 9.4; milligram per milliliter, 1028.4 [P < 0.001]). The RSDE fat material density measurement correlated to L-S less than 1 with r value of 0.74 (P < 0.001), with an area under receiver operator curve of 0.847. A threshold of 1023-mg/mL fat had 71% sensitivity and 80% specificity, and a threshold of 1027-mg/mL fat had 90% sensitivity and 61% specificity for steatosis. Conclusions The RSDE milligram-per-milliliter fat values correlate well with hepatic steatosis defined by the L-S difference less than 1 on conventional MDCT. A threshold of 1027 mg/mL can identify 90% of steatotic livers when post-IV contrast RSDE is used, without obtaining additional CU scans. However, regression equations were not helpful to convert an individual participant’s milligram-per-milliliter fat or milligram-per-milliliter water-derived from RSDE material density images to CU MDCT HU for the estimation of liver fat content.
Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).

PURPOSE Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy. PATIENTS AND METHODS AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression. CONCLUSION K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.
Creep of Anisotropic Clay: New Microplane Model

As a simpler alternative to a previous microplane model, a new microplane model is presented, in which the relative slipping of clay platelets is characterized by normal rather than shear strains on the microplanes. As is the case for Batdorf and Budianski’s slip theory of plasticity, the microplanes are constrained statically, i.e., the stress components on a microplane are the resolved components of the macroscopic stress, while the previous model used a kinematic constraint. This different type of constraint is needed to model correctly material anisotropy. The distribution function of normal strain rate intensity for microplanes of various orientations is calculated from the frequency distribution function of clay platelet orientations, which was approximately determined by other authors from x-ray diffraction measurements. The 6 × 6 fluidity matrix is calculated from the principle of complementary virtual work on the basis of deformations of individual microplanes and the current values of the stress components. The activation energy approach, validated in previous works, is used to quantify the dependence of the normal strain rates on the microplanes of all orientations as a function of the stress level and temperature. A numerical algorithm to calculate the fluidity matrix is given, and typical test data from the literature are analyzed. With only two free material parameters, good fits of the data are achieved, including their anisotropic features. The modeling is limited to deviatoric creep, and volumetric response is left for subsequent work. The proposed model could be used in finite element programs.
Motor Proficiency in Children With Neurofibromatosis Type 1

PURPOSE Neurofibromatosis type 1 (NF1) is a genetic disorder with associated musculoskeletal abnormalities, tumors, and developmental delays. The purpose of this study was to investigate and characterize the motor proficiency of children with NF1. METHODS Children with NF1 were assessed using the Bruininks-Oseretsky Test (BOT 2) instrument. The NF1 group scores were compared with age and sex-matched test norms. RESULTS Twenty-six children participated in the study. The NF1 group had statistically significant lower scores (P < .05) for the total motor composite (Z = -1.62) and 7 of the 8 subtests. Nineteen percent (n = 5) scored in the average category, 54% (n = 14) scored in the below-average category, and 27% (n = 7) scored in the well-below-average category. CONCLUSIONS Children with NF1 have significantly lower motor proficiency than the BOT 2 normative scores. The results indicate the BOT 2 is useful in identifying and characterizing delays in motor proficiency for children with NF1.
Arabidopsis microRNA expression regulation in a wide range of abiotic stress responses

Arabidopsis microRNA expression regulation was studied in a wide array of abiotic stresses such as drought, heat, salinity, copper excess/deficiency, cadmium excess, and sulfur deficiency. A home-built RT-qPCR mirEX platform for the amplification of 289 Arabidopsis microRNA transcripts was used to study their response to abiotic stresses. Small RNA sequencing, Northern hybridization, and TaqMan® microRNA assays were performed to study the abundance of mature microRNAs. A broad response on the level of primary miRNAs (pri-miRNAs) was observed. However, stress response at the level of mature microRNAs was rather confined. The data presented show that in most instances, the level of a particular mature miRNA could not be predicted based on the level of its pri-miRNA. This points to an essential role of posttranscriptional regulation of microRNA expression. New Arabidopsis microRNAs responsive to abiotic stresses were discovered. Four microRNAs: miR319a/b, miR319b.2, and miR400 have been found to be responsive to several abiotic stresses and thus can be regarded as general stress-responsive microRNA species.
The Role of Transient Receptor Potential Vanilloid 4 in Pulmonary Inflammatory Diseases

Ion channels/pumps are essential regulators of organ homeostasis and disease. In the present review, we discuss the role of the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), in cytokine secretion and pulmonary inflammatory diseases such as asthma, cystic fibrosis (CF), and acute lung injury/acute respiratory distress syndrome (ARDS). TRPV4 has been shown to play a role in lung diseases associated with lung parenchymal stretch or stiffness. TRPV4 indirectly mediates hypotonicity-induced smooth muscle contraction and airway remodeling in asthma. Further, the literature suggests that in CF TRPV4 may improve ciliary beat frequency enhancing mucociliary clearance, while at the same time increasing pro-inflammatory cytokine secretion/lung tissue injury. Currently it is understood that the role of TRPV4 in immune cell function and associated lung tissue injury/ARDS may depend on the injury stimulus. Uncovering the downstream mechanisms of TRPV4 action in pulmonary inflammatory diseases is likely important to understanding disease pathogenesis and may lead to novel therapeutics.
No simple answers for ecological immunology: relationships among immune indices at the individual level break down at the species level in waterfowl

Understanding immune function in the context of other life-history traits is crucial to understand the evolution of life histories, at both the individual and species levels. As the interest in assessing immune function for these comparative purposes grows, an important question remains unanswered: can immune function be broadly characterized using one or two simple measures? Often, interpretation of individual assays is ambiguous and relationships among different measures of immune function remain poorly understood. Thus, we employed five protocols to measure 13 variables of immune function in ten species of waterfowl (Anseriformes). All assays were based on a single blood sample subdivided into leukocyte (blood smear) and plasma (frozen until analysis) components. All assays were run using samples from every individual, and a nested analysis was used to partition variation/covariation at the levels of species and individuals within species. We detected positive correlations between functionally related measures of immunity within species, but these were absent from comparisons between species. A canonical correlation analysis revealed no significant relationships between the plasma and leukocyte assays at the levels of both individual and species, suggesting that these measures of immunity are neither competitive nor synergistic. We conclude that one measure of each assay type may be required to maximally characterize immune function in studies of a single species, while the same is not true in studies among species.