Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of the Institute of Medicine Report: Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease

The Institute of Medicine (IOM) released a groundbreaking 2010 report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease. Key recommendations included a harmonized scientific process and a general framework for biomarker evaluation with three interrelated steps: (1) Analytical validation — is the biomarker measurement accurate? (2) Qualification — is the biomarker associated with the clinical endpoint of concern? (3) Utilization — what is the specific context of the proposed use?
Occupational exposures and risk of stomach cancer by histological type

Objective To explore the relationship between stomach cancer (SC), by histological type, and occupations and occupational exposures. Methods The authors conducted a hospital-based case–control study in south-east Spain. Subjects were 399 incident histological confirmed SC cases (241 intestinal and 109 diffuse adenocarcinomas) and 455 controls frequency matched by sex, age and province of residence. Occupation was coded according to the Spanish National Classification of Occupations 1994. Occupational exposures were assessed by the FINJEM Job Exposure Matrix. ORs were estimated by unconditional logistic regression adjusting for matching variables and education, smoking, alcohol and diet. Results In men, statistically significant increased risk of the diffuse subtype was found for ‘cooks’ (OR 8.02), ‘wood-processing-plant operators’ (OR 8.13) and ‘food and related products machine operators’ (OR 5.40); for the intestinal subtype, a borderline association was found for ‘miners and quarry workers’ (OR men 4.22, 95% CI 0.80 to 22.14). Significant increased risk was observed between the diffuse subtype of SC and the highest level of exposure to ‘pesticides’ (ORH both sexes 10.39, 95% CI 2.51 to 43.02, ptrend=0.02) and between the intestinal subtype and asbestos (ORH men 3.71, 95% CI 1.40 to 9.83, ptrend=0.07). Restricted analyses of exposures of 15 years and longer showed significant associations between the diffuse subtype and the exposure to ‘wood dust’ (OR men 3.05). Conclusions This study supports the relationship previously suggested between SC and occupational exposure to dusty and high temperature environments. Several occupations may also increase the risk of diffuse SC but not the intestinal subtype.
Upper airway measurements during inspiration and expiration in infants.

Accurate measurements of the upper airway of the infant are important but are difficult to obtain reliably because of the normal variation that occurs during respiration. X-ray films of the lateral upper airway were obtained during inspiration and expiration in healthy infants, by using as a timing device a respiration monitor which was wired to the x-ray machine and was attached to the abdominal wall of the infant. Cephalometric measurements were made of 44 "normal" full-term neonates and 29 infants at 6 weeks of age. Despite significant differences in head circumference between the sexes, only the nasion to sella length was significantly longer in the boys (P less than .01). The lateral upper airway measurements were independent of weight, head circumference, and sex in the neonates and infants at 6 weeks of age but were significantly smaller during inspiration than expiration (P less than .01). The measurements progressively increased from the middle to the posterior airway space at both ages. The middle airway space behind the caudal end of the hard palate was smaller during inspiration at 6 weeks of age compared to the neonate (P less than .01). During expiration, the posterior airway space was larger at 6 weeks compared to the neonate (P less than .01). The method described in this report enables reliable roentgenographic measurements to be made of the upper airway of the infant; normal values for the changes during inspiration and expiration are provided. This may assist in the evaluation of infants with suspected upper airway obstruction.
Molecular neurotoxicology of trimethyltin: identification of stannin, a novel protein expressed in trimethyltin-sensitive cells.

The molecular basis of selective vulnerability of specific neuronal populations to neurotoxicants remains a key focus in neurotoxicology. Trimethyltin (TMT) selectively damages neurons in rodent and human central nervous system after a single exposure. By coupling subtractive hybridization with molecular cloning techniques, we isolated a cDNA specifically localized in TMT-sensitive cells. This 2.9-kilobase cDNA encodes a putative 10-kDa peptide of 88 amino acids, termed "stannin. " In immunocytochemical experiments, antisera raised against the amino terminus of stannin exhibited strong immunoreactivity in TMT-sensitive neurons in the hippocampus and entorhinal cortex, areas previously identified by in situ hybridization. Northern blot and in situ hybridization experiments detected a 3.0-kilobase stannin mRNA in brain, spleen, and kidney; expression occurred as early as embryonic day 15 in rat brain and thymus. In situ hybridization in human hippocampus demonstrated a stannin mRNA in pyramidal and dentate gyrus neurons. High stringency Southern blot analysis of genomic DNA identified stannin homologs in rabbit, Drosophila, and human. These findings indicate that stannin is present in TMT-sensitive cells and may play a role in the selective toxicity of organotin compounds.
Decreased transcription, expression and function of low-density lipoprotein receptor in leukocytes from patients with systemic lupus erythematosus

The low-density lipoprotein receptor (LDLR) is directly involved in the metabolism of low-density lipoprotein (LDL) and its impairment causes accumulation of plasmatic LDL leading to atherosclerosis, a prevalent disease in patients with systemic lupus erythematosus (SLE). We studied LDLR transcription, expression and function in leukocytes patients with SLE and normal healthy donors (NHD). The ratio LDLR/glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNAs the expression of LDLR and the uptake of LDL-DiI were significantly lower (p < 0.001) in the patients with SLE. On the contrary, patients with SLE had significantly higher (p < 0.0001) levels of total cholesterol, LDL cholesterol and anti-oxLDL autoantibodies (AAb) as compared to NHD. No correlation between LDLR transcription, expression and function with the SLE disease activity index or with treatment was found. The decreased function of LDLR was independent of treatment. It seems dependent on the sterol regulatory binding protein and may be responsible for the increase of plasma LDL cholesterol and oxLDL AAb further increasing the risk of vascular diseases.
Empirical Analysis of the Wagner Hypothesis of Government Expenditure Growth in Kenya: ARDL Modelling Approach

Government spending patterns in developing countries have changed dramatically over the last several decades. This paper aims at analysing the relation between government expenditures (GE) and economic growth in Kenya. The study focuses on testing the various versions of Wagner’s hypothesis using Kenya, data from 1967-2012 by an Autoregressive-Distributed Lag (ARDL) model. Overall, we conclude that the Musgrave version is best suited for Kenyan cases since it produced significant long-run and short-run results that were accepted by diagnosis and stability tests. The results rejected Wagner’s hypothesis in Kenya.
Educational governance in the NHS: a literature review.

PURPOSE This paper aims to survey the literature relating to educational governance's application to healthcare. Its purpose is to establish the extent to which this type of governance is recognised by healthcare staff, and to develop an understanding of how it is defined and used. DESIGN/METHODOLOGY/APPROACH The starting point for the literature review was an academic database search supplemented by a Google Scholar search. The results were sifted using evidence strength criteria and filtered for relevance using secondary keywords. FINDINGS The educational governance in healthcare literature search indicates that this is a relatively under-researched area. There are few attempts to define educational governance, although several authors note similarities with clinical governance. Authors cite educational governance as an important component of integrated approaches to healthcare governance, noting inter-dependent relationships between areas such as clinical governance, organisational development and risk management. RESEARCH LIMITATION/IMPLICATIONS: Given the diverse academic and grey literature used for the review, it was difficult to apply conventional evidence-strength scales, especially because most articles cited in the text are based on expert opinion rather than systematic review. PRACTICAL IMPLICATIONS The review highlights educational governance's value to healthcare organisations and provides references for organisational staff contemplating developing this area. ORIGINALITY/VALUE The paper is the first known attempt to survey the literature relating to National Health Service educational governance.
Utilization of concentrated growth factor as a sole sinus augmentation material

Posterior maxillary tooth loss frequently coincides with loss of available bone volume for implant placement due to both atrophy of the residual crestal bone and enlargement of the maxillary sinus. The longer the teeth have been missing, the greater the loss of osseous structure that may house implants. This necessitates augmentation of the maxillary sinus to provide adequate bone to place implants. Maxillary sinus augmentation with various bone graft material have become routine treatment over the past 38 years. Various materials have been utilized including allografts, xenografts and synthetics with varying levels of success as measured by the amount of graft maturation and its density to support implants following healing. As the use of autogenous blood products has increased in dental surgery for both soft and hard tissue applications, those materials have expanded into use when augmenting the sinus. As blood biology has grown in use with regard to grafting using the patients own blood to supply growth factors and other patient derived products, grafting has improved the clinical results we are able to achieve. These blood derived products have been mixed with packed osseous graft materials to help improve the quality and quantity of the resulting graft following healing. The case presented in this article demonstrates graft maturation as evidenced by density can be achieved using CGF alone with no added osseous graft materials. The benefit of this approach is no issues with the potential of a patient reaction to the packaged osseous graft material that are typically used and cost of treatment is reduced as packaged products are not utilized in the sinus augmentation procedure.
Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China

ABSTRACT The aim of this study was to investigate the epidemiology of pyrazinamide (PZA) resistance and the associated risk factors as well as to evaluate the pncA gene loci as a marker for PZA resistance in China. A population-based multicenter study of pulmonary tuberculosis (TB) cases was carried out from 2011 to 2013 in four Chinese districts/counties with different geographic and socioeconomic features. Testing for multidrug-resistant tuberculosis (MDR-TB) and susceptibility to PZA was done by the proportion method on Lowenstein-Jensen medium and Bactec MGIT 960, respectively. Mutations in the pncA gene were identified by sequencing. Among 878 culture-positive cases, 147 (16.7%) were resistant to PZA, with a significantly higher proportion among MDR isolates than among the first-line drug-susceptible isolates (30.2% versus 7.7%; P < 0.001). In total, 136 isolates had a nonsynonymous pncA mutation, with a comparable diagnostic performance between Beijing family and non-Beijing family as well as between MDR-TB and first-line drug-susceptible TB. Furthermore, the mutations in isolates with high-level PZA resistance (MIC > 500 mg/liter) were observed mainly in three regions of the pncA gene (codons 51 to 76, codons 130 to 142, and codons 163 to 180). Patients with prior treatment history had a significantly higher risk for PZA monoresistance (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.363 to 6.015) and MDR PZA resistance (OR, 6.47; 95% CI, 3.186 to 13.15), while the additional factors associated with MDR PZA resistance were the patient's age (OR, 1.02; 95% CI, 1.003 to 1.042), lung cavity (OR, 2.64; 95% CI, 1.296 to 5.391). These findings suggest that it is a priority to identify PZA resistance in MDR-TB and that a rapid molecular diagnostic test based on pncA mutations in the Chinese settings where MDR-TB prevalence is high should be developed.
The Parent Report Form of the CHIP–Child Edition: Reliability and Validity

BackgroundValid, comprehensive instruments to describe, monitor, and evaluate health from childhood through adolescence are almost nonexistent, but are critical for health resource planning, evaluation of policy, preventive, and clinical interventions, and understanding trajectories of health during this important period of life. ObjectivesThe objectives of this study were to describe the development, testing, and final versions of the Parent Report Form of the Child Health and Illness Profile–Child Edition (CHIP-CE/PRF), designed to measure the health of children 6 to 11 years old from the caregiver perspective. MethodsParents (N = 1049) completed a version of the CHIP-CE/PRF in 4 locations in the United States, either in clinic waiting rooms or their homes. They differed in race/ethnicity, socioeconomic level, and native language. ResultsThe Parent CHIP-CE is feasible; parents with a 5th-grade reading level complete the 76-item PRF in 20 minutes. Its domains (Satisfaction, Comfort, Risk Avoidance, Resilience, and Achievement) measure structurally distinct, interrelated aspects of health. Domain reliability is high: internal consistency = 0.79–0.88; retest reliability (ICC) = 0.71–0.85. Validity is supported. The scale scores are sensitive to predicted age, gender, and socioeconomic status differences in health. ConclusionThe CHIP–Child Edition/Parent Report Form is a psychometrically sound, conceptually based measure of child health that works well in diverse populations. It produces scores that parallel those of children on the CHIP-CE/CRF and adolescents on the CHIP-AE and allows health to be consistently assessed from childhood through adolescence. It should meet many needs for describing, monitoring, and understanding child health and evaluating outcomes of interventions.
Distinct Footprints of TCR Engagement with Highly Homologous Ligands1

T cell receptor engagement promotes proliferation, differentiation, survival, or death of T lymphocytes. The affinity/avidity of the TCR ligand and the maturational stage of the T cell are thought to be principal determinants of the outcome of TCR engagement. We demonstrate in this study that the same mouse TCR preferentially uses distinct residues of homologous peptides presented by the MHC molecules to promote specific cellular responses. The preference for distinct TCR contacts depends on neither the affinity/avidity of TCR engagement (except in the most extreme ranges), nor the maturity of engaged T cells. Thus, different portions of the TCR ligand appear capable of biasing T cells toward specific biological responses. These findings explain differences in functional versatility of TCR ligands, as well as anomalies in the relationship between affinity/avidity of the TCR for the peptide/MHC and cellular responses of T cells.
Dendritic Cell-Mediated trans-Enhancement of Human Immunodeficiency Virus Type 1 Infectivity Is Independent of DC-SIGN

ABSTRACT Dendritic cells (DCs) enhance human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T lymphocytes in trans. The C-type lectin DC-SIGN, expressed on DCs, binds to the HIV-1 envelope glycoprotein gp120 and confers upon some cell lines the capacity to enhance trans-infection. Using a short hairpin RNA approach, we demonstrate that DC-SIGN is not required for efficient trans-enhancement by DCs. In addition, the DC-SIGN ligand mannan and an anti-DC-SIGN antibody did not inhibit DC-mediated enhancement. HIV-1 particles were internalized and were protected from protease treatment following binding to DCs, but not from binding to DC-SIGN-expressing Raji cells. Thus, DC-SIGN is not required for DC-mediated trans-enhancement of HIV infectivity.
Organization of services and pattern of psychiatric care in Nicaragua: Result of a survey in 1986

ABSTRACT— Organization of services and patterns of psychiatric care were studied in Nicaragua in 1986, 7 years after the substantial changes in health policy launched after the revolution. The overall re‐organization of the system is indicated by the progressive abandoning of the mental hospital as the center of psychiatric care and the creation of 15 community‐based mental health centers now functioning throughout the country. Quality of care judged through analysis of a consecutive sample of 342 patients seen by services over a month confirmed the positive orientation of the system which seemed able to deliver good care following the new perspective of “de‐institutionalization”. Some problems emerged to a large extent common to psychiatric care in industrialized countries looking at psychotropic drug use and at the relationship between primary health care and the psychiatric system especially when care delivered in urban and rural areas was compared.
SUPPLEMENTAL DIAGNOSIS OF KUDOA FUNDULI (MYXOZOA) PARASITIZING FUNDULUS HETEROCLITUS (CYPRINODONTIDAE) FROM COASTAL NORTHEASTERN NORTH AMERICA

The diagnosis of Kudoa funduli (Hahn, 1915) Meglitsch, 1948 (Myxozoa), is supplemented through study of new material collected from Fundulus heteroclitus (Cyprinodontidae) in coastal waters of Nova Scotia, Canada, and Connecticut. Plasmodia normally develop intracellularly in striated muscle of the flank and head, eventually rupturing and releasing spores. Spores disperse along adjacent epimysium, sometimes as far as the skin surface. Some plasmodia develop extracellularly within the bony cavities of vertebrae. Formalin-fixed spores viewed with a light microscope possess rounded edges, an inconspicuous apical region, thin sutural ridges, measure 6.6–7.4 μm wide, 4.3–5 μm thick, and 5.1–5.4 μm long, and have 4 equally sized polar capsules, 1.7–2.3 μm length by 1.4–1.7 μm width. Scanning electron microscopy revealed that spores are almost stellate, with inconspicuous uplifted tips, and that, within intracellular plasmodia, are embedded in an extensive honeycomb-like matrix. Prevalence of infection of K. funduli was 100% in host populations sampled in both Nova Scotia and Connecticut. Molecular sequence data of the 18S ribosomal DNA (737 base pairs) reveal that K. funduli is a valid species and a member of a clade that includes Kudoa dianae Dyková, Avila, and Fiala, 2002, Kudoa miniauriculata Whitaker, Kent, and Sakanari, 1996, and Kudoa paniformis Kabata and Whitaker, 1981.
PTSD and Substance Use Disorder Among Veterans: Characteristics, Service Utilization and Pharmacotherapy

Objective: While there has been considerable concern about veterans with dually diagnosed posttraumatic stress disorder (PTSD) and comorbid substance use disorders, a national study of clinical characteristics, service utilization, and psychotropic medication use of such veterans in Veterans Affairs (VA) has yet to be conducted. We hypothesized that veterans having both PTSD and substance use disorder would have lower socioeconomic status, greater medical and psychiatric comorbidity, higher medical service utilization, and more psychotropic pharmacotherapy fills. Methods: National VA data from fiscal year 2012 were used to compare veterans with dually diagnosed PTSD and substance use disorder to veterans with PTSD without substance use disorder on sociodemographic characteristics, psychiatric and medical comorbidities, mental health and medical service utilization, and psychotropic pharmacotherapy. Comparisons were based on bivariate and Poisson regression analyses. Results: The sample included all 638,451 veterans who received the diagnosis of PTSD in the VA in fiscal year 2012: 498,720 (78.1%) with PTSD alone and 139,731 (21.9%) with dually diagnosed PTSD and a comorbid substance use disorder. Veterans with dual diagnoses were more likely to have been homeless and to have received a VA disability pension. Medical diagnoses that were more strongly associated with veterans with dual diagnosis included seizure disorders, liver disease, and human immunodeficiency virus (HIV). Psychiatric comorbidities that distinguished veterans with dual diagnoses included bipolar disorder and schizophrenia. Veterans with dually diagnosed PTSD and substance use disorder also had a greater likelihood of having had mental health inpatient treatment. There were no substantial differences in other measures of service use or prescription fills for psychotropic medications. Conclusions: Several substantial differences were observed, each of which represented more severe medical and psychiatric illness among veterans with dually diagnosed PTSD and substance use disorder compared to those with PTSD alone. However, effective treatments are available for these disorders and special efforts should be made to ensure that veterans with dual diagnoses receive them.
Issues in Applying Financial Econometrics to Factor-Based Modeling in Investment Management

In this article, the authors provide a nontechnical discussion of a number of practical and theoretical issues associated with implementing factor models used to explain or forecast equity returns. The first issue is determining the number of factors (i.e., the number of variables needed to explain or forecast returns). In finite markets such as stock markets, the problem of determining the true number of factors cannot be solved theoretically. Instead, asset managers must be content with approximations using model selection criteria. The authors then discuss the questions of overfitting and dimensionality reduction—both of which can lead to poor out-of-sample performance of investment or trading strategies. Overfitting entails using a model that is too complex for the data available to the modeler; thus, the resulting model fits noise. Dimensionality reduction solves the problem of dimensionality by using approximate models of reduced dimensionality that can be estimated with small samples. An important instance of applying dimensionality reduction techniques is using factor GARCH models to forecast covariance matrices. Finally, the authors discuss problems associated with backtesting. In trying to choose the best-performing model or strategy, a modeler may be tempted to run multiple backtests, thereby creating the risk of using out-of-sample backtesting as a form of in-sample testing. In turn, this leads to overfitting.