Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder resulting from pathogenic variants in the α‐L‐iduronidase (IDUA) gene. Clinical phenotypes range from severe (Hurler syndrome) to attenuated (Hurler‐Scheie and Scheie syndromes) and vary in age of onset, severity, and rate of progression. Defining the phenotype at diagnosis is essential for disease management. To date, no systematic analysis of genotype‐phenotype correlation in large MPS I cohorts have been performed. Understanding genotype‐phenotype is critical now that newborn screening for MPS I is being implemented. Data from 538 patients from the MPS I Registry (380 severe, 158 attenuated) who had 2 IDUA alleles identified were examined. In the 1076 alleles identified, 148 pathogenic variants were reported; of those, 75 were unique. Of the 538 genotypes, 147 (27%) were unique; 40% of patients with attenuated and 22% of patients with severe MPS I had unique genotypes. About 67.6% of severe patients had genotypes where both variants identified are predicted to severely disrupt protein/gene function and 96.1% of attenuated patients had at least one missense or intronic variant. This dataset illustrates a close genotype/phenotype correlation in MPS I but the presence of unique IDUA missense variants remains a challenge for disease prediction.
Toxicity of Binary Mixtures of Reactive Toxicants

This study evaluated the toxicity of binary mixtures of reactive toxicants using the Microtox test. Greater than additive effects were quite frequently observed (18%) among chemicals with different mechanisms of toxicity, and some of them were severely synergistic. The concentration-addition model, therefore, may not be appropriate for estimating the multiple toxicity of mixtures containing reactive toxicants. The slope of a chemical's concentration-response curve was found to play an important role in determining the mode of joint actions, which could be related to the complex joint action identified earlier. The results of this study have been summarized into several relationships that can be used to estimate the potential risks for mixtures with unknown toxicity. 0 7996 by John Wiley & Sons, Inc.
Association of postpartum diseases occurring within 60 days after calving with productivity and reproductive performance in dairy cows in Fukuoka: A cow-level, retrospective cohort study

Peripartum disorders in dairy cows negatively influence their productivity and reproductive performance. However, only a few reports have clearly indicated the influence of such disorders on the productivity and reproductive performance at a local-area or cow-level in Japan. This study aimed to elucidate the influence of diseases occurring within 60 days after calving on subsequent productivity and reproductive performance. Accordingly, a wide-area database on dairy production was used for epidemiological analysis; subsequently, multivariable analysis was performed to investigate the association of such diseases with productivity or reproductive performance in 6,545 cows from 178 farms in Fukuoka. We used 305-day energy-corrected milk (305 ECM) as an index of productivity and conception and culling as indices of reproductive performance. With regard to causality, mixed-effects model was used for analyzing the association between disease and productivity, and Cox proportional hazard model was used for analyzing the association between disease and reproductive performance. Compared to the disease absence group, the disease presence group demonstrated significantly lower 305 ECM [−154 kg; 95% confidence interval (CI), −229 to −79] and risk of pregnancy [hazard ratio (HR), 0.85; 95% CI, 0.80–0.91] and higher risk of culling (HR, 1.36; 95% CI, 1.17–1.59). These results indicate that, in Fukuoka, dairy cows affected by diseases within 60 days after calving exhibit lower productivity and reproductive performance. Therefore, proper dairy cow management during the peripartum period to prevent diseases during early lactation may maintain or improve productivity.
A preliminary evaluation of surface latent heat flux as an earthquake precursor

Abstract. The relationship between variations in surface latent heat flux (SLHF) and marine earthquakes has been a popular subject of recent seismological studies. So far, there are two key problems: how to identify the abnormal SLHF variations from complicated background signals, and how to ensure that the anomaly results from an earthquake. In this paper, we proposed four adjustable parameters for identification, classified the relationship and analyzed SLHF changes several months before six marine earthquakes by employing daily SLHF data. Additionally, we also quantitatively evaluate the long-term relationship between earthquakes and SLHF anomalies for the six study areas over a 20 yr period preceding each earthquake. The results suggest the following: (1) before the South Sandwich Islands, Papua, Samoa and Haiti earthquakes, the SLHF variations above their individual background levels have relatively low amplitudes and are difficult to be considered as precursory anomalies; (2) after removing the clustering effect, most of the anomalies prior to these six earthquakes are not temporally related to any earthquake in each study area in time sequence; (3) for each case, apart from Haiti, more than half of the studied earthquakes, which were moderate and even devastating earthquakes (larger than Mw = 5.3), had no precursory variations in SLHF; and (4) the correlation between SLHF and seismic activity depends largely on data accuracy and parameter settings. Before any application of SLHF data on earthquake prediction, we suggest that anomaly-identifying standards should be established based on long-term regional analysis to eliminate subjectivity. Furthermore, other factors that may result in SLHF variations should also be carefully considered.
Engagement of National Stakeholders and Communities on Health-Care Quality Improvement: Experience from the Implementation of the Partnership for HIV-Free Survival in Tanzania

The Partnership for HIV-Free Survival initiative in Tanzania integrated postnatal nutrition and mother-to-child transmission (MTCT) cascades to reduce vertical HIV transmission. Quality improvement (QI) was implemented in 30 health facilities. Net positive gain resulted in overall improvement in all indicators (above 80%) by the end of the reporting period. Retention in postnatal care (mean = 49.8, standard deviation [SD] = 27.6) and in monthly HIV services (mean = 65.4, SD = 29.5) had the lowest average but showed consecutive and significant (P ≤ .001) gains except for significant decreases in 1 of 6 periods assessed. Average antiretroviral therapy uptake among women (mean = 81.7, SD = 29.5) was highest, with an initial positive gain of 78.9% (P ≤ .001). DNA/polymerase chain reaction for HIV-exposed infants (mean = 71.8, SD = 20.9) and nutrition counseling (mean = 71.2, SD = 26.3) showed similar average performance, with the latter being the only indicator with significant equal periods of gain and decreases. The collaborative QI approach improved process indicators for reducing MTCT in resource-constrained health systems.
Punching strength of reinforced concrete flat slabs without shear reinforcement

Punching strength is a critical point in the design of flat slabs and due to the lack of a theoretical method capable of explaining this phenomenon, empirical formulations presented by codes of practice are still the most used method to check the bearing capacity of slab-column connections. This paper discusses relevant aspects of the development of flat slabs, the factors that influence the punching resistance of slabs without shear reinforcement and makes comparisons between the experimental results organized in a database with 74 slabs carefully selected with theoretical results using the recommendations of ACI 318, EUROCODE 2 and NBR 6118 and also through the Critical Shear Crack Theory, presented by Muttoni (2008) and incorporated the new fib Model Code (2010).
Double/de-biased machine learning using regularized Riesz representers

We provide adaptive inference methods for linear functionals of L1-regularized linear approximations to the conditional expectation function. Examples of such functionals include average derivatives, policy effects, average treatment effects, and many others. The construction relies on building Neyman-orthogonal equations that are approximately invariant to perturbations of the nuisance parameters, including the Riesz representer for the linear functionals. We use L1-regularized methods to learn the approximations to the regression function and the Riesz representer, and construct the estimator for the linear functionals as the solution to the orthogonal estimating equations. We establish that under weak assumptions the estimator concentrates in a 1/vn neighborhood of the target with deviations controlled by the normal laws, and the estimator attains the semi-parametric efficiency bound in many cases. In particular, either the approximation to the regression function or the approximation to the Rietz representer can be “dense” as long as one of them is sufficiently “sparse”. Our main results are non-asymptotic and imply asymptotic uniform validity over large classes of models.
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Sophisticated analytical tools for elucidating genome structure and life of bacteria yielded a new paradigm on our relation to the microbial environment. Formerly, bacteria were seen as jeopardising invaders, and studies on bacterial pathogenesis were the basis for great medical progress in the restraint of infections. Now it becomes clear that Homo sapiens is not a single-species organism, but it is to understand as a complex ecosystem assembled of a 10:1 mixture of both environmental microbial and human cells. The gargantuan diversity of prokaryotic life includes genetic multiplicity, metabolic endowment, colonised habitats, and response to physical and chemical stresses. Advances in microbiology, molecular biology, biochemistry and eukaryotic cell biology have enabled striking discoveries on how eukaryotic cells cooperate with colonising bacteria. Bacterial life in multispecies associations and biofilms limits competition, reduces temporal variance of productivity, enhances performance, and favours positive interactions among the allied members. Quorum sensing, hypermutable loci in the genome, horizontal transfer of genes distributed within the population and the enduring crosstalk with the epithelia and the innate immune system of the host warrant stability within the microbial community and maintenance of the mutually beneficial association with the host. Factors accompanying our current life such as overand malnutrition, physical inactivity, excessive use of tobacco, alcohol, drugs and medicine,
Reducing Robust Health-Relevant Cardiovascular Stress Responses Among Active-Duty Special Forces Police

Policing presents a complex set of risk factors for occupational health and safety among officers, including environmental, psychosocial, and health risks. Environmental risks include facing critical incidents such as violent offenders, hostage negotiations, intense crime scenes, and irate civilians. Critical incidents are high pressure situations that are typically time sensitive, and elicit substantial physiological threat responses. When facing a threat, the body normally responds by going into a “fight-or-flight” mode, in which a host of physiological and psychological processes are invoked to help the body cope successfully with the threat [1]. For example, heart rate increases, digestion stops, blood flow to the brain moves from prefrontal cortex (logical thought) to the hindbrain (instinctual drives), and a person becomes less cognitively aware of their surroundings and more focused on fighting or fleeing from the threat. The natural and instinctual physiological response to threat may place police officers at a greater risk of injury or death, by reducing their situational awareness (i.e., ability to notice important environmental stimuli and other threats in their environment), and split-second decision making skills (e.g. shoot/don’t shoot). Advanced police teams called Special Weapons and Tactics (SWAT) officers, are called to the highest risk encounters [2]. The current research is the first to observe robust cardiovascular reactivity among SWAT officers during multiple, active duty shifts. Significant cardiovascular reactivity may pose a health risk to SWAT officers over time. Accordingly, this research documents the case examples from one team of SWAT officers who applied a simple cardiovascular and respiratory control technique during daily activities. Results suggest that this micro-intervention may have significant positive impact on daily cardiovascular health among SWAT officers.
Cancer-associated PTEN: Structural and Functional Characterization

Phosphatase and tensin homolog detected on chromosome ten (PTEN) is a tumor suppressor gene protecting cells from developing cancer and forming tumors (Leslie and den Hertog). In addition, PTEN mediates cell cycle arrest, adhesion, migration, and apoptosis(Sun, Lesche et al. 1999). The complete loss or mutations in the PTEN gene has been implicated in many human cancers from mammary carcinoma to developmental abnormalities and autism. It is in fact the most common mutation in human cancers and are inherited in an autosomal dominant manner (Yamada and Araki 2001). In their recent Cell paper, Papa et al (Papa, Wan et al. 2014) shows a novel homodimerization characteristic of PTEN that renders it active. Mechanistically, the homodimerized active conformation exerts its phosphatase activity on downstream targets such as AKT, PIP3, and PI3K and decreases their oncogenic activity. The two mutated PTEN isoforms characterized in this study have a reversed functionality compared to wild-type protein. These findings have great implications in developing drug agents that target PI3K pathway and sensitive to PTEN mutations.
Characteristics of Non-Emergent Visits in Emergency Departments: Profiles and Longitudinal Pattern Changes in Taiwan, 2000–2010

An increasing number of emergency department (ED) visits have posed a challenge to health systems in many countries, but an understanding of non-emergent ED visits has remained limited and contentious. This retrospective study analyzed ED visits using three representative cohorts from routine data to explore the profiles and longitudinal pattern changes of non-emergent ED visits in Taiwan. Systematic-, personal-, and ED visit-level data were analyzed using a logistic regression model. Average marginal effects were calculated to compare the effects of each factor. The annual ED visit rate increased up to 261.3 per 1000 population in 2010, and a significant one-third of visits were considered as non-emergent. The rapidly growing utilization of ED visits underwent a watershed change after cost-sharing payments between patients and medical institutions were increased in 2005. In addition to cohort effects resulting from cost-sharing payment changes, all factors were significantly associated with non-emergent ED visits with different levels of impact. We concluded that non-emergent ED visits were associated with multifaceted factors, but the change to cost-sharing payment, being female, younger age, and geographical residence were the most predictive factors. This information would enhance the implementation of evidence-based strategies to optimize ED use.
Metrics based optimization of functional source code

In order to control software development, usually a set of criteria is fixed, among other things defining limits for the size of modules and functions, guiding layout principles etc. These criteria are not always observed, especially if the criteria are specified after pieces of the code are already written ‐ that is, handling legacy code. In this paper, we describe a method how the code base can semi automatically improved to conform more to the development criteria. We define a usage of a query language with which the user can employ our software complexity metrics to identify the out-of-line code parts, and select a transformation strategy that are automatically used by the tool to improve the identified parts.
An approach to discover innovation potential by means of delta applications

Although several approaches exist to integrate the customer in new product development, industrial small and middle sized enterprises do not apply these methods comprehensively. In order to overcome existing barriers the authors suggest a product based approach for customer integration. An example illustrates delta applications, which differ in their characteristic attributes from the product use case defined by the company. The approach of Delta Applications provides a neutral platform for exchange between customers and the company and overcomes existing barriers.
A Deep Convolutional Neural Network Approach to Classify Normal and Abnormal Gastric Slow Wave Initiation From the High Resolution Electrogastrogram

Objective: Gastric slow wave abnormalities have been associated with gastric motility disorders. Invasive studies in humans have described normal and abnormal propagation of the slow wave. This study aims to disambiguate the abnormally functioning wave from one of normalcy using multi-electrode abdominal waveforms of the electrogastrogram (EGG). Methods: Human stomach and abdominal models are extracted from computed tomography scans. Normal and abnormal slow waves are simulated along stomach surfaces. Current dipoles at the stomachs surface are propagated to virtual electrodes on the abdomen with a forward model. We establish a deep convolutional neural network (CNN) framework to classify normal and abnormal slow waves from the multi-electrode waveforms. We investigate the effects of non-idealized measurements on performance, including shifted electrode array positioning, smaller array sizes, high body mass index (BMI), and low signal-to-noise ratio (SNR). We compare the performance of our deep CNN to a linear discriminant classifier using wave propagation spatial features. Results: A deep CNN framework demonstrated robust classification, with accuracy above 90% for all SNR above 0 dB, horizontal shifts within 3 cm, vertical shifts within 6 cm, and abdominal tissue depth within 6 cm. The linear discriminant classifier was much more vulnerable to SNR, electrode placement, and BMI. Conclusion: This is the first study to attempt and, moreover, succeed in using a deep CNN to disambiguate normal and abnormal gastric slow wave patterns from high-resolution EGG data. Significance: These findings suggest that multi-electrode cutaneous abdominal recordings have the potential to serve as widely deployable clinical screening tools for gastrointestinal foregut disorders.
DUAL-BAND MONOPOLE ANTENNA WITH OMEGA PARTICLES FOR WIRELESS APPLICATIONS

A new design of dual-band antenna for DCS/PCS/UMTS/ WLAN/WiMAX applications is proposed. Using two metamaterials omega-shaped structures, a good impedance matching the dual-band mode is obtained. The proposed prototype antenna is fabricated on a 1.5mm thick FR4 epoxy substrate with a relative dielectric permittivity "r = 4:4 and a loss tangent tanae = 0:02. Good monopole- like radiation patterns and antenna gains over the operating bands have also been observed. Efiects of each omega particle on the antenna performance and their coupling are all examined and discussed.
Asian citrus psyllid, Diaphorina citri, vector of citrus huanglongbing disease

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is an important pest of citrus because it transmits phloem‐limited bacteria [Candidatus Liberibacter spp. , notably Ca. L. asiaticus (LAS)] associated with huanglongbing (HLB; citrus greening disease), currently considered the world's most serious disease of citrus. Asian citrus psyllid transmits LAS in a persistent manner and, although the rate of LAS transmission by ACP individuals usually is low, HLB can spread rapidly in a citrus grove and the geographic range of the disease is expanding, threatening citrus industries in new areas. Intensive chemical control of ACP is the primary management strategy currently advocated for HLB, but this strategy is costly, unsustainable, and generally ineffective. The scientific community is searching aggressively for solutions to HLB on many fronts, but it could still be years before solutions are found and implemented. Plant resistance to LAS is one area of research being pursued, whereby traits that confer resistance are identified and incorporated into citrus germplasm through conventional or transgenic methods. It remains to be seen if a solution to HLB can be found that specifically targets ACP, but research on ACP has been stepped up in a number of areas, notably on ACP–LAS–plant interactions, on host plant resistance to ACP, and on molecular methods of silencing ACP genes to induce mortality or to block its ability to transmit HLB‐causing bacteria. Advancements in these and other research areas may depend greatly on a better understanding of basic ACP biology and vector–pathogen–host plant interactions at the molecular, cellular, and community levels. Here, we present an updated review of ACP and HLB with an emphasis on the problem in Florida.
Big Business Owners in Politics

This paper investigates a little studied but common mechanism that firms use to obtain state favors: business owners themselves seeking election to top office. Using Thailand as a research setting, we find that the more business owners rely on government concessions or the wealthier they are, the more likely they are to run for top office. Once in power, the market valuation of their firms increases dramatically. Surprisingly, the political power does not influence the financing strategies of their firms. Instead, business owners in top offices use their policy-decision powers to implement regulations and public policies favorable to their firms. Such policies hinder not only domestic competitors but also foreign investors. As a result, these politically connected firms are able to capture more market share. The Author 2008. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. , Oxford University Press.
Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes

Abnormal cerebrospinal fluid (CSF) levels of β-amyloid peptides (Aβ42) and Tau and cognitive decline are typical characteristics of Alzheimer’s disease (AD). Since dysregulation in lipid metabolism accompanies abnormal amyloid formation, we quantified glycerophospholipids (GP) and sphingolipids (SP) in CSF fractions from participants with late-onset AD (LOAD, n = 29) or with Other Dementia (OD, n = 10) to determine if alterations in lipid metabolism account for pathological differences. Aβ42 and total Tau levels were determined using a sandwich ELISA. Liposomal-based fluorescent assays were used to measure phospholipase A2 (PLA2) and acid or neutral sphingomyelinase (aSMase, nSMase) activities. Supernatant fluid (SF) and nanoparticle (NP) lipids were quantified using LC-MS/MS. Although CSF Aβ42 and Tau levels are similar, phosphatidylserine (PS) in SF and ceramide (CM) levels in NP are significantly higher in OD compared with LOAD. The aSMase but not the nSMase activity is higher in OD. PLA2 activity in CSF from OD subjects positively correlates with several GP classes in SF and NP fractions but not in LOAD fractions. Our data indicate differences in CSF lipid metabolism between dementia variants. Higher levels of inflammatory and apoptotic lipids may induce faster neuronal death, resulting in the earlier cognitive decline in patients with OD phenotypes.