Miracle-dz/UniFAR-FTUs huggingface dataset:
How to describe the clinical spectrum in Pompe disease?

Pompe disease, which is also known as acid maltase deficiency and glycogen storage disease type II, derived its name from the Dutch pathologist Dr J.C. Pompe, who described it in a 7-month-old girl in 1932. In the same year, Dr Putschar presented an equally detailed report on a similar case. Both patients died in their first year of life due to generalized glycogen storage—later named glycogen storage disease type II – that affected mainly heart and skeletal muscle function. The underlying lysosomal a-glucosidase deficiency was discovered in 1963. Originally, Pompe disease was thought to be a disease of early infancy leading to death in the first year of life. However, the acid a-glucosidase deficiency turned out to occur in different degrees, with the first symptomsmanifesting at various ages, and the disease progressing at various speeds [Engel et al., 1973, 2004; Hirschhorn and Reuser, 2001]. Pompe disease is now considered to be a continuous spectrumof phenotypes, with the clinically severest, rapidly progressive phenotypes in the ultra violet, and the least severe, slowly progressive phenotypes extending into the infra red (Fig. 1). Boundaries between clinical subtypes cannot be set, although this is desirable for unraveling the genotype-phenotype correlation, discovering the factors contributing to disease progression, and judging the effects of therapeutic interventions such as enzyme replacement therapy. The recent series of ten articles on advancements in Pompe disease in the American Journal of Medical Genetics [Kishnani et al., 2012] reflects a struggle with nomenclature. Even among experts, a rich variety of nuanced terms are used to subdivide the clinical spectrum. One article distinguishes infantile onset Pompe disease (IOPD) from late onset Pompe disease (LOPD) with a caesura at the age of 1 year, while late onset Pompe disease is historically synonymous with adult onset Pompe disease—which is how it is used in the context of other articles. Terms such as classic infantile, infantile (onset), non-classic (infantile), atypical (infantile), non-infantile, and muscular variant, childhood, juvenile, adult, late(r) onset is used, sometimes to describe the same phenotypes and sometimes to describe different ones. Though consensus on nomenclature is clearly lacking, most experts seem to agree that the term classic infantile Pompe disease represents onset of symptomswithin the first year of life; it is always associated with hypertrophic cardiomyopathy, and it is always associated with virtually total lack of acid a-glucosidase activity. But late onset Pompe disease is ill defined:
Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case‐control study

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case‐control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long‐term evaluation of the risk–benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted. Int. J. Cancer 76:325–330, 1998. © 1998 Wiley‐Liss, Inc.
A new evolutionary algorithm for global numerical optimization

In this paper, a new evolutionary algorithm referred to as importance search algorithm (ISA) is designed to solve global numerical optimization problems with continuous variables. The proposed algorithm mainly consists of initialization process and iteration process in which the initialization process is used to initialize a population of random feasible solutions, and the iteration process is accomplished according to the move of the best particle in the colony. To show the effectiveness of the proposed ISA for global numerical optimization problems, it is applied to solve some typical benchmark test functions which are widely used in the literature and compared with the computational results obtained by using particle swarm optimization (PSO). The comparative results show that the proposed ISA is more effective than PSO when the problems with a large dimensions and it can And the optimal or near-optimal solutions of global numerical optimization problems.
Glutathione Facilitates Antibiotic Resistance and Photosystem I Stability during Exposure to Gentamicin in Cyanobacteria

ABSTRACT Understanding mechanisms of antibiotic resistance is important to the fields of biology and medicine. We find that glutathione contributes to antibiotic resistance in the cyanobacterium Synechocystis sp. PCC 6803. Our results also suggest that glutathione protects photosystem I from oxidative damage resulting from growth in the presence of gentamicin.
Porosity and thermal collapse measurements of H2O, CH3OH, CO2, and H2O:CO2 ices.

The majority of astronomical and laboratory based studies of interstellar ices have been focusing on ice constituents. Ice structure is a much less studied topic. Particularly the amount of porosity is an ongoing point of discussion. A porous ice offers more surface area than a compact ice, for reactions that are fully surface driven. In this paper we discuss the amount of compaction for four different ices--H2O, CH3OH, CO2 and mixed H2O : CO2 = 2 : 1--upon heating over an astronomically relevant temperature regime. Laser interference and Fourier transform infrared spectroscopy are used to confirm that for amorphous solid water the full signal loss of dangling OH bonds is not a proof for full compaction. These data are compared with the first compaction results for pure CH3OH, pure CO2 and mixed H2O : CO2 = 2 : 1 ice. Here we find that thermal segregation benefits from a higher degree of porosity.
A Bayesian Approach to Finite Mixture Models in Bioassay via Data Augmentation and Gibbs Sampling and Its Application to Insecticide Resistance

Summary. After continued treatment with an insecticide, within the population of the susceptible insects, resistant strains will occur. It is important to know whether there are any resistant strains, what the proportions are, and what the median lethal doses are for the insecticide. Lwin and Martin (1989, Biometrics45, 721–732) propose a probit mixture model and use the EM algorithm to obtain the maximum likelihood estimates for the parameters. This approach has difficulties in estimating the confidence intervals and in testing the number of components. We propose a Bayesian approach to obtaining the credible intervals for the location and scale of the tolerances in each component and for the mixture proportions by using data augmentation and Gibbs sampler. We use Bayes factor for model selection and determining the number of components. We illustrate the method with data published in Lwin and Martin (1989).
The Intersection of Firearms and Intimate Partner Homicide in 15 Nations

Intimate partners commit approximately one in three homicides against women worldwide. Little is known about situational factors that contribute to intimate partner homicides (IPH) and how they may differ across nations. This article provides a cross-national exploration of one situational factor, the use of firearms in the commission of homicides, and considers whether nations have laws designed specifically to keep firearms out of the hands of batterers. We conducted a systematic search of peer-reviewed research and governmental and nongovernmental reports for data on weapon use in IPH. Data were located for 15 nations and subnational areas, which varied from firearms being involved in no IPHs in Fiji to 59% in Antalya, Turkey. Seven nations have legislation that addresses gun ownership as it relates to those who have been charged with, convicted of, or show a propensity toward the commission of intimate partner violence. These laws vary in whether domestic violence is a factor considered in whether to allow firearm ownership or whether it served to disqualify ownership. Due to the small number of nations for which data on weapon use in IPH were located, we did not conduct any hypothesis testing. There is a need for detailed homicide surveillance systems among nations so that researchers can explore the epidemiology of these homicides and ultimately identify opportunities for intervention.
Patients with early arthritis who fulfil the 1987 ACR classification criteria for rheumatoid arthritis but not the 2010 ACR/EULAR criteria

Recently, a joint working group of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) was formed to develop new classification criteria for rheumatoid arthritis (RA),1 2 and announced the 2010 ACR/EULAR classification criteria for identifying patients with early RA.3 The present study was performed in order to determine whether the newly developed 2010 ACR/EULAR criteria would include patients who were previously diagnosed with early RA according to the 1987 ACR criteria.4 We studied 170 patients with early RA patients, who had been classified as having RA according to the 1987 ACR criteria. Early RA was defined by less than 12 months of symptoms. The 2010 ACR/EULAR criteria were applied to patients at the exact time point when they were identified as fulfilling the 1987 ACR criteria. The clinical characteristics and laboratory findings …
In vitro survival of in vitro-produced bovine embryos cryopreserved by slow freezing, fast freezing and vitrification

In order to compare the survival rate of bovine embryos cryopreserved with different protocols, oocytes obtained from abattoir-derived ovaries were used for in vitro maturation (IVM), fertilization (IVF) and co-culture. Expanded blastocysts were cryopreserved by two slowfreezing [(i) 0.5 and (ii) 1.2°C/min], (iii) one quickfreezing and two vitrification [(iv) ethylene glycol + ficoll + sucrose (EFS), and (v) glycerol (Gly) + ethylene glycol (EG)] protocols. After thawing, embryos were co-cultured on a granulosa cell monolayer and evaluated after 24 h for re-expansion. At 24, 48, 72, and 96 h the hatching rates were determined. The in vitro survival rate (hatching at 96 h) of embryos cryopreserved by the slow-freezing method with cooling rate of 0.5°C/min (58.8%) was similar to that obtained for control group (68.4%; not cryopreserved). Vitrification using Gly + EG yielded similar survival rates when compared to a slowfreezing at 1.2°C/min (36.9 and 39.4%, respectively) and higher rates than those for quick freezing and vitrification in EFS (7.0 and 14.0%, respectively). In conclusion, slow-freezing with 0.5°C/min was the best method to cryopreserve in vitro produced bovine embryos.
Mortality in patients with small choroidal melanoma. COMS report no. 4. The Collaborative Ocular Melanoma Study Group.

OBJECTIVE To describe the clinical characteristics and survival experience of a prospectively followed up group of patients with small choroidal melanoma. METHODS The Collaborative Ocular Melanoma Study (COMS) is a set of clinical trials designed to compare the role of radiotherapy and enucleation in the treatment of medium and large-size choroidal melanoma. From December 1986 to August 1989, patients with small choroidal melanoma, not large enough to be eligible for the COMS clinical trials, were offered participation in a nonrandomized prospective follow-up study. Small choroidal melanomas were defined as 1.0 to 3.0 mm in apical height and at least 5.0 mm in basal diameter. A total of 204 patients were enrolled in the study. Patients were followed up annually through August 1989. Two additional assessments of treatment status and mortality were conducted in 1993-1994 and 1995-1996. The median length of follow-up was 92 months. Eight percent of patients were treated at the time of study enrollment and an additional 33% were treated during follow-up. RESULTS Twenty-seven patients have died; 6 deaths were reported by the clinical center as due to metastatic melanoma. The Kaplan-Meier estimate of 5-year all-cause mortality was 6.0% (95% confidence interval, 2.7%-9.3%) and 8-year all-cause mortality was 14.9% (95% confidence interval, 9.6%-20.2%). CONCLUSIONS Otherwise healthy patients, average age of 60 years, without a previous diagnosis of malignant disease who have small choroidal lesions judged to be melanoma have a low risk of dying within 5 years.
Full H-band waveguide-to-coupled microstrip transition using dipole antenna with directors

In this paper, we propose low-loss and broadband terahertz (THz) waveguide-to-coupled microstrip transitions using dipole antenna with directors. The simulation and measurement show that insertion/return loss and bandwidth of the waveguide transition can be improved by adding two directors to the basic dipole antenna. The fabricated transition with two directors on a 50μm-thick quartz substrate exhibits a back-to-back insertion loss of 1.5 dB and return loss better than 15.0 dB across full Hband (220–325GHz). This belongs to the excellent performance compared with the reported H-band waveguide transitions using dipole antenna.
The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo

p36, a major in vivo substrate of protein-tyrosine kinases, is shown to be phosphorylated at serine 25, a site very close to the major site of tyrosine phosphorylation by pp60v-src, tyrosine 23 (J. R. Glenney, Jr., and B. F. Tack, Proc. Natl. Acad. Sci. USA 82:7884-7888, 1985). We present evidence suggesting that protein kinase C mediates phosphorylation of serine 25.
Increase of KCC2 in hippocampal synaptic plasticity disturbances after perinatal ethanol exposure

Low to moderate perinatal ethanol exposure (PEE) may have disastrous consequences for the central nervous system resulting notably in permanent cognitive deficits. Learning and memory are mediated in the hippocampus by long‐term potentiation (LTP) and long term depression (LTD), two forms of synaptic plasticity. PEE decreases LTP but also abnormally facilitates LTD (Kervern et al. ) through a presently unknown mechanism. We studied in rat hippocampus slice, the involvement of the chloride co‐transporters NKCC1 and KCC2, in the role of GABAA inhibitions in facilitated LTD after moderate PEE. After PEE and in contrast to control slices, facilitated LTD in CA1 field was reduced by the GABAA receptor antagonist bicuculline with no changes in sensitivity to bicuculline and in GABA and benzodiazepine binding sites. Also, sensitivity to diazepam was unaltered, whereas aberrant LTD was blocked. Immunohistochemistry and protein analysis demonstrated an increase in KCC2 protein level at cell membrane in CA1 after PEE with no change in NKCC1 expression. Specifically, both monomeric and dimeric forms of KCC2 were increased in CA1. Bumetanide (10–100 μM), a dose‐dependent blocker of NKCC1 and KCC2, or VU0240551 (10 μM) a specific antagonist of KCC2, corrected the enhanced LTD and interestingly bumetanide also restored the lower LTP after PEE. These results demonstrate for the first time an upregulation of the KCC2 co‐transporter expression after moderate PEE associated with disturbances in GABAergic neurotransmission modulating bidirectional synaptic plasticity in the hippocampus. Importantly, bumetanide compensated deficits in both LTP and LTD, revealing its potential therapeutic properties.
Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets

ABSTRACT Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in the HA activation pH (an increase in acid stability) influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either wild-type HA protein (activation pH 6.0) or an HA2-K58I point mutation (K to I at position 58) (activation pH 5.5). The VN1203-HA2-K58I virus had replication kinetics similar to those of wild-type VN1203 in MDCK and normal human bronchial epithelial cells and yet had reduced growth in human alveolar A549 cells, which were found to have a higher endosomal pH than MDCK cells. Wild-type and HA2-K58I viruses promoted similar levels of morbidity and mortality in C57BL/6J mice and ferrets, and neither virus transmitted efficiently to naive contact cage-mate ferrets. The acid-stabilizing HA2-K58I mutation, which diminishes H5N1 replication and transmission in ducks, increased the virus load in the ferret nasal cavity early during infection while simultaneously reducing the virus load in the lungs. Overall, a single, acid-stabilizing mutation was found to enhance the growth of an H5N1 influenza virus in the mammalian upper respiratory tract, and yet it was insufficient to enable contact transmission in ferrets in the absence of additional mutations that confer α(2,6) receptor binding specificity and remove a critical N-linked glycosylation site. The information provided here on the contribution of HA acid stability to H5N1 influenza virus fitness and transmissibility in mammals in the background of a non-laboratory-adapted virus provides essential information for the surveillance and assessment of the pandemic potential of currently circulating H5N1 viruses.
Biomarkers in Allergic Airway Disease: Simply Complex

Clinical diagnoses of allergic airway disease need confirmation of a relevant sensitization to allergens. Serum-based component-resolved diagnosis has become increasingly popular and allows the precise assessment of specific IgE to molecular allergens. Molecular allergen diagnosis has improved our understanding of disease phenotypes in allergic patients, including cross-reactive patterns and food allergy. Beyond sensitization profiles, characterization of the (endo-)type and severity of a local allergic disease is useful for targeted therapy with biologics in advanced allergic airway disease. Surrogate markers of treatment efficacy are increasingly under validation. Prognostic and predictive biomarkers will represent a promising option for stratified prevention strategies.
Genetic Algorithms and Kernel Matrix-based Criteria Combined Approach to Perform Feature and Model Selection for Support Vector Machines

— Feature and model selection are in the center of attention of many researches because of their impact on classifiers’ performance. Both selections are usually performed separately but recent developments suggest using a combined GA-SVM approach to perform them simultaneously. This approach improves the performance of the classifier identifying the best subset of variables and the optimal parameters’ values. Although GA-SVM is an effective method it is computationally expensive, thus a rough method can be considered. The paper investigates a joined approach of Genetic Algorithm and kernel matrix criteria to perform simultaneously feature and model selection for SVM classification problem. The purpose of this research is to improve the classification performance of SVM through an efficient approach, the Kernel Matrix Genetic Algorithm method (KMGA).
Individual and Combined Effects of Fusarium moniliforme Culture Material, Containing Known Levels of Fumonisin B1, and Salmonella Gallinarum Infection on Liver of Japanese Quail

Abstract Three hundred day-old Japanese quail (Coturnix coturnix japonica) were divided into two groups with 150 quail in each group. One group was maintained on quail mash alone, while Fusarium moniliforme culture material was added to quail mash in the second group from day 5 of age and was supplied at a rate of 150 ppm fumonisin B1 (FB1)/kg mash. At day 21, each group was further subdivided into two groups, yielding four groups with 75 birds apiece, which served as the control (group CX), the Salmonella Gallinarum alone group (group CS), the FB1 alone group (group FX), and the group fed FB1 and infected with Salmonella Gallinarum (group FS). An oral challenge with Salmonella Gallinarum organisms (2 × 104 colony-forming units/ml) was given to groups CS and FS at 21 days of age. Three quail each were necropsied on day 21 (0 day interval) from groups CX and FX only. At subsequent intervals (i.e., 1, 2, 3, 5, 7, 10, 14, and 21 days postinfection [DPI]), three quail were euthanatized from all four groups (CX, CS, FX, and FS). The gross and microscopic lesions were recorded in both mortality and euthanatized birds at the above intervals. The ultrastructural studies were done at 5 DPI. Mild to moderate hepatomegaly and pale discoloration of liver were observed in group FX, while congestion, hemorrhages, necrosis, and mild to severe hepatomegaly were the predominant gross lesions in both infected groups (CS and FS). The gross lesions in quail inoculated with Salmonella Gallinarum alone (group CS) generally developed slowly, appeared more widely scattered, and involved comparatively less surface area in contrast to the rapidly progressive and frequently confluent lesions in the combination group (FS), especially in the first 5 days of infection. Mild to marked hepatocellular swelling, multifocal hepatic necrosis, and hepatocellular and bile duct hyperplasia were the characteristic microscopic changes in the FX group. Microscopic lesions in quail of group CS comprised congestion, vacuolar changes, and focal necrosis in early stages, followed by granulomatous lesions at later intervals. Similar but more severe lesions were observed in the combination group (FS). Based on transmission electron microscopy, the maximum effect of FB1 toxicity was observed on mitochondria and endoplasmic reticulum. In general, the mitochondriae showed diverse form and structure, some of which appeared to lose their intact outer membrane, and the mitochondrial cristae were disoriented. The deformity in the cisternae structure of rough endoplasmic reticulum, with their rearrangement into round or tubular forms either bearing granular surface or leading to accumulation of smooth endoplasmic reticulum, was evident only in groups FX and FS. We conclude that the continuous presence of fumonisins in the diets of young quail might increase their susceptibility to or the severity of Salmonella Gallinarum infection.
Influence of Aerobic Fitness on Thermoregulation During Exercise in the Heat

It is believed that the adaptations induced by aerobic training would prevent athletes from overheating while retaining body electrolytes during exercise in the heat. Data from our laboratory suggest that aerobic training is not enough to induce these adaptations. This review considers the factors that can lead to hyperthermia in trained and untrained populations when exercising in the heat.