The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well‐documented ...clinical summaries and relevant information were also reviewed to investigate the mutational gene‐ or domain‐specific laboratory and clinical association. Twenty‐five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non‐hotspot mutations were dispersed across multiple exons. Genotype–phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin‐binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic‐based management of HS.
Nano‐embossed hollow spherical (NeHS) TiO2 that features both good light scattering and charge generation shows a very promising performance in high‐efficiency dye‐sensitized solar cells. A bilayered ...film structure having the bifunctional NeHS TiO2 particulate film as an overlayer exhibits conversion efficiencies as high as 10.34 % under AM‐1.5G one sun light intensity.
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with ...Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
Hemophagocytic lymphohistiocytosis (HLH) is a frequently fatal and likely underdiagnosed disease involving a final common pathway of hypercytokinemia, which can result in end-organ damage and death. ...Although an early diagnosis is crucial to decrease mortality, the definitive diagnosis is often challenging because of the lack of specificity of currently accepted diagnostic criteria and the absence of confirmatory gold standards. Because of the wide range of laboratory assays involved in the diagnosis of HLH, practicing pathologists from a broad spectrum of clinical specialties need to be aware of the disease so that they may appropriately flag results and convey them to their clinical counterparts. Our article summarizes these new advances in the diagnosis of HLH and includes a review of clinical findings, updated understanding of the pathogenesis, and promising new testing methods.
Immersive virtual reality (VR) has enormous potential for education, but classroom resources are limited. Thus, it is important to identify whether and when VR provides sufficient advantages over ...other modes of learning to justify its deployment. In a between-subjects experiment, we compared three methods of teaching Moon phases (a hands-on activity, VR, and a desktop simulation) and measured student improvement on existing learning and attitudinal measures. While a substantial majority of students preferred the VR experience, we found no significant differences in learning between conditions. However, we found differences between conditions based on gender, which was highly correlated with experience with video games. These differences may indicate certain groups have an advantage in the VR setting.
Haemosporidian parasites in the genus Plasmodium were recently detected through molecular screening in the Galapagos Penguin (Spheniscus mendiculus). We summarized results of an archipelagowide ...screen of 3726 endemic birds representing 22 species for Plasmodium spp. through a combination of molecular and microscopy techniques. Three additional Plasmodium lineages were present in Galapagos. Lineage A-infected penguins, Yellow Warblers (Setophaga petechia aureola), and one Medium Ground Finch (Geospiza fortis) was detected at multiple sites in multiple years. The other 3 lineages were each detected at one site and at one time; apparently, they were transient infections of parasites not established on the archipelago. No gametocytes were found in blood smears of infected individuals; thus, endemic Galapagos birds may be dead-end hosts for these Plasmodium lineages. Determining when and how parasites and pathogens arrive in Galapagos is key to developing conservation strategies to prevent and mitigate the effects of introduced diseases. To assess the potential for Plasmodium parasites to arrive via migratory birds, we analyzed blood samples from 438 North American breeding Bobolinks (Dolichonyx oryzivorus), the only songbird that regularly migrates through Galapagos. Two of the ephemeral Plasmodium lineages (B and C) found in Galapagos birds matched parasite sequences from Bobolinks. Although this is not confirmation that Bobolinks are responsible for introducing these lineages, evidence points to higher potential arrival rates of avian pathogens than previously thought. Parásitos de la familia Haemosporidia, del género Plasmodium recientemente fueron detectados por medio de análisis moleculares en el pingüino de las Galápagos (Spheniscus mendiculus). Resumimos los resultados de un análisis, extendido a lo largo del archipiélago, de 3726 aves endémicas representando a 22 especies para Plasmodium spp. mediante la combinación de técnicas moleculares y de microscopía. Tres linajes adicionales de Plasmodium estuvieron presentes en las Galápagos. El linaje A infectó pingüinos, individuos Setophaga petechia aureola y a un individuo de Geospiza fortis en sitios múltiples y en varios años. Los otros 3 linajes fueron detectados cada uno en un sitio y en un tiempo específico; aparentemente, fueron infecciones transitorias de parásitos no establecidos en el archipiélago. No se encontraron gametocitos en los frotis de sangre de individuos infectados; por esto, las aves endémicas de las Galápagos pueden ser hospederos finales de estos linajes de Plasmodium. Determinar cuándo y cómo llegaron los parasitos y los patógenos a las Galápagos es clave para desarrollar estrategias de conservación para prevenir y mitigar los efectos de las enfermedades introducidas. Para evaluar el potencial de llegada de Plasmodium en aves migratorias, analizamos muestras de sangre de 438 Dolichonyx oryzivorus en época reproductiva. Esta ave es la única canora que migra regularmente a través de las Galápagos. Dos de los linajes efímeros de Plasmodium (B y C) que se hallaron en las aves de las Galápagos coincidieron con secuencias de parásitos del ave canora. Aunque esto no confirma que Dolichonyx oryzivorus sea responsable de introducer estos linajes, la evidencia apunta a un potencial más alto de tasas de llegada de patógenos aviares de lo que se pensaba previamente.
COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of ...disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.
We report on a new constraint on gravitylike short-range forces, in which the interaction charge is mass, obtained by measuring the angular distribution of 5 Å neutrons scattering off atomic xenon ...gas. Around 10^{7} scattering events were collected at the 40 m small angle neutron scattering beam line located at the HANARO research reactor of the Korean Atomic Energy Research Institute. The extracted coupling strengths of new forces in the Yukawa-type parametrization are gover ^^{2}=(0.2±6.8±2.0)×10^{-15} GeV^{-2} and gover ^^{2}=(-5.3±9.0_{-2.8}^{+2.7})×10^{-17} GeV^{-2} for interaction ranges of 0.1 and 1.0 nm, respectively. These strengths correspond to 95% confidence level limits of g^{2}<(1.4±0.2)×10^{-14} GeV^{-2} and g^{2}<(1.3±0.2)×10^{-16} GeV^{-2}, improving the current limits for interaction ranges between 4 and 0.04 nm by a factor of up to 10.
Despite various treatment options for canine atopic dermatitis (cAD), therapeutic limitations still exist, including adverse effects and low absorption ratios. This study evaluated the effects ...of a membrane-free stem cell extract (MFSCE) on the clinical signs of atopic dogs. Thirty client-owned dogs previously diagnosed with cAD were separated into placebo (
= 10) and MFSCE-treated groups (
= 20). The dogs were treated with a cream (MFSCE and placebo) via dermal administration twice daily for 14 days, and the clinical response was recorded on days 0, 7, and 14. The MFSCE-treated group showed significantly decreased severity of pruritus on day 14 compared to that on day 0. In addition, the erythema, pigmentation, skin dryness, and thickness were remarkably decreased in the MFSCE-treated group on day 14 compared to those on day 0 whereas no significant changes were observed in the placebo-treated group. No general clinical signs or adverse effects were observed in this study. These results suggest that MFSCE could be a surrogate treatment option for cAD.
To determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.
We identified 6342 patients with ...stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.
In a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 95% confidence interval (CI) 1.02–1.36, 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.
In patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.
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