Miracle-dz/UniFAR-FTUs huggingface dataset:
Denosumab in hypercalcemia of malignancy: A case series

Background Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1–10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population. Methods We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution. Results Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3–195, for all patients. Conclusions Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.
Modeling disease in the mouse: Lessons from DNA damage response and cell cycle control genes

The advent of gene targeting has allowed the dissection of many essential cellular pathways, including those involved in cell cycle regulation, signal transduction, and development. However, it is becoming increasingly clear that the simple gene deletion strategy may not be sufficient for the modeling of many cancer syndromes. In this Prospect article, we will discuss the strengths and weaknesses of mouse models, how they have advanced from gene deletions to truncations, point mutations, and conditional mouse models in which expression or loss of the gene of interest is controlled either temporally or spatially. We will also consider future directions for the use of mouse models in cancer. The vastness of the field necessitates focusing on a few specific examples with the unfortunate exclusion of many excellent studies from our discussion. As such, we focus on a few specific models of human cancer syndromes, however many of the themes discussed here are applicable to other systems of genetic manipulation and may be applied across fields. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Molecular determination of X inactivation pattern correlates with phenotype in women with a structurally abnormal X chromosome

Purpose: To correlate the X inactivation pattern, as determined by one or more molecular assays, with phenotype in individuals with structurally abnormal X chromosomes.Methods: We utilized methylation analysis of androgen receptor (AR) and Fragile X (FMR1) genes and expression studies of an XIST polymorphism to assess X inactivation patterns of 28 females with structurally abnormal X chromosomes. Individuals were placed in one of three categories: (1) completely nonrandom inactivation of one X chromosome, (2) preferential or skewed inactivation of one X chromosome, or (3) random inactivation of either X chromosome.Results: In 19 of 21 cases with complete (> 7%) skewing of X inactivation, the phenotype was either normal, consistent with a single gene disorder, or consistent with classical Turner syndrome; two cases with completely nonrandom X inactivation had unexplained mental retardation phenotypes. In contrast, six of seven cases that did not exhibit completely nonrandom X inactivation were phenotypically abnormal. Carriers of two balanced translocations, two duplicated Xs, one deleted X, and one 45,X/46,X,r(X) presented with mental retardation and/or multiple congenital anomalies.Conclusion: In patients with random or skewed X inactivation, the abnormal phenotype was hypothesized to be due to functional nullisomy or disomy of X-linked genes. Based on these results, we propose that X inactivation studies should be performed on all women with structurally abnormal X chromosomes. This should aid in the understanding of abnormal phenotypes in liveborn individuals with abnormal X chromosomes and may help to predict phenotypes for prenatally detected cases in the future.
A Low Energy Oxide‐Based Electronic Synaptic Device for Neuromorphic Visual Systems with Tolerance to Device Variation

Neuromorphic computing is an emerging computing paradigm beyond the conventional digital von Neumann computation. An oxide-based resistive switching memory is engineered to emulate synaptic devices. At the device level, the gradual resistance modulation is characterized by hundreds of identical pulses, achieving a low energy consumption of less than 1 pJ per spike. Furthermore, a stochastic compact model is developed to quantify the device switching dynamics and variation. At system level, the performance of an artificial visual system on the image orientation or edge detection with 16 348 oxide-based synaptic devices is simulated, successfully demonstrating a key feature of neuromorphic computing: tolerance to device variation.
The p38 mitogen‐activated protein kinase pathway negatively regulates Ca2+‐activated K+ channel trafficking in developing parasympathetic neurons

The trafficking of large‐conductance Ca2+‐activated K+ channels (KCa) in chick ciliary ganglion neurons is regulated by growth factors. Here we show that a canonical p38 cascade inhibits KCa trafficking in ciliary ganglion neurons. Two different p38 inhibitors (SB202190 or SB203580) or over‐expression of dominant‐negative forms of several components of the p38 cascade increased KCa in ciliary neurons. Inhibition of protein synthesis or Golgi processing had no effect on this phenomenon, suggesting that p38 is acting at a distal step of the trafficking pathway. Depolymerization of filamentous actin (F‐actin) increased functional expression of KCa, whereas stabilization of F‐actin inhibited the effect of SB202190 on KCa trafficking. SB202190 also caused an immunochemically detectable increase in KCa on the plasma membrane. Inhibition of p38 decreased the extent of cortical F‐actin in ciliary neurons. Macroscopic KCa is suppressed by transforming growth factor (TGF) β3. Application of TGFβ3 increased the phosphorylation of p38 in ciliary neurons and increased cortical F‐actin. Thus, the p38 signaling cascade endogenously suppresses development of functional KCa, in part by stabilizing an F‐actin barrier that prevents plasma membrane insertion of functional channel complexes. This cascade also appears to mediate inhibitory effects of TGFβ3 on the expression of KCa.
Association of Excitatory Amino Acid Transporters, Especially EAAT2, with Cholesterol-rich Lipid Raft Microdomains

In the present study, we investigated the role of membrane cholesterol in the function of glutamate transporters. Depletion of membrane cholesterol by methyl-β-cyclodextrin resulted in reduced Na+-dependent glutamate uptake in primary cortical cultures. Glial glutamate transporter EAAT2-mediated uptake was more sensitive to this effect. Cell surface biotinylation and immunostaining experiments revealed that the loss of cholesterol significantly altered the trafficking of EAAT2 to the plasma membrane as well as their membrane distribution. These effects were also observed in neuronal glutamate transporter EAAT3 but to a lesser extent. Furthermore, the treatment of mouse brain plasma membrane vesicles with methyl-β-cyclodextrin resulted in a significant reduction in glutamate uptake, suggesting that cholesterol depletion has a direct effect on the function of the glutamate transporters. Plasma membrane cholesterol is localized within discreet microdomains known as lipid rafts. Analyses of purified lipid raft microdomains revealed that a large portion of total EAAT2 and a minor portion of total EAAT1, EAAT3, and EAAT4 were associated with lipid rafts. Artificial aggregation of lipid rafts in vivo resulted in the formation of larger EAAT2-immunoreactive clusters on the cell surface. The purified lipid raft-associated fractions were capable of Na+-dependent glutamate uptake. Our data suggest that the glutamate transporters, especially EAAT2, are associated with cholesterol-rich lipid raft microdomains of the plasma membrane and that the association with these cholesterol-rich microdomains is important for excitatory amino acid transporter localization and function.
Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis

Abstract Objectives. Recent epidemiological studies suggest that metformin treatment may reduce the risks of cancer and overall cancer mortality among patients with diabetes mellitus (DM). However, data on hepatocellular carcinoma (HCC) are very limited and inconsistent. This meta-analysis was designed to pool data currently available to determine the association between metformin use and HCC among diabetic patients. Methods. The Medline and Embase databases were searched to identify the relevant studies between January 1966 and December 2011. The overall analysis was derived using a random-effects meta-analysis model (DerSimonian and Laird method). Subgroup analysis was performed to explore the source of heterogeneity and validate the results from overall analysis. The Newcastle-Ottawa Quality assessment scales were adopted for quality assessment; Begg's funnel plot and Egger's regression asymmetry test were used to detect the publication bias. Results. A total of seven studies were identified, including three cohort studies and four case-control studies. Based on the available data, the overall prevalence of HCC was 3.40% (562/16,549) in DM patients. The overall analysis showed a significantly reduced risk of HCC in metformin users versus nonusers in diabetic patients (relative risk (RR) 0.24, 95% confidence interval (CI) 0.13–0.46, p < 0.001). Fifteen subgroup analyses were performed, and most of them (12/15 = 80%) provided supporting evidence for the results of overall analysis. Begg's (Z = –0.15, p = 0.8819) and Egger's test (t = –0.79, p = 0.468) showed no significant risk of having a publication bias. Conclusion. Metformin treatment was associated with reduced risk of HCC in diabetic patients. To clarify this relationship, more high-quality studies are required.
Simulating transoceanic migrations of young loggerhead sea turtles: merging magnetic navigation behavior with an ocean circulation model

SUMMARY Young loggerhead sea turtles (Caretta caretta) from eastern Florida, USA, undertake a transoceanic migration in which they gradually circle the Sargasso Sea before returning to the North American coast. Loggerheads possess a ‘magnetic map’ in which regional magnetic fields elicit changes in swimming direction along the migratory pathway. In some geographic areas, however, ocean currents move more rapidly than young turtles can swim. Thus, the degree to which turtles can control their migratory movements has remained unclear. In this study, the movements of young turtles were simulated within a high-resolution ocean circulation model using several different behavioral scenarios, including one in which turtles drifted passively and others in which turtles swam briefly in accordance with experimentally derived data on magnetic navigation. Results revealed that small amounts of oriented swimming in response to regional magnetic fields profoundly affected migratory routes and endpoints. Turtles that engaged in directed swimming for as little as 1–3 h per day were 43–187% more likely than passive drifters to reach the Azores, a productive foraging area frequented by Florida loggerheads. They were also more likely to remain within warm-water currents favorable for growth and survival, avoid areas on the perimeter of the migratory route where predation risk and thermal conditions pose threats, and successfully return to the open-sea migratory route if carried into coastal areas. These findings imply that even weakly swimming marine animals may be able to exert strong effects on their migratory trajectories and open-sea distributions through simple navigation responses and minimal swimming.
Enzyme-linked immunosorbent assay for Salmonella typhimurium in food: feasibility of 1-day Salmonella detection

A microtitration plate, antibody-capture, enzyme-linked immunosorbent assay was developed for detection of Salmonella typhimurium. The assay utilizes a monoclonal detector antibody which shows no cross-reactions with non-Salmonella species and only a slight cross-reaction with one other Salmonella serotype. By using only one cultural stage (in a nonselective, chemically defined medium) prior to the enzyme-linked immunosorbent assay, low numbers of cells in food (10 cells 25 g-1) were detected in 19 h. Non-Salmonella competing organisms did not interfere with detection of S. typhimurium even when present in the ratio of 10(6):1 (non-Salmonella/Salmonella spp.). The assay shows the feasibility of rapid, 1-day testing for Salmonella spp. with antibody technology.
Evaluation of Perimandibular Neurovascularization With Accessory Mental Foramina Using Cone-Beam Computed Tomography in Children

ObjectivesThe purpose of this study was to clarify the perimandibular neurovascularization with mandibular accessory mental foramina in a children population using cone-beam computed tomography (CBCT) to avoid complications during anesthetic and surgical procedures. MethodsThis retrospective study evaluated cone-beam CT images for bifid mandibular canals in the mandibles of 63 children (35 girls, 28 boys; age range, 7–16 years; mean age, 12.3 years). Both right and left sides were examined from CT images (n = 126), including axial, sagittal, cross-sectional, and panoramic views as well as reconstructed three-dimensional images, as necessary. The course, length, and superior and inferior angles between canals were classified and measured. ResultsBifid mandibular canals were observed in 34 (27%) of the 126 sides examined. The most frequently encountered type of bifid canal was the retromolar canal (11.1%), followed by the forward (7.14%), buccolingual (6.35%), and dental canal (2.4%). Mean lengths of bifid canals were 10.2 mm on the right side and 10.6 mm on the left side. Mean superior angles were 131 degrees on the right side and 147 degrees on the left side, whereas mean inferior angles were 47 degrees on the right side and 34 degrees on the left side. No statistically significant differences were found in the lengths or angles between the right and left sides or between boys and girls (P < 0.05). The most common position for the mental foramen was between the first and second premolars, and an accessory mental foramen was observed in 4 children (6.34%). ConclusionsThis study utilized CBCT images to identify bifid mandibular canals and accessory mental foramina in children. Cone-beam CT was found to be a useful technique for detecting secondary canals. However, despite the fact that CBCT uses less ionizing radiation than other types of three-dimensional imaging, unless the diagnostic information provided through CBCT improves treatment results, CBCT should not be recommended for use in children or adolescents.
Transcriptomic Analyses Reveal Novel Genes with Sexually Dimorphic Expression in the Zebrafish Gonad and Brain

Background Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. Methodology/Principal Findings We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs), 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and ‘rest-of-body’ from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel) that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4) has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. Conclusions/Significance We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar roles in gonadogenesis in zebrafish and other vertebrates, our array may even provide information on genetic disorders affecting gonadal phenotypes and fertility in mammals.
Assessment of Spatial Memory Using the T Maze

This unit describes the use of the T maze to assess spatial memory, and takes into account the alternating behavior of rats in searching for food. The task is based on the premise that animals have evolved an optimal strategy to explore their environment and obtain food with a minimum amount of effort. The T maze has been most extensively used to investigate specific aspects of spatial working memory, which is operationally defined as information that is only useful to a rat during the current experience with the task. A modification of the maze allows for the assessment of reference memory, defined as information that is useful across all exposures to the task (i.e., on any day of testing). Finally, in the absence of food‐deprivation, a simple T maze can be used as described to assess spontaneous alternation.
On-Line Parameter Estimation for Infinite-Dimensional Dynamical Systems

The on-line or adaptive identification of parameters in abstract linear and nonlinear infinite-dimensional dynamical systems is considered. An estimator in the form of an infinite-dimensional linear evolution system having the state and parameter estimates as its states is defined. Convergence of the state estimator is established via a Lyapunov estimate. The finite-dimensional notion of a plant being sufficiently rich or persistently excited is extended to infinite dimensions. Convergence of the parameter estimates is established under the additional assumption that the plant is persistently excited. A finite-dimensional approximation theory is developed, and convergence results are established. Numerical results for examples involving the estimation of both constant and functional parameters in one-dimensional linear and nonlinear heat or diffusion equations and the estimation of stiffness and damping parameters in a one-dimensional wave equation with Kelvin--Voigt viscoelastic damping are presented.
Analog Assisted Multichannel Digital Postcorrection for Time-Interleaved ADCs

This brief introduces a new digital postcorrection technique for calibrating time-interleaved analog-to-digital converters (ADCs). It utilizes one additional sub-ADC to resolve the performance degradation problem near the Nyquist rate that occurred in the conventional multichannel filtering approach. Time skew, gain, offset, and bandwidth mismatches as well as the sub-ADC nonlinearities are all included in the proposed model. One group of coefficients extracted in foreground can be applied to any input frequencies in normal operation. An additional analog subcircuit path is required, but the digital part of the implementation becomes much simpler, which ensures that the overall system complexity does not increase. Furthermore, the digital correction structure can reuse the hardware units in a time-multiplexing manner for further power and resource savings. A 12-b four-channel 1-GS/s ADC is used to demonstrate the performance of the proposed postcorrection.
The Big Five Traits as Predictors of Subjective and Psychological Well-Being

Despite considerable research on personality and “hedonic” or subjective well-being, parallel research on “eudaimonic” or psychological well-being is scarce. The current study investigated the relationship between the Big Five traits and subjective and psychological well-being among 211 men and women. Results indicated that the relationship between personality factors and psychological well-being was stronger than the relationship between personality factors and subjective well-being. Extraversion, neuroticism, and conscientiousness correlated similarly with both subjective and psychological well-being, suggesting that these traits represent personality predispositions for general well-being. However, the personality correlates of the dimensions within each broad well-being type varied, suggesting that the relationship between personality and well-being is best modeled in terms of associations between specific traits and well-being dimensions.
Developing a survey for assessing preferences in constructivist context-aware ubiquitous learning environments

This study developed a survey to explore students' preferences in constructivist context-aware ubiquitous learning environments. A constructivist context-aware ubiquitous learning (u-learning) environment survey (CULES) was developed, consisting of eight scales, including ease of use, continuity, relevance, adaptive content, multiple sources, timely guidance, student negotiation, and inquiry learning. The survey responses were gathered from 215 university students from five universities in Taiwan. The students all had actual experience of using u-learning systems in u-learning environments. Both exploratory and confirmatory factor analyses showed that the CULES had high reliability and validity. The structural model revealed that the provision of realistic and close-to-real-life information could enhance students' preferences for timely guidance, student negotiation, and inquiry-learning activities. In addition, the attainment of inquiry learning is quite challenging when designing u-learning activities, as it involves the enhancement of the other CULES scales. © 2012 Wiley Periodicals, Inc. (This study is supported by the National Science Council, Taiwan under contract numbers NSC 98-2511-S-011-005-MY3, NSC 99-2511-S-011-011-MY3, and NSC 99-2631-S-011-002.)