Miracle-dz/UniFAR-FTUs huggingface dataset:
EFFECT OF THE COMBINATION OF DEXAMETHASONE AND SODIUM IPODATE ON SERUM THYROID HORMONES IN GRAVES' DISEASE

To investigate the effect of the combination of dexamethasone (Dex) and sodium ipodate (SI) on hyperthyroidism, we studied 24 patients with typical GRAVES' disease, divided into four groups of six persons each. Three groups (Study I) were studied acutely (24 h) to determine the effects of Dex (5 mg every 12 h intramuscularly), SI (one oral dose of 3 g) and both drugs at the same doses, upon T4, T3, and rT3 at 0900 h before therapy was started and 24 h later. The group on Dex and that on SI had a similar T3 decrement of 25·9±4·0% and 35·8±5·0%, respectively, (P < 0·05), whereas the effect of both drugs combined was greater (64·2±3·6%; P<0·01, Dex, and P<0·01, SI, respectively). The increment of rT3 was markedly greater in those patients on SI than in those on Dex (561·3±149·2% and 58·9±11%, respectively, P<0·025). A fourth group (Study II) was studied for seven days while receiving both Dex (1 mg orally three times per day) and SI (500 mg orally three times per day). Both T4 (from 18·8 ± 1·1 to 13·1 ± 1·1 μg/dl, P < 0·02) and T3 (from 593 · 41 to 136·3 ± 12·7 ng/dl, P< 0·001) decreased at day 8. The initial brisk increment of rT3 at 24 h (808 ± 149%, P< 0·005) then diminished concomitantly with the fall of its precursor, T4. The pulse rate correlated with plasma T3 concentration (r= 0·67, P< 0·001) and varied from 104·7 ± 3·9 on day 1 to 77·3 ± 3·0 beats/min (P< 0·001) on day 4 and then remained stable. These results show that Dex and SI have potent inhibitory effects at the level of peripheral conversion of T4 and on the thyroid gland itself and that the combined use of these drugs significantly increases these effects. Considering the rapid clinical improvement of thyrotoxicosis achieved with both drugs, this regimen may be valuable in the initial treatment of some patients.
Predicting Gains in Dementia Caregiving

Background: Caregiver gain is an important yet less-explored phenomenon. Being conceptually distinct from burden, factors associated with burden and gain can differ. This study aims to explore factors associated with the experience of gains in dementia caregiving. Method: Cross-sectional study involving caregivers recruited from a tertiary hospital dementia clinic and the local Alzheimer’s Association. Caregivers completed a questionnaire containing the following scales: gain in Alzheimer’s care Instrument (GAIN), General Health Questionnaire (GHQ-28), Dementia Management Strategies Scale (DMSS), Revised Memory and Behavioral Problems Checklist (RMBPC) and Zarit Burden Interview (ZBI). Demographic information for the person with dementia (PWD) and the caregiver was also recorded. Initial screening with univariate analyses (t tests, ANOVAs, Pearson’s correlations) was performed to identify significant (p < 0.05) variables, which were then entered into a multiple regression model to identify variables associated with gain. Result: The final sample comprised 334 caregivers with a mean age of 51.5 years (SD = 10.9, range = 22–85), the majority of whom where Chinese (94.6%) females (71%). Mean GAIN score was 30 (SD = 6.6, range = 7–40). Regression analysis identified 3 factors significantly associated with gains (adjusted R2 32.3%): mental well-being of the caregiver, use of active management as a caregiving strategy, and participation in caregiver educational and support group programmes. Conclusion: The results have important implications for caregiver interventions. Interventions should target maintaining mental well-being, encouraging participation in educational and support programmes, and teaching appropriate coping and dementia specific management strategies to derive good outcomes.
Comparative Antigenicity and Immunogenicity of Hepadnavirus Core Proteins

ABSTRACT The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate “eAgs” do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the “preexisting” immunity problem that is inherent in the use of HBcAg for human vaccine development.
A Metabolic Study of Huntington’s Disease

Background Huntington’s disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington’s disease gene carriers (premanifest and moderate stage II/III) and controls. Methods Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. Results We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington’s disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Conclusions Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington’s disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington’s disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority of these markers do not differ markedly by disease status.
Use of an interlocking nail-hybrid fixator construct for distal femoral deformity correction in three dogs

Summary Our purpose was to report the use of an inter-locking nail-hybrid external fixator construct to correct distal femoral deformities in three dogs. Radiographs, computed tomography and a three-dimensional model were used to plan the surgical procedure. A femoral osteotomy or ostectomy was performed at the level of the centre of rotation of angulation in all three dogs. Angular and rotational deformities were corrected acutely. Distraction osteo-genesis was performed to lengthen each femur postoperatively. All three dogs had additional anatomic abnormalities of the affected hindlimb complicating the correction of the distal femoral deformity. While the interlocking nail-hybrid fixator construct allowed for stable distraction of the femur, all three dogs developed complications during the postoperative convalescent period, and each had some degree of residual lameness. Lengthening the femur following acute deformity correction is problematic and additional experimental and clinical studies are warranted to decrease postoperative morbidity and improve functional results.
Importance of the proline-rich multimerization domain on the oligomerization and nucleic acid binding properties of HIV-1 Vif

The HIV-1 viral infectivity factor (Vif) is required for productive infection of non-permissive cells, including most natural HIV-1 targets, where it counteracts the antiviral activities of the cellular cytosine deaminases APOBEC-3G (A3G) and A3F. Vif is a multimeric protein and the conserved proline-rich domain 161PPLP164 regulating Vif oligomerization is crucial for its function and viral infectivity. Here, we expressed and purified wild-type Vif and a mutant protein in which alanines were substituted for the proline residues of the 161PPLP164 domain. Using dynamic light scattering, circular dichroism and fluorescence spectroscopy, we established the impact of these mutations on Vif oligomerization, secondary structure content and nucleic acids binding properties. In vitro, wild-type Vif formed oligomers of five to nine proteins, while Vif AALA formed dimers and/or trimers. Up to 40% of the unbound wild-type Vif protein appeared to be unfolded, but binding to the HIV-1 TAR apical loop promoted formation of β-sheets. Interestingly, alanine substitutions did not significantly affect the secondary structure of Vif, but they diminished its binding affinity and specificity for nucleic acids. Dynamic light scattering showed that Vif oligomerization, and interaction with folding-promoting nucleic acids, favor formation of high molecular mass complexes. These properties could be important for Vif functions involving RNAs.
Trust-Choice Incompatibility and the Role of Automatic Activation

This study examines the influence of conscious and unconscious processes on trust and choice within an attribute framing task. Trust-choice incompatibility exists when a decision maker shows preference for one option, but trusts another option. For instance, a decision maker might prefer Butcher A, who advertises ground beef as 75% lean yet trust Butcher B, who advertises ground beef as 25% fat. McElroy and Conrad (2009) suggest that unconscious processing plays an important role in choice. A vigilance task was used to investigate unconscious processing and trust-choice incompatibility. Participants were primed with words to induce trust or doubt and then given the ground beef attribute framing task along with 7-point scales to indicate which butcher they prefer and trust.
Seizures Accelerate Functional Integration of Adult-Generated Granule Cells

In humans and experimental animals, structural and functional changes in neural circuits can accompany the development of epilepsy. In the dentate gyrus, seizures enhance adult neurogenesis, but it is unclear to what extent newborn granule cells participate in seizure-induced synaptic reorganization. During the first weeks of their existence, mouse newborn granule cells labeled with enhanced green fluorescent protein have only short dendrites that lack excitatory input. We report that pilocarpine-induced seizures accelerated the morphological development of labeled granule cells, causing their dendrites to extend through the molecular layer. In whole-cell recordings 5–16 d after seizure induction, perforant-path stimulation now evoked glutamatergic input to newborn granule cells. These synaptic responses were mediated by monosynaptic as well as recurrent polysynaptic input. Thus, seizures facilitated functional integration of adult-generated granule cells. One month later, subsequent generations of newborn cells also showed alterations in dendrite morphology, suggesting persistent effects of seizures on granule cell maturation. The sensitivity of newborn granule cells to seizures could contribute to hyperexcitability during the latent period.
Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4

ABSTRACT The adeno-associated viruses (AAVs) can package and deliver foreign DNA into cells for corrective gene delivery applications. The AAV serotypes have distinct cell binding, transduction, and antigenic characteristics that have been shown to be dictated by the capsid viral protein (VP) sequence. To understand the contribution of capsid structure to these properties, we have determined the crystal structure of AAV serotype 4 (AAV4), one of the most diverse serotypes with respect to capsid protein sequence and antigenic reactivity. Structural comparison of AAV4 to AAV2 shows conservation of the core β strands (βB to βI) and helical (αA) secondary structure elements, which also exist in all other known parvovirus structures. However, surface loop variations (I to IX), some containing compensating structural insertions and deletions in adjacent regions, result in local topological differences on the capsid surface. These include AAV4 having a deeper twofold depression, wider and rounder protrusions surrounding the threefold axes, and a different topology at the top of the fivefold channel from that of AAV2. Also, the previously observed “valleys” between the threefold protrusions, containing AAV2's heparin binding residues, are narrower in AAV4. The observed differences in loop topologies at subunit interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for mosaic capsid formation in efforts to engineer novel tropisms. Significantly, all of the surface loop variations are associated with amino acids reported to affect receptor recognition, transduction, and anticapsid antibody reactivity for AAV2. This observation suggests that these capsid regions may also play similar roles in the other AAV serotypes.
Neuregulin expression, function, and signaling in human ovarian cancer cells.

PURPOSE To investigate the expression and function of neuregulin (NRG) isoforms in ovarian cancer cell lines and tumor samples. EXPERIMENTAL DESIGN Expression of NRG-1alpha and NRG-1beta proteins were detected by immunohistochemistry and mRNA by RT-PCR. erbB receptor levels and downstream signaling proteins were measured by Western blot analysis. RESULTS Expression of NRG-1alpha and NRG-1beta proteins were detected by immunohistochemistry in 46 of 53 (87%) and 41 of 53 (77%) ovarian carcinomas, respectively. Serous carcinomas express higher levels of NRG-1alpha than endometrioid carcinomas (P = 0.017). NRG mRNA was detected by RT-PCR in 20 of 24 (83%) of ovarian carcinomas and eight of nine (89%) ovarian cancer cell lines. NRG-1alpha stimulated the growth of 5 of 14 cell lines whereas NRG-1beta stimulated 7 of 14 cell lines. The magnitude of NRG growth response was significantly associated with erbB2 expression levels. NRG-1alpha and -1beta (1 nM) growth-stimulated cell lines PE01 and PE06 demonstrated increased tyrosine phosphorylation of erbB2 and elevated tyrosine phosphorylation of ERK1 and ERK2. In contrast, the SKOV-3 cell line, the growth of which was unaffected, did not show these downstream responses. An anti-erbB3 receptor antibody (clone H3.105.5) blocked NRG-1beta growth changes and signaling in these cell lines. Conversely, the anti-erbB4 antibody (clone H4.72.8) enhanced NRG-beta1 growth stimulation. Herceptin also inhibited growth. CONCLUSIONS With NRG expression in the majority of ovarian carcinomas and cell lines, there is the potential for autocrine regulation of cell growth. Interfering with ligand-receptor interactions by receptor blocking antibodies suggests erbB3 is primarily involved in NRG-1beta-induced proliferation, with erbB4 having a more complex role.
High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program

Phase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open‐label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3‐week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M‐protein changes. Overall response rate was 67%, including 11% complete (100% M‐protein reduction), 22% very good partial (75–99% reduction), 18% partial (50–74% reduction), and 16% minimal response (25–49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.
Learning Cooperative Visual Dialog Agents with Deep Reinforcement Learning

We introduce the first goal-driven training for visual question answering and dialog agents. Specifically, we pose a cooperative ‘image guessing’ game between two agents – Q-BOT and A-BOT– who communicate in natural language dialog so that Q-BOT can select an unseen image from a lineup of images. We use deep reinforcement learning (RL) to learn the policies of these agents end-to-end – from pixels to multi-agent multi-round dialog to game reward. ,,We demonstrate two experimental results. ,,First, as a ‘sanity check’ demonstration of pure RL (from scratch), we show results on a synthetic world, where the agents communicate in ungrounded vocabularies, i.e., symbols with no pre-specified meanings (X, Y, Z). We find that two bots invent their own communication protocol and start using certain symbols to ask/answer about certain visual attributes (shape/color/style). Thus, we demonstrate the emergence of grounded language and communication among ‘visual’ dialog agents with no human supervision. ,,Second, we conduct large-scale real-image experiments on the VisDial dataset [5], where we pretrain on dialog data with supervised learning (SL) and show that the RL finetuned agents significantly outperform supervised pretraining. Interestingly, the RL Q-BOT learns to ask questions that A-BOT is good at, ultimately resulting in more informative dialog and a better team.
Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

Adult facial motor neurons continue to express full-length TrkB tyrosine kinase receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target-derived and locally produced neurotrophins in adulthood. Studies on the role of TrkB signaling in the adult CNS have been hampered by the early lethality of bdnf, nt-4/5, and trkB knock-out mice. We disrupted TrkB.FL signaling in adult facial motor neurons using adeno-associated viral vector-mediated overexpression of a naturally occurring dominant-negative TrkB receptor, TrkB.T1. Expression of TrkB.T1 resulted in neuronal atrophy and downregulation of NeuN (neuronal-specific nuclear protein) and ChAT expression in facial motor neurons. A subset of transduced neurons displayed signs of motor neuron degeneration that included dendritic beading and rounding of the soma at 2 months of TrkB.T1 expression. Cell counts revealed a significant reduction in motor neuron number in the facial nucleus at 4 months after onset of expression of TrkB.T1, suggesting that a proportion of TrkB.T1-expressing motor neurons became undetectable as a result of severe atrophy or was lost because of cell death. In contrast, overexpression of TrkB.FL did not result in a decrease in facial motor neuron number. Our results indicate that a subset of facial motor neurons remains dependent on TrkB ligands for the maintenance of structural and molecular characteristics in adulthood.
Measurement of phase and amplitude error distributions in arrayed-waveguide grating multi/demultiplexers based on dispersive waveguide

We measured the phase and amplitude error distributions in InP-based arrayed-waveguide grating (AWG) multi/demultiplexers using Fourier transform spectroscopy with interferogram restoration. The interferogram restoration was used to reduce the effect of the group-velocity dispersion of the waveguide. It was based on a wavenumber scale transformation or a dispersion balance between two arms in the interferometer. We derived a criterion for choosing the appropriate restoration method by estimating the worst-case measurement error in the presence of second order dispersion. After selecting a method using the derived criterion, we obtained isolated fringe patterns, from which we were able to obtain the phase and amplitude distributions in 50 and 200 GHz AWGs. Using the obtained distributions, we examined the origin of the crosstalk and chromatic dispersion in InP-based AWGs. The results revealed that the main origin is phase error as found with SiO/sub 2/-based AWGs.
Spore Yield and Microcycle Conidiation of Colletotrichum gloeosporioides in Liquid Culture

The effect of V8 juice concentration (5 to 40%, vol/vol), spore inoculum density (105 and 107 spores per ml), and liquid batch or fed-batch culture condition on mycelium and spore production by Colletotrichum gloeosporioides was evaluated. The amount of mycelium produced, the time required for initiation of sporulation following attainment of maximum mycelium, and the time for attainment of maximum spore concentration increased with increasing V8 juice concentration in batch culture. Cultures containing V8 juice at >10% achieved a similar spore density (apparent spore-carrying capacity) of about 0.8 mg of spores per ml (1 × 107 to 2 × 107 spores per ml) independent of inoculum density and V8 juice concentration. The relative spore yield decreased from a high of 64% of the total biomass for the low-inoculum 5% V8 culture, through 13% for the analogous 40% V8 culture, to a low of 2% for the high-inoculum 27% V8 culture. Fed-batch cultures were used to establish conditions of high spore density and low substrate availability but high substrate flux. The rate of addition of V8 juice was adjusted to approximate the rate of substrate utilization by the (increasing) biomass. The final spore concentration was about four times higher (3.0 mg of spores per ml) than the apparent spore-carrying capacity in batch culture. This high spore yield was obtained at the expense of greatly reduced mycelium, resulting in a high relative spore yield (62% of the total biomass). Microcycle conidiation occurred in the fed-batch but not batch systems. These data indicate that substrate-limited, fed-batch culture can be used to increase the amount and efficiency of spore production by C. gloeosporioides by maintaining microcycle conidiation conditions favoring allocation of nutrients to spore rather than mycelium production.