Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of seizures on stroke outcomes

Objective: We compared clinical characteristics of seizures at ischemic stroke presentation (SSP) to seizures during hospitalization post ischemic stroke (SDH), and their impacts on stroke outcome, using the Registry of the Canadian Stroke Network (RCSN) database. Methods: This cohort study included consecutive patients from the RCSN who had an acute ischemic stroke between July 2003 and March 2008. Outcome measures included morbidity, mortality, length of hospital stay, and discharge disposition. Clinical variables for either SSP or SDH were investigated and the stroke outcome was stratified by stroke severity. Results: The study included 10,261 patients with ischemic strokes: 157 patients (1.53%) had SSP and 208 patients (2.03%) had SDH. Compared to stroke patients without seizures, patients with SSP and SDH were younger, had more severe strokes (p < 0.001), a higher admission rate to the intensive care unit (p < 0.001), higher morbidity, and higher mortality (p < 0.05). SSP was associated with female sex and less limb weakness, while SDH was associated with pneumonia and the presence of hemineglect. Importantly, patients with less severe strokes had higher morbidity and mortality (p < 0.005) if SDH occurred. Variables predicting overall mortality were SDH, older age, higher Charlson-Deyo index, more severe strokes, and nonalert status on arrival (all p < 0.001). Conclusions: SSP and SDH have different characteristics. SDH indicates a poorer prognosis in patients. Increased awareness of SSP and efforts to prevent SDH may be important in improving outcomes following clinical stroke care.
Inhaled nitric oxide and neonatal brain damage: experimental and clinical evidences

Inhaled nitric oxide (iNO) has been used not only for pulmonary vasodilation in term neonates with hypoxemic respiratory failure, but also in preterm ones at risk of chronic lung disease (CLD) with variable results in prevention and treatment of CLD and/or brain injury. However, meta analysis of clinical trials does not support that iNO should be used routinely in preterm infants with hypoxic respiratory failure as it has no convincing long-term follow-up data to show its advantages in neurodevelopment. Investigation of extra-pulmonary effects of iNO through nitrosothiol hemoglobin-associated hypoxic vasodilation, as well as its intra- and extra-pulmonary anti-inflammation effect, would have biological and physiological potential in the management of the lung and brain injury of prematurity. The eligibility and safety of iNO in these premature infants at high risk of neurodevelopmental disability require more clinical and follow-up effort to test its pharmacological benefit over harm.
Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China.

BACKGROUND We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGFβ1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies. METHODS We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), and rs373759 (126713 G>A) in 141 Han Chinese patients who underwent definitive thoracic radiotherapy (50 to 77 Gy, 5 days/wk) for lung cancer (small cell or non-small cell tumors, n = 97), esophageal squamous cell carcinoma (ESCC, n = 27), or mediastinal cancer (n = 17). Clinical variables were evaluated using multivariate logistic regression models to calculate the relative risk of RP associated with the clinical variables, and a Pearson correlation analysis was used to evaluate the relationship between the SNP genotypes and alleles and the incidence of RP for the various risk factors. RESULTS The T alleles of rs1800470 (CT/TT) and rs1800469 (CT/TT) and the G allele of rs189037 (GA/GG) were associated with the risk of ≥ grade-2 RP in the ESCC patients (P = 0.0006, P = 0.0127, and P = 0.0412, respectively), and that the A alleles of rs189037 (AG/AA) and rs373759 (AG/AA) were associated with the risk of ≥ grade-2 RP in the patients with mediastinal cancer (P = 0.0063 and P = 0.0003, respectively). None of the SNP genotypes were associated with the risk of RP in lung cancer patients. CONCLUSION The T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGFβ1 and the G allele of the rs189037 (GA/GG) SNP of ATM are independent risk factors for RP in Chinese ESCC patients, and the A alleles of the rs189037 (AG/AA) and rs373759 (AG/AA) SNPs of ATM are independent risk factors for RP in Chinese patients with mediastinal cancer. These SNPs might represent useful biomarkers for personalizing radiotherapy regimens for Chinese patients with ESCC or mediastinal cancer to reduce the incidence of RP. Large-cohort studies of these SNPs in thoracic cancer patients are warranted.
The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8+ T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2−/− mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.
Portal Venous Versus Systemic Venous Drainage of Pancreas Grafts: Impact on Long‐Term Results

Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long‐term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low‐density lipoprotein, high‐density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log‐rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long‐term graft survival and function and choice of method should remain the preference of the surgeon.
Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions

Background: Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci Blmpf1 and Blmpf2 on chromosomes 17 and 11, respectively, in a C57BL/6J (B6, susceptible) and C3Hf/KAM (C3H, resistant) mouse cross. Methods: Herein, the genetic basis of bleomycin induced pulmonary fibrosis was investigated in an approach combining gene expression and sequencing data with previously mapped linkage intervals. Results: In this study, gene expression analysis with microarrays revealed 1892 genes or ESTs (expressed sequence tags) to be differentially expressed between bleomycin treated B6 and C3H mice and 67 of these genetic elements map to Blmpf1 or Blmpf2. This group included genes involved in an oxidative stress response, in apoptosis, and in immune regulation. A comparison of the B6 and C3H sequence, for Blmpf1 and Blmpf2, made using the NCBI database and available C3H sequence, revealed approximately 35% of the genes in these regions contain non-synonymous coding sequence changes. An assessment of genotype/phenotype correlation among other inbred strains revealed 36% of these B6/C3H sequence variations predict for the known bleomycin induced fibrosis susceptibility of the DBA (susceptible) and A/J (resistant) mouse strains. Conclusions: Combining genomics approaches of differential gene expression and sequence variation potentially identifies approximately 5% the linked genes as fibrosis susceptibility candidate genes in this mouse cross.
Towards the Next Generation of Personal Assistants: Systems that Know When You Forget

Recently a new class of personal assistants that are capable of addressing users' information needs proactively is emerging. Users' information needs may include timely notifications about a certain context such as location, social interactions with other people, weather, other events, etc. Personal assistants can assist people by recommending the right information at just the right time and help them in accomplishing tasks. Because of the ubiquitous nature of mobile personal assistants, they have a broad range of potential capabilities. One of these potential capabilities is to carry out sophisticated tasks for supporting failing memories. Such support of human memory has been thus far limited, merely to setting reminders and calendar events. In this paper, we present our work on developing a cutting-edge personal assistant for supporting failing memories in every day social interactions. Specifically, we envision a personal assistant that can anticipate the parts of a past conversation that you are likely to forget, hence remind you about them. Our experimental results on a real-world dataset of meetings reveals evidence that developing such systems is viable and can produce promising results.
Regenerative potential following revascularization of immature permanent teeth with necrotic pulps.

AIM To assess the regenerative potential of immature teeth with necrotic pulps following revascularization procedure in dogs. METHODOLOGY Necrotic pulps and periapical pathosis were created by infecting 108 immature teeth, with 216 root canals in nine mongrel dogs. Teeth were divided into three equal groups according to the evaluation period. Each group was further subdivided into six subgroups according to the treatment protocol including MTA apical plug, revascularization protocol, revascularization enhanced with injectable scaffold, MTA over empty canal. All root canals were disinfected with a triple antibiotic paste prior to revascularization with the exception of control subgroups. After disinfection, the root length, thickness and apical diameter were measured from radiographs. Histological evaluation was used to assess the inflammatory reaction, soft and hard tissue formation. RESULTS In the absence of revascularization, the length and thickness of the root canals did not change over time. The injectable scaffold and growth factor was no more effective than a revascularization procedure to promote tooth development following root canal revascularization. The tissues formed in the root canals resembled periodontal tissues. CONCLUSION The revascularization procedure allowed the continued development of roots in teeth with necrotic pulps.
Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice

Vaccination with recombinant outer surface protein A (OspA) has been shown to protect mice from infection with Borrelia burgdorferi, the Lyme disease agent. To determine whether antibodies to B. burgdorferi proteins other than OspA are involved in protective immunity, antibodies to OspA were removed from protective anti-B. burgdorferi serum; the residual serum was still protective. Absorption of OspA and OspB antibodies from anti-B. burgdorferi serum eliminated the protective effect. Therefore, active immunization experiments were performed to determine the roles of OspB and flagellin in protective immunity and to determine whether protective immunity induced by OspA is dose dependent. Active immunization with recombinant OspA protected mice from infection with an inoculum of 10(4) spirochetes, but this protection could be overcome with a challenge of 10(7) spirochetes; OspB protected mice from infection with an inoculum of 10(3) spirochetes but was insufficient to fully protect against 10(4) organisms; and immunization with flagellin had no protective effect. These studies suggest that OspA and OspB, but not flagellin, play roles in protective immunity to spirochete infection.
Isolation and characterization of gap junctions in the osteoblastic MC3T3‐E1 cell line

Gap junctions are channels connecting cells that function in cell‐to‐cell communication. Gap junctions are abundant in osteoblastic cells. Membranes enriched for gap junction plaques were obtained by differential centrifugation, followed by treatment of the membranes with potassium iodide and sarkosyl before sucrose density gradient centrifugation. Electron microscopy showed that the preparation was enriched for electrondense membranes consistent with gap junctions. Coomassie Blue staining of SDS‐PAGE preparations revealed a prominent band at approximately 41 kD. Western analysis with a site‐directed antibody, CT‐360 (D. Laird, California Institute of Technology, Pasadena, CA), to the C‐terminal portion of the rat heart connexin 43 molecule was positive in the MC3T3‐E1 cell line, a phenotypic osteoblastic cell line derived from normal neonatal mouse calvariae. Western analysis using a monoclonal antibody, R5.21C, to rat liver connexin 32 was negative. Additionally, a prominent band at 59 kD was detected by CT‐360 in both gap junction‐enriched preparations and cell lysates. Treatment of diluted samples of gap junction‐enriched preparations with sulfhydryl reducing agents in combination with detergents resulted in the enhancement and diminution of the 41 and 59 kD bands, respectively. Immunoprecipitation following [35S]methionine/[35S]cysteine labeling revealed a significant band detected at 122 kD in addition to the 41 kD band. To demonstrate functional gap junctions, transfer of lucifer yellow dye to surrounding cells was monitored after microinjection of a target cell. Between passages 10 and 25 in culture, functional cell coupling was found in approximately 70% of injected cells. Coupling was detected within 1–2 minutes after injection. Simultaneous microinjection of the CT‐360 antibody with lucifer yellow resulted in the decoupling of cells. In conclusion, (1) MC3T3‐E1 cells possess a 41 kD protein that is recognized by connexin 43 antibody to rat heart gap junction; (2) multimers of the MC3T3‐E1 gap junctions occur in the preparation; and (3) functional coupling demonstrated by dye transfer may be regulated by region(s) in the C terminus of the connexin molecule.
Genetic association study of phosphodiesterase 8B gene with subclinical hypothyroidism in pregnant women

Abstract Objective: To explore whether phosphodiesterase 8B (PDE8B) gene is involved in the etiology of subclinical hypothyroidism (SCH) in pregnant women. Methods: A total of 180 pregnant patients with SCH and 311 healthy, pregnant control subjects were recruited in this study to detect 4 (rs4704397, rs6885099, rs2046045, and rs12514694 in PDE8B) single nucleotide polymorphisms (SNPs). Univariate associations were studied using Pearson’s χ2 test for categorical variables and Student t/ANOVA tests for continuous ones. Nonparametric Kruskal–Wallis test were used to study the associations of TSH level in different genotypes. Genotyping of SNPs was performed by the MassARRAY® iPLEX® Gold SNP genotyping analysis technique. The SHEsis program was used to analyze the genotyping data. Results: There was a significant difference in the rate of high TSH in three genotypes of rs4704397 in all pregnant women. After adjusting for multiple testing by the program SNPSpD, allelic frequencies of rs4704397 (p = 0.016, OR = 1.692), rs6885099 (p = 0.031, OR = 0.621), and rs2046045 (p = 0.023, OR = 0.602) in PDE8B gene showed significant differences between patients with SCH and control subjects. There were no significant differences of genotype frequencies between patients and controls at any of the analyzed SNPs (p > 0.05). The haplotypes ‘‘A G C G’’ (p = 0.002; OR, 1.533; 95% CI, 1.172–2.006) and “G A A G” (p = 0.014; OR, 0.576; 95% CI, 0.369–0.899) in PDE8B were observed to be significantly associated with SCH in pregnant women. Conclusion: Genetic variation of the PDE8B gene may be involved in the etiology of SCH in pregnant women.
Deciphering Poxvirus Gene Expression by RNA Sequencing and Ribosome Profiling

ABSTRACT The more than 200 closely spaced annotated open reading frames, extensive transcriptional read-through, and numerous unpredicted RNA start sites have made the analysis of vaccinia virus gene expression challenging. Genome-wide ribosome profiling provided an unprecedented assessment of poxvirus gene expression. By 4 h after infection, approximately 80% of the ribosome-associated mRNA was viral. Ribosome-associated mRNAs were detected for most annotated early genes at 2 h and for most intermediate and late genes at 4 and 8 h. Cluster analysis identified a subset of early mRNAs that continued to be translated at the later times. At 2 h, there was excellent correlation between the abundance of individual mRNAs and the numbers of associated ribosomes, indicating that expression was primarily transcriptionally regulated. However, extensive transcriptional read-through invalidated similar correlations at later times. The mRNAs with the highest density of ribosomes had host response, DNA replication, and transcription roles at early times and were virion components at late times. Translation inhibitors were used to map initiation sites at single-nucleotide resolution at the start of most annotated open reading frames although in some cases a downstream methionine was used instead. Additional putative translational initiation sites with AUG or alternative codons occurred mostly within open reading frames, and fewer occurred in untranslated leader sequences, antisense strands, and intergenic regions. However, most open reading frames associated with these additional translation initiation sites were short, raising questions regarding their biological roles. The data were used to construct a high-resolution genome-wide map of the vaccinia virus translatome. IMPORTANCE This report contains the first genome-wide, high-resolution analysis of poxvirus gene expression at both transcriptional and translational levels. The study was made possible by recent methodological advances allowing examination of the translated regions of mRNAs including start sites at single-nucleotide resolution. Vaccinia virus ribosome-associated mRNA sequences were detected for most annotated early genes at 2 h and for most intermediate and late genes at 4 and 8 h after infection. The ribosome profiling approach was particularly valuable for poxviruses because of the close spacing of approximately 200 open reading frames and extensive transcriptional read-through resulting in overlapping mRNAs. The expression of intermediate and late genes, in particular, was visualized with unprecedented clarity and quantitation. We also identified novel putative translation initiation sites that were mostly associated with short protein coding sequences. The results provide a framework for further studies of poxvirus gene expression.
Effects of exercise‐induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used 31P‐magnetic resonance spectroscopy (31P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min‐1, CVinter‐subject = 42%) as compared with PF (46 ± 20 mM min‐1, CVinter‐subject = 44%) and tended to be higher in FF (43 ± 35 mM min‐1, CVinter‐subject = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd.
Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

A strong correlation between disordered breathing patterns, elevated sympathetic nerve activity and enhanced chemoreflex sensitivity exists in patients with heart failure. Evidence indicates that disordered breathing patterns and increased sympathetic nerve activity increases arrhythmia incidence in patients with heart failure. Enhanced coupling between sympathetic and respiratory neural drive underlies elevated sympathetic nerve activity in an animal model of sleep apnoea. We investigated the impact of carotid body chemoreceptor denervation on sympathetic nerve activity, disordered breathing and sympatho‐respiratory coupling in an animal model of heart failure. Renal sympathetic nerve activity, apnoea/hypopnoea incidence, variability measures of tidal volume and respiratory rate and arrhythmia incidence were quantified during resting breathing in heart failure animals with and without carotid body ablation. Our results indicate that carotid body chemoreceptor denervation reduces sympathetic nerve activity, disordered breathing patterns, arrhythmia incidence and sympatho‐respiratory coupling in experimental heart failure. These findings suggest that device‐oriented ablation of carotid body chemoreceptors is a viable treatment option for reduction of sympathetic nerve activity, disordered breathing patterns and arrhythmia incidence in heart failure.