Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of antidepressants among elderly subjects: trends and contributing factors.

OBJECTIVE The authors assessed changes over time in antidepressant utilization among elderly subjects regarding the prevalence of antidepressant users, shifts in prescription patterns, and related financial implications. METHOD The authors conducted a population-based study of more than 1.4 million Ontario residents aged 65 years or older. Cross-sectional data regarding annual antidepressant utilization were obtained from administrative databases for 1993 to 1997. Time series analysis was used to assess trends over time and to make future projections. RESULTS The proportion of antidepressant users increased from 9.3% of the elderly population in 1993 to 11.5% in 1997. Prescriptions for selective serotonin reuptake inhibitors (SSRIs) accounted for 9.6% of antidepressant prescriptions dispensed in the first 30 days of 1993 and 45.1% of those dispensed by the last 30 days of 1997 and were projected to increase to approximately 56% by the end of 2000. Prescriptions for tricyclic antidepressants fell from 79.0% in the first 30 days of 1993 to 43.1% by the last 30 days of 1997 and were projected to decline to approximately 28% by the end of 2000. Annual antidepressant costs (in Canadian dollars) increased by 150%, from $10.8 million in 1993 to $27.0 million in 1997. Population shifts and an increase in the prevalence of antidepressant users accounted for at least 20% of this increase, whereas the prescribing transition from tricyclic antidepressants to SSRIs accounted for at least 61% of the increase. CONCLUSIONS The introduction of SSRIs has had a substantial financial impact at the drug utilization level. Future research should address the appropriate balancing of the cost of newer agents versus their ostensible advantages.
Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms 1

The tachykinins comprise a family of closely related peptides that participate in the regulation of diverse biological processes. The tachykinin peptides substance P, neurokinin A, neurokinin A(3‐10), neuropeptide K, and neuropeptide γ are produced from a single preprotachykinin gene as a result of differential RNA splicing and differential posttranslational processing. Another tachykinin, neurokinin B, is produced from a separate preprotachykinin gene. These preprotachykinin mRNAs and peptide products are differentially distributed throughout the nervous system. Three distinct G protein‐coupled tachykinin receptors exist for these tachykinin peptides. The three receptors interact differentially with the tachykinin peptides and are uniquely distributed throughout the nervous system. The NK‐1 receptor preferentially interacts with substance P, the NK‐2 receptor prefers neurokinin A, neuropeptide K, and neuropeptide γ, and the NK‐3 receptor interacts best with neurokinin B. Examples of the roles of tachykinin peptidergic neuronal systems are taken from the spinal cord sensory system and the nigrostriatal extrapyramidal motor system. Analysis of the functional significance of multiple tachykinin peptide systems, receptor‐second messenger coupling mechanisms, and developmental and regulatory mechanisms underlying peptide mRNA and receptor expression represent areas of current and future investigation. —Helke, C. J.; Krause, J. E. ; Mantyh, P. W. ; Couture, R. ; Bannon, M. J. Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms. FASEB J. 4: 1606‐1615; 1990.
Gene expression of human DNA polymerase alpha during cell proliferation and the cell cycle

We studied the expression of the human DNA polymerase alpha gene during cell proliferation, during cell progression through the cell cycle, and in transformed cells compared with normal cells. During the activation of quiescent cells (G0 phase) to proliferate (G1/S phases), the steady-state mRNA levels, rate of synthesis of nascent polymerase protein, and enzymatic activity in vitro exhibited a substantial and concordant increase prior to the peak of in vivo DNA synthesis. In transformed cells, the respective values were amplified greater than 10-fold. In actively growing cells separated into discrete stages of the cell cycle by counterflow elutriation or by mitotic shakeoff, levels of steady-state transcripts, translation rates, and enzymatic activities of polymerase alpha were constitutively and concordantly expressed at all stages of the cell cycle, with only a moderate elevation prior to the S phase and a slight decline in the G2 phase. These findings support the conclusion that the regulation of human DNA polymerase alpha gene expression is at the transcriptional level and strongly suggest that the regulatory mechanisms that are operative during the entrance of a cell into the mitotic cycle are fundamentally different from those that modulate polymerase alpha expression in continuously cycling cells.
DAPK promoter methylation status correlates with tumor metastasis and poor prognosis in patients with non-small cell lung cancer.

OBJECTIVE This meta-analysis investigated the correlation between the promoter methylation of death-associated protein kinase (DAPK) and the clinicopathological features in patients with non-small cell lung cancer (NSCLC). METHOD Scientific literature databases were exhaustively searched to retrieve published studies relevant to DAPK methylation and NSCLC. Retrieved studies published in English and Chinese languages were screened according to the stringent predefined inclusion and exclusion criteria, and high quality studies were selected for meta-analysis. All statistical analyses were performed utilizing STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). RESULTS A total of 14 published studies (5 in English and 9 in Chinese) were enrolled in the present meta-analysis, and contained 1238 patients with NSCLC. The results indicated that NSCLC patients with metastatic phenotype were strongly associated with significantly higher methylation rate of DAPK compared to NSCLC patients without metastasis. Additionally, in NSCLC patients carrying tumors with DAPK methylation, the 5-year survival rate was remarkedly lower than NSCLC patients without DAPK methylation. However, we did not find significant correlation between DAPK methylation and histological stage or tumor node metastasis (TNM) stage in NSCLC patients. CONCLUSION Our meta-analysis results reveal that DAPK promoter methylation might be associated with tumor metastasis and poor prognosis in NSCLC patients, although no correlation with histological types and TNM stage in NSCLC patients were found.
Resonances of Characteristic Modes for Perfectly Conducting Objects

Resonances, i.e., extrema of the eigenvalues of characteristic modes for closed perfectly conducting objects are investigated. The characteristic modal solutions based on the electric, magnetic, and combined field integral operators (EFIO, MFIO, and CFIO) are studied and compared with analytical solutions for a sphere. All these formulations are found to capture both external (radiating) and internal (cavity) resonances predicted by the analytical expressions. At the internal resonances, the eigenvalues obtained with the EFIO- and MFIO-based approaches are not correct, and the corresponding modes are nonunique. These solutions also exhibit a strong duality between the electric (TM) and magnetic (TE) type modes. A connection is found between the external and internal resonances and the condition numbers of the matrices. The modal expansion of the CFIO-based solution is correct, even though it also experiences the nonuniqueness of the EFIO- and MFIO-based solutions.
Association Study Between Vitamin D Receptor Gene Polymorphisms and Patients With Parkinson Disease in Chinese Han Population

ABSTRACT Vitamin D and vitamin D receptor (VDR) have been postulated as environmental and genetic factors in neurodegenerative disorders including multiple sclerosis, Alzheimer disease, and recently Parkinson disease (PD). The purpose of this study is to explore the potential correlation between single nucleotide polymorphisms of the VDR gene (VDR) rs4334089 and rs731236 and PD. A total of 483 patients with PD and 498 age- and sex-matched controls were involved in this study. Genotypes were determined by using polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing. There were no significant differences in the genotype and allele frequencies of VDR rs4334089 and rs731236 polymorphisms between the group of patients with PD and the control group in a Chinese Han population (for VDR rs4334089: OR 1.02, 95% CI: 0.85–1.23; for VDR rs731236: OR 1.13, 95% CI: 0.75–1.71). Similarly, there were still no differences when stratifying by age or by gender. These findings suggest that VDR gene is not a susceptibility gene for PD in our population.
Ureteral access sheath provides protection against elevated renal pressures during routine flexible ureteroscopic stone manipulation.

BACKGROUND AND PURPOSE New-generation flexible ureteroscopes allow the management of proximal ureteral and intrarenal pathology with high success rates, including complete removal of ureteral and renal calculi. One problem is that the irrigation pressures generated within the collecting system can be significantly elevated, as evidenced by pyelovenous and pyelolymphatic backflow seen during retrograde pyelography. We sought to determine if the ureteral access sheath (UAS) can offer protection from high intrarenal pressures attained during routine ureteroscopic stone surgery. PATIENTS AND METHODS Five patients (average age 72.6 years) evaluated in the emergency department for obstructing calculi underwent percutaneous nephrostomy (PCN) tube placement to decompress their collecting systems. The indications for PCN tube placement were obstructive renal failure (N=1), urosepsis (N=2), and obstruction with uncontrolled pain and elevated white blood cell counts (N=2). Flexible ureteroscopy was subsequently performed with and without the aid of the UAS while pressures were measured via the nephrostomy tube connected to a pressure transducer. Pressures were recorded at baseline and in the distal, mid, and proximal ureter and renal pelvis, first without the UAS, and then with the UAS in place. RESULTS The average baseline pressure within the collecting system was 13.6 mm Hg. The mean intrarenal pressure with the ureteroscope in the distal ureter without the UAS was 60 mm Hg and with the UAS was 15 mm Hg. With the ureteroscope in the midureter, the pressures were 65.6 and 17.5 mm Hg, respectively; with the ureteroscope in the proximal ureter 79.2 and 24 mm Hg, and with the ureteroscope in the renal pelvis 94.4 and 40.6 mm Hg, respectively. All differences at each location were statistically significant (P<0.008). Compared with baseline, all pressures measured without the UAS were significantly greater, but only pressures recorded in the proximal ureter and renal pelvis after UAS insertion were significantly higher (P<0.03). CONCLUSIONS The irrigation pressures transmitted to the renal pelvis and subsequently to the parenchyma are significantly greater during routine URS without the use of the UAS. The access sheath is potentially protective against pyelovenous and pyelolymphatic backflow, with clinical implications for the ureteroscopic management of upper-tract transitional cell carcinoma, struvite stones, or calculi associated with urinary tract infection.
Conditional Deletion of Indian Hedgehog in Limb Mesenchyme Results in Complete Loss of Growth Plate Formation but Allows Mature Osteoblast Differentiation

Indian hedgehog (Ihh) is widely recognized as an essential factor for proper skeletal development. Previous in vivo studies using mutant Ihh mouse models were limited by perinatal lethality or carried out after a growth plate formed. Thus the important role of Ihh in mesenchymal cell differentiation has not been investigated. In this study, we established Prx1‐Cre;Ihhfl/fl mice to ablate Ihh specifically in limb mesenchyme to allow us to observe the phenotype continuously from prenatal development to 3 weeks of age. Mutant mice displayed severe limb abnormalities characterized by complete lack of secondary ossification center and growth plate, indicating an essential role for Ihh in the development of these structures. Interestingly, we discovered that osteoblast differentiation and bone formation could occur in conditions of deficient Ihh. This is a novel finding that has not been observed because of the early lethality of previous Ihh mutants. Mature osteoblasts expressing osteocalcin could be detected in the center of mutant bones at postnatal day 10 (P10). Osteoclasts and blood vessel formation were also present, suggesting active bone remodeling. Histomorphometric analyses show a significant increase in osteoclast number with no major changes in bone formation rate at 3 weeks of age. Mutant long bones in the limbs were deformed, with cortices comprised of irregular woven bone. Also, there was a marked decrease in gene expression of osteoblastic and osteocytic markers. Moreover, mutant long bones displayed bone dysplasia in which we observed increased osteoclast activity and partially reduced osteoblastic and osteocytic differentiation that lead ultimately to loss of bone structures at 3 weeks of age. In summary, our data show for the first time, the presence of mature osteoblasts in long bones of the limbs despite the complete loss of growth plate formation due to Ihh deficiency. These data indicate an important function for Ihh in regulating limb mesenchymal cell differentiation. © 2015 American Society for Bone and Mineral Research.
OX40 Ligation of CD4+ T Cells Enhances Virus-Specific CD8+ T Cell Memory Responses Independently of IL-2 and CD4+ T Regulatory Cell Inhibition1

We have previously shown that CD4+ T cells are required to optimally expand viral-specific memory CD8+ CTL responses using a human dendritic cell-T cell-based coculture system. OX40 (CD134), a 50-kDa transmembrane protein of the TNFR family, is expressed primarily on activated CD4+ T cells. In murine models, the OX40/OX40L pathway has been shown to play a critical costimulatory role in dendritic cell/T cell interactions that may be important in promoting long-lived CD4+ T cells, which subsequently can help CD8+ T cell responses. The current study examined whether OX40 ligation on ex vivo CD4+ T cells can enhance their ability to “help” virus-specific CTL responses in HIV-1-infected and -uninfected individuals. OX40 ligation of CD4+ T cells by human OX40L-IgG1 enhanced the ex vivo expansion of HIV-1-specific and EBV-specific CTL from HIV-1-infected and -uninfected individuals, respectively. The mechanism whereby OX40 ligation enhanced help of CTL was independent of the induction of cytokines such as IL-2 or any inhibitory effect on CD4+ T regulatory cells, but was associated with a direct effect on proliferation of CD4+ T cells. Thus, OX40 ligation on CD4+ T cells represents a potentially novel immunotherapeutic strategy that should be investigated to treat and prevent persistent virus infections, such as HIV-1 infection.
Co‐hydrolysis of lignocellulosic biomass for microbial lipid accumulation

The herbaceous perennial energy crops miscanthus, giant reed, and switchgrass, along with the annual crop residue corn stover, were evaluated for their bioconversion potential. A co‐hydrolysis process, which applied dilute acid pretreatment, directly followed by enzymatic saccharification without detoxification and liquid–solid separation between these two steps was implemented to convert lignocellulose into monomeric sugars (glucose and xylose). A factorial experiment in a randomized block design was employed to optimize the co‐hydrolysis process. Under the optimal reaction conditions, corn stover exhibited the greatest total sugar yield (glucose + xylose) at 0.545 g g−1 dry biomass at 83.3% of the theoretical yield, followed by switch grass (0.44 g g−1 dry biomass, 65.8% of theoretical yield), giant reed (0.355 g g−1 dry biomass, 64.7% of theoretical yield), and miscanthus (0.349 g g−1 dry biomass, 58.1% of theoretical yield). The influence of combined severity factor on the susceptibility of pretreated substrates to enzymatic hydrolysis was clearly discernible, showing that co‐hydrolysis is a technically feasible approach to release sugars from lignocellulosic biomass. The oleaginous fungus Mortierella isabellina was selected and applied to the co‐hydrolysate mediums to accumulate fungal lipids due to its capability of utilizing both C5 and C6 sugars. Fungal cultivations grown on the co‐hydrolysates exhibited comparable cell mass and lipid production to the synthetic medium with pure glucose and xylose. These results elucidated that combining fungal fermentation and co‐hydrolysis to accumulate lipids could have the potential to enhance the utilization efficiency of lignocellulosic biomass for advanced biofuels production. Biotechnol. Bioeng. 2013; 110: 1039–1049. © 2012 Wiley Periodicals, Inc.
Activation of Th1 Immunity Is a Common Immune Mechanism for the Successful Treatment of Hepatitis B and C: Tetramer Assay and Therapeutic Implications

Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p = 0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.
In Planta Single-Molecule Pull-Down Reveals Tetrameric Stoichiometry of HD-ZIPIII:LITTLE ZIPPER Complexes[OPEN]

Establishment of single-molecule pull-down in plants allows rapid, sensitive, and quantitative interrogation of protein interactions and reveals tetrameric HD-ZIPIII:ZPR complexes. Deciphering complex biological processes markedly benefits from approaches that directly assess the underlying biomolecular interactions. Most commonly used approaches to monitor protein-protein interactions typically provide nonquantitative readouts that lack statistical power and do not yield information on the heterogeneity or stoichiometry of protein complexes. Single-molecule pull-down (SiMPull) uses single-molecule fluorescence detection to mitigate these disadvantages and can quantitatively interrogate interactions between proteins and other compounds, such as nucleic acids, small molecule ligands, and lipids. Here, we establish SiMPull in plants using the HOMEODOMAIN LEUCINE ZIPPER III (HD-ZIPIII) and LITTLE ZIPPER (ZPR) interaction as proof-of-principle. Colocalization analysis of fluorophore-tagged HD-ZIPIII and ZPR proteins provides strong statistical evidence of complex formation. In addition, we use SiMPull to directly quantify YFP and mCherry maturation probabilities, showing these differ substantially from values obtained in mammalian systems. Leveraging these probabilities, in conjunction with fluorophore photobleaching assays on over 2000 individual complexes, we determined HD-ZIPIII:ZPR stoichiometry. Intriguingly, these complexes appear as heterotetramers, comprising two HD-ZIPIII and two ZPR molecules, rather than heterodimers as described in the current model. This surprising result raises new questions about the regulation of these key developmental factors and is illustrative of the unique contribution SiMPull is poised to make to in planta protein interaction studies.
Glutamate neurotoxicity in mesencephalic dopaminergic neurons in culture

The neurotoxic effect of glutamate in cultured mouse mesencephalic dopaminergic neurons was investigated. Neuron‐rich cell cultures were prepared from 13–14‐day‐old fetal mouse ventral mesencephalic tissue. Cultures were exposed to glutamate for 10 min and evaluated for glutamate neurotoxicity (GNT) 18–24 hr later by tyrosine hydroxylase (TH) immunostaining, microtubule associated protein‐2 (MAP2)immunostaining, and radiolabeled dopamine uptake assay.
DO MINOR HEAD IMPACTS IN SOCCER CAUSE CONCUSSIVE INJURY? A PROSPECTIVE CASE‐CONTROL STUDY

OBJECTIVEOur objective was to determine whether minor head trauma in elite soccer matches causes measurable impairment in brain function. METHODSBaseline neuropsychological testing was completed by professional soccer players in the Norwegian elite league, Tippeligaen, before the 2004 and 2005 seasons (n = 462). A player who experienced a head impact during a league match completed a follow-up test the next day (head impact group). Videotapes of all impacts were collected and reviewed. A group of players without head impacts was also tested after a league match to serve as controls (matched control group; n = 47). RESULTSA total of 228 impacts were identified, and 44 (19.3%) of these were followed up with a CogSport test (CogState, Ltd., Charlton South, Australia; the players who were tested tended to have more severe injuries, but there were only 6 cases with loss of consciousness). The head impact group had a greater change in reaction time from baseline to follow-up compared with the matched control group with regard to the 3 simplest tasks. The largest deficits were seen among the players reporting acute symptoms after the impact, but deficits were also demonstrated among asymptomatic players. Players who experienced 1 or more head impacts during the 2004 season showed a reduction in neuropsychological performance when tested before the 2005 season. However, none of these players was impaired when compared with the test manufacturer's normative data. CONCLUSIONA reduced neuropsychological performance was found after minor head impacts in soccer, even in allegedly asymptomatic players. However, the long-term cognitive consequences are uncertain.