Miracle-dz/UniFAR-FTUs huggingface dataset:
Rising prevalence of antidepressants among US youths.

OBJECTIVE To examine changes in antidepressant (ATD) prevalence and the sociodemographic and clinical correlates of ATD use among youths who are treated in community practice settings. METHODS A retrospective study was undertaken using large data sets from 3 US sites. Outpatient prescription and clinical service records of youths who were aged 2 to 19 and enrolled in Midwestern Medicaid (MWM) and mid-Atlantic Medicaid (MAM) state programs and a group-model health maintenance organization (HMO) were organized into seven 1-year cross-sectional data sets from 1988 through 1994 to evaluate ATD utilization patterns. RESULTS In 1994, ATD prevalence per 1000 youths was 19.10 (MWM), 17.78 (MAM), and 12.85 (HMO), which represented a consistent increase in prevalence from 1988-1994: 2.9-fold (MWM), 4.6-fold (MAM), and 3.6-fold (HMO). Despite the rapidly expanding use of selective serotonin reuptake inhibitors prescribed mainly for depression, more than half of ATD use in 1994 was still attributable to tricyclic antidepressants prescribed mainly for attention-deficit/hyperactivity disorder. ATD prevalence was generally predominant among 10- to 14-year-old boys and among 15- to 19-year-old girls. In the Medicaid populations, 42% (MAM) and 72% (MWM) of ATD-treated youths had primary care services, whereas the bulk of the remainder had psychiatric services. Attention-deficit/hyperactivity disorder followed by depression led the physician-reported primary care diagnoses associated with ATD use, whereas that diagnostic rank order was reversed for youths who received psychiatric services. CONCLUSIONS ATD treatments among youths substantially increased in the 1990s. This was generated primarily by primary care providers, and thus evaluations of the outcome of ATD treatment need to target primary care in addition to psychiatric providers. Longitudinal study designs are needed to evaluate the use of ATDs in youths in regard to the duration of treatment, combination medications, and the reasons for treatment.
Paclitaxel-associated hypersensitivity reactions: experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center.

PURPOSE : This study expands the existing limited data as to whether patients developing clinically significant paclitaxel-induced hypersensitivity reactions can continue to be treated with this important antineoplastic agent and how such retreatment might be undertaken. PATIENTS AND METHODS More than 450 patients received paclitaxel, either as a single agent or in a combination regimen, for a female pelvic malignancy in the Gynecologic Oncology Program of the Cleveland Clinic Cancer Center from January 1995 through December 1998. RESULTS Of the more than 450 patients, 44 (approximately 9%) developed at least one episode of a clinically relevant hypersensitivity reaction to the cytotoxic drug. All 43 individuals (plus an additional four patients referred to our center after having previously experienced a severe paclitaxel-associated hypersensitivity reaction at another institution) who were retreated with paclitaxel were ultimately able to receive the agent. Five patients required treatment with a standardized desensitization regimen, developed by our group, to successfully receive paclitaxel. DISCUSSION On the basis of this large single-institution study of paclitaxel-associated hypersensitivity reactions, we conclude that with appropriate precautions essentially all individuals experiencing these reactions can be safely treated with this agent.
Norepinephrine increases blood pressure but not survival with anthrax lethal toxin in rats*

Objectives: The response of anthrax lethal toxin (LeTx) induced shock and lethality to conventional therapies has received little study. Previously, fluids worsened outcome in LeTx-challenged rats in contrast to its benefit with lipopolysaccharide (LPS) or Escherichia coli. The current study investigated norepinephrine treatment. Measurements and Main Results: Sprague-Dawley rats (n = 232) weighing between 230 and 250 g were challenged with similar lethal (80%) 24-hour infusions of either LPS or LeTx, or with diluent only. Toxin-challenged animals were also randomized to receive 24-hour infusions with one of three doses of norepinephrine (0.03, 0.3, or 3.0 &mgr;g/kg/min) or placebo started 1 hour after initiation of challenge. All toxin animals received similar volumes of fluid over the 24 hours (equivalent to 4.0–4.3 mL/kg/hr). Although the intermediate norepinephrine dose (0.3 &mgr;g/kg/min for 24 hours) improved survival with LPS (p = 0.04) and increased blood pressure before the onset of lethality with LeTx (p < 0.0001), it did not improve survival with the latter (p = ns). Furthermore, neither increasing nor decreasing norepinephrine doses improved survival with LeTx. Conclusion: Hypotension with LeTx may not be a primary cause of lethality in this model. Rather, LeTx may cause direct cellular injury insensitive to vasopressors. These findings suggest that during anthrax infection and shock, along with hemodynamic support, toxin-directed treatments may be necessary as well.
Relevance of the Attention Effect in the Brazilian Stock Market

ABSTRACT This article aims to analyze the impact of investor attention in the Brazilian stock market, particularly the effect of positive pressure on asset prices verified by Barber and Odean (2008). Using the methodology of Da and colleagues (2011), we seek to assess whether investor attention, as measured by the volume of searches on Google, can explain abnormal variations in market activity and asset returns. The results indicated that the Internet search data does explain variations in turnover rate and trading volume of assets. However, unlike the results of studies conducted in other countries, the price pressure hypothesis was not observed in the Brazilian market.
All-Carbon Molecules: Evidence for the Generation of Cyclo[18]carbon from a Stable Organic Precursor

The unambiguous structural characterization of a single-sized all-carbon molecule requires its chemical synthesis. For cyclo[18]carbon, ab initio calculations predict a relatively stable, cyclic D9h ground state geometry with alternating C-C (1.36 angstroms) and C≡C (1.20 angstroms) bonds. The synthesis and x-ray crystal structure of a direct precursor to C18 are described. The analysis of laser flash heating experiments on this precursor by time-of-flight mass spectroscopy shows a sequence of retro-Diels-Alder reactions leading to C18 as the predominant fragmentation pattern. Structural evidence is provided for the generation of an all-carbon molecule from a well-characterized organic precursor.
Enamel matrix proteins and guided tissue regeneration with titanium-reinforced expanded polytetrafluoroethylene membranes in the treatment of infrabony defects: a comparative controlled clinical trial.

BACKGROUND Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects. METHODS Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium-reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year. RESULTS The 1-year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures. CONCLUSIONS The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically-sensitive sites and in reducing patient morbidity.
Binding of Active (57 kDa) Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) to Tissue Inhibitor of Metalloproteinase (TIMP)-2 Regulates MT1-MMP Processing and Pro-MMP-2 Activation*

Previous studies have shown that membrane type 1-matrix metalloproteinase (MT1-MMP) (MMP-14) initiates pro-MMP-2 activation in a process that is tightly regulated by the level of tissue inhibitor of metalloproteinase (TIMP)-2. However, given the difficulty in modulating TIMP-2 levels, the direct effect of TIMP-2 on MT1-MMP processing and on pro-MMP-2 activation in a cellular system could not be established. Here, recombinant vaccinia viruses encoding full-length MT1-MMP or TIMP-2 were used to express MT1-MMP alone or in combination with various levels of TIMP-2 in mammalian cells. We show that TIMP-2 regulates the amount of active MT1-MMP (57 kDa) on the cell surface whereas in the absence of TIMP-2 MT1-MMP undergoes autocatalysis to a 44-kDa form, which displays a N terminus starting at Gly285 and hence lacks the entire catalytic domain. Neither pro-MT1-MMP (N terminus Ser24) nor the 44-kDa form bound TIMP-2. In contrast, active MT1-MMP (N terminus Tyr112) formed a complex with TIMP-2 suggesting that regulation of MT1-MMP processing is mediated by a complex of TIMP-2 with the active enzyme. Consistently, TIMP-2 enhanced the activation of pro-MMP-2 by MT1-MMP. Thus, under controlled conditions, TIMP-2 may act as a positive regulator of MT1-MMP activity by promoting the availability of active MT1-MMP on the cell surface and consequently, may support pericellular proteolysis.
Long-Term Results After Total Knee Arthroplasty with Contemporary Rotating-Hinge Prostheses

Background: Total knee arthroplasty (TKA) with a rotating-hinge prosthesis is considered a salvage procedure. While excellent immediate stability is achieved, the historically high failure rate has tempered its use. The goal of this study was to determine clinical outcomes, radiographic results, and survivorship after TKA with contemporary rotating-hinge components. Methods: We identified 408 consecutive TKAs performed with rotating-hinge components for nononcologic indications from 2002 to 2012 at a single academic institution. Two hundred and sixty-four knees (65%) had rotating-hinge TKA components implanted for aseptic etiologies, while 144 knees (35%) were managed with the components in 2-stage reimplantation following infection. Rotating-hinge TKA implants were used for complex primary procedures in 74 knees (18%) and as a revision construct in 334 knees (82%). Clinical outcomes were assessed with the Knee Society scoring system, survivorship analyses, and cumulative incidence of revision. The mean age of the patients at the time of the index arthroplasty was 69 years, and the mean duration of follow-up was 4 years (range, 2 to 12 years). Results: At the most recent follow-up, the mean Knee Society knee score had increased from 51 points preoperatively to 81 points (p < 0.0001), and the mean Knee Society functional score had increased from 26 to 36 points (p < 0.0001). At a mean of 4 years, loosening of components was observed in 13 (3.7%) of 349 knees. At the most recent follow-up, 59 revision procedures and 25 reoperations had been performed. The cumulative incidence of any revision was 9.7% at 2 years and 22.5% at 10 years. The cumulative incidence of revision for aseptic loosening was 1.7% at 2 years and 4.5% at 10 years. Metaphyseal cones were used in 114 knees (28%). Survivorship analysis revealed a trend toward a lower risk of revision (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.39 to 1.22; p = 0.20) and reoperation (HR = 0.51; 95% CI = 0.22 to 1.19; p = 0.12) in patients with metaphyseal cones, despite their use in the most severe of bone defects. Conclusions: Contemporary rotating-hinge TKA implants had a low 10-year cumulative incidence of revision for aseptic loosening of 4.5%. Greater use of metaphyseal fixation has aided this improvement. Patients can expect substantial improvements in clinical outcomes with this revision strategy. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization

Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective.
Takotsubo Cardiomyopathy: What we have Learned in the Last 25 Years? (A Comparative Literature Review)

We performed a comparative literature review, to elucidate the major features of the Takotsubo (stress) cardiomyopathy (TCM) collected in last 25 years. TCM is characterized by left- or biventricular apical ballooning with a clinical presentation, electrocardiographic abnormalities, and biomarker profils similar to those seen in acute myocardial infarction. Epidemiological studies have shown that TCM is more common in postmenopausal women; however exact figures are not available. The underlying aetiology is still largely undetermined. Elevated catecholamine levels, lack of estrogen, disturbed myocardial fatty acid metabolism and plaque rupture with spontaneous thrombolysis are potentially discussed mechanisms responsible for inducing a prolonged stunned myocardium. Strong emotional or physical stress is the most frequently described trigger in the literature. Therapy recommendations include appropriate antiplatelet treatment, β-blockers and ACE inhibitors. The abnormal kinetics usually resolve or improve within a month and carry a favorable prognosis in most cases. However, all the suspected complications of an acute myocardial infarction, including cardiogenic shock or lethal arrhythmias, may still occur.
Encephalopathy of Infancy with Intracerebral Calcification and Chronic Spinal Fluid Lymphocytosis - Another Case of the Aicardi-Goutières Syndrome

Another case of the Aicardi-Goutières syndrome is presented. The female child was diagnosed at 4 months of age, when irritability, lack of fixation and dystonic movements were noted. Also, extensive intracerebral calcification was found on computed tomography. Nuclear magnetic resonance imaging confirmed extensive white matter disease. Repeated examination of the spinal fluid revealed chronic spinal fluid lymphocytosis. This condition belongs to the encephalopathies of infancy with intracranial calcification of genetic aetiology and unknown pathogenesis. Differentiation against other presumed entities in this group, as well as the wider differential diagnosis, are discussed.
Essays in Financial Economics

This thesis consists of three chapters that study separate subjects in the area of corporate governance and financial intermediation. In the first chapter, I study a protectionist anti-takeover law introduced in 2014 in France that covers a subset of all firms in the economy. The law decreased affected firms’ likelihood of becoming the target of a merger or acquisition and had a negative impact on shareholder value. There is no evidence that management of those firms subsequently altered firm policies in its interest. Investment, employment, wages, profitability, and capital structure remain unchanged. The share of annual CEO compensation consisting of equity instruments increased by 8.4 percentage points, suggesting that boards reacted to the loss in monitoring by the takeover market by increasing the pay-for-performance sensitivity. In the second chapter, which is co-authored work with Rüdiger Fahlenbrach, we conduct a detailed analysis of investors in successful initial coin offerings (ICOs). The average ICO has 4,700 contributors. The median participant contributes small amounts and many investors sell their tokens before the underlying product is developed. Large presale investors obtain tokens at a discount and flip part of their allocation shortly after the ICO. ICO contributors lack the protections traditionally afforded to investors in early stage financing. Nevertheless, returns nine months after the ICO are positive on average, driven mostly by an increase in the value of the Ethereum cryptocurrency. In the third chapter, which is joint work with Christoph Herpfer, we investigate how bankers use information from lending relationships to help borrowers combine resources in strategic alliances. Firms that have borrowed from the same banker or share an indirect connection through a network of bankers are significantly more likely to enter an alliance. Consistent with bankers overcoming informational frictions, their ability to facilitate alliances decreases with network distance, and is stronger for opaque borrowers. Firms connected to more potential partners via banker networks enter more alliances. These alliances are associated with positive announcement returns and brokering banks are more likely to receive future underwriting mandates.
Active Implant PeriApical Lesion : A Case Report Treated Via Guided Bone Regeneration With a 5-Year Clinical and Radiographic Follow-Up

Implant peri-apical lesion (IPL) is a periapical lesion, usually asymptomatic, in which the coronal portion of the implant achieves a normal bone to implant interface. A case of IPL following immediate implant placement and treated with guided bone regeneration (GBR) principles is described. Five-year clinical and radiographic followup with cone-beam assessment showed complete healing of the bone. GBR principles applied to IPL could completely solve the lesion.
Gag-derived proteins of HIV-1 isolates from Indian patients: cloning, expression, and purification of p17 of B- and C-subtypes.

A simple and efficient method for expression in Escherichia coli and purification of matrix protein, p17, of human immunodeficiency virus type 1 (HIV-1) of both B- and C-subtypes is described. DNA sequences encoding p17 of B- and C-subtype were cloned from respective gag sequences. The gag sequences were obtained by PCR amplification using DNA extracted from peripheral blood lymphocytes of an HIV-1 infected patient from India. A T7-promoter-based expression system was optimized for expression of p17 in soluble form. p17 (B- and C-subtype) was purified to near homogeneity using conventional chromatographic techniques. Purification of p17 (C-subtype) is described for the first time with yield of 7.7 mg from a 1-liter culture. The yield of p17 (B-subtype) is 14.7 mg from a 1-liter culture, which is severalfold better than that reported earlier. N-terminal sequencing and CD spectra of the purified proteins, p17B and p17C, show that the proteins are properly processed and well-folded. The immunoreactivity of both types of p17 to sera from HIV-infected individuals is comparable.
Codon Optimization of Gene Fragments EncodingPlasmodium falciparum Merzoite Proteins Enhances DNA Vaccine Protein Expression and Immunogenicity in Mice

ABSTRACT In contrast to conventional vaccines, DNA and other subunit vaccines exclusively utilize host cell molecules for transcription and translation of proteins. The adenine plus thymine content of Plasmodium falciparum gene sequences (∼80%) is much greater than that of Homo sapiens(∼59%); consequently, codon usage is markedly different. We hypothesized that modifying codon usage of P. falciparumgenes encoded by DNA vaccines from that used by the parasite to those resembling mammalian codon usage would lead to increased P. falciparum protein expression in vitro in mouse cells and increased antibody responses in DNA-vaccinated mice. We synthesized gene fragments encoding the receptor-binding domain of the 175-kDaP. falciparum erythrocyte-binding protein (EBA-175 region II) and the 42-kDa C-terminal processed fragment of the P. falciparum merozoite surface protein 1 (MSP-142) using the most frequently occurring codon in mammals to code for each amino acid, and inserted the synthetic genes in DNA vaccine plasmids. In in vitro transient-expression assays, plasmids containing codon-optimized synthetic gene fragments (pS plasmids) showed greater than fourfold increased protein expression in mouse cells compared to those containing native gene fragments (pN plasmids). In mice immunized with 0.5, 5.0, or 50 μg of the DNA plasmids, the dose of DNA required to induce equivalent antibody titers was 10- to 100-fold lower for pS than for pN plasmids. These data demonstrate that optimizing codon usage in DNA vaccines can improve protein expression and consequently the immunogenicity of gene fragments in DNA vaccines for organisms whose codon usage differs substantially from that of mammals.
The interaction of pH and cyclic adenosine 3',5'-monophosphate on activation of motility in Triton X-100 extracted bull sperm.

The motility of demembranated bull sperm was found to be governed by the concentrations of cyclic adenosine 3', 5'-monophosphate (cAMP) and Ca2+ at low pH (6.6-7.1), and was less sensitive to these variables at higher pH (7.4-7.8). Although motility was generally found to increase with increasing pH in the range from 6.6 to 7.8, the addition of exogenous cAMP markedly and selectively improved the motility at the lower end of the range (pH 6.6-7.1). In the presence of 10 microM cAMP, low Ca2+ (8.0 X 10(-8) M), and a high concentration of Mg-adenosine 5'-triphosphate (ATP, 8 mM), demembranated sperm at pH 6.8 and 7.1 exhibited swimming similar to that of live ejaculated sperm. At a free Ca2+ concentration of 4.4 X 10(-5) M, the motility was rapidly inhibited at pH 6.8-7.1, whereas at pH 7.4-7.8, the activity was not greatly affected. Since calcium is known to antagonize the cAMP pathway by activating Ca2+-dependent phosphodiesterase and Ca2+-dependent phosphatase, this further supports the idea that cAMP-dependent activation is crucial for motility at low pH. Our results demonstrate that the flagellar axoneme can function normally at relatively acidic pH, and produce vigorous swimming at high levels of ATP. The ATP content of live sperm was measured and found to be high enough (approximately 8 mM) to support the vigorous motility seen at pH 6.6-7.1 in the models. (ABSTRACT TRUNCATED AT 250 WORDS)