Miracle-dz/UniFAR-FTUs huggingface dataset:
Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major depression: exploratory study.

BACKGROUND The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants. The aim of the study was to compare the costs and outcomes of using amitriptyline, citalopram and fluoxetine in the treatment of major depression. METHODS Ninety patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from major depression were treated with amitriptyline (N = 31), citalopram (N = 29) and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the number of hospitalization-free days) were assessed in a prospective, open, intent-to-treat study. RESULTS Neither cost nor effectiveness were significantly different among the treatment groups. CONCLUSION Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies. There is no advantage in restricting patients from treatment with SSRIs, which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants.
If a US Drug Abuse Epidemic Fails to Include a Major East Coast City, Can It Be Called an Epidemic?

The title of this article reflects one of the curious realities of drug abuse awareness in the United States. The best illustrative metaphor is “If a tree falls in the forest and no one is there to hear it, does it make a sound? ” In this case however, the question is: “If a US drug abuse epidemic fails to include a major east coast city, can it be called an epidemic? ” The most recent manifestation of this unusual “geographic myopia” concerns the recognition (or lack thereof) of the serious methamphetamine problem that has gripped large areas of the Western US for over a decade and within the past 5 years has spread into midwestern US communities. Methamphetamine didn’t sneak up on the US. Methamphetamine use has been a problem in the US before. During in the late 1960s and early 1970s, the problems created by amphetamine/methamphetamine were considered by many to be among the most serious of all the psychoactive substance use problems in that period of high drug use. Worldwide, amphetamine/methamphetamine is a far
Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.

BACKGROUND Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported. METHODS Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings. RESULTS Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =. 004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%). CONCLUSION The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.
A transcription factor with homology to the AP‐1 family links RNA transcription and DNA replication in the lytic cycle of Epstein‐Barr virus.

oriLyt, the lytic origin of DNA replication of Epstein‐Barr virus (EBV), ensures viral DNA amplification during the productive or lytic phase of the virus' life cycle. To understand the contribution of cis‐ and transacting elements involved in DNA replication of oriLyt, a detailed mutational analysis was undertaken which defined BZLF1, a viral transcriptional activator, as an essential replication factor. The BZLF1 protein belongs to the extended fos/jun family of transcription factors and binds to specific BZLF1 binding motifs within oriLyt, as well as to consensus AP‐1 sites. Recombinant, chimeric transcription factors identified the transcriptional activation domain of BZLF1 as being necessary to mediate DNA replication, a function which could not be substituted by any other transcription factor tested, including jun, E2, myc or VP16.
Invasive Mycosis Due to Species of Blastobotrys in Immunocompromised Patients with Reduced Susceptibility to Antifungals

ABSTRACT Cases of invasive mycosis due to Blastobotrys serpentis and B. proliferans identified by sequencing in a preterm patient and a rhabdomyosarcoma patient, respectively, are reported. Both species revealed elevated fluconazole and echinocandin MICs by the CLSI broth microdilution method. Additionally, B. serpentis exhibited high amphotericin B MICs, thus posing serious therapeutic challenges.
Impact of a CT Colonography Screening Program on Endoscopic Colonoscopy in Clinical Practice

OBJECTIVEThe potential effect of CT colonography (CTC) on endoscopic colonoscopy (EC) has been the topic of much speculation. The aim of this study was to evaluate the impact of a CTC screening program on colonoscopy in clinical practice.METHODSAt our institution a third-party reimbursed CTC colorectal cancer (CRC) screening program was established in 2004. The number of CTC monthly exams performed, monthly EC total and screening exams performed, EC with polypectomy performed, and the number of referrals for EC screening exams requested were prospectively examined in the first 33 months after introduction of a CTC CRC screening program.RESULTSThe mean number of overall (378.5 vs 413.1) and screening (150.7 vs 162.9) colonoscopy exams performed per month did not change significantly after screening CTC was introduced. The mean number of monthly CTC exams performed rose significantly throughout the first year of the study from 39 initially to a peak of 147.6 cases per month but decreased slightly to 114.3 monthly exams at the end of 2006. A mean 10.0 patients per month were sent for EC after a positive CTC exam. The mean number of monthly colonoscopies with polypectomy remained constant after the introduction of CTC (197.0 vs 180.2). Monthly referrals for screening EC exams initially decreased but were unchanged 3 yr after institution of a CTC screening program (255.0 vs 253.5). CONCLUSIONS(a) In our tertiary care center the initiation of a screening CTC program did not result in a decrease in the number of total colonoscopy exams, screening colonoscopy exams performed, nor requests for screening colonoscopy. (b) Only a small number of CTC exams were referred for EC with polypectomy, therefore a CTC screening program may not increase the overall number of therapeutic colonoscopies performed.
Wideband filtering power divider based on coupled-lines and short-circuited stubs

A novel wideband filtering power divider based on coupled-lines and short-circuited stubs is proposed in this paper. By using multisection λ/4 coupled-lines with two short-circuited stubs placed in shunt with the input port of the power divider, the presented circuit can successfully realize wideband property and high frequency selectivity. In addition, two resistors are properly selected according to the even-/odd-mode analysis for improving the isolation performance. For demonstration, two typical ideal simulations with 15-dB bandwidth of 80% and 20-dB bandwidth of 56% operating at 2 GHz are implemented, respectively. The simulated results show excellent agreement with theoretically predicated results.
Therapies for diabetic dyslipidaemia

Correction of diabetic dyslipidaemia in diabetic patients is the most important factor in reducing cardiac risk. Diabetic dyslipidaemia is characterized by elevated triglycerides, low total high‐density lipoprotein (HDL) and small dense low‐density lipoprotein (LDL) particles. The most important therapeutic goal in diabetic dyslipidaemia is correction of the non‐HDL‐cholesterol (HDL‐C) level. Glycaemic control with particular attention to postprandial glucose control plays a role not only in improving dyslipidaemia but also in lowering cardiac events. Pioglitazone is particularly effective for improving the manifestations of diabetic dyslipidaemia, in addition to its favorable effects on systemic inflammation and hyperglycaemia. Use of statins in addition to lifestyle change is recommended in most if not all type 2 diabetic patients and the goal should be to lower the LDL to a level recommended for the patient with existing cardiovascular disease (CVD) (non‐HDL‐C level <100 mg/dl). In addition, therapies for normalization of HDL and triglyceride levels should be deployed. Most patients with type 2 diabetes (T2D) will require combining a lipid‐lowering therapy with therapeutic lifestyle changes to achieve optimal lipid levels. Combinations usually include two or more of the following: a statin, nicotinic acid, omega‐3 fats and bile acid sequestrants (BASs). Fibrates may also be of use in diabetic patients with persistently elevated triglycerides and depressed HDL‐C levels, although their role in lowering adverse CV events is questionable.
The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

OBJECTIVE Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate-release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND METHODS Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). RESULTS The bioavailability of 1,000 mg Met DR b.i. d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. CONCLUSIONS Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.
An Effective Approach to Ground Moving Target Imaging for Single Channel SAR System

Based on the envelopes and the characteristics of Doppler spectrum of returns in single channel synthetic aperture radar (SAR) systems a method is proposed, which adopts two order Keystone transform to adjust the range curvature of echo data, then range walk rates of echoes' envelopes are estimated to make some adjustments of walk and the Doppler parameters of moving targets are obtained through analyzing the Doppler spectrum of the moving targets. At last the images and positions of ground moving targets are gained, which make it possible that the moving targets can be indicated in right locations in SAR image. In addition the key motion parameters of moving targets can be estimated by the relationship between the Doppler parameters and motion parameters of ground moving targets. The results of the measured data show that this method can image ground moving targets and estimate motion parameters effectively
Susceptibility of Aedes albopictus C6/36 cells to viral infection

The susceptibility of the C6/36 clone of Aedes albopictus monolayer cell cultures was determined with 46 prototype viruses passed through three subcultures. Viral growth was confirmed by titration of the passage material in other susceptible host systems. Nineteen viruses demonstrated good growth in C6/36 cells: coxsackievirus group A type 10 and group B types 2, 3, 4, and 5; enterovirus 69; mumps virus; poliovirus types 1 to 3; reovirus types 1 to 3; vaccinia virus; dengue virus type 2; eastern equine encephalomyelitis virus; La Crosse virus; Rocio virus; and St. Louis encephalitis virus. Ten viruses did not adapt to growth in the C6/36 cultures. Seventeen other virus strains displayed only limited growth which was primarily restricted to the initial C6/36 passage or was detected by hemagglutinin reactions without observable cell degeneration. Of the 46 viruses, 33 (72%) were capable of initiating infection with a demonstrable cytopathic effect in the initial C6/36 passage. Hemagglutination or complement fixation titers or both were obtained with dengue virus type 2, eastern equine encephalomyelitis virus, La Crosse virus, mumps virus, reovirus types 1 to 3, and Rocio, St. Louis encephalitis, and vaccinia viruses.
Human Non-Small Cell Lung Tumors and Cells Derived from Normal Lung Express Both Estrogen Receptor α and β and Show Biological Responses to Estrogen

Lung cancer is becoming increasingly common in women and in the United States accounts for more female cancer deaths annually than breast cancer. Many epidemiological studies have provided evidence that women are more susceptible than men to the adverse effects of tobacco smoke. These observations suggest the possible role of estrogens in lung carcinogenesis. We report here the expression of mRNA for estrogen receptor alpha (ERalpha) and beta (ERbeta) in cultured human non-small cell lung cancer cells, cultured lung fibroblasts, and primary cultures of normal bronchial epithelium. Western analysis of ERalpha suggested that the main protein expressed in lung tumor cells is a variant, probably attributable to alternative splicing. Protein for ERbeta was found to be a mixture of full-length as well as alternatively spliced variants. beta-Estradiol produced a proliferative response in vitro in both normal lung fibroblasts and cultured non-small cell lung tumor cells. This effect was also observed in vivo. In this regard, beta-estradiol stimulated growth of the non-small cell lung tumor line, H23, grown as tumor xenografts in SCID mice. This effect was blocked by fluvestrant (ICI 182,780). In paraffin sections of non-small cell lung tumors, ERbeta immunoreactivity was localized to the nucleus, whereas ERalpha immunoreactivity was mainly localized to the cytoplasm, suggesting that both nuclear and cytoplasmic signaling may be involved in estrogenic responses in the lung. To show that the ERs found in the lung are functional, we demonstrated that beta-estradiol stimulated transcription of an estrogen response element-luciferase construct transfected in non-small cell lung tumor cell lines. Antiestrogens blocked this effect. Treatment of lung fibroblasts with beta-estradiol also increased secretion of hepatocyte growth factor by 2-fold. These results suggest that estrogen signaling plays a biological role in both the epithelium and the mesenchyme in the lung and that estrogens could potentially promote lung cancer, either through direct actions on preneoplastic or neoplastic cells or through indirect actions on lung fibroblasts. Additionally, it is possible that antiestrogens may have therapeutic value to treat or prevent lung cancer.
Analysis of Jumping-Landing Manoeuvers after Different Speed Performances in Soccer Players

Purpose Running at high speed and sudden change in direction or activity stresses the knee. Surprisingly, not many studies have investigated the effects of sprinting on knee’s kinetics and kinematics of soccer players. Hence, this study is aimed to investigate indices of injury risk factors of jumping-landing maneuvers performed immediately after sprinting in male soccer players. Methods Twenty-three collegiate male soccer players (22.1±1.7 years) were tested in four conditions; vertical jump (VJ), vertical jump immediately after slow running (VJSR), vertical jump immediately after sprinting (VJFR) and double horizontal jump immediately after sprinting (HJFR). The kinematics and kinetics data were measured using Vicon motion analyzer (100Hz) and two Kistler force platforms (1000Hz), respectively. Results For knee flexion joint angle, (p = 0.014, η = 0.15) and knee valgus moment (p = 0.001, η = 0.71) differences between condition in the landing phase were found. For knee valgus joint angle, a main effect between legs in the jumping phase was found (p = 0.006, η = 0.31), which suggests bilateral deficit existed between the right and left lower limbs. Conclusion In brief, the important findings were greater knee valgus moment and less knee flexion joint angle proceeding sprint (HJFR & VJFR) rather than no sprint condition (VJ) present an increased risk for knee injuries. These results seem to suggest that running and sudden subsequent jumping-landing activity experienced during playing soccer may negatively change the knee valgus moment. Thus, sprinting preceding a jump task may increase knee risk factors such as moment and knee flexion joint angle.
Spectrum aggregation and management framework for pre-5G applications

This article presents discussion behind emerging need for the Unified Traffic Steering (UTS) approach in the evolving mobile networks to efficiently handle multitude of 3GPP radio access schemes and technologies. Considering the approaching 5G networks which will introduce yet another Radio Access Technology (RAT) to the equation, we need to think of tight radio level integration of all available RATs with the available spectrum resources and spectrum access schemes. That is a must to allow efficient radio resources utilization in mobile networks to cope with the booming mobile data demand in evolving mobile broadband use cases. For that purpose, analysis of traffic steering functionalities was performed based on the 3GPP standards, which lead to the formulation of UTS framework. UTS framework is considered as the enabler for unified 5G architecture, where UTS-logic plays as central entity, serving as engine to coordinate traffic steering mechanisms with respect to scenarios, feature groups, operator strategies and load conditions taking into account mobile demand and SON decisions.
New insights into microRNAs in skin wound healing

Chronic wounds are a major burden to overall healthcare cost and patient morbidity. Chronic wounds affect a large portion of the US, and billions of healthcare dollars are spent in their treatment and management. microRNAs (miRNAs) are small, noncoding double‐stranded RNAs that post‐transcriptionally downregulate the expression of protein‐coding genes. Studies have identified miRNAs involved in all three phases of wound healing including inflammation, proliferation, and remodeling. Some miRNAs have been demonstrated in vitro with primary keratinocyte wound healing model and in vivo with mouse wound healing model through regulation of miRNA expression to affect the wound healing process. This review updates the current miRNAs involved in wound healing and discusses the future therapeutic implications and research directions. © 2015 IUBMB Life, 67(12):889–896, 2015
Topically Applied AaeIAP1 Double-Stranded RNA Kills Female Adults of Aedes aegypti

Abstract Aedes aegypti (L.) (Diptera: Culicidae) is the primary vector of both dengue and yellow fever. Use of insecticides is one of the primary ways to control this medically important insect pest. However, few new insecticides have been developed for mosquito control in recent years. As a part of our effort to develop new insecticides to control mosquitoes, an inhibitor of apoptosis protein 1 gene in Aedes aegypti (AaeIAP1) was targeted for the development of molecular pesticides. Herein, for the first time, we report that topically applied AaeIAP1 double-stranded RNA products are able to kill female adults of Ae. aegypti. Our results indicate that critical pathways or genes could be targeted to develop molecular pesticides for the control of medically important diseases vectors.
The targeting of drugs parenterally by use of microspheres.

The use of microspheres as drug carrier systems is reviewed and discussed and specific details are given of recent work conducted as part of a joint program between the Schools of Pharmacy at Nottingham and Copenhagen. The physicochemical properties that influence the fate and deposition of colloidal particles following parenteral administration include particle size, surface charge, and surface hydropho-bicity. Adsorbed blood components also play a significant role. Drug targeting can be achieved in certain instances, although following intravenous administration, the major site of particle deposition is the liver. A relocation of the particles can be achieved by pharmaceutical formulation (e.g., coating with nonionic surfactants). In vivo experiments using the rabbit demonstrate the important characteristics of a model microsphere controlled release system based on DEAE-cellulose. The use of monoclonal antibodies as a coating agent to increase site specificity is also discussed.
People with dementia in the emergency department: Behavioural symptoms and use of restraint

Behavioural and psychological symptoms of dementia (BPSD) include symptoms such as aggression and psychosis. BPSD is common, complex and multifactorial and can be associated with the environment and unmet needs such as hunger and pain (3). Guidelines recommend using non-pharmacological strategies as the first line approach to manage BPSD, and reserve use of antipsychotic medications for severe symptoms where the behaviour is distressing to the person, or where there is a risk of harm to self or others (4).
Osteopontin as a therapeutic target for cancer

Introduction: Cancer is a complex pathological disorder, established as a result of accumulation of genetic and epigenetic changes, which lead to adverse alterations in the cellular phenotype. Tumor progression involves intricate signaling mediated through crosstalk between various growth factors, cytokines and chemokines. Osteopontin (OPN), a chemokine-like protein, is involved in promotion of neoplastic cancer into higher grade malignancies by regulating various facets of tumor progression such as cell proliferation, angiogenesis and metastasis. Areas covered: Tumors as well as stroma-derived OPN play key roles in various signaling pathways involved in tumor growth, angiogenesis and metastasis. OPN derived from tumor-activated macrophages modulates the tumor microenvironment and thereby regulate melanoma growth and angiogenesis. OPN also regulates hypoxia-inducible factor-1α-dependent VEGF expression leading to breast tumor growth and angiogenesis in response to hypoxia. Thus, a clear understanding of the molecular mechanism underlying OPN-mediated regulation will shed light on exciting avenues for further investigation of targeted therapies. Silencing of OPN using RNAi technology, blocking OPN activity using specific antibodies and small-molecule inhibitors might provide novel strategies, which would aid in developing effective therapeutics for the treatment of various types of cancer. Expert opinion: This review focuses on new possibilities to exploit OPN as a tumor and stroma-derived therapeutic target to combat cancer.