Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Hemodynamic Responses to Selective Inhibitors of Cyclic Nucleotide Phosphodiesterases in Conscious Rats

Summary: Selective inhibition of either the low Km cyclic AMP (cAMP) or low Km cyclic GMP (cGMP) phosphodiesterase (PDE) promotes vasorelaxation and, consequently, produces depressor effects. To evaluate the systemic and regional hemodynamic effects of selective inhibitors of these PDE isozymes, CI-930 (0.1–10 mg/kg), an inhibitor of low Km cAMP PDE, or zaprinast (3–30 mg/kg), an inhibitor of low Km cGMP PDE, was given i.v. to conscious, normotensive rats. The rats were chronically instrumented with vascular catheters and either an ultrasonic transit-time flow probe around the ascending aorta or miniaturized pulsed Doppler flow probes around the superior mesenteric and left renal arteries and the abdominal aorta. CI-930 and zaprinast, at cumulative doses of 3 and 30 mg/kg, respectively, produced comparable reductions in mean arterial pressure (- 22 ± 3 and - 19 ± 4 mm Hg, respectively) and total peripheral resistance (-0.41 ± 0.07 and −0.42 ± 0.06 mm Hg/ml/min, respectively) but affected other hemodynamic variables differently. CI-930 at 3 mg/kg increased the heart rate (HR), maximal aortic flow acceleration (dF/dt), and peak aortic flow and decreased the stroke volume (SV). Cardiac output (CO) was not affected by CI-930. Zaprinast at 30 mg/kg increased the CO, dF/dt, and peak aortic blood flow. The HR and SV were unaffected by zaprinast. Although both CI-930 and zaprinast increased the dF/dt and peak aortic flow, these parameters were affected more by CI-930 than by zaprinast. CI-930 decreased hindquarter, mesenteric, and renal vascular resistances in a dose-dependent manner. Since the doses of zaprinast at which significant reductions in hindquarter, mesenteric, and renal vascular resistances first occurred were 10,18, and 30 mg/kg, respectively, these vascular beds may be differentially sensitive to the vasorelaxant effects of zaprinast. It is concluded that, although selective inhibitors of either low Km cGMP or low Km cAMP PDE decrease blood pressure by lowering the total peripheral resistance in conscious rats, the accompanying hemodynamic patterns for each agent are different.
The use of illicit substances in adolescent schizophrenia inpatients

Illicit substance use is a common co-morbidity in adolescent-onset schizophrenia/ schizoaffective patients. This study aimed to evaluate the rates of substance use among adolescent schizophrenia inpatients as compared to the general adolescent population. A total of 188 inpatients consecutively admitted to psychiatric adolescent inpatient unit were compared to a representative sample of 26,543 control adolescents screened for substance use by the Israel Anti-Drug Authority during the same time period. All illicit substances, except for opiates, were used in significantly higher rates by the inpatient sample. The distribution of the used psychoactive substances was different in the inpatient setting. Specific prevention and treatment programs must be developed in order to cope with this crucial clinical issue in these high-risk patients.
Somatic and germline mutations of the TSH receptor and thyroid diseases

The TSH receptor (TSH-R) belongs to the superfamily of Gprotein-coupled receptors (GPCRs) (Nagayama & Rapoport, 1992; Vassart & Dumont, 1992), in a subfamily whose prototypic members are rhodopsin and adrenergic receptors (Helmreich & Hofmann, 1996). A common characteristic of GPCRs is the presence of seven transmembrane segments, subdividing the molecules into an extracellular domain (aminoterminal segments plus three extracellular loops), a transmembrane barrel (seven a helices) and an intracytoplasmic domain (three intracytoplasmic loops plus the carboxylterminal segment). Together with the other glycoprotein hormone receptors (LH/CG-R and FSH-R), the TSH-R is characterized by a particularly long aminoterminal segment (398 residues), which is responsible for high affinity binding of TSH (Parmentier et al., 1989). The intracytoplasmic domain of GPCRs contains the site(s) of interactions with G proteins, the transducers between activated receptors and the various effectors (O'Dowd et al., 1988). In human thyroid cells TSH-R interacts functionally with the Gs and Gq proteins (Fig. 1): the TSH-R is preferentially coupled to Gs leading to a stimulation of the cyclic AMP (cAMP) cascade, but at higher thyrotropin concentrations the TSH-R is also coupled to Gq, leading to the activation of the phospholipase C cascade and thus stimulating the production of diacylglycerol and inositolphosphate (IP3) (Laurent et al., 1987). As activation of phospholipase C pathway requires concentration of TSH five to 10 times higher than those needed for activation of the cAMP pathway, it is generally accepted that the main effect of TSH on the thyroid gland is to control cAMP concentrations. The cAMP pathway has been shown to positively control the function (thyroid hormones secretion) and growth of thyrocytes whereas the phospholipase C pathway is principally involved in control of iodination and thyroid hormone synthesis (Dumont et al., 1992)(Fig. 1). Because the cAMP cascade has a central role in thyroid cell function and proliferation, it is expected that interruption or inappropriate stimulation of this cascade could lead to various thyroid diseases.
Disparities in the Age-Related Rates of Colorectal Cancer in the United States

The incidence of colorectal cancer (CRC) among Americans under the age of 50 years is increasing. The purpose of this study was to identify racial and socioeconomic disparities associated with this trend. The National Cancer Data Base was used to identify patients with CRC from 1998 to 2011. Patients were stratified by age (<50 versus >60 years), with ages 50 to 60 years omitted from the analysis to minimize overlapping trends between the two age groups. Relative frequencies (RFs) by year were plotted against demographic variables. Changes in RF over time and intervals from diagnosis to treatment (including surgery and chemotherapy) were compared. A total of 1,213,192 patients were studied; 885,510 patients with colon cancer and 327,682 with rectal or rectosigmoid cancer. Patients <50 years had higher RF for stage III/IV CRC compared with >60 years, with the highest rate of increase in stage III colon cancer (0.198% per year). Patients <50 years had higher RF for CRC if they were African-American or Hispanic. Hispanic patients <50 years had the highest rates of increase for both colon (RF = 0.300% per year) and rectal cancer (RF = 0.248% per year). Compared with race, other variables including education and income were not found to have as strong an association on age-related rates of CRC. No clinically significant differences were observed for time from diagnosis to treatment in either age group. Important racial disparities are associated with differences in age-related CRC rates, warranting further investigation to develop improved strategies for the earlier detection of CRC in these populations.
Review: IT-Dependent Strategic Initiatives and Sustained Competitive Advantage: A Review and Synthesis of the Literature

The role of information systems in the creation and appropriation of economic value has a long tradition of research, within which falls the literature on the sustainability of IT-dependent competitive advantage. In this article, we formally define the notion of IT-dependent strategic initiative and use it to frame a review of the literature on the sustain- ability of competitive advantage rooted in information systems use. We offer a framework that articulates both the dynamic approach to IT-dependent strategic advantage currently receiving attention in the literature and the underlying drivers of sustainability. This framework models how and why the characteristics of the IT-dependent strategic initiative enable sustained competitive advantage, and how the determinants of sustainability are developed and strengthened over time. Such explanation facilitates the pre-implementation analysis of planned initiatives by innovators, as well as the post-implementation evaluation of existing initiatives so as to identify the basis of their sustainability. In carrying out this study, we examined the interdisciplinary literature on strategic information systems. Using a structured methodology, we reviewed the titles and abstracts of 648 articles drawn from information systems, strategic management, and marketing literature. We then examined and individually coded a relevant subset of 117 articles. The literature has identified four barriers to erosion of competitive advantage for IT-dependent strategic initiatives and has surfaced the structural determinants of their magnitude. Previous work has also begun to theorize about the process by which these barriers to erosion evolve over time. Our review reveals that significant exploratory research and theoretical development have occurred in this area, but there is a paucity of research providing rigorous tests of theoretical propositions. Our work makes three principal contributions. First, it formalizes the definition of IT-dependent strategic initiative. Second, it organizes the extant interdisciplinary research around an integrative framework that should prove useful to both research and practice. This framework offers an explanation of how and why IT-dependent strategic initiatives contribute to sustained competitive advantage, and explains the process by which they evolve over time. Finally, our review and analysis of the literature offers the basis for future research directions.
Size selectivity of escape holes in conger tube traps for inshore hagfish Eptatretus burgeri and white-spotted conger Conger myriaster in Tokyo Bay

In Tokyo Bay, conger tube-trap fishers voluntarily deployed escape holes of at least 13 mm diameter to reduce the by-catch of young conger smaller than the marketable size of 35 cm total length. Comparative fishing experiments in Tokyo Bay were carried out using tube traps with seven hole diameters (3, 9, 13.5, 14, 15, 17, and 19 mm), to obtain the size-selectivity of the escape-hole size for inshore hagfish Eptatretus burgeri and white-spotted conger Conger myriaster. On the assumption of the geometrical similarity in the combination of body g and hole perimeter m at a given retention probability, a single master curve s(R)=exp(−13.52+11.31R)/(1+exp[−13.52+11.31R]) was estimated for the two species in terms of relative R=g/m using the Share Each LEngth’s Catch Total (SELECT) process based on a multinomial distribution. Almost all conger and hagfish with a girth equivalent to the hole perimeter were able to pass through the hole. Thus, the two species have a high ability to escape through a narrow space by squeezing the body through the hole in the rigid PVC tube. Optimum escape-hole size is discussed from several objectives for conger tube-trap fishery management, e.g. reduction of hagfish by-catch. This study also specifies the conditions for pooling data when fishing experiments using more than two fishing gears are replicated.
Heavy metals in aromatic spices by inductively coupled plasma-mass spectrometry

ABSTRACT Objective of this study was to determine the content of Cd, Hg, As and Pb in common spices traded in the Italian market, using inductively coupled plasma-mass spectrometry (ICP-MS). The results were compared with the maximum limits established by the national Legislative Decree (LD) no. 107 implementing the Council Directive 88/388/EEC and by international organisations, such as Food and Agriculture Organization (FAO) and World Health Organization (WHO). Food safety for spices was assessed considering the tolerable weekly intake (TWI) and the provisional tolerable weekly intake (PTWI), respectively, for Cd and Hg and the 95% lower confidence limit of the benchmark dose of 1% extra risk (BMDL01) for As and Pb. Investigated elements in all samples were within the maximum limits as set by the national and international normative institutions. Nevertheless, the heavy metal content of some spices exceeded the PTWI, TWI and BMDL01, which needs attention when considering consumer’s health.
Atopic eczema in children: another harmful sequel of divorce

Background: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children.
Agro-Ecology for Potential Adaptation of Horticultural Systems to Climate Change: Agronomic and Energetic Performance Evaluation

Adaptation can be a key factor that will shape the future severity of climate change impacts on food production. The objective of this study was to assess the suitability of an agro-ecological approach based on various techniques as potential adaptation strategy in organic horticultural systems. A long-term field experiment was set up in Southern Italy, combining: (i) appropriate soil surface shaping; (ii) cash crop rotation; (iii) agro-ecological service crops (ASC) introduction as living mulch and complementary crops; (iv) tailored organic fertilization; and (v) alternative tillage strategies. In this paper, the first two-year results on cauliflower (Brassica oleracea L.) and tomato (Solanum lycopersicum L.) crops, as well as energy consumptions through the Energy Analysis (EA) method are reported. Due to the climatic conditions that occurred, which were characterized by the absence of extreme climatic events (particularly rainfall), it was not possible to verify if the designed experimental device was able to mitigate the impact of climate change, whereas the EA indicated that total energy inputs were lower when ASC are introduced in cropping systems.
Flow of nitrogen from the rumen and abomasum in cattle and sheep given protein-free nutrients by intragastric infusion

1. Three experiments were conducted to determine the flow of nitrogen through the rumen and abomasum when cows, steers and lambs were totally nourished on volatile fatty acids infused into the rumen. 2. In two dairy cows (650–700 kg) and two large steers (370–405 kg) the daily flow of non-ammonia-N (NAN) from the rumen was 50.7 and 58 mg/kg live weight (W)0.75 respectively. 3. The flows of NAN through the rumen and abomasum in four young steers (240 315 kg) were 85.0 (SE 21.0) and 195 (SE 7.0) mg/kg W0.75 respectively. 4. In the third experiment the effects of altering rumen pH and osmotic pressure on flow of NAN through the rumen and abomasum were investigated in lambs. While rumen pH and osmotic pressure influenced rumen volume and outflow they had no significant effect on NAN flow. The mean values for NAN outflow from the rumen and abomasum were 76 and 181 mg N/kg W0.75 respectively. 5. Abomasal NAN flow increased with increasing abomasal pH. When osmotic pressure was greater than about 330 mosmol/l in the rumen there was a net inflow of water, while below this value there was net loss of water. 6. For all experiments the flow of N both from the rumen and abomasum was highly variable; this has to be considered if a constant value is used for endogenous N in estimating dietary N in the abomasum. 7. With N-free infusion the rumen NHa concentration varied from 50 to 120 mg NHa-N/I. 8. The amino acid composition of rumen and abomasal N was also determined. Relative to tissue Nit contained a higher proportion of cysteine.
Using Contextual Analyses to Examine the Meaning of Neuropsychological Variables Across Samples of English-Speaking and Spanish-Speaking Older Adults

Abstract The meanings of several target neuropsychological variables, including measures of executive functioning, were examined using contextual analysis across a sample of English-speakers and a sample of Spanish-speakers. Results of the contextual analysis, which examined the contributions of the latent constructs of memory, psychomotor speed, visual spatial ability, and knowledge and comprehension, to the target neuropsychological variables indicate that each of the target variables likely reflects the unique contribution of several reference abilities. These findings provide evidence that the neuropsychological variables are multi-dimensional. The patterns of relations were similar across the samples of English and Spanish speakers. (JINS, 2012, 18, 223–233)
Comment on “New therapeutic agents in diabetic nephropathy”

Correspondence to Alain Gay, M.D. Bayer AG, Mullerstrasse, 178, Berlin 13342, Germany Tel: +49-3046-8192003 Fax: +49-3046-8992003 E-mail: alain.gay@bayer.com We have read with great interest the article “New therapeutic agents in diabetic nephropathy” Korean J Intern Med 2017;32:11-25 by Yaeni Kim and Cheol Whee Park [1]. The authors stated that ‘the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) trial using mineralocorticoid receptor blockers (MT-3995, BAY 94-3995, and BAY 94-8862) has shown limited efficacy in the early stages of diabetic nephropathy and concerns regarding the development of hyperkalemia need to be addressed. This statement is not correct because: (1) the PRIORITY study is still ongoing, the results have not been reported yet [2]; (2) secondly the drug being tested is this research is spironolactone and not MT-3995, BAY 94-3995, and BAY 94-8862; and (3) BAY 94-3995 does not exist. If the authors would rather refer to BAY 94-8862 then we would like to underline the following: BAY 94-8862 has now an INN (international nonproprietary name) which is finerenone. Finerenone has shown in a phase IIb study in patients with diabetic kidney disease (DKD) a significant and dose-dependent reduction of urine albumin-to-creatinine ratio after 90 days. Hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10 mg groups; the incidence was 3.2% in the 15 mg group and ≤ 2.2% in all other finerenone groups. Therefore, the risk of hyperkalaemia was low in patients with DKD who received finerenone for 90 days in addition to standard of care [3]. We hope that the authors will correct their publication accordingly.
Methods for compensation of the light attenuation with depth of images captured by a confocal microscope

A confocal laser scanning microscope (CLSM) enables us to capture images from a biological specimen in different depths and obtain a series of precisely registered fluorescent images. However, images captured from deep layers of the specimen may be darker than images from the topmost layers because of light loss distortions. This effect causes difficulties in subsequent analysis of biological objects. We propose a solution using two approaches: either an online method working already during image acquisition or an offline method assisting as a postprocessing step. In the online method, the gain value of a photomultiplier tube of a CLSM is controlled according to the difference of mean image intensities between the reference and currently acquired image. The offline method consists of two stages. In the first stage, a standard histogram maintaining relative frequencies of gray levels and improving brightness and contrast is created from all images in the series. In the second stage, individual image histograms are warped according to this standard histogram. The methods were tested on real confocal image data captured from human placenta and rat skeletal muscle specimens. It was shown that both approaches diminish the light attenuation in images captured from deep layers of the specimen. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Axillary Surgery in Breast Cancer Management: Background, Incidence and Extent of Nodal Spread, Extent of Surgery and Accurate Axillary Staging, Surgical Procedures

The prime objectives of axillary surgery in the management of breast cancer are 1) accurate staging, 2) treatment to cure and 3) quantitative information of metastatic lymph nodes for prognostic purposes and allocation to adjuvant protocols. It is generally agreed that axillary node status in potentially curable breast cancer is considered the single best predictor of outcome and the main determinant of allocation to adjuvant therapy. No physical examination, no imaging techniques, and no molecular biologic markers can today replace axillary surgery for staging purposes. The objectives of axillary surgery are best obtained by carrying out a complete axillary clearance. Nonetheless, less radical surgery is generally performed by carrying out a sampling procedure with a yield of about 4 nodes or a partial axillary dissection level I-II with at least 10 nodes recovered. Understaging the axilla is detrimental to outcome and, furthermore, locoregional tumor control is important for survival. Axillary surgery should therefore be conducted in accordance with high professional standards.
Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis

The goal of this study was to use bioengineered injectable microgels to enhance the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix repair in a reversible animal model of osteoarthritis (OA). A module of perlecan (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo. Articular cartilage damage was induced in mice using a reversible model of experimental OA and was treated by intra-articular injection of PlnD1-HA particles with BMP2 bound to HS. Control injections consisted of BMP2-free PlnD1-HA particles, HA particles, free BMP2 or saline. Knees dissected following these injections were analyzed using histological, immunostaining and gene expression approaches. Our results show that knees treated with PlnD1-HA/BMP2 had lesser OA-like damage compared to control knees. In addition, the PlnD1-HA/BMP2-treated knees had higher mRNA levels encoding for type II collagen, proteoglycans and xylosyltransferase 1, a rate-limiting anabolic enzyme involved in the biosynthesis of glycosaminoglycan chains, relative to control knees (PlnD1-HA). This finding was paralleled by enhanced levels of aggrecan in the articular cartilage of PlnD1-HA/BMP2-treated knees. Additionally, decreases in the mRNA levels encoding for cartilage-degrading enzymes and type X collagen were seen relative to controls. In conclusion, PlnD1-HA microgels constitute a formulation improvement compared to HA for efficient in vivo delivery and stimulation of proteoglycan and cartilage matrix synthesis in mouse articular cartilage. Ultimately, PlnD1-HA/BMP2 may serve as an injectable therapeutic agent for slowing or inhibiting the onset of OA after knee injury.