Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Pdgfrb‐Cre transgenic mice reveals reduction of ROSA26 reporter activity in remodeling arteries

With the intention to modulate gene expression in vascular mural cells of remodeling vessels, we generated and characterized transgenic mouse lines with Cre recombinase under the control of the platelet‐derived growth factor receptor‐β promoter, referred to as Tg(Pdgfrb‐Cre)35Vli. Transgenic mice were crossed with the Gt(ROSA)26Sortm1Sor strain and examined for Cre activation by β‐galactosidase activity, which was compared with endogenous Pdgfrb expression. In addition, Pdgfrb‐Cre mice were used to drive expression of a conditional myc‐tagged Cthrc1 transgene. There was good overlap of β‐galactosidase activity with endogenous Pdgfrb immunoreactivity. However, dedifferentiation of vascular mural cells induced by carotid artery ligation revealed a dramatic discrepancy between ROSA26 reporter activity and Pdgfrb promoter driven Cre dependent myc‐tagged Cthrc1 transgene expression. Our studies demonstrate the capability of the Pdgfrb‐Cre mouse to drive conditional transgene expression as a result of prior Cre‐mediated recombination in tissues known to express endogenous Pdgfrb. In addition, the study shows that ROSA26 promoter driven reporter mice are not suitable for lineage marking of smooth muscle in remodeling blood vessels. genesis 49:673–680, 2011. © 2011 Wiley‐Liss, Inc.
Lack of microsatellite instability in gastrointestinal stromal tumors

The microsatellite instability (MSI) phenotype may constitute an important biomarker for patient response to immunotherapy, particularly to anti-programmed death-1 inhibitors. MSI is a type of genomic instability caused by a defect in DNA mismatch repair (MMR) proteins, which is present mainly in colorectal cancer and its hereditary form, hereditary nonpolyposis colorectal cancer. Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor α (PDGFRA), which are oncogenes that predict the response to imatinib mesylate. In addition to KIT/PDGFRA mutations, other molecular alterations are important in GIST development. In GISTs, the characterization of the MSI phenotype is scarce and the results are not consensual. The present study aimed to assess MSI in a series of 79 GISTs. The evaluation of MSI was performed by pentaplex polymerase chain reaction comprising five markers, followed by capillary electrophoresis. The expression of MMR proteins was evaluated by immunohistochemistry. Regarding the KIT/PDGFRA/B-Raf proto-oncogene, serine/threonine kinase molecular profile of the 79 GISTs, 83.6% of the tumors possessed KIT mutations, 10.1% had PDGFRA mutations and 6.3% were triple wild-type. The mutated-PDGFRA cases were associated with gastric location and a lower mitotic index compared with KIT-mutated and wild-types, and these patients were more likely to be alive and without cancer. MSI analysis identified 4 cases with instability in one marker, however, additional evaluation of normal tissue and immunohistochemical staining of MMR proteins confirmed their microsatellite-stable nature. The results of the present study indicated that MSI is not involved in GIST tumorigenesis and, therefore, cannot serve as a biomarker to immunotherapy response in GIST.
Signaling Mechanism of HIV-1 gp120 and Virion-Induced IL-1β Release in Primary Human Macrophages1

HIV-1 envelope glycoprotein gp120 induces, independently of infection, the release of proinflammatory cytokines, including IL-1β from macrophages, that are implicated in the pathogenesis of HIV-associated dementia. However, the signal transduction pathways involved have not been fully defined. Previously, our laboratory reported that soluble gp120 activates multiple protein kinases in primary human monocyte-derived macrophages, including the Src family kinase Lyn, PI3K, and the focal adhesion-related proline-rich tyrosine kinase Pyk2. In this study we showed that gp120 induces IL-1β release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to Giα protein. Using pharmacological inhibitors and small interfering RNA gene knockdown, we demonstrated that concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1β production. By coimmunoprecipitation and immunofluorescence confocal microscopy, we showed that CCR5 activation by gp120 triggered the assembly of a signaling complex involving endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn. Finally, we demonstrated that virion-associated gp120 induced similar response, as structurally intact whole virions also triggered IL-1β release and re-localization of PI3K and Pyk2. This study identifies a novel signaling mechanism for HIV-1-induced IL-1β production by primary human macrophages that may be involved in the neuropathogenesis of HIV-associated dementia.
Predictors of Surgery and Consult with an Oncologist for Adjuvant Chemotherapy in Early Stage NSCLC Patients in Alberta, Canada

Introduction: In the fall of 2004, adjuvant chemotherapy for early stage non-small cell lung cancer (NSCLC) patients was approved for coverage by the Alberta Cancer Board, the provincial agency responsible for systemic therapy in the province of Alberta. The purpose of this study was to measure the proportion of early stage NSCLC patients diagnosed between 2004 and 2006 that received surgery and subsequently had a consult with an oncologist at a cancer facility, and to identify factors related to receiving surgery and having a consult that could be addressed. Methods: A retrospective observational study was conducted. All patients diagnosed with stage IB, IIA, or IIB NSCLC in Alberta from 2004 to 2006 were identified from the Alberta cancer registry. Date of definitive surgery, gender, age at diagnosis, and area of residence were also obtained from the cancer registry and evaluated as predictors for surgery and oncology consult. Date of consult with an oncologist was obtained from the electronic medical record of the Alberta Cancer Board. Results: There were 561 patients diagnosed with stage IB–IIB NSCLC from 2004 to 2006, 352 of whom had surgery and 255 of whom subsequently had a consult with an oncologist. Age and residence at diagnosis were both strongly associated with the likelihood of receiving surgery and the likelihood of attending a consult with an oncologist. Discussion: Several areas of further research have been identified by this study including age and rural residence on treatment/referral patterns.
Red cell distribution width predicts new-onset atrial fibrillation after coronary artery bypass grafting

Abstract Introduction. Red cell distribution width (RDW) has been associated with poor outcomes in patients with cardiovascular diseases. However, little is known about the role of RDW in prediction of new-onset atrial fibrillation (AF) after coronary artery bypass grafting (CABG). We aimed to investigate the relation between the RDW and postoperative AF in patients undergoing CABG. Methods. A total of 132 patients undergoing nonemergency CABG were included in the study. Patients with previous atrial arrhythmia or requiring concomitant valve surgery were excluded. We retrospectively analyzed 132 consecutive patients (mean age, 60.55 ± 9.5 years; 99 male and 33 female). The RDW level was determined preoperatively and on postoperative Day 1. Results. Preoperative RDW levels were significantly higher in patients who developed AF than in those who did not (13.9 ± 1.4 vs. 13.3 ± 1.2, p = 0.03). There was not any correlation between postoperative RDW levels and AF. Using a cutpoint of 13.45, the preoperative level correlated with the incidence of AF with a sensitivity of 61% and specificity of 60%. Conclusion. Preoperative RDW level predicts new-onset AF after CABG in patients without histories of AF.
O brother, where art thou? The fraternal birth-order effect on male sexual orientation.

Sigmund Freud has a lot to answer for. As the 20th century began, he convinced medical professionals that abnormal family relationships caused children to develop a homosexual orientation, which could be “cured” by psychoanalysis. Not until the 1970s would psychiatric and psychological associations finally repudiate this idea that gay people have any illness that needs treating. Since then, a host of reports bolster the idea that prenatal events, rather than family relations, affect the likelihood that a person will grow up to be straight or gay. For example, for each additional brother that precedes him, a boy’s chance of growing up to be gay increases by a third. If Freud had known that, he might have suggested that the presence of older brothers shifts family dynamics, subjecting the youngest son to a social milieu that leads to homosexuality. However, in this issue of PNAS, Anthony Bogaert (1) provides evidence that the social influence of an older brother is irrelevant to whether his younger brother will develop a homosexual orientation. It is the number of older biological brothers the mother carried, not the presence of older brothers while growing up, that makes some boys grow up to be gay. Older stepbrothers in the home have no effect, although older biological brothers raised apart still exert their influence. These data, by elimination, strengthen the notion that the common denominator between biological brothers, the mother, provides a prenatal environment that fosters homosexuality in her younger sons.
Kohonen Neural Networks and Language

Kohonen neural networks are a type of self-organizing network that recognizes the statistical characteristics of input datasets. The application of this type of neural network to language theory is demonstrated in the present note by showing three brief applications: recognizing word borders, learning the limited phonemes of one's native tongue, and category-specific naming impairments.
Interpreting nurses' responses to clinical documentation alerts.

OBJECTIVE To understand how nurses respond to alerts that detect attempts to enter into electronic health records patient weights that vary significantly from previously recorded weights. METHODS Examination of subsequent patient weights to determine if the alerts were true positive (TP) or false positive (FP), and whether nurses overrode alerts, changed their entry or quit without storing a value. RESULTS Alerts occurred 2.74%, with 41.9% TP and 58.1% FP. Nurses overrode 30.3% of TP and 97.3% of FP alerts. CONCLUSIONS The alert has an acceptable FP rate and does not appear to cause nurses to change entries to satisfy the alert. The alert improves recording of patient weights.
HUBUNGAN KEMAMPUAN MEMBACA PEMAHAMAN DENGAN KEMAMPUAN MEMAHAMI SOAL CERITA MATEMATIKA SEKOLAH DASAR

Kemampuan membaca mutlak dimiliki siswa karena keterampilan membaca besar manfaatnya untuk mempelajari bidang studi lain. Dalam membaca terkandung prinsip yaitu memahami inti yang dibaca atau menemukan isi bacaan. Hal ini sesuai dengan salah satu komponen pembelajaran di SD khususnya tingkat tinggi yaitu membaca pemahaman. Kemampuan membaca pemahaman adalah kesanggupan siswa untuk memahami suatu bacaan yang meliputi kesanggupan memahami makna kata, makna kalimat, isi pokok paragraf, dan isi bacaan. Kemampuan membaca pemahaman bermanfaat pada Mata Pelajaran Matematika, khususnya soal cerita yang disajikan dalam bentuk kalimat-kalimat verbal dan menanyakan kuantitas-kuantitas tertentu. Untuk itu diperlukan kemampuan memahami bacaan dari soal cerita. Kemampuan membaca pemahaman dapat mempengaruhi kemampuan dalam menyelesaikan masalah matematika. Masalah matematika dikemas dalam bentuk soal cerita yang berkaitan dengan kehidupan sekitar siswa, sehingga siswa harus membaca teks soal cerita terlebih dulu sebelum menyelesaikan soal tersebut. Teks bacaan yang harus dibaca terlebih dahulu dan kesulitan dalam mengubah kalimat bahasa ke dalam kalimat matematika yang membuat siswa merasa jenuh saat menyelesaikan soal cerita
Maternal Child‐Rearing Behaviors and Correlates in Rural Minority Areas of Yunnan, China

&NA; An epidemiological survey of maternal child‐rearing behaviors was conducted in the rural minority areas of Yunnan, China. An interview of 2019 rural mothers of Hani, Yi, Hui, Miao, and Han and 544 urban mothers with children younger than 7 years of age showed that 51.7% of these rural mothers placed their infants in swaddling clothes. In the rural sample, exclusive breastfeeding occurred at frequency rates of 76.7% and 34.2% during 3 and 6 months postpartum, respectively Maternal training and playing behaviors were reported less frequently, whereas physical punishment for children's misbehavior was more commonly found in the childrearing behavior of rural mothers. Maternal child‐rearing behaviors differed significantly among ethnic groups as well as between urban and rural areas. Maternal child‐rearing behaviors were significantly associated with maternal education level, family type, family income, maternal age at delivery, and number of children in the family. Children's gender had no significant association with maternal child‐rearing behaviors.
Plug Flow Cytometry

Although flow cytometry has the powerful ability to rapidly screen large collections of cells, the technology has yet to be efficiently applied to large‐scale screening operations involving multiple discrete suspensions. High‐throughput flow cytometry would be beneficial to many areas of biological investigation, such as modern drug discovery, which involves testing of cellular targets against millions of potentially valuable compounds. The authors have developed a flow injection analysis approach to automated sample handling in which individual sample suspensions are sequentially inserted as plugs of precisely defined volumes into a flowing fluid which delivers them to the laser beam. The unit describes the basic elements and concepts of this plug flow system and discusses representative applications.
Heterozygous Avellino Corneal Dystrophy 9 Years After Photorefractive Keratectomy: Natural or Laser-Induced Accelerated Course?

Purpose: To report a photorefractive keratectomy (PRK)-treated patient who first developed stromal opacities with a typical granular pattern 9 years after surgery, which was confirmed as heterozygous Avellino dystrophy by DNA analysis. Methods: A 37-year-old woman, who had undergone PRK 17 years ago, has been followed for glaucoma and corneal dystrophy. She had preoperative clear corneas in both eyes. Results: Nine years after PRK, at the age of 29 years, 2-3 small, white, anterior stromal corneal opacities were first detected in both eyes. Seventeen years postoperatively, multiple anterior stromal corneal deposits with a dot, crumb, or snowflake appearance were noted to the same degree in both eyes. The intervening cornea was relatively clear. Her DNA was heterozygous for the R124H mutation. Conclusions: Slowly developing, mild corneal deposits occurred after PRK in this patient with heterozygote Avellino corneal dystrophy. Various clinical manifestations can occur after excimer laser refractive surgery in patients with Avellino corneal dystrophy.
Temperature Guided Radiofrequency Catheter Ablation of Myocardium: Comparison of Catheter Tip and Tissue Temperatures In Vitro

Temperature monitoring during RF ablation has been proposed as a means of controlling the creation of the lesion. However, in vivo studies have shown poor correlation between lesion size and catheter tip temperature. Thus, we hypothesized a difference between catheter tip and tissue temperatures during RF catheter ablation, and that this difference may depend on flow passing the ablation site, tip electrode length, and catheter‐tissue orientation. In vitro studies were performed using four different ablation catheters (tip electrode length: 2, 4. or 6 mm) with a thermistor or a thermocouple as temperature sensor. Set temperature was 70°C and pulse duration was 30 seconds. Pieces of porcine left ventricle were immersed in a bath of isotonic saline‐dextrose solution at 37°C. The ablation catheters were positioned perpendicularly, obliquely, or parallel to the endocardium. A temperature sensor was inserted from the epicardial side and positioned 1 mm beneath the catheter‐tissue interface. Experiments were made with a flow of 200 mL/min passing the ablation site or with no flow. The catheter tip and tissue temperatures differed significantly (P < 0.0001) during ablation. This difference increased with time, with flow passing the ablation site, with the length of the tip electrode, and when the catheter was positioned perpendicularly or obliquely to the endocardium as compared to the parallel catheter‐tissue orientation (P < 0.05), In conclusion, the tissue temperature may far exceed the catheter tip temperature, and intramyocardial superheating resulting in steam formation and popping may occur despite a relatively low catheter tip temperature. (PACE 1997; 20[Pt. I]:1252‐1260)
Nutrition and Multiple Organ Failure

Normal cellular homeostasis is dependent on adequate oxygenation, substrate delivery and excretion of metabolites. The development of modern medicine has experienced a remarkable progress of knowledge in this area over the recent decades. Circulatory and respiratory support modalities for critically ill patients have been developed due both to increased understanding of cellular and organ metabolism and to improved technology. Improvements are dependent on both artificial organs and supportive modalities including drug therapy. Such basal devices provide means by which the cellular supply of oxygen, energy and excretion of metabolites are fulfilled. The progress in nutrition research also represents a giant step forward including decreased morbidity and improved therapeutic outcome in patients suffering from a variety of disorders such as injury, infection with septic complications and eventual multiple organ failure (Baue, 1991 ; Phelps et al. 1991). For several reasons it has, however, been difficult to confirm or demonstrate the role of nutrition in itself to predict outcome in severely ill patients. There are several reasons for this : the difficulty of conducting controlled studies in patients with life-threatening disorders, the heterogeneity of patients treated in intensive care units, and the ignorance of modern principles in clinical studies with appropriately designed protocols (Friedman et al. 1981). Intravenous nutrition was developed when it was recognized that patients without early and uncomplicated recovery suffered from progressive starvation leading to the appearance of complications such as increased susceptibility to infection and impaired wound healing. Such observations have since then been repeatedly confirmed by systematic evaluation in
The influence of diltiazem and nifedipine on renal function in the rat

1 The effect of intravenous administration of the calcium‐entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone‐anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. 2 Diltiazem was infused at 5, 10 and 20 μg kg−1 min−1. Blood pressure did not change following 5 μg kg−1 min−1 diltiazem but was significantly reduced, by 12 mmHg, after 10 μg kg−1 min−1 and by 17 mmHg after 20 μg kg−1 min−1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. 3 Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 μg kg−1 min−1 diltiazem, 20% and 24% respectively, by 10 μg kg−1 min−1 diltiazem, but were unchanged by 20 μg kg−1 min−1. 4 Infusion of nifedipine at 0.5, 1.0 and 2.0 μg kg−1 min−1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 μg kg−1 min−1 only, while g.f. r. did not change at any dose. 5 Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 μg kg−1 min−1 nifedipine, 127%, 197% and 194% respectively, by 1.0 μg kg−1 min−1, while these variables remained unchanged by a dose of 2.0 μg kg−1 min−1. 6 These data show that doses on diltiazem and nifedipine, which had little or no effect on blood pressure, had minimal actions on renal haemodynamics. However, at 5 and 10 μg kg−1 min−1 diltiazem and 0.5 and 1.0 μg kg−1 min−1 nifedipine these compounds exhibited direct tubular actions, causing both a diuresis and natriuresis, while at the highest dose of each drug these actions were masked by a concomitant reduction in blood pressure.
Essential Trace Element and Mineral Deficiencies and Cardiovascular Diseases: Facts and Controversies

Deficiencies of minerals and trace elements are common and widespread, and are associated with adverse cardiovascular endpoints. Emerging evidence indicates that, diet rich in these nutrients constitutes a modifiable lifestyle factor that might reduce the risk of cardiovascular disease (CVD). However, the clinical significance of these nutrients in optimizing cardiovascular health and/or ameliorating cardiovascular pathologies is currently debatable. This review aims to explore evidences in favor or against the role of these nutrients in the pathogenesis, progression, management and endpoints of CVDs, and extend the discussion on some discrepant research findings. Literature search was conducted in PubMed, Medline, Scopus and EMBASE databases on studies published in English between 1963 and 2016 using appropriate terms such as minerals, Trace elements, Chromium, Copper, Iron, Magnesium, Selenium, Manganese, Zinc deficiencies and CVD. Indeed, trace elements and minerals play significant cardio protective roles when they are present in adequate pharmacologic concentrations due to their antioxidant, anti-inflammatory and immune function modulatory activities. The discrepant results recorded in some studies could be due to the effects of several poorly adjusted covariates such as interactions between paired/complementary micronutrients, absence of uniformly accepted cut off values for normal range, individual susceptibility and environmental factors and several methodology inadequacies. Supplementation of these nutrients in pharmacologic doses in high-risk individuals or those with known deficiency states is cardioprotective.