Miracle-dz/UniFAR-FTUs huggingface dataset:
Different inflammatory mechanisms in lungs of severe and mild asthma: crosstalk of NF‐kappa‐B, TGFβ1, Bax, Bcl‐2, IL‐4 and IgE

Objective: To examine differences in the apoptotic, inflammatory, allergic and immunological features in the lungs of adults with asthma. Material and methods: Thirty‐six patients with mild asthma (MA), 16 with severe asthma (SA) and 20 healthy volunteers (HVs) were enrolled. Bronchoalveolar lavage fluid (BALF) was processed into cell‐free fluid for enzyme‐linked immunosorbent assay detecting soluble TGFβ1, IL‐4 and IgE and BALF lymphocytes for immunocytochemical staining of cellular Bax, Bcl‐2 and nuclear factor‐Kappa‐B (NFκB). Results: Cellular NFκB expression was higher in SA than in MA and HVs, while extracellular TGFβ1 was high in both the SA and MA groups but low in the HVs. Bcl‐2/Bax ratio was higher in SA than in MA and in MA than in HV groups and correlated significantly with NFκB level. Interestingly, the levels of IgE and, to a lesser extent, IL‐4 were higher in MA than in SA and both were much higher than in HVs, and were inversely correlated with NFκB level in the SA group and with TGFβ1 level in the MA group. Conclusions: NFκB has a central role in the perpetuation of persistent inflammation in SA and might induce apoptosis via Bcl‐2. The SA group appears not associated much with allergen‐based IgE and IL‐4 reactions as efficiently as in MA. This was supported by the lower levels of IgE and IL‐4 in SA compared to MA. TGFβ1 appears to be associated with asthma pathogenesis, especially allergen‐based MA.
Developing an Evidence-Based, Nurse-Led Psychoeducational Intervention With Peer Support in Gynecologic Oncology

Background: The physical and psychosocial impact of radiotherapy for gynecologic cancer requires complex interventions to address treatment-related, psychosocial, and psychosexual and survivorship needs. A multidisciplinary approach is required to address these needs, but standard practice is varied and lacks a sound evidence base. Objective: The aim of this study was to describe the process of development and pilot testing of a novel evidence-based, complex psychoeducational intervention aiming to improve psychosocial outcomes for gynecologic-oncology patients treated curatively with radiotherapy. Methods: The intervention combines tailored nursing consultations with telephone peer support pretreatment, midtreatment, end of treatment, and posttreatment. The UK Medical Research Council framework for developing complex interventions was used to produce an evidence-based, feasible, and acceptable intervention. Results: Intervention manuals and study materials were informed by literature reviews of best-available evidence, relevant theory, and iterative consumer and expert consultations. The nurse manual specified content for consultations providing self-care information, coaching tailored to individual needs, and multidisciplinary care coordination. The peer manual described phone consultations aimed at providing psychosocial support and encouraging adherence to self-care strategies. Three peers and 1 nurse underwent rigorous skills and knowledge-based intervention delivery training. The intervention was pilot tested with 6 patients. Qualitative feedback led to minor design and content changes. Conclusions: The intervention was found to be feasible, relevant, and acceptable to participants and clinicians and is currently being tested in a national randomized controlled trial (PeNTAGOn). Implications for Practice: The Medical Research Council framework is useful in developing nursing interventions. The specific methods and strategies described are useful for designing future complex studies targeting patient supportive care.
Specific Activation of mTORC1 by Rheb G-protein in Vitro Involves Enhanced Recruitment of Its Substrate Protein*

Rheb G-protein plays critical roles in the TSC/Rheb/mTOR signaling pathway by activating mTORC1. The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTORC1 immunoprecipitated by the use of anti-raptor antibody from mammalian cells starved for nutrients. The low in vitro kinase activity against 4E-BP1 of this mTORC1 preparation is dramatically increased by the addition of recombinant Rheb. On the other hand, the addition of Rheb does not activate mTORC2 immunoprecipitated from mammalian cells by the use of anti-rictor antibody. The activation of mTORC1 is specific to Rheb, because other G-proteins such as KRas, RalA/B, and Cdc42 did not activate mTORC1. Both Rheb1 and Rheb2 activate mTORC1. In addition, the activation is dependent on the presence of bound GTP. We also find that the effector domain of Rheb is required for the mTORC1 activation. FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb-dependent activation of mTORC1 in vitro, because the preparation of mTORC1 that is devoid of FKBP38 is still activated by Rheb. The addition of Rheb results in a significant increase of binding of the substrate protein 4E-BP1 to mTORC1. PRAS40, a TOR signaling (TOS) motif-containing protein that competes with the binding of 4EBP1 to mTORC1, inhibits Rheb-induced activation of mTORC1. A preparation of mTORC1 that is devoid of raptor is not activated by Rheb. Rheb does not induce autophosphorylation of mTOR. These results suggest that Rheb induces alteration in the binding of 4E-BP1 with mTORC1 to regulate mTORC1 activation.
Mechanistic Evaluation of the Impact of Smoking and Chronic Obstructive Pulmonary Disease on the Nasal Epithelium

Chronic obstructive pulmonary disease (COPD) is one of the major causes of chronic morbidity and mortality worldwide. The development of markers of COPD onset is hampered by the lack of accessibility to the primary target tissue, and there is a need to consider other sample sources as surrogates for biomarker research. Airborne toxicants pass through the nasal epithelium before reaching the lower airways, and the similarity with bronchial histology makes it an attractive surrogate for lower airways. In this work, we describe the transcriptomics findings from the nasal epithelia of subjects enrolled in a clinical study focusing on the identification of COPD biomarkers. Transcriptomic data were analyzed using the biological network approach that enabled us to pinpoint the biological processes affected in the upper respiratory tract in response to smoking and mild-to-moderate COPD. Our results indicated that nasal and lower airway immune responses were considerably different in COPD subjects and caution should be exercised when using upper airway samples as a surrogate for the lower airway. Nevertheless, the network approach described here could present a sensitive means of identifying smokers at risk of developing COPD.
A methodology for evaluation time approximation

This paper describes a feed-forward neural network model (FFNNM) for complexity prediction of path related objective functions, mainly average path length (APL) of an arbitrary Boolean function (BF). The proposed model is determined by neural training process of evaluation time derived from the Monte Carlo data of randomly generated BFs. Experimental results show a good correlation between the ISCAS benchmark circuits and those predicted by the FFNNM. This model is capable of providing an estimation of the performance of a circuit prior to its final implementation.
Primary linitis plastica carcinoma of the colon and rectum

Background. Linitis plastica carcinoma (LPC) usually shows a scirrhous growth pattern with a severe stromal desmoplastic reaction. Another growth pattern showing lymphangiosis carcinomatosa rather than scirrhous growth pattern, however, was noted. This study was designed to clarify the clinical and pathologic characteristics of colorectal LPC.
A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that usually results in respiratory failure and death. Pirfenidone was approved as the first licensed therapy for IPF in Europe based on phase III trials where patients with a forced vital capacity (FVC) >50% of predicted were included. The aim of this study was to characterise patients treated with pirfenidone in Swedish clinical practice and to describe the adherence to the reimbursement restriction since reimbursement was only applied for patients with FVC below 80% of predicted. Methods This was a retrospective, observational chart review of IPF patients treated with pirfenidone from three Swedish university clinics. Patients initiated on treatment during the period 28 June 2012 to 20 November 2014 were included. Data on patient characteristics, basis of diagnosis, treatment duration, quality of life, and adverse drug reactions (ADRs) were collected from medical charts. Results Forty-four patients were screened and 33 were included in the study. The mean treatment duration from start of pirfenidone until discontinuation or end of study was 38 weeks. At the initiation of pirfenidone treatment, FVC was 62.7% (12.1) [mean (SD)], diffusion capacity (DLco) was 45.1% (13.8) of predicted, and the ratio of forced expiratory volume on 1 sec (FEV1) to FVC was 0.78 (0.1). The percentage of patients with an FVC between 50 and 80% was 87%. Ten of the patients had ADRs including gastrointestinal and skin-related events, cough and signs of impaired hepatic function, but this led to treatment discontinuation in only two patients. Conclusion Data from this chart review showed that adherence to the Swedish reimbursement restriction was followed in the majority of patients during the study period. At the start of pirfenidone treatment, lung function, measured as FVC, was lower in the present cohort of Swedish IPF patients compared with other registry and real-life data. About a third of the patients had ADRs, but discontinuation of the treatment because of ADRs was relatively uncommon.
Blind adaptive equalizer for IIR channels with common zeros

This paper considers the problem of blind adaptive equalization of single-input multiple-output IIR channels without requiring the channel diversity condition. That is, the parallel sub-channels in the fractionally sampled model can have common factors. We develop an equalizer based on IIR prediction of the received signal. The predictor parameters are estimated by using the recursive extended least squares (RELS) algorithm. It is proved that the adaptive equalizer is globally stable and the prediction error converges in a Cesaro sense almost sure (a.s.) (with probability one) towards a scalar multiple of the input symbol sequence
The effects of non-selective and cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs on heterotopic ossification in rats.

BACKGROUND Review of the literature revealed several experimental studies on the effects of selective COX-2 inhibitors on fracture healing, but no reports were encountered regarding the effects of these compounds on experimental heterotopic bone formation, so the present study was conducted. MATERIAL/METHODS Thirty adult male Wistar rats were divided into three groups of ten animals each. Tibial and femoral bones were collected from the rats, cleaned and demineralized, and diaphyseal parts were implanted in muscle pouches created in the right gluteal region, one into each rat. Group 1 received DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), a highly selective COX-2 inhibitor, at a dose of 1.1 mg/kg/day. Group 2 received 2 mg/kg/day of indomethacin. The drugs were administered by oral gavage with 0.5% methyl cellulose as a delivery vehicle for eleven days, beginning on the first postoperative day. Group 3 received only methyl cellulose. RESULTS Thirty days after the implantation of the demineralized bone matrix, 6/10 of DFU-treated, 9/9 of the indomethacin-treated, and 8/9 of the control rats displayed new bone formation. CONCLUSIONS The results of this study suggest that no form of non-steroidal anti-inflammatory drug has inhibitory effects on heterotopic bone formation in rats. In our opinion, bone formation is a quite complex process that requires several events and is regulated by several factors, so further investigations other than those using non-steroidal anti-inflammatory drugs are required.
Effective adenovirus‐mediated gene expression in adult murine skeletal muscle

We established an efficient method for obtaining expression of a foreign marker gene transferred in vitro into myoblasts and in vivo into adult mouse skeletal muscles using adenovirus vector. After infection of the C2 myoblasts with the adenovirus vector containing the β‐actin promoter with cytomegalovirus (CMV) enhancer (CAG promoter) AxCALacZ, significantly greater number of cells express β‐galactosidase when compared with the adenovirus vector expressing the lacZ gene under the control of the SRα viral terminal repeat promoter (AxSRLacZL) or the myosin heavy chain (MHC) IIB promoter (AxMHCLacZ). We also injected AxCALacZ into the skeletal muscles of 5‐ to 6‐week‐old C57BL/10 mice and determined that more than 60% of their muscle fibers expressed the lacZ gene 7 days after injection. The CAG promoter may have application in the development of gene therapy for Duchenne muscular dystrophy (DMD) using adenovirus vector. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 592–599, 1999
A differential deficit in time- versus event-based prospective memory in Parkinson's disease.

OBJECTIVE The aim of the current study was to clarify the nature and extent of impairment in time- versus event-based prospective memory in Parkinson's disease (PD). Prospective memory is thought to involve cognitive processes that are mediated by prefrontal systems and are executive in nature. Given that individuals with PD frequently show executive dysfunction, it is important to determine whether these individuals may have deficits in prospective memory that could impact daily functions, such as taking medications. Although it has been reported that individuals with PD evidence impairment in prospective memory, it is still unclear whether they show a greater deficit for time- versus event-based cues. METHOD Fifty-four individuals with PD and 34 demographically similar healthy adults were administered a standardized measure of prospective memory that allows for a direct comparison of time-based and event-based cues. In addition, participants were administered a series of standardized measures of retrospective memory and executive functions. RESULTS Individuals with PD demonstrated impaired prospective memory performance compared to the healthy adults, with a greater impairment demonstrated for the time-based tasks. Time-based prospective memory performance was moderately correlated with measures of executive functioning, but only the Stroop Neuropsychological Screening Test emerged as a unique predictor in a linear regression. CONCLUSIONS Findings are interpreted within the context of McDaniel and Einstein's (2000) multiprocess theory to suggest that individuals with PD experience particular difficulty executing a future intention when the cue to execute the prescribed intention requires higher levels of executive control.
CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage

Background and Purpose— Morbidity and mortality in spontaneous intracerebral hemorrhage (ICH) are correlated with hematoma progression. We hypothesized that the presence of tiny, enhancing foci (“spot sign”) within acute hematomas is associated with hematoma expansion. Methods— We prospectively studied 39 consecutive patients with spontaneous ICH by computed tomography angiography within 3 hours of symptom onset. Scans were reviewed by 3 readers. Patients were dichotomized according to the presence or absence of the spot sign. Clinical and radiological outcomes were compared between groups. The predictive value of this sign was assessed in a multivariate analysis. Results— Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (P<0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for expansion were 91%, 89%, 77%, 96%, and 8.5, respectively. Interobserver agreement was high (&kgr;=0.92 to 0.94). In patients with the spot sign, mean volume change was greater (P=0.008), extravasation more common (P=0.0005), and median hospital stay longer (P=0.04), and fewer patients achieved a good outcome (modified Rankin Scale score <2), although the latter was not significant (P=0.16). No differences in hydrocephalus (P=1.00), surgical intervention (P=1.00), or death (P=0.60) were noted between groups. In multiple regression, the spot sign independently predicted hematoma expansion (P=0.0003). Conclusions— The computed tomography angiography spot sign is associated with the presence and extent of hematoma progression. Fewer patients achieve a good clinical outcome and hospital stay was longer. Further studies are warranted to validate the ability of this sign to predict clinical outcomes.
Women in Interventional Cardiology: Small Numbers, Big Impact.

Interventional cardiology requires extensive training, has unpredictable and long work hours, is physically and mentally demanding, and requires cognitive, technical, and leadership skills. For those that follow the calling, the rewards are immeasurable, improving and saving lives. I do not often think of myself as a minority, but as a female interventional cardiologist, and one of the few women in a leadership position within the field, I am a minority. This position comes with great responsibility—to broadcast the female workforce shortage and highlight the positive impact that women have on our profession and patients. The truth is in the numbers. Little progress has been made with respect to increasing representation of women in interventional cardiology in the past decade. The American Board of Internal Medicine tracks board certification and fellow workforce data annually. Although women still comprise about half of residents completing internal medicine, 50% of trainees in rheumatology, infectious disease, palliative care, and geriatrics are women. Among cardiology subspecialties, heart failure has the highest percentage of women at 35%. 1 At a glance, it appears that women are choosing specialties with more predicable schedules or that require more compassion, but this may also reflect the mindset of individuals that choose internal medicine. The primary message from these statistics is that we need to reach women at an earlier stage in life, as young as high school but no later than medical school, to expose them to cardiology. My story is similar to many I have heard from my interventional colleagues. I was …
Autoregulation of blood flow: Vessel diameter changes in response to different temperatures

Autoregulation of blood flow is a marvelous phenomenon balancing blood supply and tissue demand. Although many chemically-based explanations for this phenomenon have been proposed and some of them are commonly used today, biomechanical aspects of this phenomenon was neglected. The biomechanical aspect provides insights to us to model vessel diameter changes more precisely and comprehensively. One important aspect of autoregulation phenomenon is temperature changes of the tissue resulted from tissue metabolism. We hypothesize that temperature changes can affect the mechanical properties of the vessel wall leading to vessel diameter changes during autoregulation. Mechanical modeling of vessel diameter changes can also be useful to explain other phenomena in which the vessel diameter changes in response to temperature alterations. Through the mechanical modeling of any vessel, the analysis of temperature-induced changes in vessel diameter can be done more precisely.
The MemoSlide: An explorative study into a novel mechanical follow-the-leader mechanism

Follow-the-leader propagation allows for the insertion of flexible surgical instruments along curved paths, reducing the access required for natural orifice transluminal endoscopic surgery. Currently, the most promising follow-the-leader instruments use the alternating memory method containing two mechanical memory-banks for controlling the motion of the flexible shaft, which reduces the number of actuators to a minimum. These instruments do, however, require concentric structures inside the shaft, limiting its miniaturization. The goal of this research was, therefore, to develop a mechanism conforming the principles of the alternating memory method that could be located at the controller-side instead of inside the shaft of the instrument, which is positioned outside the patient and is therefore less restricted in size. First, the three-dimensional motion of the shaft was decoupled into movement in a horizontal and vertical plane, which allowed for a relatively simple planar alternating memory mechanism design for controlling planar follow-the-leader motion. Next, the planar movement of the alternating memory mechanism was discretized, increasing its resilience to errors. The resulting alternating memory mechanism was incorporated and tested in a proof-of-concept prototype called the MemoSlide. This prototype does not include a flexible shaft, but was fully focused on proving the function of the alternating memory mechanism. Evaluation of the MemoSlide shows the mechanism to work very well, being able to transfer any planar path that lays within its physical boundaries along the body of the mechanism without accumulating errors.
Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway

The angiotensin converting enzyme 2-angiotensin-(1–7)-Mas axis (ACE2-Ang-(1–7)-Mas axis) is reported to participate in lipid metabolism in kidney, but its precise effects and underlying mechanisms remain unknown. We hypothesized that Ang-(1–7) reduces lipid accumulation and improves renal injury through the low density lipoprotein receptor–sterol regulatory element binding proteins 2–SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1–7) and STD+Ang-(1–7). After 10 weeks of feeding, mice were administered Ang-(1–7) or saline for two weeks. We found that high inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat diet with Ang-(1–7) induced significant improvement in inflammatory status, following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury. In conclusion, the anti-inflammatory effect of Ang-(1–7) alleviates renal injury triggered by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway.
Quantified EEG Activity in Adolescent Attention Deficit Hyperactivity Disorder

The aim of this study was to explore elements of the maturational and cortical hypoarousal models in adolescent ADHD, by examining EEG activity in a rest eyes open condition, in 26 adolescent unmedicated ADHD males and 26 age and sex matched normal controls. ADHD adolescents were found to have increased anterior EEG absolute theta activity and reduced posterior relative beta activity compared with controls. These results lend some support to the continuation of a maturational lag and reduced cortical arousal in adolescent ADHD. These measures need to be further explored using concomitant EEG with electrodermal measures of arousal.