Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrical Propagation in the Mechanisms of Torsion and Suction in a Three-phase Heart

Background: The hypothesis of Torrent Guasp considers that the ventricular myocardium consists of a continuous muscular bandthat begins at the level of the pulmonary valve and ends at the level of the aortic root, limiting both ventricular chambers. Thisanatomy would provide the interpretation for two fundamental aspects of left ventricular dynamics: the mechanism of left ventriculartorsion and rapid diastolic filling due to the suction effect.Objectives: The aim of this study was to investigate the electrical activation of the endocardial and epicardial bands to understandventricular torsion, the mechanism of active suction during the diastolic isovolumic phase and the significance of the residual volume.Methods: Five patients underwent three-dimensional electroanatomic mapping. As the descending band is endocardial and theascending band is epicardial, two sites of puncture were used.Results: Three-dimensional endo-epicardial mapping demonstrates an electrical activation sequence in the area of the apical loop inagreement with the synchronic contraction of the descending and ascending band segments. The simultaneous and opposing radialactivation of the ascending band segment, starting in the descending band segment, in the area in which both band segments intertwine,is consistent with the mechanism of ventricular torsion. The late activation of the ascending band segment is consistent withits persistent contraction during the initial period of the isovolumic diastolic phase (the basis of the suction mechanism), and takesplace without need of postulating further electrical activation after the QRS complex.Conclusions: This study explains the process of ventricular torsion and the suction mechanism, and demonstrates that the activationof the ascending band segment completes the QRS, ruling out the traditional concept of passive relaxation during isovolumic diastole.
The incubation process for the creation of viable firms: the case of ARCA Consortium

The aim of this study is to demonstrate that academic incubators play a key role in firm viability. This study develops a new analytic systemic framework that reveals the processes and factors that determine the effectiveness of the incubation process supported by university incubators. We analyse the effectiveness of the incubation process in the incubator of the ARCA Consortium by means of a single case study with an embedded design. In this study, adopting a systemic perspective, we shift the focus from the firm to the context, shedding light on the systemic actions that create the prerequisite conditions for the achievement of the firms' viability.
Comprehensive Geriatric Assessment and quality of life after localized prostate cancer radiotherapy in elderly patients

Introduction Radiotherapy can diminish quality of life (QoL) for prostate cancer patients. Our objective was to evaluate the effect of radiotherapy on QoL in men aged 75 years or older treated with radiotherapy for a localized prostate cancer, and to identify predictors of reduced QoL. Patients and methods We prospectively administered a battery of geriatric (MNA, GDS, Get up and Go Test, CIRS-G, ADL, IADL, MMSE), toxicity (IPSS; IIEF 5), and QoL (QLQ C30) screening tests in 100 elderly patients before and two months after prostate cancer radiotherapy (NCT 02876237). Patients ≥ 75 years undergoing radiotherapy with a curative intent for localized prostate cancer with or without androgen deprivation therapy (ADL) were eligible for study inclusion. Correlations between patient-assessed QoL and tumor characteristics, radiotherapy treatment or CGA parameters were sought using the Fisher or the Mann and Whitney tests. Changes in QoL parameters over time were analyzed using the Wilcoxon signed-rank test. Results At study entry, scores for IADL impairments were present in 51%, reduced autonomy in activities of daily living in 16%, cognitive impairment found in 20%, depression-related symptoms in 31%, and 66% of patients had significant co-morbidities. Eight percent were judged to be at risk of fall and 2% were found to be undernourished. Severely impaired (IPSS ≥ 20) urinary function was observed in 11.2% and 13.5% of patients before and two months after completion of radiotherapy respectively. Significantly decreased QoL (> 20 points) at two months after treatment was found in 13% of patients and a moderate but clinically relevant reduction (10 to 20 points) in 17% of patients. No tumor characteristic, treatment, or oncogeriatric parameter was predictive of reduced QoL following prostate cancer radiotherapy. Conclusion Despite sometimes markedly diminished oncogeriatric parameters, prostate cancer radiotherapy was generally well tolerated in these elderly patients. We found no predictive factor to determine which patients would experience impaired quality of life following radiotherapy.
Reactive stroma component COL6A1 is upregulated in castration-resistant prostate cancer and promotes tumor growth

Castration-resistant prostate cancer (CRPC) remains the most critical challenge in the clinical management of prostate cancer (PCa). Reactive stromal changes in PCa are likely involved in the emergence of CRPC. In the present study, we identified a novel oncogene termed COL6A1 which was upregulated in the reactive stroma of CRPC. We established an androgen-independent LNCaP (LNCaP-AI) cell line in steroid-reduced (SR) medium within 2 months. We examined COL6A1 expression with western blot during the LNCaP-AI induction, and studied the function of COL6A1 in vitro and in vivo. Immunohistochemical staining of COL6A1 was performed in ten pairs of androgen-sensitive PCa and CRPC samples. We demonstrated that COL6A1 expression was markedly increased in LNCaP-AI cells and CRPC tissues compared with LNCaP cells and paired androgen-sensitive PCa specimens. In vitro, COL6A1 knockdown resulted in G1-S cell cycle arrest and descended vitality. Overexpression of COL6A1 was associated with accelerated S phase entry and elevated vitality in prostate cancer cells. COL6A1 also promoted tumorigenesis of LNCaP cells in vivo. Taken together, these data suggest an important role of COL6A1 in the molecular etiology of castration-resistant prostate cancer, and support the potential use of COL6A1 in CRPC therapy.
Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma

Abstract. Objective: The aim of this study was to establish a preclinical mouse model to study metastases of paediatric rhabdomyosarcoma at the macroscopic and cellular levels, with different imaging methods. Experimental Design: The alveolar rhabdomyosarcoma cell line Rh30 was stably transfected with the red fluorescent protein (DsRed2) then was xenotransplanted (intravenous injection [n = 8], and footpad injection [n = 8]) into nude mice (NMRI nu/nu). Macroscopic imaging of metastases was performed using DsRed2‐fluorescence and flat‐panel volumetric computed tomography scan. In a further series of animals (n = 8), in vivo cell trafficking of rhabdomyosarcoma cells using cellular imaging with an Olympus OV100 variable‐magnification small‐animal imaging system was used. Results: Metastases in the pelvis, thoracic wall and skin were visualized by fluorescence imaging. Pelvic metastases were found after tail vein injection and at other metastatic sites after footpad injection. Flat‐panel volumetric computed tomography scan data allowed highly specific analysis of contrast between tumour and surrounding tissue. Correlation between fluorescence and flat‐panel volumetric computed tomography scan imaging data was observed. Single‐cell imaging visualized tumour cells in the vessels and demonstrated the arrest of tumour cells at vessel junctions followed by extravasation of the tumour cells. Conclusion: We established a model for visualization of experimental metastatic invasion and describe relevant tools for imaging childhood rhabdomyosarcoma metastases at the macroscopic and cellular levels. Imaging of cell trafficking visualized the behaviour of tumour cells and development of metastases by accumulation and extravasation of rhabdomyosarcoma cells.
Leo Kanner and autism: a 75-year perspective

Abstract In 1943, Leo Kanner published the first systematic description of early infantile autism. He concluded that this was a neurodevelopmental disorder and that ‘these children have come into the world with an innate inability to form the usual, biologically provided contact with people’. Moreover, his astute descriptions of parental behavior in his first publications were prescient and underlie later recognition of the importance of genetics. Our understanding has grown over the ensuing years with revisions in diagnostic classification, recognition of the broader autism phenotype in families, appreciation of the importance of developmental models, advances in genetic methodology, better understanding of the relationship to intellectual deficits, recognition of syndromic autism in neurogenetic sydromes, advances in neuroimaging, and advances in animal models, both mutant mouse models and transgenic non human primate models. Kanner recognized diagnostic heterogeneity and opined that the children had not read those diagnostic manuals and did not easily fall into clear cut categories. Such heterogeneity continues to confound our diagnostic efforts. Always an advocate for children, when reviewing the DSM III criteria in 1980, Kanner emphasized that no matter how well developed our criteria each child must be treated as a unique person.
A Simple Heuristic for Joint Inventory and Pricing Models with Lead Time and Backorders

We study a joint inventory and pricing problem in a single-stage system with a positive lead time. We consider both additive and multiplicative demand forms. This problem is, in general, intractable due to its computational complexity. We develop a simple heuristic that resolves this issue. The heuristic involves a myopic pricing policy that generates each period’s price as a function of the initial inventory level and a base-stock policy for inventory replenishment. In each period, the firm monitors its so-called price-deflated inventory position and places an order to reach a target base-stock level. The price-deflated inventory position weights the on-hand and pipeline inventory according to a factor that reflects the sensitivity of price to the net inventory level. To assess the effectiveness of our heuristic, we construct an upper bound to the exact system. The upper bound is based on an information-relaxation approach and involves a penalty function derived from the proposed heuristic. A numerical study suggests that the heuristic is near-optimal. The heuristic approach can be applied to a wide variety of inventory systems, such as systems with fixed ordering costs or fixed batch sizes. The heuristic enables us to explore the use of price as a lever to balance supply and demand. Our findings indicate that a responsive strategy (that effectively reduces the replenishment lead time) leads to a more stable pricing policy and that the value of dynamic pricing increases with lead time. This paper was accepted by Martin Lariviere, operations management .
Underwater color constancy: enhancement of automatic live fish recognition

We present in this paper some advances in color restoration of underwater images, especially with regard to the strong and non uniform color cast which is typical of underwater images. The proposed color correction method is based on ACE model, an unsupervised color equalization algorithm. ACE is a perceptual approach inspired by some adaptation mechanisms of the human visual system, in particular lightness constancy and color constancy. A perceptual approach presents a lot of advantages: it is unsupervised, robust and has local filtering properties, that lead to more effective results. The restored images give better results when displayed or processed (fish segmentation and feature extraction). The presented preliminary results are satisfying and promising.
Scaling in blast neurotrauma

The high incidence of blast exposure on today’s battlefield has been strongly associated with traumatic brain injuries. Anecdotal evidence of prolonged apnea following blast exposure has been observed in military personnel and is commonly reproduced in animal neurotrauma models. Animal models have shown that apnea tolerance is both dose and species-dependent; important factors include primary blast characteristics (peak overpressure, P, and duration, Δt) and animal size. Experimental data on apnea from head exposure to primary blast were obtained from 121 tests using four different-sized animal models with thoracic blast protection: mouse, rabbit, ferret and pig with peak incident pressure and overpressure duration ranging from 99.7 to 1084.6kPa and 0.6 to 8.0ms, respectively. Apnea risk was assessed using logistic regression with a log-linear dose-response. Scaling procedures were explored based upon the body mass or brain mass of the animal. Scaling effects were largest in the small animal models. When scaling was applied to existing rodent neurotrauma models, scaled duration ranged from 17.65 to 540 ms, with most larger in duration than the typical blast exposure range seen in combat (~1-40 ms duration). It is imperative that appropriate scaling procedures between species are derived and implemented to properly correlate animal model pathophysiological outcomes with human response.
Thermal proteome profiling of breast cancer cells reveals proteasomal activation by CDK4/6 inhibitor palbociclib

Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that are not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it. We further show that palbociclib treatment increases proteasome activity independently of the ubiquitin pathway. This leads to cellular senescence which can be counteracted by proteasome inhibitors. Palbociclib-induced proteasome activation and senescence is mediated by reduced proteasomal association of ECM29. Loss of ECM29 activates the proteasome, blocks cell proliferation and induces senescence. Finally, we find that ECM29 mRNA levels are predictive of relapse-free survival in breast cancer patients treated with endocrine therapy. In conclusion, thermal proteome profiling identifies the proteasome and ECM29 protein as mediators of palbociclib activity in breast cancer cells.
Crimean–Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures

Crimean–Congo haemorrhagic fever (CCHF) is a widespread tick‐borne viral zoonosis with a case‐fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre‐clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.
New Insights into the Control of Pulsatile GnRH Release: The Role of Kiss1/Neurokinin B Neurons

Gonadotropin-releasing hormone (GnRH) is the ultimate output signal of an intricate network of neuroendocrine factors that, acting on the pituitary, trigger gonadotropin release. In turn, gonadotropins exert their trophic action on the gonads to stimulate the synthesis of sex steroids thus completing the gonadotropic axis through feedback regulatory mechanisms of GnRH release. These feedback loops are predominantly inhibitory in both sexes, leading to tonic pulsatile release of GnRH from puberty onward. However, in the female, rising levels of estradiol along the estrous cycle evoke an additional positive feedback that prompts a surge-like pattern of GnRH release prior to ovulation. Kisspeptins, secreted from hypothalamic Kiss1 neurons, are poised as major conduits to regulate this dual secretory pathway. Kiss1 neurons are diverse in origin, nature, and function, convening distinct neuronal populations in two main hypothalamic nuclei: the arcuate nucleus (ARC) and the anteroventral periventricular nucleus. Recent studies from our group and others point out Kiss1 neurons in the ARC as the plausible generator of GnRH pulses through a system of pulsatile kisspeptin release shaped by the coordinated action of neurokinin B (NKB) and dynorphin A (Dyn) that are co-expressed in Kiss1 neurons (so-called KNDy neurons). In this review, we aim to document the recent findings and working models directed toward the identification of the Kiss1-dependent mechanisms of GnRH release through a synoptic overview of the state-of-the-art in the field.
Evaluation of Collagen, Calcium Alginate Protectants on Healing of External Wound on Teat in Cows

A total number of 36 cross bred jersey cows with external teat injury without involving the teat cistern and with exposed teat sinus were subjected for the present study. Clinical examination of teat for its shape, length, distance from the ground and etiology of the teat wounds were recorded. Following preoperative evaluation, the animals were divided into Group I with 12 animals and treatment group with 24 animals each. Group I were treated with Povidone iodine solution. In treatment (Group II), after suturing the wound was protected with sheets of collagen and calcium alginate as protectants. The application of collagen based teat protectant is an effective methodology for favoring healing process of external injuries when compared to the conventional antiseptic drugs using Povidone iodine.
Helicopter main gearbox bearing defect identification with acoustic emission techniques

Helicopter transmission integrity is critical to the safety operation. Among all mechanical failures in helicopter transmission, the main gearbox (MGB) failures occupy approximately 16%. Great effort has been paid in early prevention and diagnosis of MGB failures. As a commonly employed monitoring technology, vibration analysis suffers from strong background noise due to variable transmission paths from the bearing to the receiving externally mounted vibration sensor. The background noise can mask the signal signature of interest. This paper reports on an investigation to identify the presence of a bearing defect in a CS29 Category `A' helicopter main gearbox with acoustic emission (AE) technologies. This investigation involved performing the tests for faultfree condition, minor bearing damage and major bearing damage conditions under different power levels. The bearing faults were seeded on one of the planet gears of the second epicyclic stage. To overcome the issue of low signal to noise ratio (SNR), AE sensor was directly attached on the dish of planet carrier. The AE signal was transferred wireless to avoid complex wiring inside MGB. The analysis results proved the feasibility of using AE sensor as in-situ bearing defect identification.
Towards harmonization of external quality assessment/proficiency testing in hemostasis

Abstract Quality in diagnostic testing represents a key target of laboratory medicine, for which an assurance around the quality of testing is expected from all involved in the process. Laboratories attempt to assure the quality of their testing by various processes, but especially by performance of internal quality control and external quality assessment (EQA). This is especially true for tests of hemostasis and coagulation. EQA in general provides information on test accuracy and on evaluation of long-term laboratory performance. EQA providers support laboratory performance by various means, including distribution of material for testing of analytes (“proficiency testing”), educational support through expert advice, distribution of publications or case series. Participation in EQA is often a laboratory accreditation requirement. This review aims to identify some of the strengths and weaknesses of EQA, and targets attempts towards harmonization of EQA practice, in order to achieve the best outcome for participant laboratories and, thus, for patients and their clinical care providers.
Habituation effects in computer security warning

ABSTRACT Security warning is a form of computer dialog communication used to inform the users on the risks of allowing random applications to run on a computer system. Accordingly, it is specifically designed to impersonate a legitimate security alerting function (e.g., notify, warn, and advice) to a user about the consequence effect of an action. However, most of the computer users tend to ignore those security warnings conveying the same message over and over again. This eventually leads to habituation. Considering the fact that there is a significant lack of focus paid to address this issue, the main objective of this article is to describe and summarize the related studies on users’ habituation to the security warnings. This article presents a systematic literature review to explore the current key issues, challenges, and the possible solutions related to habituation effects in security warnings. It is expected that this article could contribute to a more complete understanding of the habituation effects in security warnings and eventually bring benefits to the research communities or general publics.