Miracle-dz/UniFAR-FTUs huggingface dataset:
c‐Src kinase contributes on endothelial cells mechanotransduction in a heat shock protein 70‐dependent turnover manner

Shear stress changes are associated with a repertory of signaling cascade modulating vascular phenotype. As shear stress‐related tensional forces might be associated with pathophysiological susceptibility, a more comprehensive molecular map needs to be addressed. Thus, we subjected human umbilical vein endothelial cells (HUVECs) to a circuit of different tensional forces in vitro considering the following three groups: (a) physiological blood flow shear stress condition (named Normo), (b) a hypertensive blood flow shear stress (named Hyper), and (c) these hyper‐stressed cells were returned to Normo condition (named Return). The samples were properly collected to allow different methodologies analysis. Our data showed a pivotal involvement of c‐Src on driving the mechanotransduction cascade by modulating signaling related with adhesion, survival (PI3K/Akt) and proliferative phenotype. Moreover, c‐Src seems to develop important role during extracellular matrix remodeling. Additionally, proteomic analysis showed strong involvement of heat shock protein 70 (HSP70) in the hypertensive‐stressed cells; it being significantly decreased in return phenotype. This result prompted us to investigate 20S proteasome as an intracellular proteolytic alternative route to promote the turnover of those proteins. Surprisingly, our data reveled significant overexpression of sets of proteasome subunit α‐type (PSMA) and β‐type (PSMB) genes. In conjunction, our data showed c‐Src as a pivotal protein to drive mechanotransduction in endothelial cells in a HSP70‐dependent turnover scenario. Because shear patterns is associated with pathophysiological changes, such as atherosclerosis and hypertension, these results paved new road to understand the molecular mechanism on driving mechanotransduction in endothelial cells and, if drugable, these targets must be considered within pharmacological treatment optimization.
Unsuitability of indigenous South American Rutaceae as potential hosts of Diaphorina citri.

BACKGROUND 'Candidatus Liberibacter asiaticus' is transmitted by Diaphorina citri, an insect with a wide range of hosts in Rutaceae. Species related to Citrus occur in Brazilian forests where they may serve as hosts for psyllids and infested citrus orchards. RESULTS The suitability of plants as hosts of D. citri was classified into four groups. Group I (high suitability): Citrus × aurantium 'Valencia', 'Citrus limonia', Murraya paniculata (syn. Murraya exotica L.) (Aurantioideae: Aurantieae) and Bergera koenigii (Aurantioideae: Clauseneae). Group II (intermediate to low suitability): Citrus (Poncirus) trifoliata 'Pomeroy', Citrus wintersii, Swinglea glutinosa (Aurantieae) and Clausena lansium (Clauseneae). Group III (not suitable): Aegle marmelos, Atalantia buxifolia, Citrus ('Microcitrus') sp. (Aurantieae) and Helietta apiculata (Amyridoideae). Group IV (non-hosts): Glycosmis pentaphylla (Clauseneae), Balfourodendron riedelianum, Casimiroa edulis, Esenbeckia febrifuga, Esenbeckia leiocarpa, Metrodorea stipularis, Zanthoxylum rhoifolium (Amyridoideae) and Dictyoloma vandellianum (Cneoroideae). Insects survived longer on newly differentiated leaves compared with fully expanded soft leaves. Psyllids either did not develop or did not survive for long on most Group IV species, all of which, with the exception of G. pentaphylla, occur naturally in Brazilian forests. CONCLUSION Citrus relatives occurring in forests near citrus orchards are not suitable hosts of D. citri and, therefore, do not contribute to huanglongbing spread. © 2018 Society of Chemical Industry.
The effects of exhaustive swimming and probiotic administration in trained rats: Oxidative balance of selected organs, colon morphology, and contractility.

The duration and intensity of exercise are significant factors in oxidative, morphological, and functional changes of the gastrointestinal tract. This study aimed to investigate the effects of both exhaustive swimming and probiotic VSL#3 on rats that had been previously trained with moderate swimming. The rats were divided into four groups labeled: control (C), probiotic (P), exercise (E), and probiotic-exercise (PE). Groups P and PE were fed with probiotic mixture VSL#3. Groups E and PE had a 5-week moderate swimming program (1 h/day for 5 days/week), followed by a 1-week exhaustive swimming program (trained like in moderate program but 3 times with 150 min resting sessions, for 5 days/week). At the end of the program, the rats were euthanized. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels were measured in tissue samples from the gastrocnemius muscle, heart, liver, kidney, and colon. In vitro contractile activity and histomorphology of the colon were also determined. Exercise and/or probiotic decreased the oxidative stress and also increased the level of one or more of the antioxidant enzymes in some of the organs. Probiotics had more pronounced effects on colon morphology than exercise but unexpectedly this effect was non-trophic. In the colon, the thickness of the tunica muscularis and the number of goblet cells were not affected; however, probiotic administration decreased the crypt depth and tunica mucosa thickness. Exercise increased the Emax value of acetylcholine (ACh), while decreased its sensitivity. These findings suggest that exhaustive swimming does not cause oxidative stress and that probiotic consumption improves oxidative balance in trained rats. The probiotic intake does not alter the effect of exercise on the contractile activity of the colon. Colon mucosal changes induced by probiotics are independent of exercise.
Assessment of the impact of 10-day intermittent hypoxia on the autonomic control measured by heart rate variability.

PURPOSE The purpose of this study is to establish the alterations in the activity of the autonomic nervous system (ANS) via heart rate variability (HRV) in subjects exposed to 1 h of exogenous hypoxia for 10 consecutive days. METHODS Twelve healthy non-smoker males at mean age of 29.8 ± 7.4 (mean ± SD) breathed hypoxic air delivered through hypoxicator (FiО2 = 12.3% ± 1.5%) for 1 h in 10 consecutive days. Pulse oximetry and electrocardiography were monitored during the visit and HRV was calculated for the entire 1-h hypoxic period. RESULTS Comparing the last hypoxic visit to the first, subjects had higher standard deviation of normal-to-normal interbeat intervals (SDNNs) (65.7 ± 32.5 vs. 81.1 ± 32.0 ms, p = 0.013) and root mean square of successive R-R interval difference (RMSSD) (58.1 ± 30.9 vs. 76.5 ± 34.6 ms, p = 0.029) as well as higher lnTotal power (8.1 ± 1.1 vs. 8.5 ± 0.9 ms2, p = 0.015) and high frequency (lnHF) (6.8 ± 1.3 vs. 7.5 ± 1.2 ms2, p = 0.05) and lower LF/HF (2.4 ± 1.4 vs. 1.5 ± 1.0, p = 0.026). Changes in saturation (87.0 ± 7.1 vs. 90.8 ± 5.0%, p = 0.039) and heart rate (67.1 ± 8.9 vs. 62.5 ± 6.0 beats/min, p = 0.040) were also observed. CONCLUSIONS Intermittent hypoxic training consisting of 1-h hypoxic exposure for 10 consecutive days could diminish the effects of acute exogenous hypoxia on the ANS characterized by an increased autonomic control (SDNN and total power) with augmentation of the parasympathetic nervous system activity (increased RMSSD and HF and decreased LF/HF). Therefore, it could be applied as a pre-acclimatization technique aiming at an increase in the autonomic control and oxygen saturation in subjects with upcoming sojourn to high altitude.
Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis

With the continuing progress in managing patients with thalassemia, especially in the setting of iron overload and iron chelation, the life span of these patients is increasing, while concomitantly increasing incidences of many diseases that were less likely to show when survival was rather limited. Hepatocellular carcinoma (HCC) is a major life-threatening cancer that is becoming more frequently identified in this population of patients. The two established risk factors for the development of HCC in thalassemia include iron overload and viral hepatitis with or without cirrhosis. Increased iron burden is becoming a major HCC risk factor in this patient population, especially in those in the older age group. As such, screening thalassemia patients using liver iron concentration (LIC) measurement by means of magnetic resonance imaging (MRI) and liver ultrasound is strongly recommended for the early detection of iron overload and for implementation of early iron chelation in an attempt to prevent organ-damaging iron overload and possibly HCC. There remain lacking data on HCC treatment outcomes in patients who have thalassemia. However, a personalized approach tailored to each patient's comorbidities is essential to treatment success. Multicenter studies investigating the long-term outcomes of currently available therapeutic options in the thalassemia realm, in addition to novel HCC therapeutic targets, are needed to further improve the prognosis of these patients.
A Comprehensive Digital Program for Smoking Cessation: Assessing Feasibility in a Single-Group Cohort Study

Background Cigarette smoking remains the leading cause of preventable death and disease worldwide. Evidence-based approaches are available, but few people access them. Although digital solutions offer great promise for population reach, few multicomponent programs exist. Pivot is a comprehensive digital solution combining a Food and Drug Administration–cleared carbon monoxide (CO) breath sensor; cigarette logging; a 6-phase, app-delivered smoking cessation program based on the US Clinical Practice Guidelines; and dedicated human coaching via text-based chat. Objective The purpose of this study was to assess program engagement, changes in attitudes toward smoking, self-reported changes in smoking behavior, and program acceptability for the initial phase of Pivot: Explore. Methods A total of 48 participants enrolled, and 41 completed the study. About half the participants (54%, 22/41) were men, and the mean age was 43 years. Most (85%, 35/41) were daily smokers and smoked an average of 12 cigarettes per day. Explore includes CO breath sensing, logging cigarettes in-app, learning via in-app activities, and dedicated human coaching through a text messaging interface. Participants completed surveys at baseline and exit assessing attitudes toward quitting including readiness, perceived difficulty, and confidence in quit success. At exit, participants also completed a survey of changes in smoking behavior and ratings of program acceptability. Results More than 80% of participants (34-39 of 41) took ≥1 CO breath sample each day, and more than 55% (23-27 of 41) took ≥5 samples each day. More than 65% of participants (27-34 of 41) logged ≥1 cigarette using the in-app logging feature each day. All 9 in-app activities had completion rates ≥80% (33-40 of 41). Response to coach-initiated outreach was also high, with all contacts receiving ≥73% (30-39 of 41) response. In matched pair analyses, significant positive changes in mean attitudes toward quitting (scale 1-10) were evident from baseline (T1) to study exit (T2), including increased readiness to quit (T1 mean=6.1, T2 mean=7.4, P=.005), lower perceived difficulty (T1 mean=3.7, T2 mean=5.6, P=.001), and greater expectations of success (T1 mean=4.5, T2 mean=6.5, P<.001). At exit, 78% (32/41) of participants reported decreasing the number of cigarettes smoked per day during the study. Participants rated program quality and satisfaction very high (mean ≥8 for all items). Conclusions These results support the feasibility and acceptability of the initial 9-day phase of Pivot: Explore. Participants had high levels of engagement with sensing, logging, learning, and coaching. Attitudes toward quitting improved significantly, and the majority of users indicated decreasing smoking behavior. Explore was designed to raise smoker awareness and motivation. Additional research is underway to assess how users progress through the full Pivot smoking cessation program and determine the program’s effectiveness for achieving sustained cessation.
Dual Effect of Glucuronidation of a Pyrogallol-Type Phytophenol Antioxidant: A Comparison between Scutellarein and Scutellarin

To explore whether and how glucuronidation affects pyrogallol-type phytophenols, scutellarein and scutellarin (scutellarein-7-O-glucuronide) were comparatively investigated using a set of antioxidant analyses, including spectrophotometric analysis, UV-vis spectra analysis, and ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis. In spectrophotometric analyses of the scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radicals (PTIO•) and the reduction of Cu2+ ions, scutellarein showed lower IC50 values than scutellarin. However, in •O2−-scavenging spectrophotometric analysis, scutellarein showed higher IC50 value than scutellarin. The analysis of UV-Vis spectra obtained after the Fe2+-chelating reaction of scutellarin showed a typical UV-Vis peak (λmax = 611 nm), while scutellarein showed no typical peak. In UPLC-ESI-Q-TOF-MS/MS analysis, mixing of scutellarein with DPPH• yielded MS peaks (m/z 678, 632, 615, 450, 420, 381, 329, 300, 288, 227, 196, 182, 161, and 117) corresponding to the scutellarein-DPPH adduct and an MS peak (m/z 570) corresponding to the scutellarein-scutellarein dimer. Scutellarin, however, generated no MS peak. On the basis of these findings, it can be concluded that glucuronidation of pyrogallol-type phytophenol antioxidants has a dual effect. On the one hand, glucuronidation can decrease the antioxidant potentials (except for •O2− scavenging) and further lower the possibility of radical adduct formation (RAF), while on the other hand, it can enhance the •O2−-scavenging and Fe2+-chelating potentials.
GP-confirmed complete Achilles tendon rupture using pocket-sized ultrasound: a case report

Background: Studies outside of Ireland have demonstrated that GPs believe point-of-care tests (POCTs) are useful and would like to have more of these t sts available in daily practice. This study establishes the vi ws of Irish GPs on this topic for the first time and als explores GPs’ perceptions of barri rs to having POCT d vices in primary care. i : To e tablish Irish GPs’ perception of the ben fits and barri rs to POCT use. Design & etti : A q antitative cross-sec ional obs rvational survey of Irish GPs attending c tinui g medical ducational meeting (CME) in Nove ber 2015. Method: Data was collected using an anonymous and confidential questionnaire. Results: Out of a total of 250, 70% of GPs (n = 143) completed the questionnaire. Of these, 92% (n = 132) indicated they would like to have access to POCTs. Guidance in decision making 43% (n = 61), reduced referral rates 29% (n = 42), and diagnosis assistance 13% (n = 18) were the main benefits expressed. Cost 45% (n = 64) and time 34% (n = 48) were the main barriers identified. Conclusion: This study proved that Irish GPs would also like increas d ccess to POCTs. They feel that these tests would b nefit patient care. Unsurprisingly, co t and time were two barriers identified to using POCT devices, which supports outc mes f m studies. Radical chang s would b required in primary c r to facilitate impl mentation of POCTs and attentio mu t b paid to how the costs of POCTs will be funded. This study may act as a prompt for future internation l research to further explore this area. Varzgaliene L et al. BJGP Open ; DOI: 10.3399/bjgpopen17X101229 1 of 7 RESEARCH
A case series on the conservative management of the bony skull in patients with aggressive skin carcinomas of the scalp

Abstract Few studies examine techniques of surgical resection for scalp malignancies to ensure clear margins. We present a case series utilizing outer cortex removal in patients without evidence of bony or pericranial invasion. A retrospective casenote review is presented of three cases treated in a tertiary Head and Neck Cancer Centre. An outer table removal approach was utilized based on the absence of bony involvement either on pre-operative imaging or from intra-operative findings. All cases underwent an outer table drilldown procedure. Tumour histology included high grade carcinoma of unknown origin, malignant cylindroma and squamous cell carcinoma. Complete excisions with adequate deep margins were achieved in 100% cases. Overall disease-free survival was 66.6% and local control rate was 100%. This technique allows a high degree of local control, notably at the deep margin. There is little morbidity and it avoids the complications associated with full thickness calvarial resection.
Prediagnostic electrocardiographic and echocardiographic findings of biopsy‐proven hypertrophic cardiomyopathy

We present two cases of biopsy‐proven hypertrophic cardiomyopathy (HCM). Both cases showed abnormal electrocardiographic (ECG) findings more than 8 years before diagnosis. A 16‐year‐old healthy male experienced a rescued cardiac arrest. Another male adolescent showed abnormal Q wave and thickened ventricular wall at 15 years old. Retrospective analyses of ECGs performed at 6 years old indicated abnormal ECG findings. However, the diagnosis was normal because no ventricular wall thickening was present in echocardiography. For early diagnosis of HCM to prevent sudden cardiac arrest or death, it is essential to establish ECG and echocardiographic criteria to screen HCM in the young.
Developing a Physical Vocabulary for the Contemporary Actor

One of the distinguishing qualities of live theatre is its built-in ephemerality: yet all too often this involves the loss not only of the fruits of theatrical experience but of ‘experience’ itself, understood as the learning of craft – and this puts experimental companies and practitioners alike in danger of constantly reinventing the wheel. Connecting this to the needs of serious performers to acquire a wide range of expressive movements, and to explore the process of relating these movements to thoughts and feelings, Lea Logie discusses both common elements and contrasting approaches in the work of some of the great European practitioners, whose insights are too valuable to be forgotten or consigned to scholarly archives. Lea Logie is a tutor in Theatre and Drama Studies at Murdoch University, Western Australia, where she specializes in cross-cultural studies of Asian and western theatre.
Cellular Immunotherapy of Canine Cancer

Infusions with immune cells, such as lymphocytes or natural killer (NK) cells, represent one of several modalities of immunotherapy. In human patients with advanced B-cell leukemia or lymphoma, infusions with chimeric antigen receptor (CAR) T-lymphocytes have shown promising responses. However, the scientific and clinical development of cell-based therapies for dogs, who get cancer of similar types as humans, is lagging behind. One reason is that immune cells and their functionality in dogs are less well characterized, largely due a lack of canine-specific reagents to detect surface markers, and specific cytokines to isolate and expand their immune cells. This review summarizes the current status of canine cancer immunotherapies, with focus on autologous and allogeneic T-lymphocytes, as well as NK cells, and discusses potential initiatives that would allow therapies with canine immune cells to “catch up” with the advances in humans.
Transcatheter Aortic Valve Replacement in the Era of Quality Assessment.

The Donabedian model, which was originally developed by Dr Avedis Donabedian in 1966, is one of the most well-known conceptual models for assessing the quality of health care. In this model, the quality of care can be assessed as a triad of structure, process, and outcome constructs. Structure is defined as the context in which care is delivered (eg, hospital buildings, staff, financing, and equipment). Process denotes what is actually done in giving and receiving care. Outcome refers to the effects of care on the health status of patients and populations.1 In the field of percutaneous coronary intervention (PCI), the Physician Consortium for Performance Improvement and 3 professional societies proposed quality measures in 2013.2 They included structural measures, such as operator and hospital PCI volume, and process measures, such as indication of PCI and post-PCI optimal medical therapy. In addition, risk-standardized hospital 30-day mortality and readmission after PCI have been developed by the American College of Cardiology and serve as outcome measures.3–5 Metrics have also been established for cardiovascular surgery by the Society of Thoracic Surgeons. For surgical aortic valve replacement, selection and duration of antibiotic prophylaxis are assessed as process measures, and 30-day mortality and a composite of mortality and major morbidity are evaluated as outcome measures.6 Relative to PCI and surgical aortic valve replacement, the quality framework in transcatheter aortic valve replacement (TAVR) is significantly less developed. To date, TAVR volume has been promulgated as a marker of TAVR quality and incorporated as a requirement for launching or maintaining a TAVR program in the United States. In the current 2012 National Coverage Determination by the Centers for Medicare and Medicaid Services, a cardiovascular surgeon and an interventional cardiologist need a combined experience of at least 20 TAVR procedures in the prior year or 40 in the prior 2 years to maintain a TAVR program.7 Similarly, in a 2018 expert consensus statement from 4 US professional societies, operator TAVR experience is described as a requirement for launching a new TAVR program (experience with >100 transfemoral TAVRs lifetime, including 50 TAVRs as primary operator). 8 At its essence, procedural volumes represent a structural measure within the Donabedian framework. Structural measures have the benefit of being easy to measure but are essentially surrogates of the metrics of the greatest interest patient outcomes. Quality assessment groups, such as the National Quality Forum, have developed sophisticated and comprehensive frameworks and tools to assess the suitability of structural and process measures as quality indicators.8 However, an ideal feature of a structural quality measure would be an association between that measure and ultimate outcomes of interest. To this end, there are several reports showing the volume-outcome relationship in TAVR.9,10 Circulation: Cardiovascular Quality and Outcomes