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Crystallization is a fundamental natural phenomenon and the ubiquitous physical process in materials science for the design of new materials. So far, experimental observations of the structural dynamics in crystallization have been mostly restricted to slow dynamics. We present here an exclusive way to explore the dynamics of crystallization in highly controlled conditions (i.e., in the absence of impurities acting as seeds of the crystallites) as it occurs in vacuum. We have measured the early formation stage of solid Xe nanoparticles nucleated in an expanding supercooled Xe jet by means of an X-ray diffraction experiment with 10-fs X-ray free-electron laser (XFEL) pulses. We found that the structure of Xe nanoparticles is not pure face-centered cubic (fcc), the expected stable phase, but a mixture of fcc and randomly stacked hexagonal close-packed (rhcp) structures. Furthermore, we identified the instantaneous coexistence of the comparably sized fcc and rhcp domains in single Xe nanoparticles. The observations are explained by the scenario of structural aging, in which the nanoparticles initially crystallize in the highly stacking-disordered rhcp phase and the structure later forms the stable fcc phase. The results are reminiscent of analogous observations in hard-sphere systems, indicating the universal role of the stacking-disordered phase in nucleation.
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Femtosecond laser pulses have opened new frontiers for the study of ultrafast phase transitions and nonequilibrium states of matter. In this Letter, we report on structural dynamics in atomic clusters pumped with intense near-infrared (NIR) pulses into a nanoplasma state. Employing wide-angle scattering with intense femtosecond x-ray pulses from a free-electron laser source, we find that highly excited xenon nanoparticles retain their crystalline bulk structure and density in the inner core long after the driving NIR pulse. The observed emergence of structural disorder in the nanoplasma is consistent with a propagation from the surface to the inner core of the clusters.
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OBJECTIVES: To report 1-year clinical outcomes of bioresorbable vascular scaffold (BVS) in acute coronary syndromes (ACS) population. BACKGROUND: BVS use has rapidly extended to high-risk patients as those presenting with ACS. To date limited data have been reported on BVS performance in ACS patients. METHODS: RAI is a multicenter, prospective registry that included 1,505 patients treated with at least 1 successful BVS implantation. A subgroup analysis on ACS patients was performed and the 1-year outcomes of this cohort compared to the remaining stable coronary artery disease (SCAD) population are reported here. Coprimary endpoints were target-lesion revascularization (TLR) and scaffold thrombosis (ScT) at 1-year follow-up. RESULTS: Fifty-nine percent of the patients presented with ACS, of whom 36.5% with ST-elevation myocardial infarctions. ACS patients were significantly younger, with a better cardiovascular risk profile, a lower rate of multivessel disease, chronic total occlusion or in-stent restenosis and a lower Syntax score. Predilation and postdilation were performed in 97.4% and in 96.5% of cases, respectively. No differences were noted in terms of TIMI 3 final flow, but acute gain was greater in ACS compared to SCAD group (P < 0.001). At one-year follow-up no differences were found in terms of TLR (3.3% vs. 3.3%, P = 0.98), and device-oriented composite end-point (4.3% vs. 3.4%, P = 0.4) between ACS and SCAD groups. The rate of definite/probable ScT was numerically higher in ACS vs. stable CAD patients (1.3% vs. 0.8%, P = 0.2). CONCLUSIONS: Our data suggest that the use of BVS in ACS patients is associated with a numerically higher rate of ScT compared to SCAD population numerically higher, but without statistical significance.
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Implantes Absorbibles , Síndrome Coronario Agudo/terapia , Angina Inestable/terapia , Angioplastia Coronaria con Balón/instrumentación , Infarto del Miocardio sin Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/mortalidad , Anciano , Angina Inestable/diagnóstico por imagen , Angina Inestable/mortalidad , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/mortalidad , Trombosis Coronaria/mortalidad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/mortalidad , Estudios Prospectivos , Diseño de Prótesis , Sistema de Registros , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. RESULTS: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1-73·1). 5-year overall survival was 81·8% (95% CI 77·5-86·2) with chemoradiotherapy versus 76·7% (72·1-81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54-1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3-79·9) versus 68·6% (63·1-73·4; HR 0·71, 95% CI 0·53-0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity. INTERPRETATION: Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/terapia , Quimioradioterapia Adyuvante , Fraccionamiento de la Dosis de Radiación , Neoplasias Endometriales/terapia , Procedimientos Quirúrgicos Ginecológicos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Australia , Canadá , Carboplatino/administración & dosificación , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Quimioradioterapia Adyuvante/efectos adversos , Quimioradioterapia Adyuvante/mortalidad , Cisplatino/administración & dosificación , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Europa (Continente) , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/mortalidad , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Nueva Zelanda , Paclitaxel/administración & dosificación , Radioterapia Adyuvante , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent. METHODS: We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in the non-overlap group. The most frequent overlap configuration was the marker-to-marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker (6%) types. Patients of the overlap group had higher prevalence of multivessel disease and higher SYNTAX score, and required more frequently the use of intravascular imaging. At a median follow-up of 368 days, no difference was observed between overlap and non-overlap groups in terms of a device-related composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of a patient-related composite endpoint (any death, any MI, any revascularization) (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5% vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs. 1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of the overlap population according to overlap configurations used, no difference was observed in terms of the device- or patient-related composite endpoints. CONCLUSIONS: Outcomes of patients with or without overlapping BVS were comparable at mid-term follow-up despite higher angiographic complexity of the overlap subset. © 2017 Wiley Periodicals, Inc.
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Implantes Absorbibles , Fármacos Cardiovasculares/administración & dosificación , Materiales Biocompatibles Revestidos , Everolimus/administración & dosificación , Isquemia Miocárdica/cirugía , Intervención Coronaria Percutánea/instrumentación , Anciano , Fármacos Cardiovasculares/efectos adversos , Angiografía Coronaria , Everolimus/efectos adversos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Estudios Prospectivos , Diseño de Prótesis , Recurrencia , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48·6 Gy) in 1·8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. FINDINGS: Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for health-related quality of life. Median follow-up was 42·3 months (IQR 25·8-55·1). At completion of radiotherapy and at 6 months, EORTC QLQ-C30 functioning scales were significantly lower (worse functioning) and health-related quality of life symptom scores higher (worse symptoms) for the chemoradiotherapy group compared with radiotherapy alone, improving with time. At 12 and 24 months, global health or quality of life was similar between groups, whereas physical functioning scores remained slightly lower in patients who received chemoradiotherapy compared with patients who received radiotherapy alone. At 24 months, 48 (25%) of 194 patients in the chemoradiotherapy group reported severe tingling or numbness compared with 11 (6%) of 170 patients in the radiotherapy alone group (p<0·0001). Grade 2 or worse adverse events were found during treatment in 309 (94%) of 327 patients in the chemoradiotherapy group versus 145 (44%) of 326 patients in the radiotherapy alone group, and grade 3 or worse events were found in 198 (61%) of 327 patients in the chemoradiotherapy group versus 42 (13%) of 326 patients in the radiotherapy alone group (p<0·0001), with most of the grade 3 adverse events being haematological (45%). At 12 and 24 months, no significant differences in grade 3 or worse adverse events were found between groups; only grade 2 or higher sensory neuropathy adverse events persisted at 24 months (25 [10%] of 240 patients in the chemoradiotherapy group vs one [<1%] of 247 patients in the radiotherapy alone group; p<0·0001). INTERPRETATION: Despite the increased physician and patient-reported toxicities, this schedule of adjuvant chemotherapy given during and after radiotherapy in patients with high-risk endometrial cancer is feasible, with rapid recovery after treatment, but with persistence of patient-reported sensory neurological symptoms in 25% of patients. We await the analysis of primary endpoints before final conclusions are made. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and Canadian Cancer Society Research Institute.
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Adenocarcinoma de Células Claras/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Cistadenocarcinoma Seroso/terapia , Neoplasias Endometriales/terapia , Calidad de Vida , Radioterapia Adyuvante/efectos adversos , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/secundario , Anciano , Carboplatino/administración & dosificación , Estudios de Casos y Controles , Cisplatino/administración & dosificación , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/secundario , Neoplasias Endometriales/patología , Neoplasias Endometriales/radioterapia , Femenino , Estudios de Seguimiento , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Humanos , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Paclitaxel/administración & dosificación , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.
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Antibióticos Antineoplásicos/efectos adversos , Doxorrubicina/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/diagnóstico , Adulto , Antraciclinas/efectos adversos , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/terapia , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiologíaRESUMEN
OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24âhours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.
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Antiarrítmicos/uso terapéutico , Fibrilación Atrial/prevención & control , Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Anciano , Fibrilación Atrial/sangre , Fibrilación Atrial/epidemiología , Femenino , Humanos , Incidencia , Losartán/uso terapéutico , Neoplasias Pulmonares/sangre , Masculino , Metoprolol/uso terapéutico , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Estudios ProspectivosRESUMEN
Modern cancer therapies are highly effective in the treatment of various malignancies, but their use is limited by the potential for cardiotoxicity. The most frequent and typical clinical manifestation of cardiotoxicity is left ventricular dysfunction, induced not only by cytotoxic conventional cancer therapy like anthracyclines, but also by new antitumor targeted therapy such as trastuzumab. The current standard for monitoring cardiac function, based on periodic assessment of left ventricular ejection fraction detects cardiotoxicity only when a functional impairment has already occurred, precluding any chance of preventing its development. A novel approach, based on the use of cardiac biomarkers has emerged in the last decade, resulting in a cost-effective diagnostic tool for early, real-time identification, assessment and monitoring of cardiotoxicity. In particular, prophylactic treatment with enalapril in patients with an early increase in troponin after chemotherapy has been shown to be very effective in preventing left ventricular dysfunction and associated cardiac events. In patients developing cancer treatment induced-cardiomyopathy, complete left ventricular ejection fraction recovery and a reduction of cardiac events may be achieved only when left ventricular dysfunction is detected early after the end of cancer treatment and treatment with angiotensin-converting enzyme inhibitors, possibly in combination with beta-blockers, is promptly initiated.
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Antineoplásicos/efectos adversos , Cardiopatías/inducido químicamente , Algoritmos , Antraciclinas/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Cardiopatías/diagnóstico , Cardiopatías/prevención & control , Humanos , Trastuzumab , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/terapiaRESUMEN
We describe the design of a modular sensorized climbing wall for motion analysis in a naturalistic environment. The wall is equipped with force sensors to measure interaction forces between the athlete and the wall, which can be used by experienced instructors, athletes, or therapists, to gain insights into the quality of motion. A specifically designed triaxial load cell is integrated into each hold placement, invisible to the climber, and compatible with standard climbing holds. Data collected through the sensors is sent to an app running on a portable device. The wall can be adapted to different uses. To validate our design, we recorded a repeated climbing activity of eleven climbers with varying degrees of expertise. Analysis of the interaction forces during the exercise demonstrates that the sensor network design can provide valuable information to track and analyze exercise performance changes over time. Here we report the design process as well as the validation and testing of the sensorized climbing wall.
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The interaction between tumor cells and activated fibroblasts determines malignant features of desmoplastic carcinomas such as rapid growth, progression towards a metastatic phenotype, and resistance to chemotherapy. On one hand, tumor cells can activate normal fibroblasts and even reprogram them into CAFs through complex mechanisms that also involve soluble factors. Among them, transforming growth factor beta (TGF-ß) and Platelet-Derived Growth Factor (PDGF) have an established role in the acquisition of pro-tumorigenic phenotypes by fibroblasts. On the other hand, activated fibroblasts release Interleukin-6 (IL-6), which increases tumor-cell invasiveness and chemoresistance. However, the interplay between breast cancer cells and fibroblasts, as well as the modes of action of TGF-ß, PDGF, and IL-6, are difficult to investigate in vivo. Here, we validated the usage of advanced cell culture models as tools to study the interplay between mammary tumor cells and fibroblasts, taking mouse and human triple-negative tumor cells and fibroblasts as a case study. We employed two different settings, one permitting only paracrine signaling, the other both paracrine and cell-contact-based signaling. These co-culture systems allowed us to unmask how TGF-ß, PDGF and IL-6 mediate the interplay between mammary tumor cells and fibroblasts. We found that the fibroblasts underwent activation induced by the TGF-ß and the PDGF produced by the tumor cells, which increased their proliferation and IL-6 secretion. The IL-6 secreted by activated fibroblasts enhanced tumor-cell proliferation and chemoresistance. These results show that these breast cancer avatars possess an unexpected high level of complexity, which resembles that observed in vivo. As such, advanced co-cultures provide a pathologically relevant tractable system to study the role of the TME in breast cancer progression with a reductionist approach.
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Introduction: Climbing imposes substantial demands on the upper limbs and understanding the mechanical loads experienced by the joints during climbing movements is crucial for injury prevention and optimizing training protocols. This study aimed to quantify and compare upper limb joint loads and muscle activations during isometric finger hanging exercises with different arm lock-off positions. Methods: Seventeen recreational climbers performed six finger dead hangs with arm lock-offs at 90° and 135° of elbow flexion, as well as arms fully extended. Upper limb joint moments were calculated using personalized models in OpenSim, based on three-dimensional motion capture data and forces measured on an instrumented hang board. Muscle activations of upper limb muscles were recorded with surface electromyography electrodes. Results: Results revealed that the shoulder exhibited higher flexion moments during arm lock-offs at 90° compared to full extension (p = 0.006). The adduction moment was higher at 135° and 90° compared to full extension (p < 0.001), as well as the rotation moments (p < 0.001). The elbows exhibited increasing flexion moments with the increase in the arm lock-off angle (p < 0.001). Muscle activations varied across conditions for biceps brachii (p < 0.001), trapezius (p < 0.001), and latissimus dorsi, except for the finger flexors (p = 0.15). Discussion: Our findings indicate that isometric finger dead hangs with arms fully extended are effective for training forearm force capacities while minimizing stress on the elbow and shoulder joints. These findings have important implications for injury prevention and optimizing training strategies in climbing.
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The structure and dynamics of isolated nanosamples in free flight can be directly visualized via single-shot coherent diffractive imaging using the intense and short pulses of x-ray free-electron lasers. Wide-angle scattering images encode three-dimensional (3D) morphological information of the samples, but its retrieval remains a challenge. Up to now, effective 3D morphology reconstructions from single shots were only achieved via fitting with highly constrained models, requiring a priori knowledge about possible geometries. Here, we present a much more generic imaging approach. Relying on a model that allows for any sample morphology described by a convex polyhedron, we reconstruct wide-angle diffraction patterns from individual silver nanoparticles. In addition to known structural motives with high symmetries, we retrieve imperfect shapes and agglomerates that were not previously accessible. Our results open unexplored routes toward true 3D structure determination of single nanoparticles and, ultimately, 3D movies of ultrafast nanoscale dynamics.
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The aims of this study were to assess the behavior of a vibrating platform under different conditions and to compare the effects of an 8-week periodized training program with whole-body vibration (WBV) alone or in combination with conventional strength training (ST). Vibrating frequencies, displacements, and peak accelerations were tested through a piezoelectric accelerometer under different conditions of load and subjects' position. Eighteen national-level female athletes were assigned to 1 of 3 different groups performing WBV, conventional ST, or a combination of the 2 (WBV + ST). Isometric maximal voluntary contraction, dynamic maximal concentric force, and vertical jump tests were performed before and after the conditioning program. Vibrating displacements and maximum accelerations measured on the device were not always consistent with their expected values calculated from the display and manufacturers' information (sinusoidal waveforms). The WBV alone or in combination with low-intensity resistance exercise did not seem to induce significant enhancements in force and power when compared with ST. It appears that WBV cannot substitute parts of ST loading in a cohort of young female athletes. However, vibration effects might be limited by the behavior of the commercial platforms as the one used in the study. More studies are needed to analyze the performances of devices and the effectiveness of protocols.
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Rendimiento Atlético , Fuerza Muscular , Entrenamiento de Fuerza , Vibración , Adulto , Femenino , Humanos , Contracción Isométrica , Adulto JovenRESUMEN
BACKGROUND: We compared the safety and effectiveness of left internal mammary artery (LIMA) angiography through right radial (Rad) or femoral (Fem) artery access with a single-catheter technique. METHODS: LIMA selective imaging was attempted through Rad access with a Bartorelli-Cozzi 5.2Fr catheter in 190 consecutive patients. They were compared with 190 consecutive patients in whom LIMA was imaged with a mammary catheter via Fem access. Successful LIMA imaging within 15 min and time needed for imaging were efficacy end-point. Safety metrics were cerebral ischemic events and access site complications. RESULTS: Overall success rate of Rad LIMA imaging was 62 %. The success rate of Fem LIMA imaging was 97 %. In Rad group, patient age emerged as the single independent correlate of success at multivariate analysis (OR 9.938, CI 0.902-0.977 p = 0.002), with 77 % success rate in the lowest age quartile (<67 years). Median time needed to obtain selective LIMA imaging was significantly longer in Rad than in Fem (5.5 min vs. 4.0 min, p < 0.001), but right radial access was not a significant predictor of time needed to image LIMA at multivariate analysis (K 0.726, CI [-0.130-1.581], p = 0.09). Access site complications (6 vs. 0 cases, p = 0.030), and clinically significant bleeding (4 vs. 0 cases, p = 0.1) occurred in Fem group only. No peri-procedural cerebrovascular events were seen in either Group. CONCLUSIONS: Right radial artery is a suboptimal, yet reasonable access for LIMA-graft selective imaging in younger patients. The technique is free from vascular complications and peri-procedural cerebrovascular events.
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Arterias Mamarias , Arteria Radial , Humanos , Anciano , Arteria Radial/diagnóstico por imagen , Angiografía Coronaria/métodos , Arterias Mamarias/diagnóstico por imagen , Arteria Femoral/diagnóstico por imagen , CatéteresRESUMEN
Single-shot coherent diffraction imaging (CDI) is a powerful approach to characterize the structure and dynamics of isolated nanoscale objects such as single viruses, aerosols, nanocrystals and droplets. Using X-ray wavelengths, the diffraction images in CDI experiments usually cover only small scattering angles of a few degrees. These small-angle patterns represent the magnitude of the Fourier transform of the 2D projection of the sample's electron density, which can be reconstructed efficiently but lacks any depth information. In cases where the diffracted signal can be measured up to scattering angles exceeding â¼10°, i.e. in the wide-angle regime, some 3D morphological information of the target is contained in a single-shot diffraction pattern. However, the extraction of the 3D structural information is no longer straightforward and defines the key challenge in wide-angle CDI. So far, the most convenient approach relies on iterative forward fitting of the scattering pattern using scattering simulations. Here the Scatman is presented, an approximate and fast numerical tool for the simulation and iterative fitting of wide-angle scattering images of isolated samples. Furthermore, the open-source software implementation of the Scatman algorithm, PyScatman, is published and described in detail. The Scatman approach, which has already been applied in previous work for forward-fitting-based shape retrieval, adopts the multi-slice Fourier transform method. The effects of optical properties are partially included, yielding quantitative results for small, isolated and weakly interacting samples. PyScatman is capable of computing wide-angle scattering patterns in a few milliseconds even on consumer-level computing hardware, potentially enabling new data analysis schemes for wide-angle coherent diffraction experiments.
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Aortic valve stenosis and aortic aneurysmal disease are increasingly prevalent with advancing age. When associated, their treatment is very challenging. A female patient with previous Tirone-David procedure presented to our hospital with acute heart failure. She was diagnosed with severe aortic stenosis, aneurysm of the aortic arch and the descending thoracic aorta. She underwent successful concomitant aortic arch TEVAR and transcatheter aortic valve repair, with optimal acute and mid-term result. Our case demonstrates that a careful pre-procedural planning, along with a good cooperation between interventional cardiologists, cardiac surgeons, radiologists and clinical cardiologists, are essential in order to guarantee an excellent outcome for the patient.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Estenosis de la Válvula Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Disección Aórtica/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/cirugía , Prótesis Vascular , Femenino , Humanos , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: This systematic review focused on rare histological types of corpus uteri malignancy, including uterine carcinosarcoma (UCS), uterine clear cell carcinoma (UCCC), and uterine papillary serous carcinoma (UPSC), and it is proposed to assist with clinical decision-making. Adjuvant treatment decisions must be made based on available evidences. We mainly investigated the role of vaginal interventional radiotherapy (VIRt) in UCS, UCCC, and UPSC managements. MATERIAL AND METHODS: A systematic research using PubMed and Cochrane library was conducted to identify full articles evaluating the efficacy of VIRt in early-stage UPSC, UCCC, and UCS. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials as well as in PROSPERO for ongoing or recently completed systematic reviews. Survival outcomes and toxicity rates were obtained. RESULTS: All studies were retrospective. For UCS, the number of evaluated patients was 432. The 2- to 5-year average local control (LC) was 91% (range, 74.2-96%), disease-free survival (DFS) 88% (range, 82-94%), overall survival (OS) 79% (range, 53.8-84.3%), the average 5-year cancer-specific survival (CSS) was 70% (range, 70-94%), and G3-G4 toxicity was 0%. For UCCC, the number of investigated patients was 335 (UCCC - 124, mixed - 211), with an average 5-year LC of 100%, DFS of 83% (range, 82-90%), OS of 93% (range, 83-100%), and G3-G4 toxicity of 0%. For UPSC, the number of examined patients was 1,092 (UPSC - 866, mixed - 226). The average 5-year LC was 97% (range, 87.1-100%), DFS 84% (range, 74.7-95.6%), OS 93% (range, 71.9-100%), CSS 89% (range, 78.9-94%), and G3-G4 toxicity was 0%. CONCLUSIONS: These data suggest that in adequately selected early-stage UPSC and UCCC patients, VIRt alone may be suitable in women who underwent surgical staging and received adjuvant chemotherapy. In early-stage UCS, a multidisciplinary therapeutic approach has to be planned, considering high-rate of pelvic and distant relapses.
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This paper deals with a multiphysics numerical modelling via finite element method (FEM) of an air-coupled array piezoelectric micromachined ultrasonic transducers (PMUTs). The proposed numerical model is fully 3D with the following features: the presence of the fabrication induced residual stresses, which determine a geometrically non-linear initial deformed configuration of the diaphragms and a remarkable shift of the fundamental frequency; the multiple coupling between different physics, namely electro-mechanical-coupling for the piezo-electric model, acoustic-structure interaction at the acoustic-structure interface and pressure acoustics in the surrounding air. The model takes into account the complete set of PMUTs belonging to the silicon die in a 4 x 4 array configuration and the protective package, as well. The results have been validated by experimental data, in terms of initial static pre-deflected configuration of the diaphragms and frequency response function of the PMUT. The numerical procedure was applied, to analyze different package configurations of the device, to study the influence of the holes on the acoustic transmission in terms of SPL and propagation pattern and consequently extract a set of design guidelines.