Neuromechanics of finger hangs with arm lock-offs: analyzing joint moments and muscle activations to improve practice guidelines for climbing.

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.

Advanced Cell Culture Models Illuminate the Interplay between Mammary Tumor Cells and Activated Fibroblasts.

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.

Design of a sensor network for the quantitative analysis of sport climbing.

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.

Three-dimensional femtosecond snapshots of isolated faceted nanostructures.

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.

The Scatman: an approximate method for fast wide-angle scattering simulations.

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 ∼10°, 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.

Comparing Left Internal Mammary Angiography via Right Radial or Femoral Access With a Single-Catheter Technique.

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.

Crystallization kinetics of atomic crystals revealed by a single-shot and single-particle X-ray diffraction experiment.

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.

[A case of concomitant aortic stenosis and aortic arch aneurysm: a combined endovascular approach]. / Aneurisma dell'arco aortico e stenosi valvolare aortica: un approccio endovascolare combinato.

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.

Adjuvant vaginal interventional radiotherapy in early-stage non-endometrioid carcinoma of corpus uteri: a systematic review.

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.

Imaging plasma formation in isolated nanoparticles with ultrafast resonant scattering.

We have recorded the diffraction patterns from individual xenon clusters irradiated with intense extreme ultraviolet pulses to investigate the influence of light-induced electronic changes on the scattering response. The clusters were irradiated with short wavelength pulses in the wavelength regime of different 4d inner-shell resonances of neutral and ionic xenon, resulting in distinctly different optical properties from areas in the clusters with lower or higher charge states. The data show the emergence of a transient structure with a spatial extension of tens of nanometers within the otherwise homogeneous sample. Simulations indicate that ionization and nanoplasma formation result in a light-induced outer shell in the cluster with a strongly altered refractive index. The presented resonant scattering approach enables imaging of ultrafast electron dynamics on their natural timescale.

Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial.

AIMS: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12 months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36 month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36 months. METHODS AND RESULTS: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36 months. No differences were observed in biomarker concentration between the two study arms, 'prevention' vs. 'troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36 months was 23.4 ng/L, higher (N.S.) than at baseline, 17.6 ng/L. PTX3 peaked at 5.2 ng/mL 1 month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26 ng/L 1 month after CT and returned to 3 ng/L until the last measurement at 36 months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24 mL/m2 . CONCLUSIONS: First-in-life CT with median cumulative dose of anthracyclines of 180 mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51 years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

The role of vaginal brachytherapy in stage I endometrial serous cancer: a systematic review.

PURPOSE: Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT). MATERIAL AND METHODS: A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews. RESULTS: All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%. CONCLUSIONS: These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.

On the Effects of Package on the PMUTs Performances-Multiphysics Model and Frequency Analyses.

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.

Characterizing crystalline defects in single nanoparticles from angular correlations of single-shot diffracted X-rays.

Characterizing and controlling the uniformity of nanoparticles is crucial for their application in science and technology because crystalline defects in the nanoparticles strongly affect their unique properties. Recently, ultra-short and ultra-bright X-ray pulses provided by X-ray free-electron lasers (XFELs) opened up the possibility of structure determination of nanometre-scale matter with Å spatial resolution. However, it is often difficult to reconstruct the 3D structural information from single-shot X-ray diffraction patterns owing to the random orientation of the particles. This report proposes an analysis approach for characterizing defects in nanoparticles using wide-angle X-ray scattering (WAXS) data from free-flying single nanoparticles. The analysis method is based on the concept of correlated X-ray scattering, in which correlations of scattered X-ray are used to recover detailed structural information. WAXS experiments of xenon nanoparticles, or clusters, were conducted at an XFEL facility in Japan by using the SPring-8 Ångstrom compact free-electron laser (SACLA). Bragg spots in the recorded single-shot X-ray diffraction patterns showed clear angular correlations, which offered significant structural information on the nanoparticles. The experimental angular correlations were reproduced by numerical simulation in which kinematical theory of diffraction was combined with geometric calculations. We also explain the diffuse scattering intensity as being due to the stacking faults in the xenon clusters.

Utility of Blood Flow/Resistance Index Ratio (Qx) as a Marker of Stenosis and Future Thrombotic Events in Native Arteriovenous Fistulas.

Objective: The resistance index (RI) and the blood flow volume (Qa) are the most used Doppler ultrasound (DUS) parameters to identify the presence of stenosis in arteriovenous fistula (AVF). However, the reliability of these indexes is now matter of concern, particularly in predicting subsequent thrombosis. In this study, we aimed at testing the diagnostic capacity of the Qa/RI ratio (Qx) for the early identification of AVF stenosis and for thrombosis risk stratification. Methods: From a multicentre source population of 336 HD patients, we identified 119 patients presenting at least one "alarm sign" for clinical suspicious of stenosis. Patients were therefore categorized by DUS as stenotic (n = 60) or not-stenotic (n = 59) and prospectively followed. Qa, RI, and QX, together with various clinical and laboratory parameters, were recorded. Results: Qa and Qx were significantly higher while RI was significantly lower in non-stenotic vs. stenotic patients (p < 0.001 for each comparison). At ROC analyses, Qx had the best discriminatory power in identifying the presence of stenosis as compared to Qa and RI (AUCs 0.976 vs. 0.953 and 0.804; p = 0.037 and p < 0.0001, respectively). During follow-up, we registered 30 thrombotic events with an incidence rate of 12.65 (95% CI 8.54-18.06) per 100 patients/year. In Cox-regression proportional hazard models, Qx showed a better capacity to predict thrombosis occurrence as compared to Qa (difference between c-indexes: 0.012; 95% CI 0.004-0.01). Conclusions: In chronic haemodialysis patients, Qx might represent a more reliable and valid indicator for the early identification of stenotic AVFs and for predicting the risk of following thrombosis.

High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses - 14 years of single-centre experience.

PURPOSE: To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. MATERIAL AND METHODS: From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. RESULTS: The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. CONCLUSIONS: HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

Incidence, Management, Prevention and Outcome of Post-Operative Atrial Fibrillation in Thoracic Surgical Oncology.

Atrial fibrillation (AF) is a common supraventricular arrhythmia, a recognized risk factor for ischemic stroke, as a potential driver for heart failure (HF). Cancer patients have an increased risk for AF, even not including any cancer-specific treatment, as surgery or chemotherapy. The mechanism is multifactorial, with inflammation and changes in autonomic tone as critical actors. Commonly, AF is a recurrent complication of the post-operative period in cancer surgery (especially thoracic). Recent papers confirmed a significant incidence of post-operative (non-cardiac surgery) AF (PAF), partially mitigated by the use of prophylactic (rate o rhythm control) treatments. A relevant difference, in terms of mean hospitalization time, emerges between patients developing PAF and those who do not, while long term impact remains a matter of debate, due to several potential confounding factors. Besides clinical predictors, structural (i.e., echocardiographic) and bio-humoral findings may help in risk prediction tasks. In this respect, pre-operative natriuretic peptides (NPs) concentrations are nowadays recognized as significant independent predictors of perioperative cardiovascular complications (including PAF), while elevated post-operative levels may further enhance risk stratification. The aim of the present paper is to trace the state of the art in terms of incidence, management, prevention, and outcome of PAF in the field of thoracic surgical oncology.

Ultrafast Structural Dynamics of Nanoparticles in Intense Laser Fields.

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.