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Purpose: This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1. Methods: Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression. Results: JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors. Conclusion: The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategy in the future treatment of TNBC. [ABSTRACT FROM AUTHOR]

Introduction: To update the European guidelines for the assessment of voice quality (VQ) in clinical practice. Methods: Nineteen laryngologists–phoniatricians of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP) participated to a modified Delphi process to propose statements about subjective and objective VQ assessments. Two anonymized voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 3/4. The statements with ≥ 3/4 score by 60–80% of experts were improved and resubmitted to voting until they were validated or rejected. Results: Of the 90 initial statements, 51 were validated after two voting rounds. A multidimensional set of minimal VQ evaluations was proposed and included: baseline VQ anamnesis (e.g., allergy, medical and surgical history, medication, addiction, singing practice, job, and posture), videolaryngostroboscopy (mucosal wave symmetry, amplitude, morphology, and movements), patient-reported VQ assessment (30- or 10-voice handicap index), perception (Grade, Roughness, Breathiness, Asthenia, and Strain), aerodynamics (maximum phonation time), acoustics (Mean F0, Jitter, Shimmer, and noise-to-harmonic ratio), and clinical instruments associated with voice comorbidities (reflux symptom score, reflux sign assessment, eating-assessment tool-10, and dysphagia handicap index). For perception, aerodynamics and acoustics, experts provided guidelines for the methods of measurement. Some additional VQ evaluations are proposed for voice professionals or patients with some laryngeal diseases. Conclusion: The ELS-UEP consensus for VQ assessment provides clinical statements for the baseline and pre- to post-treatment evaluations of VQ and to improve collaborative research by adopting common and validated VQ evaluation approach. [ABSTRACT FROM AUTHOR]

Objectives: The anterior, percutaneous Botulinum neurotoxin (BoNT) injection in the lateral cricoarytenoid muscle (LCA) guided by laryngeal electromyography (LEMG) is considered the golden standard treatment for several neurolaryngological disorders. The study presented in this article aims to assess the effectiveness of an alternative approach by which the injection is performed laterally under ultrasound monitoring. Study design: Anatomical dissection study in human cadavers. Settings: Academic health care center. Methods: Ultrasound-guided bilateral dye (0.1 mL of dye solution containing cold-curing polymers, latex, acrylates, acrylic esters, alcohol, and green color) injection in the LCA was performed by means of 24G needles and 1 mL syringes using the lateral approach. The dye location and distribution were assessed by anatomic dissection, performed immediately after the injection. Results: In 9/10 specimens, the dye was exclusively detectable in the LCA. In 1/10 case (left side), the dye could not be delivered in the LCA because of unintended penetration of the thyroid cartilage by the needle during injection. Anatomic dissection confirmed that the dye spread neither into the thyroarytenoid (TA) nor the cricothyroid muscle (CT). Conclusions: The anatomic dissection following lateral dye injection in the LCA under ultrasound guide confirmed the precision of this approach in delivery a substance exclusively in a pre-determined target. This feature makes this method an interesting addition or alternative to the standard LEMG-guided BoNT injection at least when the LCA is its target. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Objectives: Previous meta-analyses suggested that mindfulness-based interventions (MBIs) may have beneficial effects on telomere length (TL) and telomerase activity (TA), two biological markers of cellular aging and cell stress. The present review aimed to provide the most comprehensive synthesis of the available evidence to date and tested a number of important effect moderators. Method: Twenty-five studies (18 RCTs, 1 RCT and cohort study, 6 non-randomized studies) with 2099 participants in total were obtained with a systematic literature search, 10 studies had not been included in any previous meta-analysis. Effect sizes were aggregated with random-effects models, the risk of bias was evaluated with standardized checklists, and the most influential moderators were identified with a machine-learning approach. Results: On average, MBIs had small-to-medium effects on TL (g = 0.23, 95% CI = [0.07, 0.39], p = 0.006) and TA (g = 0.37 [0.01, 0.73], p = 0.046), which, however, were driven by retrospective case–control studies with experienced meditators (TL) and by studies without control interventions and studies from Asia (TA). Most studies had an unclear risk of bias and low analytic power, and there was an indication of publication bias among the TL studies. Conclusions: TL may not be a useful outcome to assess the efficacy of common MBIs. Effects on TA were smaller than previously assumed and may not be specific for MBIs; TA likely is increased by other active interventions as well. More high-quality and high-powered studies, which also apply open-science practices, are needed to move the field forward. [ABSTRACT FROM AUTHOR]

Purpose: Since the introduction of transcutaneous-transcricoidal needle approaches, electromyography (EMG) of the posterior cricoarytenoid muscle (PCA) became easier to perform and teach. Among the Neurolaryngology working group of the European Laryngological Society, several centers have adopted PCA EMG as part of their routine EMG workup in vocal fold immobility collectively gathering long-term experience. The purpose is to give an update and an extension to already existing guidelines on laryngeal EMG with specific regard to PCA EMG. Methods: Consensus of all co-authors is based on continuous exchange of ideas and on joint laryngeal EMG workshop experiences over at least 7 years. A Delphi method of consensus development was used, i.e., the manuscript was circulated among the co-authors until full agreement was achieved. Results: Step-by-step instructions on how to perform and interpret PCA EMG are provided. Conclusions: Further research should include the establishment of normal values for PCA and thyroarytenoid muscle (TA) EMG as well as studies on the nature of some unusual activation pattern commonly seen in chronically lesioned PCA. [ABSTRACT FROM AUTHOR]

The Nemhauser–Trotter theorem states that the standard linear programming (LP) formulation for the stable set problem has a remarkable property, also known as (weak) persistency: for every optimal LP solution that assigns integer values to some variables, there exists an optimal integer solution in which these variables retain the same values. While the standard LP is defined by only non-negativity and edge constraints, a variety of other LP formulations have been studied and one may wonder whether any of them has this property as well. We show that any other formulation that satisfies mild conditions cannot have the persistency property on all graphs, unless it is always equal to the stable set polytope. [ABSTRACT FROM AUTHOR]

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Purpose: In clinical practice, laryngo(strobo)scopy (LS) is still mainly used for diagnostics and management of unilateral vocal fold paralysis (UFVP), although only laryngeal electromyography (LEMG) can provide information on causes of vocal fold immobility, especially on possible synkinetic reinnervation after recurrent laryngeal nerve (RLN) injury. The goal of this retrospective study was the evaluation whether signs of synkinetic reinnervation in LS can be objectified in comparison to LEMG data. Methods: Between 1/2015 and 2/2018, 50 patients with laryngostroboscopically suspected UVFP received routine LEMG examination. The LEMG findings were retrospectively compared with LS findings. The LEMG data analysis focused on the diagnosis of synkinetic reinnervation of the TA/LCA and/or PCA. The digital LS recordings were retrospectively re-evaluated by phoniatricians considering 22 selected laryngostroboscopic parameters. Results: LEMG revealed synkinesis in 23 (46%) and absence of synkinesis in 27 (54%) patients. None of the 22 parameters showed significant association between patients with synkinetic reinnervation and LS findings. The only laryngostroboscopic parameter that was significantly associated with a silent LEMG signal compared to single fiber activity in LEMG was a length difference on the side of the UVFP (p-value 0.0001; OR 14.5 (95% CI 3.047–66.81; Sensitivity 0.5; Specificity 0.9355). Conclusion: Our findings show that synkinesis cannot be diagnosed using only LS. This study underlines the importance of LEMG in clinical routine for detection of laryngeal synkinesis in patients with UVFP before any further therapeutic steps are initiated to avoid later therapy failure. [ABSTRACT FROM AUTHOR]

Preparing and observing quantum states of nanoscale particles is a challenging task with great relevance for quantum technologies and tests of fundamental physics. In contrast to atomic systems with discrete transitions, nanoparticles exhibit a practically continuous absorption spectrum and thus their quantum dynamics cannot be easily manipulated. Here, we demonstrate that charged nanoscale dielectrics can be artificially endowed with a discrete level structure by coherently interfacing their rotational and translational motion with a superconducting qubit. We propose a pulsed scheme for the generation and read-out of motional quantum superpositions and entanglement between several levitated nanoparticles, providing an all-electric platform for networked hybrid quantum devices. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes a first attempt to quantify LEMG data based on turn number calculation. The results obtained for both healthy and ailing thyroarytenoid (TA) muscles of patients with unilateral vocal fold immobility (UVFI) were compared with the respective qualitative evaluation concerning volitional activity to determine whether the two types of analyses deliver similar results. Methods: LEMG data obtained from 44 adults with UVFI were considered for the study. Semiquantitative evaluation of TA volitional activity and turn number were assessed for the ailing and the healthy TA and the difference in percentage was calculated. Paired data were compared with the Wilcoxon signed-rank test. The volitional activity assessment and the turn number evaluation were compared with the Kruskal–Wallis test, and their relationship was tested with the Kendall rank correlation. Results: Datasets of 27 patients were considered compatible with turns/s calculation. The results showed that complete paralysis correlated with no turns; single fiber volitional activity with 62–208 turns/s, strongly decreased volitional activity with 198–501 turns/s; and dense volitional activity with 441–1234 turns/s. On the ailing VF only, the Kruskal–Wallis test showed a statistically significant difference (p = 0.0001), and the Kendall rank correlation a positive relationship (r = 0.853,p ≤ 0.0001) between the volitional activity rating and the turn number assessment. Conclusions: Our preliminary results showed that turn number evaluation is an effective tool to confirm LEMG qualitative analysis, and that, in combination with laryngostroboscopy and voice assessment, can help improving the accuracy of the diagnosis and prognosis and the effectiveness of the chosen therapy. [ABSTRACT FROM AUTHOR]

Purpose: Persistent unilateral vocal fold paralysis (UFVP) with glottal insufficiency often requires type I medialization thyroplasty (MT). Previous implants cannot be adjusted postoperatively if necessary. The newly developed APrevent® VOIS implant (VOIS) can provide postoperative re-adjustment to avoid revision MT. The objective of this pilot study is to evaluate the VOIS intraoperatively concerning voice improvement, surgical feasibility and device handling. Methods: During routine MT, VOIS was applied short time in eight patients before the regular implantation of the Titanium Vocal Fold Medialization Implant (TVFMI™). In all patients, perceptual voice sound analysis using R(oughness)–B(reathiness)–H(oarseness)-scale, measurement of M(aximum)–P(honation)–T(ime) and glottal closure in videolaryngoscopy were performed before and after implanting VOIS/TVFMI™. Acoustic analyses of voice recordings were performed using freeware praat. Surgical feasibility, operative handling and device fitting of VOIS and TVFMI™ were assessed by the surgeon using V(isual)-A(nalog)-S(cale). Data were statistically analyzed with paired t test. Result: All patients showed significant improvement of voice sound parameters after VOIS/TVFMI™ implantation. The mean RBH-scale improved from preoperative R = 2.1, B = 2.3, H = 2.5 to R = 0.6, B = 0.3, H = 0.8 after VOIS and R = 0.5, B = 0.3, H = 0.8 after TVFMI™ implantation. The mean MPT increased from preoperative 7.9 to 14.6 s after VOIS and 13.8 s after TVFMI™ implantation. VOIS/TVFMI™ achieved complete glottal closure in 7/8 patients. The satisfaction with intraoperative device fitting and device handling of VOIS was as good as that of TVFMI™. Conclusion: The novel APrevent® VOIS implant showed similar intraoperative voice improvement compared to routinely used TVFMI™ without adverse device events and with safe device fitting. [ABSTRACT FROM AUTHOR]

Copyright of BHM Berg- und Hüttenmännische Monatshefte is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Laryngeal electromyography (LEMG) has been considered as gold standard in diagnostics of vocal fold movement impairment, but is still not commonly implemented in clinical routine. Since the signal interpretation of LEMG signals (LEMGs) is often a subjective and semi-quantitative matter, the goal of this study was to evaluate the inter-rater reliability of neurolaryngologists on LEMGs of volitional muscle activity. Methods: For this study, 52 representative LEMGs of 371 LEMG datasets were selected from a multicenter registry for a blinded evaluation by 7 experienced members of the neurolaryngology working group of the European Laryngological Society (ELS). For the measurement of the observer agreement between two raters, Cohen's Kappa statistic was calculated. For the interpretation of agreements of diagnoses among the seven examiners, we used the Fleiss' Kappa statistic. Result: When focusing on the categories "no activity", "single fiber pattern", and "strongly decreased recruitment pattern", the inter-rater agreement varied from Cohen's Kappa values between 0.48 and 0.84, indicating moderate to near-perfect agreement between the rater pairs. Calculating with Fleiss' Kappa, a value of 0.61 showed good agreement among the seven raters. For the rating categories, the Fleiss' Kappa value ranged from 0.52 to 0.74, which also showed a good agreement. Conclusion: A good inter-rater agreement between the participating neurolaryngologists was achieved in the interpretation of LEMGs. More instructional courses should be offered to broadly implement LEMG as a reliable diagnostic tool in evaluating vocal fold movement disorders in clinical routine and to develop future algorithms for therapy and computer-assisted examination. [ABSTRACT FROM AUTHOR]

Purpose: To describe the use of a myocutaneous serratus anterior free flap (SAFF) for tongue reconstruction after salvage subtotal (STG) and total glossectomy (TG).Methods: In this prospective case series, seven patients underwent salvage STG or TG and reconstruction with a myocutaneous SAFF between 10/2015 and 02/2017. Functional and oncologic outcomes were prospectively evaluated. Donor side morbidity was determined using the Disabilities of the Arm, Shoulder and Hand (DASH) score.Results: SAFF with mean skin paddles of 6.7 cm × 8.7 cm was used in five STG and two TG patients, respectively. There was a 100% flap survival and a mean DASH score of 10.8 reflected normal arm and shoulder function after surgery. One year after salvage surgery, 1 (14.3%) and 4 (57.1%) patients were tracheostomy and gastrostomy tube dependent. Gastrostomy tube dependence was significantly worse in patients with tumors of the base of tongue compared to other tumor sites (p = 0.030) and in patients who underwent transcervical compared to transoral tumor resection (p = 0.008). Local recurrence rate was 57.1% with a disease-free survival of 17.6 months.Conclusion: The myocutaneous SAFF represents a safe and reliable flap for tongue reconstruction after salvage glossectomy with satisfying functional outcomes and low donor side morbidity. [ABSTRACT FROM AUTHOR]

Participation is usually regarded as a good practice in environmental policymaking, but its effects on policy strategies are unclear. Based on literature research, surveys, and interviews with participants, the present paper assesses whether decisional participation in formulating Austria's National Adaptation Strategy (NAS) was worth the effort. Assessed against the goals of the participation process, we find that it raised awareness for adaptation and facilitated an exchange among the participants and that it improved the content of the NAS. However, regarding the goal of enhancing the acceptance of and commitment to the NAS, we find that this has been achieved among those who participated but not among high-level policymakers who are responsible for implementing the NAS. We conclude that (decisional) participation has its benefits in formulating comprehensive policy strategies but that it is most likely not able to overhaul their well-documented weaknesses, among them weak political commitment and implementation failures. [ABSTRACT FROM AUTHOR]

Winter is an ecologically challenging season for ectothermic cold-water fish in natural streams because of reduced flow and freezing. Hydropower regulation in many northern rivers increase winter stream flow and temperatures, and reduce ice formation and surface ice cover. From a background review of knowledge about e.g. Atlantic salmon ( Salmo salar) and brown trout ( Salmo trutta) winter survival strategies, we explore responses to hydropower impacts as a basis for adaptive management, mitigating strategies, and future research. Winter intensity and duration, hydrologic conditions and channel characteristics drive complex ice processes which become more complex and pervasive in smaller, high-gradient streams. Stream ice formation may be divided into the dynamic period 'freeze-up' in early winter with sub-surface ice, more stable 'mid-winter' with surface ice, and the ecologically challenging 'ice break-up' in winter-spring with potential mechanical ice runs and scouring. The characteristics of periods vary depending on climate and hydropower regulation. In reaches downstream of power-plant outlets water temperature may increase and reduce surface ice formation. The mid-winter period destabilize or become absent. In bypass reaches flows decrease and facilitate freezing and ice production. Knowledge about longitudinal water temperature changes is limited. Hydro-peaked systems may aggravate high-low flow effects. A basic winter survival strategy in salmon and trout is energy storage, but also reduced metabolism, tolerance and starvation effected by quiescence. Energy storage may depend on local conditions, but there is little indication of adaptation to local thermal climates. Intraspecific phenotypic plasticity is important. The main behavioural strategy is risk-reducing sheltering in the substratum or deep areas, and nocturnal activity. Local movements between daytime refuges and nighttime slow-current activity areas are usually limited to meters. Larger fish may move more and aggregate in restricted suitable deep-slow refuge habitats such as pools and deep glides. Fish cope with ordinary thermal ice phenomena, and do not appear to become trapped in ice. Surface ice may reduce fish metabolism, but other factors, e.g. availability of substrate shelter, may override this effect. Mechanical ice break-ups and less surface ice may reduce survival. An adaptive mitigating strategy may be higher regulated flows in winter which increase rearing and/or resting habitat and survival, but studies are few and knowledge is limited. However, higher regulated flows also affect temperature regime. Low flows increase ice formation, reduce and fragment available habitat, and may reduce egg and fish survival. Influx of ground water may mitigate these impacts, as will stabilize minimum flows. Sudden drops in regulated water discharge should be avoided. Fish may strand, in particular at low temperatures in the daytime when fish are less mobile and seek shelter. The challenging winter season is understudied, and important management considerations and future research areas for better adaptive management are suggested. [ABSTRACT FROM AUTHOR]

Nanomechanical devices have attracted the interest of a growing interdisciplinary research community, since they can be used as highly sensitive transducers for various physical quantities. Exquisite control over these systems facilitates experiments on the foundations of physics. Here, we demonstrate that an optically trapped silicon nanorod, set into rotation at MHz frequencies, can be locked to an external clock, transducing the properties of the time standard to the rod's motion with a remarkable frequency stability fr/Δfrof 7.7 × 1011. While the dynamics of this periodically driven rotor generally can be chaotic, we derive and verify that stable limit cycles exist over a surprisingly wide parameter range. This robustness should enable, in principle, measurements of external torques with sensitivities better than 0.25 zNm, even at room temperature. We show that in a dilute gas, real-time phase measurements on the locked nanorod transduce pressure values with a sensitivity of 0.3%. [ABSTRACT FROM AUTHOR]

The present study is an effort to deepen the understanding of Indian summer monsoon rainfall (ISMR) on decadal to multi-decadal timescales. We use ensemble simulations for the period AD 1600-2000 carried out by the coupled Atmosphere-Ocean-Chemistry-Climate Model (AOCCM) SOCOL-MPIOM. Firstly, the SOCOL-MPIOM is evaluated using observational and reanalyses datasets. The model is able to realistically simulate the ISMR as well as relevant patterns of sea surface temperature and atmospheric circulation. Further, the influence of Atlantic Multi-decadal Oscillation (AMO), Pacific Decadal Oscillation (PDO), and El Niño Southern Oscillation (ENSO) variability on ISMR is realistically simulated. Secondly, we investigate the impact of internal climate variability and external climate forcings on ISMR on decadal to multi-decadal timescales over the past 400 years. The results show that AMO, PDO, and Total Solar Irradiance (TSI) play a considerable role in controlling the wet and dry decades of ISMR. Resembling observational findings most of the dry decades of ISMR occur during a negative phase of AMO and a simultaneous positive phase of PDO. The observational and simulated datasets reveal that on decadal to multi-decadal timescales the ISMR has consistent negative correlation with PDO whereas its correlation with AMO and TSI is not stationary over time. [ABSTRACT FROM AUTHOR]

We present matter-wave interferometry as a tool to advance spectroscopy for a wide class of nanoparticles, clusters and molecules. The high sensitivity of de Broglie interference fringes to external perturbations enables measurements in the limit of an individual particle absorbing only a single photon on average, or even no photon at all. The method allows one to extract structural and electronic information from the loss of the interference contrast. It is minimally invasive and works even for dilute ensembles. [ABSTRACT FROM AUTHOR]

This study combines advanced characterization techniques with conventional Charpy impact tests to relate the mechanical properties to the microstructure of technically pure molybdenum, especially regarding its toughness. V-notched samples with different orientations were prepared from a rolled molybdenum plate in stress-relieved and recrystallized condition. The ductile-to-brittle transition-temperature was analyzed in terms of the delamination behavior influenced by the microstructure. A pronounced increase of toughness was found for specific oriented samples, which can be explained by macroscopic delamination. Elongated grains led to enhanced delamination in Charpy impact tests with variations for different orientations. In general, delamination occurs as a result of brittle fracture; however, an increase in toughness in the Charpy impact test can be provoked. This mechanism is called thin sheet toughening or delamination toughening. Electron backscatter diffraction measurements were performed to get a deeper knowledge about crack propagation and delamination behavior in the rolled plate. Recrystallization shifts the transition region to significantly higher temperatures, which is explained by the globular grain shape as well as grain boundary segregation. The occurrence of delamination is discussed, taking texture, grain shape and segregation effects into account. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the oral health status and dental care behaviours of patients treated for head and neck squamous cell carcinoma (HNSCC) in an Austrian tertiary hospital. Materials and methods: Dental care behaviours, oral hygiene level, caries, and periodontal parameters were assessed in 48 patients treated for HNSCC >6 months ago. Results: Only 52 % requested a dental check-up after HNSCC diagnosis and prior to treatment, and of those, 80 % received some type of dental treatment. At time-point of clinical examination, 69 % of the patients had consulted a dentist within the last year, but 88 % still needed dental treatment; 75 % had at least one tooth with caries and 78 % had moderate to severe periodontitis. Conclusion: Although it was recommended, only half of the patients did consult a dentist prior to HNSCC treatment and oral health appeared, in general, low prioritized. Clinical relevance: About 90 % of the current group of head and neck squamous cell carcinoma cancer patients presented large treatment needs, both in regard with caries and periodontal disease, about 20 months after cancer treatment. [ABSTRACT FROM AUTHOR]