bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new perspective on calmodulin-regulated calcium and ROS homeostasis upon carbon black nanoparticle exposure
Authors: Verma Nisha , Pink Mario , Schmitz-Spanke Simone 
Published: March 2021

AbstractToxicological studies propose that exposure to carbon black nanoparticles induces organ injuries and inflammatory responses. Besides, current understanding of the molecular mechanisms implies that carbon black nanoparticles (CBNP) exposure induces the production of reactive oxygen species (ROS) causing inflammation, mitochondrial dysfunction or disturbance in calcium homeostasis. However, the precise mechanisms whereby CBNP exert these effects in the lung are still not fully understood. To gain insight into the possible mechanism of CBNP exerted toxicity, human alveolar epithelial cells (A549) were exposed to different concentrations of CBNP and for different timepoints. The reaction of the cells was monitored by the systematic use of cell-based measurements of calcium and ROS, in the presence and absence of calcium (Ca2+) pump inhibitors/chelators and antioxidants. Followed by an in-depth PCR analysis of 84 oxidative stress-related genes. The measurements revealed, as compared to the control, that exposure to CBNP nanoparticles leads to the generation of high ROS levels, as well as a disturbance in calcium homeostasis, which remained primarily unchanged even after 24 h of exposure. Nevertheless, in presence of antioxidants N-acetylcysteine (NAC) and Trolox, ROS formation was considerably reduced without affecting the intracellular calcium concentration. On the other hand, Ca2+ pump inhibitors/chelators, BAPTA (1,2-bis(o-amino phenoxy)ethane-N, N, N′, N′-tetraacetic acid) and verapamil not only decreased the Ca2+ overload, but also further decreased the ROS formation, indicating its role in CBNP-induced oxidative stress. Further, a PCR array analysis of A549 cells in presence and absence of the calmodulin (CaM) antagonist W7, indicated toward nine altered oxidative stress-related genes which further confirmed our cytotoxicity results. Obtained data suggested that CBNP exposure elevates calcium ion concentration, which further contributes to oxidative stress, via the calcium-binding protein CaM. Its inhibition with W7 leads to downregulation in gene expression of nine oxidative stress-related genes, which otherwise, as compared to control, show increased gene expression. The results of the study thus confirm that exposure of lung epithelial cells to CBNP leads to oxidative stress; however, the oxidative stress itself is a result of a disturbance in both calcium and ROS homeostasis, and should be considered while searching for a new strategy for prevention of CBNP-induced lung toxicity.
Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19
Authors: Huijghebaert Suzy , Hoste Levi , Vanham Guido 
Published: March 2021

Abstract
Purpose
Nasal irrigation or nebulizing aerosol of isotonic or hypertonic saline is a traditional method for respiratory or nasal care. A recent small study in outpatients with COVID-19 without acute respiratory distress syndrome suggests substantial symptom resolution. We therefore analyzed pharmacological/pharmacodynamic effects of isotonic or hypertonic saline, relevant to SARS-CoV-2 infection and respiratory care.

Methods
Mixed search method.

Results
Due to its wetting properties, saline achieves an improved spreading of alveolar lining fluid and has been shown to reduce bio-aerosols and viral load. Saline provides moisture to respiratory epithelia and gels mucus, promotes ciliary beating, and improves mucociliary clearance. Coronaviruses and SARS-CoV-2 damage ciliated epithelium in the nose and airways. Saline inhibits SARS-CoV-2 replication in Vero cells; possible interactions involve the viral ACE2-entry mechanism (chloride-dependent ACE2 configuration), furin and 3CLpro (inhibition by NaCl), and the sodium channel ENaC. Saline shifts myeloperoxidase activity in epithelial or phagocytic cells to produce hypochlorous acid. Clinically, nasal or respiratory airway care with saline reduces symptoms of seasonal coronaviruses and other common cold viruses. Its use as aerosol reduces hospitalization rates for bronchiolitis in children. Preliminary data suggest symptom reduction in symptomatic COVID-19 patients if saline is initiated within 48 h of symptom onset.

Conclusions
Saline interacts at various levels relevant to nasal or respiratory hygiene (nasal irrigation, gargling or aerosol). If used from the onset of common cold symptoms, it may represent a useful add-on to first-line interventions for COVID-19. Formal evaluation in mild COVID-19 is desirable as to establish efficacy and optimal treatment regimens.
Convolutional neural networks for PET functional volume fully automatic segmentation: development and validation in a multi-center setting
Authors: Iantsen Andrei , Ferreira Marta , Lucia Francois , Jaouen Vincent , Reinhold Caroline , Bonaffini Pietro , Alfieri Joanne , Rovira Ramon , Masson Ingrid , Robin Philippe , Mervoyer Augustin , Rousseau Caroline , Kridelka Frédéric , Decuypere Marjolein , Lovinfosse Pierre , Pradier Olivier , Hustinx Roland , Schick Ulrike , Visvikis Dimitris , Hatt Mathieu 
Published: March 2021

AbstractPurposeIn this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics.MethodsIn cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing).ResultsThe model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training.ConclusionThe proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context.
Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNA Covid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation
Authors: Cohen Dan , Krauthammer Shir Hazut , Wolf Ido , Even-Sapir Einat 
Published: March 2021

Abstract
Purpose
Nationwide mass vaccination against Covid-19 started in Israel in late 2020. Soon we identified on [18F]FDG PET-CT studies vaccine-associated hypermetabolic lymphadenopathy (VAHL) in axillary or supraclavicular lymph nodes (ASLN) ipsilateral to the vaccination site. Sometimes, differentiation between the malignant and benign nature of the hypermetabolic lymphadenopathy (HLN) could not be made, and equivocal HLN (EqHL) was reported. The purpose of the study was to determine the overall incidence of VAHL after BNT162b2 vaccination and also its relevance to PET-CT interpretation in oncologic patients.

Methods
A total of 951 consecutive patients that underwent [18F]FDG PET-CT studies in our department were interviewed regarding the sites and dates of the vaccine doses. A total of 728 vaccinated patients (All-Vac group) were included: 346 received the first dose only (Vac-1 group) and 382 received the booster dose as well (Vac-2 group). Studies were categorized as no HLN, malignant-HLN (MHL), VAHL, or EqHL. In studies with VAHL, location, [18F]FDG-intensity uptake and nodes size were recorded.

Results
The incidences of HLN were 45.6%, 36.4%, and 53.9% in All-Vac, Vac-1, and Vac-2 groups, respectively. VAHL was reported in 80.1% of vaccinated patients with HLN. Lower incidences of VAHL were found during the first 5 days or in the third week after the first vaccine and beyond 20 days after the booster dose. In 49 of 332 (14.8%) vaccinated patients, we could not determine whether HLN was MHL or VAHL. Breast cancer and lymphoma were the leading diseases with EqHL.

Conclusion
VAHL is frequently observed after BNT162b2 administration, more commonly and with higher intensity following the booster dose. To minimize false and equivocal reports in oncological patients, timing of [18F]FDG PET-CT should be based on the time intervals found to have a lower incidence of VAHL, and choice of vaccine injection site should be advised, mainly in patients where ASLN are a relevant site of tumor involvement.
The Relationship Between Co‐morbidity, Screen‐Detection and Outcome in Patients Undergoing Resection for Colorectal Cancer
Authors: Johnstone Mark S. , McMillan Donald C. , Horgan Paul G. , Mansouri David 
Published: March 2021

AbstractBackgroundBowel cancer screening increases early stage disease detection and reduces cancer‐specific mortality. We assessed the relationship between co‐morbidity, screen‐detection and survival in colorectal cancer.MethodsA retrospective, observational cohort study compared screen‐detected (SD) and non‐screen‐detected (NSD) patients undergoing potentially curative resection (April 2009–March 2011). Co‐morbidity was quantified using ASA, Lee and Charlson Indices. Systemic inflammatory response was measured using the neutrophil lymphocyte ratio (NLR). Covariables were compared using crosstabulation and the χ2 test for linear trend. Survival was analysed using Cox Regression.ResultsOf 770 patients, 331 had SD‐ and 439 NSD‐disease. A lower proportion of SD patients had a high ASA (≥3) compared to NSD (27.2% vs 37.3%; p = 0.007). There was no significant difference in the proportion of patients with a high (≥2) Lee Index (16.3% SD vs 21.9% NSD; p = 0.054) or high (≥3) Charlson Index (22.7% SD vs 26.9% NSD; p = 0.181). On univariate analysis, NSD (HR 2.182 (1.594–2.989;p < 0.001)), emergency presentation (HR 3.390 (2.401–4.788; p < 0.001)), advanced UICC‐TNM (III or IV) (p < 0.001), high ASA (≥3) (HR 1.857 (1.362–2.532; p < 0.001)), high Charlson Index (≥3) (HR 1.800 (1.333–2.432; p < 0.001)) and high (≥3) NLR (HR 1.825 (1.363–2.442; p < 0.001)) were associated with poorer overall survival (OS). NSD predicted poorer cancer‐specific survival (CSS) (HR 2.763 (1.776–4.298; p < 0.001)). On multivariate analysis, NSD retained significance as an independent predictor of poorer OS (HR 1.796 (1.224–2.635; p = 0.003)) and CSS (HR 1.924 (1.193–3.102; p = 0.007)).ConclusionsPatients with SD cancers have significantly lower ASA scores. After adjusting for ASA, co‐morbidity and a broad range of covariables, SD patients retain significantly better OS and CSS.
Solving the migration–recombination equation from a genealogical point of view
Authors: Alberti F. , Baake E. , Letter I. , Martínez S. 
Published: March 2021

AbstractWe consider the discrete-time migration–recombination equation, a deterministic, nonlinear dynamical system that describes the evolution of the genetic type distribution of a population evolving under migration and recombination in a law of large numbers setting. We relate this dynamics (forward in time) to a Markov chain, namely a labelled partitioning process, backward in time. This way, we obtain a stochastic representation of the solution of the migration–recombination equation. As a consequence, one obtains an explicit solution of the nonlinear dynamics, simply in terms of powers of the transition matrix of the Markov chain. The limiting and quasi-limiting behaviour of the Markov chain are investigated, which gives immediate access to the asymptotic behaviour of the dynamical system. We finally sketch the analogous situation in continuous time.
CAS-LSM Datasets for the CMIP6 Land Surface Snow and Soil Moisture Model Intercomparison Project
Authors: Jia Binghao , Wang Longhuan , Wang Yan , Li Ruichao , Luo Xin , Xie Jinbo , Xie Zhenghui , Chen Si , Qin Peihua , Li Lijuan , Chen Kangjun 
Published: March 2021

AbstractThe datasets of the five Land-offline Model Intercomparison Project (LMIP) experiments using the Chinese Academy of Sciences Land Surface Model (CAS-LSM) of CAS Flexible Global-Ocean-Atmosphere-Land System Model Grid-point version 3 (CAS FGOALS-g3) are presented in this study. These experiments were forced by five global meteorological forcing datasets, which contributed to the framework of the Land Surface Snow and Soil Moisture Model Intercomparison Project (LS3MIP) of CMIP6. These datasets have been released on the Earth System Grid Federation node. In this paper, the basic descriptions of the CAS-LSM and the five LMIP experiments are shown. The performance of the soil moisture, snow, and land-atmosphere energy fluxes was preliminarily validated using satellite-based observations. Results show that their mean states, spatial patterns, and seasonal variations can be reproduced well by the five LMIP simulations. It suggests that these datasets can be used to investigate the evolutionary mechanisms of the global water and energy cycles during the past century.
Impact of the April–May SAM on Central Pacific Ocean sea temperature over the following three seasons
Authors: Liu Ting , Li Jianping , Sun Cheng , Lian Tao , Zhang Yazhou 
Published: March 2021

AbstractAlthough the impact of the extratropical Pacific signal on the El Niño–Southern Oscillation has attracted increasing concern, the impact of Southern Hemisphere Annular Mode (SAM)-related signals from outside the southern Pacific Basin on the equatorial sea temperature has received less attention. This study explores the lead correlation between the April–May (AM) SAM and central tropical Pacific sea temperature variability over the following three seasons. For the positive AM SAM case, the related simultaneous warm SST anomalies in the southeastern Indian Ocean favor significant regulation of vertical circulation in the Indian Ocean with anomalous ascending motion in the tropics. This can further enhance convection over the Marine Continent, which induces a significant horizontal Kelvin response and regulates the vertical Walker circulation. These two processes both result in the anomalous easterlies east of 130° E in the equatorial Pacific during AM. These easterly anomalies favor oceanic upwelling and eastward propagation of the cold water into the central Pacific. The cold water in turn amplifies the development of the easterly wind and further maintains the cold water into the boreal winter. The results presented here not only provide a possible link between extratropical climate variability in the Indian Ocean and climate variation in the equatorial Pacific, but also shed new light on the short-term prediction of tropical central Pacific sea temperature.
Patterns of cervical lymph node metastasis in supraglottic laryngeal cancer and therapeutic implications of surgical staging of the neck
Authors: Kürten Cornelius H. L. , Zioga Eleni , Gauler Thomas , Stuschke Martin , Guberina Maja , Ludwig Johannes M. , Deuss Eric , Mattheis Stefan , Lang Stephan , Hussain Timon 
Published: March 2021

Abstract
Purpose
Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions.

Methods
Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail.

Results
On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients.

Conclusion
Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.
Audiological practice and COVID-19: recommendations that audiological centers can use to maintain the safety and quality of service—expert opinion
Authors: Rajeswaran Ranjith , Tavora-Vieira Dayse , Mertens Griet , Dillon Margaret , Narayan Saranya , Kameswaran Mohan , Kurz Anja 
Published: March 2021

Abstract
Purpose
Audiology is an essential service for some patient groups and some interventions. This article sets forth experience-based recommendations for how audiological centers can continue to safely and effectively function during COVID-19.

Methods
The recommendations are the result of panel discussion and are based on the clinical experience of the panelists/authors.

Results
The recommendations cover which patient groups and which interventions should be treated when and whether this can be performed in the clinic or remotely; how to maintain the safety of workplace via optimizing patient flow within the clinic and the sanitation of rooms and equipment; and overcoming communication challenges that COVID-19 intensifies.

Conclusion
For essential audiological services to continue under COVID-19, safety measures must be implemented and maintained, and treatment and communication strategies must be adapted to offset communication difficulties due to personal protective equipment (PPE) and social distancing and to bolster patient confidence. In short, it is vital that staff feel safe, that patients either feel the clinic is safe enough to visit or that remote treatment may be an option, and that clinics and patients have a broad agreement on the urgency of any needed service. We hope that these recommendations help clinics effectively accomplish these goals.
A model to differentiate WAD patients and people with abnormal pain behaviour based on biomechanical and self-reported tests
Authors: Monaro Merylin , De Rosario Helios , Baydal-Bertomeu José María , Bernal-Lafuente Marta , Masiero Stefano , Macía-Calvo Mónica , Cantele Francesca , Sartori Giuseppe 
Published: March 2021

AbstractThe prevalence of malingering among individuals presenting whiplash-related symptoms is significant and leads to a huge economic loss due to fraudulent injury claims. Various strategies have been proposed to detect malingering and symptoms exaggeration. However, most of them have been not consistently validated and tested to determine their accuracy in detecting feigned whiplash. This study merges two different approaches to detect whiplash malingering (the mechanical approach and the qualitative analysis of the symptomatology) to obtain a malingering detection model based on a wider range of indices, both biomechanical and self-reported. A sample of 46 malingerers and 59 genuine clinical patients was tested using a kinematic test and a self-report questionnaire asking about the presence of rare and impossible symptoms. The collected measures were used to train and validate a linear discriminant analysis (LDA) classification model. Results showed that malingerers were discriminated from genuine clinical patients based on a greater proportion of rare symptoms vs. possible self-reported symptoms and slower but more repeatable neck motions in the biomechanical test. The fivefold cross-validation of the LDA model yielded an area under the curve (AUC) of 0.84, with a sensitivity of 77.8% and a specificity of 84.7%.
Phase-field modelling for fatigue crack growth under laser shock peening-induced residual stresses
Authors: Seiler Martha , Keller Sören , Kashaev Nikolai , Klusemann Benjamin , Kästner Markus 
Published: March 2021

AbstractFor the fatigue life of thin-walled components, not only fatigue crack initiation, but also crack growth is decisive. The phase-field method for fracture is a powerful tool to simulate arbitrary crack phenomena. Recently, it has been applied to fatigue fracture. Those models pose an alternative to classical fracture-mechanical approaches for fatigue life estimation. In the first part of this paper, the parameters of a phase-field fatigue model are calibrated and its predictions are compared to results of fatigue crack growth experiments of aluminium sheet material. In the second part, compressive residual stresses are introduced into the components with the help of laser shock peening. It is shown that those residual stresses influence the crack growth rate by retarding and accelerating the crack. In order to study these fatigue mechanisms numerically, a simple strategy to incorporate residual stresses in the phase-field fatigue model is presented and tested with experiments. The study shows that the approach can reproduce the effects of the residual stresses on the crack growth rate.
Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome
Authors: Zhang Yanqin , Böckhaus Jan , Wang Fang , Wang Suxia , Rubel Diana , Gross Oliver , Ding Jie 
Published: March 2021

Abstract
Background
Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS.

Methods
Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated.

Results
Median age was 15 years (range 1.5–46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants.

Conclusions
Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants.