bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine Agonist-Resistant Microprolactinoma—Mechanisms, Predictors and Management: A Case Report and Literature Review
Authors: Szmygin Hanna , Szydełko Joanna , Matyjaszek-Matuszek Beata
Published: May 2022

Objective: Prolactinomas are the most common type of functional, hormone-secreting pituitary adenomas that account for about 40% of total pituitary adenomas. Typical clinical presentations include loss of menstrual periods (amenorrhea) and galactorrhoea in women and sexual dysfunction in men. Prolactinomas are preferentially treated with dopamine agonists and respond to such therapy with hormonal normalisation and tumour shrinkage. However, about 10–20% of prolactinomas are resistant to dopamine agonists. The management of dopamine agonist-resistant prolactinomas poses a therapeutic challenge and includes several possible approaches. Design and Methods: In this study, we present a case report of a woman diagnosed with microprolactinoma at the age of 27 who did not fully respond either to treatment with dopamine agonists nor to transsphenoidal surgery. This was followed by a review of literature on the current state of knowledge about the mechanisms, predictors, and management of dopamine agonist-resistant prolactinomas on the basis of recent scientific literature published up to November 2021 and searches of the PubMed, Google Scholar, and Web of Science databases. Results and Conclusions: The exact mechanisms underlying dopamine agonists’ resistance in lactotroph tumours are not fully understood, yet refractory prolactinomas pose a great challenge in everyday clinical practice. Several predictive factors that contribute to poor response to medical treatment have been identified, among them the elevated Ki-67 index. Recently, various alternative medical treatments have been considered, but their usefulness remains to be evaluated. A return of menses can serve as a first clinical indication of successful medical treatment.
Evaluating the Influence of ipRGCs on Color Discrimination
Authors: Ohtsu Masaya , Kurata Akihiro , Hirai Keita , Tanaka Midori , Horiuchi Takahiko
Published: May 2022

To investigate the influence of intrinsically photosensitive retinal ganglion cells (ipRGCs) on color discrimination, it is necessary to create two metameric light stimuli (metameric ipRGC stimuli) with the same amount of cone and rod stimulation, but different amounts of ipRGC stimulation. However, since the spectral sensitivity functions of cones and rods overlap with those of ipRGCs in a wavelength band, it has been difficult to independently control the amount of stimulation of ipRGCs only. In this study, we first propose a method for calculating metameric ipRGC stimulation based on the orthogonal basis functions of human photoreceptor cells. Then, we clarify the controllable range of metameric ipRGC stimulation within a color gamut. Finally, to investigate the color discrimination by metameric ipRGC stimuli, we conduct subjective evaluation experiments on 24 chromaticity coordinates using a multispectral projector. The results reveal a correlation between differences in the amount of ipRGC stimulation and differences in color appearance, indicating that ipRGCs may influence color discrimination.
Sharp Profile for Icebreaking Propellers to Improve Their Ice and Hydrodynamic Characteristics
Authors: Andryushin Alexander Vladislavovich , Ryabushkin Sergey Vladimirovich , Voronin Alexander Yurievich , Shapkov Egor Vladimirovich
Published: May 2022

Stern-first operation under severe ice conditions (ridges) is one of the most effective modes to increase the operating efficiency of icebreakers and ice ships. However, when a ship overcomes the ridge astern, the propellers continuously interact with ice blocks, and ice moment affects the propeller and the main engine. This leads to propeller speed drop and propeller thrust reduction. Propeller stop is also possible. This is the reason why the propeller ice moment needs to be decreased. Blade profiles with a sharp leading edge are used for this purpose because their thickness is significantly less than that of a traditional icebreaking profile. The application of sharp profiling makes it possible to significantly reduce the ice moment (ice loads) on the propeller, reduce the drop in its speed, and increase the hydrodynamic thrust. The main task when installing blades with sharp profiles is to ensure the strength of their leading edges exposed to ice pressure. In this article, the authors tackle upon some methods of assigning integral and local ice loads on propellers. Solutions for ensuring the local strength of the blade edges were developed and presented. The influence of sharp profiling on the hydrodynamic and cavitation characteristics of ice propellers was considered. The article presents examples of calculating the hydrodynamic propeller thrust and moment, as well as ice loads on a propeller with a sharp and traditional profile, when an ice ship moves through a ridged ice isthmus with its stern first.
Multi-Level Federated Network Based on Interpretable Indicators for Ship Rolling Bearing Fault Diagnosis
Authors: Wang Shuangzhong , Zhang Ying
Published: May 2022

The federated learning network requires all the connection weights to be shared among the server and clients during training which increases the risk of data leakage. Meanwhile, the traditional federated learning method has a poor diagnostic effect for non-independently identically distributed data. In order to address these issues, a multi-level federated network based on interpretable indicators was proposed in this manuscript. Firstly, an interpretable adaptive sparse deep network is constructed based on the interpretability principle. Secondly, the relevance map of the network is constructed based on interpretable indicators. Based on this map, the contribution of the connection weights in the network is used to build a multi-level federated network. Finally, the effectiveness of the proposed algorithm has been proved through experimental validation in the paper.
Geochronological Evidence Inferring Carbonate Compensation Depth Shoaling in the Philippine Sea after the Mid-Brunhes Event
Authors: Xu Dong , Yi Liang , Yuan Haifan , Chen Weiwei
Published: May 2022

Carbonate compensation depth (CCD) is an important factor in the global deep ocean and in global carbon cycling; however, its variabilities have not been well documented in previous studies. In this study, we investigate two deep-sea cores collected from the Philippine Sea in terms of geochronology and geochemical properties over the past ~900 kyr. The principle results are as follows: (1) Two magnetozones are determined from the sediment’s magnetic records, which can be correlated with the Brunhes and Matuyama chrons in the geomagnetic polarity timescale. (2) The age models can be refined by tuning the Ba and Sm intensities of the two studied cores to the global ice volume, and the estimated sediment accumulation rate is ~4 mm/kyr. (3) Chalky mud and the bulk carbon δ13C record vary abruptly at ~430 ka and imply 200 m shoaling of the CCD. Based on these results, a close link is inferred between marine productivity, aeolian dust, and CCD changes, which can be correlated with a major change that occurred during the Mid-Brunhes Event. Therefore, we propose that the sedimentary processes in the Philippine Sea are evidence of global climate change, providing a unique window to observe interactions between various environmental systems.
Underwater Chatter for the Win: A First Assessment of Underwater Soundscapes in Two Bays along the Eastern Cape Coast of South Africa
Authors: Schoeman Renée P. , Erbe Christine , Plön Stephanie
Published: May 2022

In 2014, the South African government launched ‘Operation Phakisa’ under which port developments play a significant role in supporting ocean economic growth. These developments will likely increase vessel traffic to and from South African ports, making it imperative to monitor for changes in underwater sound budgets with potential negative effects on marine life. However, no soundscape studies have been conducted around South Africa, resulting in an absence of baseline measurements. This study provides a first description of the underwater soundscape in St. Francis Bay and Algoa Bay, Eastern Cape. Soundscape measurements identified major soundscape contributors, temporal patterns in broadband sound levels, and underlying environmental drivers. Applicability of modelled vessel noise and wind noise maps to predict large-scale spatial variation in sound budgets was assessed. Our study shows that sounds from biological sources and wind dominated at all recording sites, with fish choruses driving temporal patterns as a function of time of year and position of the sun. Sound from vessels was present at all sites but most notable in long-term spectral levels measured in Algoa Bay. Sound propagation models predicted a further increase in the contribution of vessel noise towards shipping lanes and east Algoa Bay. Our study provides a building block to monitor for shifts in sound budgets and temporal patterns in these two bays under a developing ocean economy. Furthermore, our study raises concerns that vessel noise is likely a significant contributor in shallow waters elsewhere along the South African coast where vessel density is known to be higher (i.e., Durban and Cape Town).
Experimental Research on Overwater and Underwater Visual Image Stitching and Fusion Technology of Offshore Operation and Maintenance of Unmanned Ship
Authors: Chen Yuanming , Hong Xiaobin , Chen Weiguo , Wang Huifang , Fan Tianhui
Published: May 2022

The new way of offshore operation and maintenance based on unmanned ships has outstanding advantages. Aiming at the problem of lack of overall understanding of the complex environment above and under the water surface during the operation and maintenance of unmanned ships, a stitching and fusion technology of overwater and underwater visual images for unmanned ships is proposed. The software and hardware framework of the overwater and underwater visual image fusion system is constructed, the image processing methods in different environments are defined, and the accurate acquisition of obstacle information is realized. In the two experimental scenarios, the stitching accuracy of the obstacle model based on an extended neighborhood method can reach more than 85% within the obstacle distance of 8 m and more than 80% within the obstacle distance of 14 m. An image-driven Frustum–PointNets detection algorithm is proposed to obtain comprehensive obstacle avoidance information. In addition, the average accuracy of the three-dimensional detection of the algorithm is up to 91.40%. These results are significant and have a good reference value, as it demonstrates that the stitching and fusion method can effectively obtain the comprehensive information of overwater and underwater objects for unmanned ship.
Extreme Wind Wave Climate off Jeddah Coast, the Red Sea
Authors: Alsaaq Faisal , V.R. Shamji
Published: May 2022

Climate change can give rise to significant changes in the intensity and frequency of extreme events. In the present study, extreme wave events off the central-eastern coast of the Red Sea, near the city of Jeddah, were investigated using a 39-year wave hindcast generated using WaveWatch III configured at a 3.3 km resolution forced with ERA5 reanalysis winds. The validated model outputs were used to derive the annual and seasonal climatology for the region at a few selected locations off the Jeddah coast. The study revealed robust temporal and spatial variability in the region, considering the influence of both northern and southern Red Sea waves that meet at the convergent zone. Generalized Pareto Distribution (GPD) and Generalized Extreme Value (GEV) were two models used for the estimation of extreme wave analysis in the study region. The extreme significant wave heights were estimated for 10, 25, 50, and 100-year return periods. For offshore locations, the estimated return periods using the GPD method were 3.27, 3.44, and 3.38 m, respectively. GPD with the POT method was the more suitable approach, as it produced reduced bias and RMSE. At all locations, linear trends show an increase during the summer, winter, and pre-summer periods. No significant increase in the Hs trend was observed at the selected locations near and off the coast. However, the decrease in trend observed at all locations during the pre-winter period was noticeable for the 99th percentile Hs.
Population Genomics Reveals Population Structure and Mating-Type Loci in Marssonina brunnea
Authors: Cheng Qiang , Yang Hougang , Chen Junxiang , Zhao Lijuan
Published: May 2022

Marssonina brunnea is an important fungal pathogen of poplar trees. We collected 32 M. brunnea f.sp. multigermtubi (MbMu) and three M. brunnea f.sp. monogermtubi (MbMo) isolates from four poplar species in three Chinese regions and performed genome resequencing. An annotation of SNPs of MbMu indicated that the SNPs potentially have a functional effect on 69.2% of the predicted genes. Using the SNP dataset of nonredundant isolates, a structure and principal component analysis revealed that MbMu and MbMo belong to two genetically distinct populations. By contrast, subpopulation structures could not be found among MbMu isolates. A neighbor-net analysis and a homoplasy index test provided evidence of recombination among MbMu isolates. The short distance (109–174 bp) of linkage disequilibrium half-decay supported the presence of a high level of recombination in the MbMu population. The genetic architectures of the MAT loci of MbMu and MbMo were revealed by searching genome assemblies or by homology-based cloning, and a BLAST search verified each isolate carrying one of the two opposite MAT loci. This study revealed that the MbMu population contains a wide range of functional variants, shows high-frequency recombination, and exhibits heterothallic mating systems, indicating high evolutionary potential and a resultant threat to poplar plantations.
Temporal Dynamics of Incidence of Shot Hole Disease Affected by Training Systems and Cultivar Susceptibilities in an Integrated Plum Orchard
Authors: Molnár Bianka , Szabó Szilárd , Holb Imre J.
Published: May 2022

Shot hole disease (SHD) can cause severe epidemics in plum orchards, depending on cultivar susceptibility and training system; however, the combined effect on the progress of temporal disease and on the possible reduction in SHD in the disease management was not investigated. The aim of this 3-year study was (i) to monitor and analyze the temporal dynamics of SHD progress under four training systems (4 × 1.5, 4 × 2, 5 × 2.5 and 6 × 3 m) and on four plum cultivars (‘Čačanska lepotica’, ‘Bluefre’, ‘Stanley’ and ‘President’) in an integrated plum orchard; (ii) to identify those time periods when training system and cultivar combinations can reduce the disease development. Both SHD incidences and the area under the disease progress curves (AUDPC) were significantly affected by the training system, cultivar and year. Plum cultivars with high or mid–high susceptibility to SHD showed continuous SHD development from May to November, while cultivars with low susceptibility to SHD showed no symptoms until mid-summer and then progressed slowly until November. High (4 × 1.5 m) vs. low (6 × 3 m) density training systems reduced SHD incidence and AUDPC consistently for three cultivars (‘Čačanska lepotica’, ‘Stanley’ and ‘President’) in September, October and November, compared to the high-density training system. Only cv. ‘Bluefre’ showed no effect either on disease incidence or AUDPC, due to very high disease incidences in all training systems from September to November. In conclusions, combinations of training system and cultivar can significantly reduce SHD incidence, which may be successfully used as a part of the integrated pest management approach during the establishment new plantations.
Pan-Genomes Provide Insights into the Genetic Basis of Auricularia heimuer Domestication
Authors: Guo Yuxiu , Liu Zhenhua , Fu Yongping , Li Yu , Dai Yueting , Xiao Shijun
Published: May 2022

In order to reveal the genetic variation signals of Auricularia heimuer that have occurred during their domestication and to find potential functional gene families, we constructed a monokaryotic pan-genome of A. heimuer representing four cultivated strains and four wild strains. The pan-genome contained 14,089 gene families, of which 67.56% were core gene families and 31.88% were dispensable gene families. We screened substrate utilization-related genes such as the chitinase gene ahchi1 of the glycoside hydrolase (GH) 18 family and a carbohydrate-binding module (CBM)-related gene from the dispensable families of cultivated populations. The genomic difference in the ahchi1 gene between the wild and cultivated genomes was caused by a 33 kb presence/absence variation (PAV). The detection rate of the ahchi1 gene was 93.75% in the cultivated population, significantly higher than that in the wild population (17.39%), indicating that it has been selected in cultivated strains. Principal component analysis (PCA) of the polymorphic markers in fragments near the ahchi1 gene was enriched in cultivated strains, and this was caused by multiple independent instances of artificial selection. We revealed for the first time the genetic basis of the ahchi1 gene in domestication, thereby providing a foundation for elucidating the potential function of the ahchi1 gene in the breeding of A. heimuer.
CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma
Authors: Nishimura Kenichi , Konishi Tatsuya , Ochi Toshiki , Watanabe Ryuta , Noda Terutaka , Fukumoto Tetsuya , Miura Noriyoshi , Miyauchi Yuki , Kikugawa Tadahiko , Takenaka Katsuto , Saika Takashi
Published: May 2022

Immune checkpoint inhibitor (ICI) therapy increases the risk of immune-related adverse events (irAEs). In particular, combination checkpoint blockade (CCB) targeting inhibitory CTLA-4 and PD-1 receptors could lead to irAEs at a higher rate than ICI monotherapy. Management of irAEs is important while using ICIs. However, there are no reliable biomarkers for predicting irAEs. The aim of this study was to elucidate early B cell changes after CCB therapy in patients with renal cell carcinoma (RCC) and verify whether B cells can be a predictor of irAEs. This prospective cohort study was conducted with 23 Japanese patients with metastatic RCC. An increase in the proportion of CD21lo B cells and CD21lo memory B cells was confirmed following CCB therapy. Although there were no differences in clinical outcomes between irAE and no-irAE groups, the proportion of CD21lo B cells at baseline was lower in the irAE group, with a significant increase after the first cycle of CCB therapy. Further analysis revealed a moderate correlation between irAEs and CD21lo B cell levels at baseline (area under the curve: 0.83, cut-off: 3.13%, sensitivity: 92.3, specificity: 70.0). This finding indicates that patients with low baseline CD21lo B cell levels warrant closer monitoring for irAEs. The clinical registration number by the Certified Review Board of Ehime University is No. 1902011.
Association between Large Arteries Diameter and Heart Function in Subjects Free of Cardiovascular Diseases
Authors: von Krüchten Ricarda , Lorbeer Roberto , Peters Annette , Bamberg Fabian , Schlett Christopher L. , Mujaj Blerim
Published: May 2022

To investigate the association between Aorta (Ao), pulmonary artery (PA) diameters and the PA/Ao ratio with right (RV) and left ventricle (LV) volumetric properties in subjects free of cardiovascular diseases. In the KORA-MRI study, 339 subjects (mean age 56.3 ± 9.1 years; 43.7% female) underwent whole-body 3T-MRI. Ao and PA were measured on DIXON sequences. Cvi42 quantified cardiac functional parameters from a SSFP sequence. The relationship between ascending (AAo), and descending aorta (DAo), as well as PA diameters, and RV and LV function were assessed using linear regression models adjusted for age, sex, and cardiovascular risk factors. AAo and DAo diameter were associated with LV end-diastolic volume (β = 4.52, p = 0.015; ß = 7.1, p ≤ 0.001), LV end-systolic volume (β = 2.37, p = 0.031; ß = 3.66, p = 0.002), while DAo associated with RV end-diastolic volume (β = 6.45, p = 0.006) and RV end-systolic volume (β = 3.9, p = 0.011). PA diameter was associated with LV end-diastolic volume (β = 4.81, p = 0.003). Interestingly, the PA/Ao ratio was only associated with RV end-diastolic and end-systolic volume (β = 4.48, p = 0.029; ß = 2.82, p = 0.037). Furthermore, we found different relationships between men and women. Ao and PA diameter were associated with LV and RV volumetric parameters in subjects free of cardiovascular diseases suggesting that ventricular volumetric performance directly relates to vascular diameter properties.
B-Type Natriuretic Peptide at Admission Is a Predictor of All-Cause Mortality at One Year after the First Acute Episode of New-Onset Heart Failure with Preserved Ejection Fraction
Authors: Ghilencea Liviu-Nicolae , Bejan Gabriel-Cristian , Zamfirescu Marilena-Brîndusa , Stănescu Ana Maria Alexandra , Matei Lavinia-Lucia , Manea Laura-Maria , Kilic Ismail Dogu , Bălănescu Serban-Mihai , Popescu Andreea-Catarina , Myerson Saul Gareth
Published: May 2022

Background: Heart failure with preserved ejection fraction (HFpEF) has been assessed extensively, but few studies analysed the predictive value of the NT-proBNP in patients with de novo and acute HFpEF. We sought to identify NT-proBNP at admission as a predictor for all-cause mortality and rehospitalisation at 12 months in patients with new-onset HFpEF. Methods: We analysed 91 patients (73 ± 11 years, 68% females) admitted for de novo and acute HFpEF, using the Cox proportional hazard risk model. Results: An admission NT-proBNP level above the threshold of 2910 pg/mL identified increased all-cause mortality at 12 months (AUC = 0.72, sensitivity = 92%, specificity = 53%, p < 0.001). All-cause mortality adjusted for age, gender, medical history, and medication in the augmented NT-proBNP group was 16-fold higher (p = 0.018), but with no difference in rehospitalisation rates (p = 0.391). The predictors of increased NT-proBNP ≥ 2910 pg/mL were: age (p = 0.016), estimated glomerular filtration rate (p = 0.006), left atrial volume index (p = 0.001), history of atrial fibrillation (p = 0.006), and TAPSE (p = 0.009). Conclusions: NT-proBNP above 2910 pg/mL at admission for de novo and acute HFpEF predicted a 16-fold increased mortality at 12 months, whereas values less than 2910 pg/mL forecast a high likelihood of survival (99.3%) in the next 12 months, and should be considered as a useful prognostic tool, in addition to its utility in diagnosing heart failure.
Singlet Oxygen In Vivo: It Is All about Intensity
Authors: Hackbarth Steffen , Islam Rayhanul , Šubr Vladimír , Etrych Tomáš , Fang Jun
Published: May 2022

The presented work addresses the influence of illumination intensity on the amount and locations of singlet oxygen generation in tumor tissue. We used time-resolved optical detection at the typical emission wavelength around 1270 nm and at 1200 nm where there is no singlet oxygen phosphorescence to determine the phosphorescence kinetics. The discussed data comprise in vivo measurements in tumor-laden HET-CAM and mice. The results show that illumination that is too intense is a major issue, affecting many PDT treatments and all singlet oxygen measurements in vivo so far. In such cases, photosensitization and oxygen consumption exceed oxygen supply, limiting singlet oxygen generation to the blood vessels and walls, while photosensitizers in the surrounding tissue will likely not participate. Being a limitation for the treatment, on one hand, on the other, this finding offers a new method for tumor diagnosis when using photosensitizers exploiting the EPR effect. In contrast to high-intensity PDT, some papers reported successful treatment with nanoparticular drugs using much lower illumination intensity. The question of whether, with such illumination, singlet oxygen is indeed generated in areas apart from vessels and walls, is addressed by numerical analysis. In addition, we discuss how to perform measurements at such low intensities.
Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
Authors: Klumpers Marije J. , Witte Ward De , Gattuso Giovanna , Schiavello Elisabetta , Terenziani Monica , Massimino Maura , Gidding Corrie E. M. , Vermeulen Sita H. , Driessen Chantal M. , Van Herpen Carla M. , Van Meerten Esther , Guchelaar Henk-Jan , Coenen Marieke J. H. , Te Loo D. Maroeska W. M.
Published: May 2022

Nephrotoxicity is a common and dose-limiting side effect of platinum compounds, which often manifests as acute kidney injury or hypomagnesemia. This study aimed to investigate the genetic risk loci for platinum-induced nephrotoxicity. Platinum-treated brain tumor and head–neck tumor patients were genotyped with genome-wide coverage. The data regarding the patient and treatment characteristics and the laboratory results reflecting the nephrotoxicity during and after the platinum treatment were collected from the medical records. Linear and logistic regression analyses were performed to investigate the associations between the genetic variants and the acute kidney injury and hypomagnesemia phenotypes. A cohort of 195 platinum-treated patients was included, and 9,799,032 DNA variants passed the quality control. An association was identified between RBMS3 rs10663797 and acute kidney injury (coefficient −0.10 (95% confidence interval −0.13–−0.06), p-value 2.72 × 10−8). The patients who carried an AC deletion at this locus had statistically significantly lower glomerular filtration rates after platinum treatment. Previously reported associations, such as BACH2 rs4388268, could not be replicated in this study’s cohort. No statistically significant associations were identified for platinum-induced hypomagnesemia. The genetic variant in RBMS3 was not previously linked to nephrotoxicity or related traits. The validation of this study’s results in independent cohorts is needed to confirm this novel association.
From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine
Authors: Maintz Laura , Bieber Thomas , Simpson Helen D. , Demessant-Flavigny Anne-Laure
Published: May 2022

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient’s age and disease stage.
Merkel Cell Carcinoma Display PIEZO2 Immunoreactivity
Authors: García-Mesa Yolanda , Martín-Sanz Raquel , García-Piqueras Jorge , Cobo Ramón , Muñoz-Bravo Saray , García-Suárez Olivia , Martín-Biedma Benjamín , Vega José Antonio , Feito Jorge
Published: May 2022

As an essential component of mechano-gated ion channels, critically required for mechanotransduction in mammalian cells, PIEZO2 is known to be characteristically expressed by Merkel cells in human skin. Here, we immunohistochemically investigated the occurrence of Piezo channels in a case series of Merkel cell carcinoma. A panel of antibodies was used to characterize Merkel cells, and to detect PIEZO2 expression. All analyzed tumors displayed PIEZO2 in nearly all cells, showing two patterns of immunostaining: membranous and perinuclear dot-like. PIEZO2 co-localized with cytokeratin 20, chromogranin A, synaptophysin and neurofilament. Moreover, neurofilament immunoreactive structures resembling nerve-Merkel cell contacts were occasionally found. PIEZO2 was also detected in cells of the sweat ducts. The role of PIEZO2 in Merkel cell carcinoma is still unknown, but it could be related with the mechanical regulation of the tumor biology or be a mere vestige of the Merkel cell derivation.
VH3-53/66-Class RBD-Specific Human Monoclonal Antibody iB20 Displays Cross-Neutralizing Activity against Emerging SARS-CoV-2 Lineages
Authors: Kulemzin Sergey V. , Sergeeva Maria V. , Baranov Konstantin O. , Gorchakov Andrey A. , Guselnikov Sergey V. , Belovezhets Tatyana N. , Volkova Olga Yu. , Najakshin Alexander M. , Chikaev Nikolai A. , Danilenko Daria M. , Taranin Alexander V.
Published: May 2022

Immune evasion of SARS-CoV-2 undermines current strategies tocounteract the pandemic, with the efficacy of therapeutic virus-neutralizing monoclonal antibodies (nAbs) being affected the most. In this work, we asked whether two previously identified human cross-neutralizing nAbs, iB14 (class VH1-58) and iB20 (class VH3-53/66), are capable of neutralizing the recently emerged Omicron (BA.1) variant. Both nAbs were found to bind the Omicron RBD with a nanomolar affinity, yet they displayed contrasting functional features. When tested against Omicron, the neutralizing activity of iB14 was reduced 50-fold, whereas iB20 displayed a surprising increase in activity. Thus, iB20 is a unique representative of the VH3-53/66-class of nAbs in terms of breadth of neutralization, which establishes it as a candidate for COVID-19 therapy and prophylactics.
Data-Driven EEG Theta and Alpha Components Are Associated with Subjective Experience during Resting State
Authors: Tarailis Povilas , De Blasio Frances M. , Simkute Dovile , Griskova-Bulanova Inga
Published: May 2022

The resting-state paradigm is frequently applied to study spontaneous activity of the brain in normal and clinical conditions. However, the relationship between the ongoing experience of mind wandering and the individual biological signal is still unclear. We aim to estimate associations between subjective experiences measured with the Amsterdam Resting-State Questionnaire and data-driven components of an electroencephalogram extracted by frequency principal component analysis (f-PCA). Five minutes of resting multichannel EEG was recorded in 226 participants and six EEG data-driven components were extracted—three components in the alpha range (peaking at 9, 10.5, and 11.5 Hz) and one each in the delta (peaking at 0.5 Hz), theta (peaking at 5.5 Hz) and beta (peaking at 17 Hz) ranges. Bayesian Pearson’s correlation revealed a positive association between the individual loadings of the theta component and ratings for Sleepiness (r = 0.200, BF10 = 7.676), while the individual loadings on one of the alpha components correlated positively with scores for Comfort (r = 0.198, BF10 = 7.115). Our study indicates the relevance of assessments of spontaneous thought occurring during the resting-state for the understanding of the individual intrinsic electrical brain activity.
Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs
Authors: De Corso Eugenio , Pipolo Carlotta , Cantone Elena , Ottaviano Giancarlo , Gallo Stefania , Canevari Frank Rikki Mauritz , Macchi Alberto , Monti Giulia , Cavaliere Carlo , La Mantia Ignazio , Torretta Sara , Bussu Francesco , Scarano Emanuele , Petrone Paolo , Ghidini Angelo , Lucidi Daniela , Garzaro Massimiliano , Trimarchi Matteo , Seccia Veronica , Passali Giulio Cesare , Salsi Daria , Cuda Domenico , Pasquini Ernesto , Malvezzi Luca , Settimi Stefano , Paludetti Gaetano , Galli Jacopo
Published: May 2022

Background: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. Methods: A survey was set up on Survey Monkey®. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. Results: Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. Conclusions: Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.
Novel Biomarkers of Renal Dysfunction and Congestion in Heart Failure
Authors: Zdanowicz Agata , Urban Szymon , Ponikowska Barbara , Iwanek Gracjan , Zymliński Robert , Ponikowski Piotr , Biegus Jan
Published: May 2022

Heart failure is a major public health problem and, despite the constantly emerging, new, effective treatments, it remains a leading cause of morbidity and mortality. Reliable tools for early diagnosis and risk stratification are crucial in the management of HF. This explains a growing interest in the development of new biomarkers related to various pathophysiological mechanisms of HF. In the course of this review, we focused on the markers of congestion and renal dysfunction in terms of their interference with cardiovascular homeostasis. Congestion is a hallmark feature of heart failure, contributing to symptoms, morbidity, and hospitalizations of patients with HF and has, therefore, become a therapeutic target in AHF. On the other hand, impaired renal function by altering the volume status contributes to the development and progression of HF and serves as a marker of an adverse clinical outcome. Early detection of congestion and an adequate assessment of renal status are essential for the prompt administration of patient-tailored therapy. This review provides an insight into recent advances in the field of HF biomarkers that could be potentially implemented in diagnosis and risk stratification of patients with HF.
Estimation and Inference for the Threshold Model with Hybrid Stochastic Local Unit Root Regressors
Authors: Chen Chaoyi , Stengos Thanasis
Published: May 2022

In this paper, we study the estimation and inference of the threshold model with hybrid local stochastic unit root regressors. Our main contribution is to propose an estimator that generalizes the threshold model with various forms of nonstationary regressors and to obtain its limiting distribution theory. In particular, our proposed model generalizes the threshold model with unit root, local-to-unity, and stochastic unit root regressors. We provide the estimation strategy for the least squares estimator and derive the asymptotic results for the proposed estimator. Depending on the diminishing rate of the threshold effect, we find that the limiting distribution of the threshold estimator takes different forms. Monte Carlo simulations are used to assess our proposed estimator’s finite sample performance, which is found to perform well.
Seasonal Pattern in Serum Estradiol, Progesterone, and Prolactin Concentrations in Rescued Wild Female Taiwanese Pangolin (Manis pentadactyla pentadactyla)
Authors: Arora Bharti , Pei Kurtis Jai-Chyi , Ganswindt Andre
Published: May 2022

Pangolins are under severe threat of surging poaching rates globally; therefore, there is a demand to ascertain reproductive measures to ensure captive breeding and management strategies. Due to the absence of substantial information on the pangolin, endocrinology and reproductive physiology studies around the globe are merely based on captive observations that have failed to report the chronographs and hormonal cyclicity of the reproductive events. This study attempts to evaluate the annual pattern of reproductive steroids (estradiol-17β and progesterone) and prolactin in 16 wild female Taiwanese pangolins rehabilitated by Pingtung Rescue Center of Endangered Wild Animals, Taiwan. Novel immunoassays, i.e., chemiluminometric assays, have been used to quantify the serum reproductive steroids and contribute to a better understanding of the endocrine correlates of function in the Taiwanese pangolin. The hematological findings were characterized by monthly median concentration. The circulating reproductive hormones demonstrated seasonal reproductive activity by confirming a peak in serum estradiol concentrations in December and considerably higher progesterone concentrations in November/December, and March/April. The rise in prolactin in December and peak values in April suggest participation in the ovulatory process and mating. Collectively, these findings can help maximize the reproductive efficiency of pangolin species in captivity, i.e., by timely pairing and prioritizing the care of the breeding pairs to optimize breeding efforts and, therefore, effectively support conservation breeding programs and restore the natural population in the ecosystems.
The Identification of Stakeholders’ Living Contexts in Stakeholder Participation Data: A Semantic, Spatial and Temporal Analysis
Authors: Marzouki Amal , Mellouli Sehl , Daniel Sylvie
Published: May 2022

Stakeholders’ Participation (SP) aims to involve stakeholders in decision-making processes about significant choices affecting their organizations, cities, or communities. Stakeholders’ participation is maintained through SP processes (SPPs) that may be traditional (e.g., physical assemblies) or online (e.g., online forums). Whether traditional or online, the purpose of SPPs is to collect and analyze data in a way that it would bring a benefit to a given decision-making process. In SPPs, stakeholders try to communicate (a part of) their living contexts, i.e., to present their objectives, daily problems, intentions, and issues they are facing within their environment. A major challenge of decision-makers is then to ensure that the living contexts of stakeholders are considered in SPPs for an effective implementation of project and policies. This paper focuses on the specific issue of the “stakeholders’ living context identification” and attempts to account for how stakeholders implicitly identify their living contexts in their SP comments. Based on a qualitative analysis of SP data from four case studies in two countries, this paper identified a set of semantic, spatial, and temporal patterns allowing to capture the stakeholders’ living contexts in SPPs data. Moreover, a conceptual model emphasizing the importance for decision-makers to capture and understand semantic, spatial, and temporal dimensions in SPPs is proposed.
Herd It in the Gobi: Deserting Pastoralism?
Authors: Sternberg Troy , Mayaud Jerome R. , Ahearn Ariell
Published: May 2022

Global drylands host more than USD 1 trillion in resource extraction investments, which serve to reconfigure communities and landscapes. In Mongolia’s Gobi Desert mega-mining brings social challenges and environmental changes that question if nomadic herding and mining can co-exist. Whilst company and community conflict are common, nascent frameworks and mediation models suggest alternate ways to resolve the mining–community conundrum. Here we investigate environmental transformations that herders encounter in the presence of the Oyu Tolgoi mega-mine in Mongolia’s Khanbogd soum (district). Using socio-economic and physical data collected through interviews, field studies and climate records, we assessed local engagement and adaptation to large-scale mining. Combining qualitative and quantitative methods enabled us to examine the implications of mining for herder lives and lands in an integrated way. This study presents a holistic assessment of the roles of herders, governments and mines in reshaping pastoralism. In our chosen case study, we find that—contrary to common narratives—mining and herding can, and do, coexist in Khanbogd soum, though ongoing challenges exist which deserve critical attention.
A New Spatial Criteria Method to Delimit Rural Settlements towards Boundaries Equity: Land Use Optimization for Decision Making in Galicia, NW Spain
Authors: Barbosa Vasco , Santé-Riveira Inés , Crecente-Maseda Rafael , Redondo Carlos Díaz , Trinidad Juan Porta , López Jorge Parapar , Biempica Ramón Doallo , Ferreira Neto José Ambrósio
Published: May 2022

Rural settlements (RS) are a reality of rural areas. They consist of cluster of buildings and ways of life mainly associated with activities related to agriculture. As economic policies applied in rural development have evolved, the physical delimitation of rural areas has become more important because such areas are recipients of financial support, which depends on an area’s characteristics. Thus, it is necessary to formulate a new spatial approach for RS delimitation. The objective of this study is to define spatial criteria for identification and delimitation of the RS to recognize the morphological context of each RS. With respect to methodology, RS in the community of Galicia, Northwestern Spain were studied, and factors for spatial characterization were defined according to experts’ evaluations. Subsequently, spatial restrictions and conditions were identified for the delimitation of boundaries. The criteria that this research proposes reveal numerically adjustable factors that can recognize and interpret the morphological characteristics of each RS, which is also evidenced by the results of RS delimitations. It can be concluded that the numerically defined criteria associated with a spatial operation allow the adaptation to the morphological characteristics of any RS, as well as spatial equity by recognizing the differentiation of building structures and land uses of each RS, rather unlike the criteria defined by the law.
Rethinking the Contribution of Land Element to Urban Economic Growth: Evidence from 30 Provinces in China
Authors: Xu Guoliang , Yin Xiaonan , Wu Guangdong , Gao Ning
Published: May 2022

In China, disputes regarding the benefits and drawbacks of land finance have been heated, but the role of land in urban economic growth has received insufficient attention, particularly on a macro scale. This research used the Cobb–Douglas production function model to investigate the role of land in urban economic growth. Then, we conducted an empirical test using panel data from 30 provinces from 2000 to 2019, with the goal of revealing the role of land in urban growth and spatio-temporal inequalities in China. Furthermore, to find the spatial steady-state level of land contributions, σ convergence, absolute β convergence, and condition β convergence tests were applied. The results show that: (1) China’s urban economic development was influenced by the combined element of land, capital, and labor; (2) the contribution of land to China’s urban economy experienced a turning point during the “12th Five-Year Plan”; (3) the spatio-temporal convergence of the contribution of land showed convergence in the east but nonconvergence in the central and western regions; and (4) β convergence demonstrated convergence in eastern, central, and western China. Given the complex and turbulent international political and economic context, the Chinese government should think about how to foster continuous energy by supporting land-supply policies that are adapted to local needs.
Assessment of the Morphological Pattern of the Lebanon Cedar under Changing Climate: The Mediterranean Case
Authors: Özcan Ali , Velázquez Javier , Rincón Víctor , Gülçin Derya , Çiçek Kerim
Published: May 2022

The effects of climate change on species can influence the delicate balance in ecosystems. For this reason, conservation planning needs to take account of connectivity and the related ecological processes within the framework of climate change. In this study, we focus on the change in the ecological connectivity of the Lebanon cedar (Cedrus libani A. Rich.), which is widely distributed in the Mediterranean, particularly in the Amanus and Taurus Mountains. To this end, we evaluated the changes in spatial units providing connectivity in the potential and future distributions of the species through ecological niche modelling, morphological spatial pattern analysis, and landscape metrics. The results suggest that the species is moving to the northeast. According to the future projections, we predict that the potential habitat suitability of the species will shrink significantly and that, in the case of pessimistic scenarios, the extent of the suitable habitats will decrease, particularly in the western and central Taurus Mountain chains. A comparison of potential and future cores indicates that there will be a slight increase under the RCP 4.5 2050 scenario, whereas core areas will decrease in the RCP 4.5 2070, RCP 8.5 2050, and RCP 8.5 2070 scenarios. In addition, it is predicted that bridges would increase in the RCP 4.5 2070 and RCP 8.5 2050 scenarios but decrease in other scenarios.
The Impact of Brownfields on Residential Property Values in Post-Industrial Communities: A Study from the Eastern Part of the Czech Republic
Authors: Turečková Kamila , Martinát Stanislav , Nevima Jan , Varadzin František
Published: May 2022

Dilapidated, neglected, or abandoned sites and buildings (so-called brownfields) are frequently neither visually attractive nor aesthetically valuable. Indeed, neglected brownfields contribute to the emergence of both objective and subjective barriers to the social, economic, and environmental development of communities. We also know that the occurrence of decayed brownfields affect the prices of residential housing in their vicinity. In our paper, we seek to better understand the impact of brownfields on the perceived value of neighbouring properties. We are also keen to shed more light on the factors behind the allegedly undesirable impact of brownfields on property values. Our research is based primarily on data obtained from a survey of 1,152 respondents in ten municipalities situated at the eastern part of the Czech Republic, where neglected brownfields frequently occur. The findings are complemented by an analysis of sales of residential properties located in proximity to brownfield sites, to further confirm our preliminary survey results. The results confirmed that neglected brownfields tend to negatively affect the value of neighbouring residential properties. Our results also signal that the concentration of socially unacceptable behaviour is considered a key issue for distorting property prices around brownfields. Our analyses have confirmed that distance from a particular brownfield is one of the factors significantly influencing property prices. We claim that neglected brownfields create negative externalities that require public sector interventions and better planning. We urgently need more systematic support for brownfield regeneration to improve the quality of life of residents in affected communities.