bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative contrast‐enhanced ultrasound for the differentiation of kidney allografts with significant histopathological injury
Authors: Vičič Eva , Kojc Nika , Hovelja Tomaž , Arnol Miha , Ključevšek Damjana 
Published: September 2021

AbstractObjectiveTo identify specific quantitative contrast‐enhanced ultrasound (CEUS) parameters that could distinguish kidney transplants with significant histopathological injury.MethodsSixty‐four patients were enrolled in this prospective observational study. Biopsies were performed following CEUS and blood examination.Results28 biopsy specimens had minimal changes (MC group), while 36 had significant injury (SI group). Of these, 12 had rejection (RI group) and 24 non‐rejection injury (NRI group). In RI and NRI groups, temporal difference in time to peak (TTP) between medulla and cortex (ΔTTPm‐c) was significantly shorter compared to the MC group (5.77, 5.92, and 7.94 s, P = 0.048 and 0.026, respectively). Additionally, RI group had significantly shorter medullary TTP compared to the MC group (27.75 vs. 32.26 s; P = 0.03). In a subset of 41 patients with protocol biopsy at 1‐year post‐transplant, ΔTTPm‐c was significantly shorter in the SI compared to the MC group (5.67 vs. 7.67 s; P = 0.024). Area under receiver operating characteristic curves (AUROCs) for ΔTTPm‐c was 0.69 in all patients and 0.71 in patients with protocol biopsy.ConclusionsRI and NRI groups had shorter ΔTTPm‐c compared to the MC group. AUROCs for both patient groups were good, making ΔTTPm‐c a promising CEUS parameter for distinguishing patients with significant histopathological injury.
Greater axial elongation associated with low accommodative lag: new insights on accommodative lag theory for myopia
Authors: Thakur Swapnil , Verkicharla Pavan K 
Published: September 2021

AbstractPurposeWe aimed to test the accommodative lag and mechanical tension theories for myopia by assessing the influence of the lag of accommodation on axial elongation by using three different near targets that are known to influence the accommodative response differently.MethodsForty‐two young adults were recruited for the study. Axial length was measured using a non‐contact biometer, before and immediately after a 15 minute visual task, with one of the three near targets placed 20 cm from the eye: reading text from a paper, reading text from a smartphone and watching a video on a smartphone. The accommodative response was determined using an open‐field autorefractor while the participants viewed the near target monocularly.ResultsLag of accommodation was significantly different for the three tasks: watching a video (mean ± standard error of the mean [SEM] 0.92 ± 0.10 D); reading text on the smartphone (0.59 ± 0.08 D); and reading text on paper (0.24 ± 0.09 D). There was a significant (p < 0.05) increase in axial length after reading text from a paper (10.5 ± 1.9 µm after 15‐min) and reading text from a smartphone (5.2 ± 2.7 µm), but not after watching a video on a smartphone (−0.5 ± 1.7 µm, p = 0.47). Vitreous chamber depth increased significantly more with the reading tasks compared with watching a video (reading text from a paper and smartphone: 33.9 ± 4 µm and 31.7 ± 4 µm vs. watching a video on a smartphone: 14.6 ± 5 µm, p = 0.001).ConclusionGreater changes in axial length associated with the low lag of accommodation failed to support the theory that lag of accommodation during visual tasks could be the trigger for axial elongation. Reading on paper and smartphone at the closest reading distance may stimulate high accommodative demand and axial elongation as a consequence, possibly due to increased “ciliary muscle tension” during accommodation.
Novel mutations of TYK2 leading to divergent clinical phenotypes
Authors: Lv Ge , Sun Gan , Wu Peilin , Du Xiao , Zeng Ting , Wen Wen , Zhou Lina , An Yunfei , Tang Xuemei , He Tingyan , Zhao Xiaodong , Du Hongqiang 
Published: September 2021

AbstractBackgroundTYK2 deficiency is a rare primary immunodeficiency disease caused by loss‐of‐function mutations of TYK2 gene, which is initially proposed as a subset of hyper‐IgE syndrome (HIES). However, accumulating evidence suggests TYK2‐deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system.MethodPathogenic effects of patients were confirmed by qRT‐PCR, Western blot, and protein stability assays. The responses to cytokines including IFN‐α/β/γ, IL‐6, IL‐10, IL‐12, and IL‐23 of peripheral blood mononuclear cells (PBMCs) from these patients were detected by Western blot, qRT‐PCR, and flow cytometry. The differentiation of T and B cells was detected by flow cytometry.ResultsWe described five more TYK2‐deficient cases presenting with or without hyper‐IgE levels, atopy, and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high‐throughput sequencing and confirmed by Sanger sequencing. The patients showed heterogeneous responses to various cytokine treatments, including IFN‐α/β/γ, IL‐6, IL‐10, IL‐12, and IL‐23. The homeostasis of lymphocytes is also disrupted.ConclusionBased on our findings, we propose that TYK2 works as a multi‐tasker in orchestrating various cytokine signaling pathways, differentially combined defects which account for the expressed clinical manifestations.
Maintaining or letting go of couplehood: Perspectives of older male spousal dementia caregivers
Authors: Stefánsdóttir Olga Ásrún , Munkejord Mai Camilla , Sveinbjarnardóttir Eydís Kristín 
Published: September 2021

AbstractDespite the negative implications for their own health, spouses continue to support each other and maintain their couplehood for as long as possible, including when one of them develops a severe illness. However, with some exceptions, the experiences of older male spousal caregivers have been largely overlooked, and our knowledge of the relational aspects of spousal dementia care is scarce. To respond to this knowledge gap, this article explores the following research questions: How do older male spousal caregivers of wives with dementia talk about changes in their couplehood? What transitions or phases in the relationship can be identified as the caring process evolves and the wife's health continues to deteriorate? To answer these questions, we analyse in‐depth interviews with eight purposefully selected men aged 67–92 years old from Iceland and Norway. Our findings reveal that the participants felt that they were gradually losing their couplehood in the sense that they lost their shared everyday life routines, intimacy, joint activities, meaningful communication, and dreams and hopes for the future. Four phases of the dementia caring process were identified: the denial phase, the battle phase, the new reality phase and the redefinition phase. We hope that our findings spur more research on relational challenges as experienced by spouses caring for partners with cognitive decline. In conclusion, we argue that interdisciplinary clinical guidelines for a couple‐centred approach in elder care should be developed to urge professional care providers to pay attention to the various changes and challenges that dementia couples undergo to meet not only the health and care needs of dementia patients but also those of their spouses.
Suitability assessment of global, continental and national digital elevation models for geomorphological analyses in Italy
Authors: Zingaro Marina , La Salandra Marco , Colacicco Rosa , Roseto Rodolfo , Petio Paolo , Capolongo Domenico 
Published: September 2021

AbstractDigital elevation models (DEMs) represent a fundamental resource in geomorphological analysis. The increasing availability of open‐access DEMs over wide areas is advantageous, but requires an evaluation of DEM quality and errors. This work applies a hierarchical assessment of global, continental and national DEMs in Italy in order to explore the differences and analyze the vertical accuracy, spatial error distribution and agreement of morphometric measurements. The selected DEMs are compared with local reference data as a ground points dataset, extracted from the national geodetic network, and regional DEMs at high spatial resolution, through both a qualitative and a quantitative approach. The results identify limits and potentialities of the selected DEMs, showing accuracy and errors in height representation, also affected by the topographic characteristics of the surface, such as steep slope in mountain zones and some defects in hydromorphological derivatives that could condition the geomorphological applications.
Foreign direct investment and regional innovation: Evidence from China
Authors: Jiang Haiwei , Liang Yousha , Pan Shiyuan 
Published: September 2021

AbstractThis paper studies the impact of foreign direct investment (FDI) on regional innovation, which is measured by patent applications and patent citations, based on city‐level data in China from 1995 to 2015. Using an instrumental variable approach, this paper demonstrates that FDI not only promotes the quantity of regional innovation, but also improves the quality of regional innovation in China. The findings are robust to various specifications of the empirical model and measurements. In addition, we highlight the channel of improving local absorptive capacity and market competition through which FDI exerts positive influence on regional innovation, and show that FDI acts as a substitute for local financial development to raise regional innovation.
The oestrous cycle and skeletal muscle atrophy: Investigations in rodent models of muscle loss
Authors: Rosa‐Caldwell Megan E. , Mortreux Marie , Kaiser Ursula B. , Sung Dong‐Min , Bouxsein Mary L. , Dunlap Kirsten R. , Greene Nicholas P. , Rutkove Seward B. 
Published: September 2021

New Findings
What is the central question of this study?Is the oestrous cycle affected during disuse atrophies and, if so, how are oestrous cycle changes related to musculoskeletal outcomes?
What is the main finding and its importance?Rodent oestrous cycles were altered during disuse atrophy, which was correlated with musculoskeletal outcomes. However, the oestrous cycle did not appear to be changed by Lewis lung carcinoma, which resulted in no differences in muscle size in comparison to healthy control animals. These findings suggest a relationship between the oestrous cycle and muscle size during atrophic pathologies.
AbstractRecent efforts have focused on improving our understanding of female muscle physiology during exposure to muscle atrophic stimuli. A key feature of female rodent physiology is the oestrous cycle. However, it is not known how such stimuli interact with the oestrous cycle to influence muscle health. In this study, we investigated the impact of muscle atrophic stimuli on the oestrous cycle and how these alterations are correlated with musculoskeletal outcomes. A series of experiments were performed in female rodents, including hindlimb unloading (HU), HU followed by 24 h of reloading, HU combined with dexamethasone treatment, and Lewis lung carcinoma. The oestrous cycle phase was assessed throughout each intervention and correlated with musculoskeletal outcomes. Seven or 14 days of HU increased the duration in dioestrus or metoestrus (D/M; low hormones) and was negatively correlated with gastrocnemius mass. Time spent in D/M was also negatively correlated with changes in grip strength and bone density after HU, and with muscle recovery 24 h after the cessation of HU. The addition of dexamethasone strengthened these relationships between time in D/M and reduced musculoskeletal outcomes. However, in animals with Lewis lung carcinoma, oestrous cyclicity did not differ from that of control animals, and time spent in D/M was not correlated with either gastrocnemius mass or tumour burden. In vitro experiments suggested that enhanced protein synthesis induced by estrogen might protect against muscle atrophy. In conclusion, muscle atrophic insults are correlated with changes in the oestrous cycle, which are associated with deterioration in musculoskeletal outcomes. The magnitude of oestrous cycle alterations depends on the atrophic stimuli.
Characterization of the Formability of High-Purity Polycrystalline Niobium Sheets for Superconducting Radiofrequency Applications
Authors: Croteau Jean-François , Robin Guillaume , Cantergiani Elisa , Atieh Said , Jacques Nicolas , Mazars Gilles , Martiny Marion 
Published: September 2021

Abstract
The forming limit diagram (FLD) of high-purity niobium sheets used for the manufacturing of superconducting radiofrequency (SRF) cavities is presented. The Marciniak (in-plane) test was used with niobium blanks with a thickness of 1 mm and blank carriers of annealed oxygen-free electronic (OFE) copper. A high formability was measured, with an approximate true major strain at necking for plane strain of 0.44. The high formability of high-purity niobium is likely caused by its high strain rate sensitivity of 0.112. Plastic strain anisotropies (r-values) of 1.66, 1.00, and 2.30 were measured in the 0 deg, 45 deg, and 90 deg directions. However, stress–strain curves at a nominal strain rate of ∼10−3 s−1 showed similar mechanical properties in the three directions. Theoretical calculations of the forming limit curves (FLCs) were conducted using an analytical two-zone model. The obtained results indicate that the anisotropy and strain rate sensitivity of niobium affect its formability. The model was used to investigate the influence of strain rate on strains at necking. The obtained results suggest that the use of high-speed sheet forming should further increase the formability of niobium.
The FTO rs17817449 Polymorphism is Not Associated With Sedentary Time, Physical Activity, or Cardiorespiratory Fitness: Findings From the GENADIO Cross-Sectional Study
Authors: Martorell Miquel , Mardones Lorena , Petermann-Rocha Fanny , Martinez-Sanguinetti Maria Adela , Leiva-Ordoñez Ana Maria , Troncoso-Pantoja Claudia , Flores Fernando , Cigarroa Igor , Perez-Bravo Francisco , Ulloa Natalia , Mondaca-Rojas Daniel , Diaz-Martinez Ximena , Celis-Morales Carlos , Villagran Marcelo , _ _ 
Published: September 2021

Background: Genetic variants within the FTO gene have been associated with increased adiposity and metabolic markers; however, there is limited evidence regarding the association of FTO gene variants with physical activity-related variables. The authors aimed to investigate the association of the rs17817449 single-nucleotide polymorphism of FTO with physical activity, sedentary time, and cardiorespiratory fitness in Chilean adults. Methods: A total of 409 participants from the GENADIO study were included and genotyped for the rs17817449 single-nucleotide polymorphism of FTO in this cross-sectional study. Physical activity and sedentary time were measured with ActiGraph accelerometers. Cardiorespiratory fitness was assessed using the Chester step test. The associations were assessed by using multivariate regression analyses. Results: No associations were found for FTO variant with physical activity levels and cardiorespiratory fitness. The risk allele (G) of the FTO was found to be associated with sedentary time in the minimally adjusted model (β = 19.7 min/d; 95% confidence interval, 4.0 to 35.5, per each copy of the risk allele; P = .006), but the association was no longer significant when body mass index was included as a confounder (P = .211). Conclusion: The rs17817449 single-nucleotide polymorphism of the FTO gene was not associated with the level of physical activity, cardiorespiratory fitness, and sedentary behaviors in Chilean adults.
Deep learning and capsule endoscopy: automatic identification and differentiation of small bowel lesions with distinct haemorrhagic potential using a convolutional neural network
Authors: Mascarenhas Saraiva Miguel José , Afonso João , Ribeiro Tiago , Ferreira João , Cardoso Helder , Andrade Ana Patricia , Parente Marco , Natal Renato , Mascarenhas Saraiva Miguel , Macedo Guilherme 
Published: September 2021

ObjectiveCapsule endoscopy (CE) is pivotal for evaluation of small bowel disease. Obscure gastrointestinal bleeding most often originates from the small bowel. CE frequently identifies a wide range of lesions with different bleeding potentials in these patients. However, reading CE examinations is a time-consuming task. Convolutional neural networks (CNNs) are highly efficient artificial intelligence tools for image analysis. This study aims to develop a CNN-based model for identification and differentiation of multiple small bowel lesions with distinct haemorrhagic potential using CE images.DesignWe developed, trained, and validated a denary CNN based on CE images. Each frame was labelled according to the type of lesion (lymphangiectasia, xanthomas, ulcers, erosions, vascular lesions, protruding lesions, and blood). The haemorrhagic potential was assessed by Saurin’s classification. The entire dataset was divided into training and validation sets. The performance of the CNN was measured by the area under the receiving operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsA total of 53 555 CE images were included. The model had an overall accuracy of 99%, a sensitivity of 88%, a specificity of 99%, a PPV of 87%, and an NPV of 99% for detection of multiple small bowel abnormalities and respective classification of bleeding potential.ConclusionWe developed and tested a CNN-based model for automatic detection of multiple types of small bowel lesions and classification of the respective bleeding potential. This system may improve the diagnostic yield of CE for these lesions and overall CE efficiency.
Following the science? Views from scientists on government advisory boards during the COVID-19 pandemic: a qualitative interview study in five European countries
Authors: Colman Elien , Wanat Marta , Goossens Herman , Tonkin-Crine Sarah , Anthierens Sibyl 
Published: September 2021

IntroductionIn order to tackle the pandemic, governments have established various types of advisory boards to provide evidence and recommendations to policy makers. Scientists working on these boards have faced many challenges, including working under significant time constraints to produce ‘evidence’ as quickly as possible. However, their voices are still largely missing in the discussion. This study explores the views and experiences of scientists working on government advisory boards during the COVID-19 pandemic, with the aim to learn lessons for future pandemic management and preparedness.MethodsWe conducted online video or telephone semi-structured interviews between December 2020 and April 2021 with 21 scientists with an official government advisory role during the COVID-19 pandemic in Belgium, the Netherlands, UK, Sweden and Germany. The interviews were audio-recorded and transcribed and analysed using a combination of inductive and deductive thematic analysis techniques.ResultsScientists viewed the initial focus on biomedically oriented work during the pandemic as somewhat one-dimensional, but also highlighted difficulties of working in an interdisciplinary way. They found it difficult at times to ensure that the evidence is understood and taken on board by governments. They found themselves taking on new roles, the boundaries of which were not clearly defined. Consequently, they were often perceived and treated as a public figure.ConclusionScientists working on advisory boards in European countries faced similar challenges, highlighting key lessons to be learnt. Future pandemic preparedness efforts should focus on building interdisciplinary collaboration through development of scientists’ skills and appropriate infrastructure; ensuring transparency in how boards operate; defining and protecting the boundaries of the scientific advisor role; and supporting scientists to inform the public in the fight against disinformation, while dealing with potential hostile reactions.
Eosinophilic features in clear cell renal cell carcinoma correlate with outcomes of immune checkpoint and angiogenesis blockade
Authors: Yoshida Takashi , Ohe Chisato , Ikeda Junichi , Atsumi Naho , Ohsugi Haruyuki , Sugi Motohiko , Higasa Koichiro , Saito Ryoichi , Tsuta Koji , Matsuda Tadashi , Kinoshita Hidefumi 
Published: September 2021

BackgroundClear cell renal cell carcinoma (ccRCC) displays heterogeneity in appearance—a distinctive pale clear to eosinophilic cytoplasm; however, little is known about the underlying mechanisms and clinical implications. We investigated the role of these eosinophilic features in ccRCC on oncological outcomes and response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).MethodsOne-hundred and thirty-eight ccRCC cases undergoing radical surgery (cohort 1) and 54 metastatic ccRCC cases receiving either TKIs or ICIs (cohort 2) were included. After histological evaluation, all cases were divided into three phenotypes based on the eosinophilic features at the highest-grade area: clear, mixed, or eosinophilic type. Gene expression and immunohistochemical analyses were performed to explore the potential mechanisms of these phenotypes in cohort 1. Further, the association of the three phenotypes with the best objective response to TKI or ICI, clinical benefit (complete/partial response or stable disease), and overall survival (OS) was assessed in cohort 2.ResultsThe clear type was significantly associated with increased hypoxia as well as angiogenesis gene signatures compared with the eosinophilic type. Gene signatures and protein expression related to effector T cell and immune checkpoint molecules were elevated to a greater extent in the eosinophilic type, followed by the mixed and clear types. The mixed and eosinophilic types exhibited greater PBRM1-negativity and increased prevalence of the epithelial-mesenchymal transition gene signature than the clear type. In the mixed/eosinophilic types of cohort 2, significant clinical benefit was observed in the ICI therapy group versus the TKI therapy group (p=0.035), and TKI therapy vs ICI therapy was an independent factor for worse prognosis of OS (HR 3.236; p=0.012).ConclusionThe histological phenotype based on the eosinophilic features, which are linked to major immunological mechanisms of ccRCC, was significantly correlated with therapeutic efficacy.