bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study
Authors: Giotakis Aris I. , Dudas Jozsef , Glueckert Rudolf , Dejaco Daniel , Ingruber Julia , Fleischer Felix , Innerhofer Veronika , Pinggera Leyla , Bektic-Tadic Ljilja , Gabriel Sarah A. M. , Riechelmann Herbert 
Published: January 2021

AbstractEpithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial–mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18–vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3–6 times higher compared to the control patients. In the epithelial layer, cytokeratin–vimentin-double-positive EMT cells were observed 3–5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.
Simple method of thawing cryo-stored samples preserves ultrastructural features in electron microscopy
Authors: Galhuber Markus , Kupper Nadja , Dohr Gottfried , Gauster Martin , Kwapiszewska Grazyna , Olschewski Andrea , Jandl Katharina , Gschwandtner Elisabeth , Schweiger Martina , Kratky Dagmar , Leitinger Gerd , Prokesch Andreas , Kolb Dagmar 
Published: January 2021

AbstractPreservation of ultrastructural features in biological samples for electron microscopy (EM) is a challenging task that is routinely accomplished through chemical fixation or high-pressure freezing coupled to automated freeze substitution (AFS) using specialized devices. However, samples from clinical (e.g. “biobanking” of bulk biopsies) and preclinical (e.g. whole mouse tissues) specimens are often not specifically prepared for ultrastructural analyses but simply immersed in liquid nitrogen before long-term cryo-storage. We demonstrate that ultrastructural features of such samples are insufficiently conserved using AFS and developed a simple, rapid, and effective method for thawing that does not require specific instrumentation. This procedure consists of dry ice-cooled pre-trimming of frozen tissue and aldehyde fixation for 3 h at 37 °C followed by standard embedding steps. Herein investigated tissues comprised human term placentae, clinical lung samples, as well as mouse tissues of different composition (brown adipose tissue, white adipose tissue, cardiac muscle, skeletal muscle, liver). For all these tissues, we compared electron micrographs prepared from cryo-stored material with our method to images derived from directly prepared fresh tissues with standard chemical fixation. Our protocol yielded highly conserved ultrastructural features and tissue-specific details, largely matching the quality of fresh tissue samples. Furthermore, morphometric analysis of lipid droplets and mitochondria in livers of fasted mice demonstrated that statistically valid quantifications can be derived from samples prepared with our method. Overall, we provide a simple and effective protocol for accurate ultrastructural and morphometric analyses of cryo-stored bulk tissue samples.
Expression and enhancement of FABP4 in septoclasts of the growth plate in FABP5-deficient mouse tibiae
Authors: Bando Yasuhiko , Tokuda Nobuko , Ogasawara Yudai , Onozawa Go , Nagasaka Arata , Sakiyama Koji , Owada Yuji , Amano Osamu 
Published: January 2021

AbstractIn our previous study, fatty acid-binding protein 5 (FABP5) was expressed in septoclasts with long processes which are considered to resorb uncalcified matrix of the growth plate (GP) cartilage, and no apparent abnormalities were detected in the histo-architecture of the GP of FABP5-deficient (FABP5−/−) mice. Those finding lead us to hypothesize that another FABP can compensate the deletion of FABP5 in septoclasts of its gene-mutant mice. Based on the hypothesis, the present study examined the expression levels of several other FABPs in septoclasts and their morphology in FABP5−/− mouse tibiae. Processes of FABP5−/− septoclasts tend to be shorter than wild septoclasts. FABP4-positive septoclasts in FABP5−/− mice were more numerous than those cells in wild mice.Peroxisome proliferator-activated receptor (PPAR) γ was expressed in FABP4-positive septoclasts of FABP5−/− mice as well as mice administered with GW1929, a PPARγ agonist, suggesting that the occurrence of PPARγ induces an increase of FABP4-positive septoclasts. The present finding suggests that the functional exertion of FABP5 in septoclasts is supplemented by FABP4 in normal and FABP5−/− mice, and that the expression of FABP4 is up-regulated in accompany with PPARγ in FABP5−/− for maintenance of resorptive activity in the GP.
Diverse functions of myosin VI in spermiogenesis
Authors: Zakrzewski Przemysław , Lenartowska Marta , Buss Folma 
Published: January 2021

AbstractSpermiogenesis is the final stage of spermatogenesis, a differentiation process during which unpolarized spermatids undergo excessive remodeling that results in the formation of sperm. The actin cytoskeleton and associated actin-binding proteins play crucial roles during this process regulating organelle or vesicle delivery/segregation and forming unique testicular structures involved in spermatid remodeling. In addition, several myosin motor proteins including MYO6 generate force and movement during sperm differentiation. MYO6 is highly unusual as it moves towards the minus end of actin filaments in the opposite direction to other myosin motors. This specialized feature of MYO6 may explain the many proposed functions of this myosin in a wide array of cellular processes in animal cells, including endocytosis, secretion, stabilization of the Golgi complex, and regulation of actin dynamics. These diverse roles of MYO6 are mediated by a range of specialized cargo-adaptor proteins that link this myosin to distinct cellular compartments and processes. During sperm development in a number of different organisms, MYO6 carries out pivotal functions. In Drosophila, the MYO6 ortholog regulates actin reorganization during spermatid individualization and male KO flies are sterile. InC. elegans, the MYO6 ortholog mediates asymmetric segregation of cytosolic material and spermatid budding through cytokinesis, whereas in mice, this myosin regulates assembly of highly specialized actin-rich structures and formation of membrane compartments to allow the formation of fully differentiated sperm. In this review, we will present an overview and compare the diverse function of MYO6 in the specialized adaptations of spermiogenesis in flies, worms, and mammals.
Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle
Authors: Palmer Megan A. , Smart Eleanor , Haslam Iain S. 
Published: January 2021

AbstractCholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.
Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation
Authors: Evert Katja , Dienemann Thomas , Brochhausen Christoph , Lunz Dirk , Lubnow Matthias , Ritzka Markus , Keil Felix , Trummer Matthias , Scheiter Alexander , Salzberger Bernd , Reischl Udo , Boor Peter , Gessner André , Jantsch Jonathan , Calvisi Diego F. , Evert Matthias , Schmidt Barbara , Simon Michaela 
Published: January 2021

AbstractBetween April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.
Calendar age and puberty-related development of regional gray matter volume and white matter tracts during adolescence
Authors: Ando Ayaka , Parzer Peter , Kaess Michael , Schell Susanne , Henze Romy , Delorme Stefan , Stieltjes Bram , Resch Franz , Brunner Romuald , Koenig Julian 
Published: January 2021

Abstract
Background
Adolescence is a critical time for brain development. Findings from previous studies have been inconsistent, failing to distinguish the influence of pubertal status and aging on brain maturation. The current study sought to address these inconsistencies, addressing the trajectories of pubertal development and aging by longitudinally tracking structural brain development during adolescence.

Methods
Two cohorts of healthy children were recruited (cohort 1: 9–10 years old; cohort 2: 12–13 years old at baseline). MRI data were acquired for gray matter volume and white matter tract measures. To determine whether age, pubertal status, both or their interaction best modelled longitudinal data, we compared four multi-level linear regression models to the null model (general brain growth indexed by total segmented volume) using Bayesian model selection.

Results
Data were collected at baseline (n = 116), 12 months (n = 97) and 24 months (n = 84) after baseline. Findings demonstrated that the development of most regional gray matter volume, and white matter tract measures, were best modelled by age. Interestingly, precentral and paracentral regions of the cortex, as well as the accumbens demonstrated significant preference for the pubertal status model. None of the white matter tract measures were better modelled by pubertal status.
Limitations: The major limitation of this study is the two-cohort recruitment. Although this allowed a faster coverage of the age span, a complete per person trajectory over 6 years of development (9–15 years) could not be investigated.

Conclusions
Comparing the impact of age and pubertal status on regional gray matter volume and white matter tract measures, we found age to best predict longitudinal changes. Further longitudinal studies investigating the differential influence of puberty status and age on brain development in more diverse samples are needed to replicate the present results and address mechanisms underlying norm-variants in brain development.
Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training Network
Authors: Rajula Hema Sekhar Reddy , Manchia Mirko , Agarwal Kratika , Akingbuwa Wonuola A. , Allegrini Andrea G. , Diemer Elizabeth , Doering Sabrina , Haan Elis , Jami Eshim S. , Karhunen Ville , Leone Marica , Schellhas Laura , Thompson Ashley , van den Berg Stéphanie M. , Bergen Sarah E. , Kuja-Halkola Ralf , Hammerschlag Anke R. , Järvelin Marjo Riitta , Leval Amy , Lichtenstein Paul , Lundstrom Sebastian , Mauri Matteo , Munafò Marcus R. , Myers David , Plomin Robert , Rimfeld Kaili , Tiemeier Henning , Ystrom Eivind , Fanos Vassilios , Bartels Meike , Middeldorp Christel M. 
Published: January 2021

AbstractThe Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
Review: Advances in the methodology and application of tracing in karst aquifers
Authors: Benischke Ralf 
Published: January 2021

AbstractTracer methods have been widely used in many fields of environmental and natural sciences, and also in human health sciences. In particular, tracers are used in the study of karst hydrogeology, typically focusing on phenomena such as sinkholes, sinking rivers and large karst springs. It is known that tracers have been used since antiquity. The aim of tracer tests has been to investigate underground flow paths, transport processes and water–rock interactions, and to get an insight into the functioning of a karst aquifer. In karst hydrogeology, tracer methods are the most important investigation tools beside conventional hydrological methods. In early times, tracer methods were applied only to investigate underground flow-paths. Later they were also used to elucidate transport processes associated with water flow, and today they are often the basis, together with detailed hydrological information, of groundwater protection investigations and aquifer modelling. Many substances (spores, microspheres, bacteriophages, salt tracers, fluorescent dyes, radioactive substances) have been investigated for their properties and potential usage in environmental investigations, in particular the often unknown and inaccessible underground systems of karst areas. A great number of analytical techniques is available. This includes instrumentation for laboratory applications and direct online, on-site or in-situ field measurements. Modern instruments have a high capability for data acquisition, storage and transmission in short intervals, as a basis for quantitative evaluation and modelling. This enables research on the hydrological and hydrochemical dynamics of aquifers and their response to different natural or anthropogenic impacts.
Outcome prediction in aneurysmal subarachnoid hemorrhage: a comparison of machine learning methods and established clinico-radiological scores
Authors: Dengler Nora Franziska , Madai Vince Istvan , Unteroberdörster Meike , Zihni Esra , Brune Sophie Charlotte , Hilbert Adam , Livne Michelle , Wolf Stefan , Vajkoczy Peter , Frey Dietmar 
Published: January 2021

AbstractReliable prediction of outcomes of aneurysmal subarachnoid hemorrhage (aSAH) based on factors available at patient admission may support responsible allocation of resources as well as treatment decisions. Radiographic and clinical scoring systems may help clinicians estimate disease severity, but their predictive value is limited, especially in devising treatment strategies. In this study, we aimed to examine whether a machine learning (ML) approach using variables available on admission may improve outcome prediction in aSAH compared to established scoring systems. Combined clinical and radiographic features as well as standard scores (Hunt & Hess, WFNS, BNI, Fisher, and VASOGRADE) available on patient admission were analyzed using a consecutive single-center database of patients that presented with aSAH (n = 388). Different ML models (seven algorithms including three types of traditional generalized linear models, as well as a tree bosting algorithm, a support vector machine classifier (SVMC), a Naive Bayes (NB) classifier, and a multilayer perceptron (MLP) artificial neural net) were trained for single features, scores, and combined features with a random split into training and test sets (4:1 ratio), ten-fold cross-validation, and 50 shuffles. For combined features, feature importance was calculated. There was no difference in performance between traditional and other ML applications using traditional clinico-radiographic features. Also, no relevant difference was identified between a combined set of clinico-radiological features available on admission (highest AUC 0.78, tree boosting) and the best performing clinical score GCS (highest AUC 0.76, tree boosting). GCS and age were the most important variables for the feature combination. In this cohort of patients with aSAH, the performance of functional outcome prediction by machine learning techniques was comparable to traditional methods and established clinical scores. Future work is necessary to examine input variables other than traditional clinico-radiographic features and to evaluate whether a higher performance for outcome prediction in aSAH can be achieved.
Preservation of kidney function irrelevant of total kidney volume growth rate with tolvaptan treatment in patients with autosomal dominant polycystic kidney disease
Authors: Horie Shigeo , Muto Satoru , Kawano Haruna , Okada Tadashi , Shibasaki Yoshiyuki , Nakajima Koji , Ibuki Tatsuki 
Published: January 2021

Abstract
Background
Tolvaptan slowed the rates of total kidney volume (TKV) growth and renal function decline over a 3-year period in patients with autosomal dominant polycystic kidney disease (ADPKD) enrolled in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial (NCT00428948). In this post hoc analysis of Japanese patients from TEMPO 3:4, we evaluated whether the effects of tolvaptan on TKV and on renal function are interrelated.

Methods
One hundred and forty-seven Japanese patients from TEMPO 3:4 were included in this analysis (placebo, n = 55; tolvaptan, n = 92). Tolvaptan-treated patients were stratified into the responder group (n = 37), defined as tolvaptan-treated patients with a net decrease in TKV from baseline to year 3, and the non-responder group (n = 55), defined as tolvaptan-treated patients with a net increase in TKV.

Results
Mean changes during follow-up in the placebo, responder, and non-responder groups were 16.99%, − 8.33%, and 13.95%, respectively, for TKV and − 12.61, − 8.47, and − 8.58 mL/min/1.73 m2, respectively, for estimated glomerular filtration rate (eGFR). Compared with the placebo group, eGFR decline was significantly slowed in both the responder and non-responder groups (P < 0.05).

Conclusion
Tolvaptan was effective in slowing eGFR decline, regardless of TKV response, over 3 years in patients with ADPKD in Japan. Treatment with tolvaptan may have beneficial effects on slowing of renal function decline even in patients who have not experienced a reduction in the rate of TKV growth by treatment with tolvaptan.
Pegasus: sound continuous invariant generation
Authors: Sogokon Andrew , Mitsch Stefan , Tan Yong Kiam , Cordwell Katherine , Platzer André 
Published: January 2021

AbstractContinuous invariants are an important component in deductive verification of hybrid and continuous systems. Just like discrete invariants are used to reason about correctness in discrete systems without having to unroll their loops, continuous invariants are used to reason about differential equations without having to solve them. Automatic generation of continuous invariants remains one of the biggest practical challenges to the automation of formal proofs of safety for hybrid systems. There are at present many disparate methods available for generating continuous invariants; however, this wealth of diverse techniques presents a number of challenges, with different methods having different strengths and weaknesses. To address some of these challenges, we develop Pegasus: an automatic continuous invariant generator which allows for combinations of various methods, and integrate it with the KeYmaera X theorem prover for hybrid systems. We describe some of the architectural aspects of this integration, comment on its methods and challenges, and present an experimental evaluation on a suite of benchmarks.