bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of the late endocytic pathway in Charcot–Marie–Tooth type 2B disease
Authors: Romano Roberta , Rivellini Cristina , De Luca Maria , Tonlorenzi Rossana , Beli Raffaella , Manganelli Fiore , Nolano Maria , Santoro Lucio , Eskelinen Eeva-Liisa , Previtali Stefano C. , Bucci Cecilia 
Published: April 2020

AbstractThe small GTPase RAB7A regulates late stages of the endocytic pathway and plays specific roles in neurons, controlling neurotrophins trafficking and signaling, neurite outgrowth and neuronal migration. Mutations in the RAB7A gene cause the autosomal dominant Charcot–Marie–Tooth type 2B (CMT2B) disease, an axonal peripheral neuropathy. As several neurodegenerative diseases are caused by alterations of endocytosis, we investigated whether CMT2B-causing mutations correlate with changes in this process. To this purpose, we studied the endocytic pathway in skin fibroblasts from healthy and CMT2B individuals. We found higher expression of late endocytic proteins in CMT2B cells compared to control cells, as well as higher activity of cathepsins and higher receptor degradation activity. Consistently, we observed an increased number of lysosomes, accompanied by higher lysosomal degradative activity in CMT2B cells. Furthermore, we found increased migration and increased RAC1 and MMP-2 activation in CMT2B compared to control cells. To validate these data, we obtained sensory neurons from patient and control iPS cells, to confirm increased lysosomal protein expression and lysosomal activity in CMT2B-derived neurons. Altogether, these results demonstrate that in CMT2B patient-derived cells, the endocytic degradative pathway is altered, suggesting that higher lysosomal activity contributes to neurodegeneration occurring in CMT2B.
A classification for partial subscapularis tendon tears
Authors: Martetschläger Frank , Zampeli Frantzeska , Tauber Mark , Habermeyer Peter , Leibe Markus 
Published: April 2020

AbstractPurposeThe aim of the study was to analyze partial subscapularis tendon (SSC) tears and provide a descriptive classification.MethodsThe retrospective study included 50 patients with arthroscopically confirmed partial SSC tears. Internal rotation (IR) force measurements and IR ROM have been made and compared to the healthy contralateral side. Then the footprint of the SSC was routinely investigated by arthroscopy with standardized measurement of the bony footprint lesion. The partial tears were classified according to the mediolateral and craniocaudal extension of the rupture in the transverse and coronal plane, respectively.ResultsPartial SSC tears could be classified into split lesions (type 1,n = 11) and 3 further groups depending on the mediolateral peeled-off length of the bony footprint (type 2: < 10 mm,n = 20; type 3: 10–15 mm,n = 10; type 4: > 15 mm,n = 9). Type 2–4 could be further divided depending on the craniocaudal peeled-off length of the bony footprint (group A: < 10 mm, group B: 10–15 mm, group C: > 15 mm). Significantly decreased IR strength was shown for types 2–4 (p < 0.05) but not for split lesions as compared to healthy side. Types 1–4 showed significant decreased active IR ROM and all except type 3 (n.s.) which showed decreased passive IR ROM compared to the healthy side (p < 0.05).ConclusionWe present a novel classification for partial SSC tears for a more detailed and reproducible description. This can help to improve the current knowledge about the appropriate treatment. It could be shown that partial tears of the subscapularis can have an impact on IR strength and motion.Level of evidenceIII
Suppression of Gq and PLC gene expression has a small effect on quantum bumps in vivo in Periplaneta americana
Authors: Ignatova Irina I. , French Andrew S. , Torkkeli Päivi H. , Liu Hongxia , Frolov Roman V. 
Published: April 2020

AbstractVisual signal transmission byDrosophila melanogasterphotoreceptors is mediated by a Gq protein that activates a phospholipase C (PLC). Mutations and deficiencies in expression of either of these proteins cause severe defects in phototransduction. Here we investigated whether these proteins are also involved in the cockroach,Periplaneta americana, phototransduction by silencing Gq α-subunit (Gqα) and phosphoinositide-specific phospholipase C (PLC) by RNA interference and observing responses to single photons (quantum bumps, QB). We found (1) non-specific decreases in membrane resistance, membrane capacitance and absolute sensitivity in the photoreceptors of both Gqα and PLC knockdowns, and (2) small changes in QB statistics. Despite significant decreases in expressions of Gq and PLC mRNA, the changes in QB properties were surprisingly modest, with mean latencies increasing by ~ 10%, and without significant decrease in their amplitudes. To better understand our results, we used a mathematical model of the phototransduction cascade. By modifying the Gq and PLC abundances, and diffusion rates for Gq, we found that QB latencies and amplitudes deteriorated noticeably only after large decreases in the protein levels, especially when Gq diffusion was slow. Also, reduction in Gq but not PLC lowered quantum efficiency. These results suggest that expression of the proteins may be redundant.
Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants
Authors: Szpecht Dawid , Al-Saad Salwan R. , Karbowski Lukasz M. , Kosik Katarzyna , Kurzawińska Grażyna , Szymankiewicz Marta , Drews Krzysztof , Seremak-Mrozikiewicz Agnieszka 
Published: April 2020

Abstract
Background/introduction
Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH.

Material and methods
The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655.

Results
IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046–79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms.

Conclusion
The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.
The impact of maintenance therapy on sleep-wake rhythms and cancer-related fatigue in pediatric acute lymphoblastic leukemia
Authors: Steur L. M. H. , Kaspers G. J. L. , van Someren E. J. W. , van Eijkelenburg N. K. A. , van der Sluis I. M. , Dors N. , van den Bos C. , Tissing W. J. E. , Grootenhuis M. A. , van Litsenburg R. R. L. 
Published: April 2020

Abstract
Purpose
To assess the impact of maintenance therapy and the additional impact of dexamethasone treatment on cancer-related fatigue and sleep-wake rhythms in pediatric acute lymphoblastic leukemia (ALL) patients and to determine the association between these outcomes.

Methods
A national cohort of pediatric ALL patients (≥ 2 years) was included (± 1 year post-diagnosis). Patients receiving dexamethasone were assessed twice (assessment with and without dexamethasone). Actigraphy assessments were used to calculate sleep-wake outcomes with nonparametric methods. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Sleep-wake rhythms and cancer-related fatigue were compared between patients participating in the assessment without dexamethasone and healthy children (linear regression) and between assessments with and without dexamethasone (mixed models). Using linear regression, associations between sleep-wake outcomes and cancer-related fatigue were determined during assessments with and without dexamethasone.

Results
Responses were collected for 125 patients (113 assessments with and 81 without dexamethasone). The sleep-wake rhythm was less stable (p = 0.03) and less robust (p = 0.01), with lower physical activity levels (p < 0.001) and higher cancer-related fatigue levels (p < 0.001) in ALL patients compared to healthy children. Physical activity was lower (p = 0.001) and cancer-related fatigue more severe (p ≤ 0.001) during assessments with dexamethasone compared to without dexamethasone. Sleep-wake outcomes were significantly associated with cancer-related fatigue during periods without dexamethasone, but not during periods with dexamethasone.

Conclusion
Sleep-wake rhythms are disturbed, physical activity levels lower, and cancer-related fatigue levels higher during maintenance therapy. Interventions aimed to enhance sleep-wake rhythms during maintenance therapy could improve cancer-related fatigue. Families should be supported in coping with the additional burden of dexamethasone treatment to improve well-being of ALL patients.
9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes
Authors: Keller Sebastian , Polanski Witold Henryk , Enzensperger Christoph , Reichmann Heinz , Hermann Andreas , Gille Gabriele 
Published: April 2020

Abstractβ-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.
Sequence-based comparison of field and vaccine strains of infectious bursal disease virus in Ethiopia reveals an amino acid mismatch in the immunodominant VP2 protein
Authors: Shegu Dereje , Sori Teshale , Tesfaye Asaminew , Belay Alebachew , Mohammed Hawa , Degefa Teferi , Getachew Belayneh , Abayneh Takele , Gelaye Esayas 
Published: April 2020

AbstractSequencing of the VP2 region was carried out to identify amino acid mismatches between vaccine strains and field isolates of infectious bursal disease virus (IBDV). Viruses were isolated in chicken embryo fibroblast (DF-1) cells using pooled samples of bursa collected from nine outbreaks, which affected 30,250 chickens in five localities, with an overall mortality of 47.87%. Virus strains were identified by comparing the deduced amino acid sequence between positions 232 and 446 of the immunodominant VP2 epitope. All of the pooled samples were positive for IBDV. RT-PCR yielded a 645-bp DNA fragment of the VP2 gene. Phylogenetic analysis of this fragment revealed clustering of these isolates with very virulent IBDV strains. The amino acid sequences of these isolates were identical to those of the European very virulent strains UK 661 and DV 86, except at position 222, but differed from the vaccine strains used in Ethiopia, suggesting the possible introduction of virulent virus strains to Ethiopia from Europe. Our study demonstrates the widespread presence of very virulent strains of IBDV on poultry farms in Ethiopia and demonstrates the need to evaluate the protective level of existing vaccines against circulating field viruses.
Challenges in physician-patient communication for optimal management of systemic sclerosis-associated interstitial lung disease: a discourse analysis
Authors: Denton Christopher P. , Laird Bee , Moros Lizette , Flores Jose Luis Luna 
Published: April 2020

Abstract
Introduction
Systemic sclerosis (SSc) is a rare, potentially life-threatening condition. The prognosis is difficult to predict, and treatment is complex. This can be difficult to understand or explain, posing challenges for effective physician-patient communication. Our study assessed communication between physicians and patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) to identify information gaps and needs.

Methods
Twenty-three 20-min consultations between physicians (rheumatologists, pulmonologists) and patients (19 real, 4 actors) with diagnosed SSc-ILD across 6 countries were observed and recorded. Interactional sociolinguistic discourse analysis was used to understand the pattern and meaning of communication, whether the needs of both participants were met, and the level of understanding between participants.

Results
In most consultations, patients were given little opportunity to explain their concerns or ask questions. Physicians used plain language but would revert to medical terminology for complex issues. Patients would also use medical terminology, despite not fully understanding the terms, which led to some physicians mistakenly believing that patients had a better understanding than they did. Differences in cognitive models between physicians and patients were often responsible for misunderstandings. However, during effective consultations, patients were invited to tell their story, and physicians used techniques to check and demonstrate understanding, express empathy and build rapport.

Conclusions
Communication challenges between physicians and patients limit joint understanding of SSc-ILD and may result in both parties misunderstanding important information and patients being less aware of self-help management approaches. Strategies should be developed with physicians to facilitate effective communication and increase patient understanding and support.

Key Points• Physicians and patients have different explanatory models for SSc-ILD.• The differences between the physician-constructed model of SSc-ILD and the personal model patients construct often result in misunderstandings. • Many patients with SSc have learned the medical terminology for their condition, but their often limited understanding may lead to missed opportunities for physicians to provide clear explanations and correct misperceptions.• The style of consultation determines the information patients share and the degree to which they feel supported by, and confident in, their physicians’ care.
Fiddler crabs and their above-ground sedimentary structures: a review
Authors: Pardo Juan C. F. , Stefanelli-Silva Gabriel , Christy John H. , Costa Tânia M. 
Published: April 2020

AbstractFiddler crabs are abundant, semi-terrestrial crustaceans inhabiting tropical, subtropical and warm temperate coasts worldwide. Some species build above-ground sedimentary structures at or near the opening to their burrows. The functions and shapes of these constructions vary interspecifically and according to the sex of the builder. Here, we compile the dispersed reports on these structures, suggest uniform naming for different shapes, review explanations for their functions and explore associations between the attributes of builders and their structures. We found that 47 fiddler crab species build at least one type (or subtype) of structure, including chimneys, hoods, pillars, semidomes, mudballs, and rims. Sedimentary structures show a strong association with sediment type as well as builder front type, genus and sex, but not with fiddler crab clade. Experimental studies have revealed distinct, sometimes multiple functions for some of these structures (e.g., female attraction, reduction of aggressive behavior and/or landmark orientation); however, most studies have been observational leaving the proposed functions of these structures for many species untested. Both field and laboratory experiments as well as observational studies can help us to better understand these sedimentary structures and their role in fiddler crab behavior and ecology.
Atomically Layered Helium Films at Ultralow Temperatures: Model Systems for Realizing Quantum Materials
Authors: Saunders John , Cowan Brian , Nyéki Jan 
Published: April 2020

AbstractThis year is also the 50th anniversary of the discovery of exfoliated graphite as a particularly uniform substrate (Thomy and Duval in J Chim Phys 66:1966, 1969.10.1051/jcp/196966s21966, J Chim Phys 67:286, 1970.10.1051/jcp/1970670286, J Chim Phys 67:1101, 1970.10.1051/jcp/1970671101). In this article, we focus on the study of helium films on graphite-based substrates at ultralow temperatures. We provide a flavour of the historical development of this subject and a perspective on the current status. We discuss how atomically layered helium films provide model systems for the realization of a broad range of quantum materials of generic significance. Future prospects arising from new techniques and new substrates will also be discussed.
Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation
Authors: Pal Akos , Asad Yasmin , Ruddle Ruth , Henley Alan T. , Swales Karen , Decordova Shaun , Eccles Suzanne A . , Collins Ian , Garrett Michelle D. , De Bono Johann , Banerji Udai , Raynaud Florence I. 
Published: April 2020

Abstract
Introduction
To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal transduction inhibitors identified in preclinical models have previously been confirmed in early clinical studies. This study explores whether metabolic signatures could be used as biomarkers for the multi-AGC kinase inhibitor AT13148.

Objectives
To identify metabolomic changes of biomarkers of multi-AGC kinase inhibitor AT13148 in cells, xenograft / mouse models and in patients in a Phase I clinical study.

Methods
HILIC LC–MS/MS methods and Biocrates AbsoluteIDQ™ p180 kit were used for targeted metabolomics; followed by multivariate data analysis in SIMCA and statistical analysis in Graphpad. Metaboanalyst and String were used for network analysis.

Results
BT474 and PC3 cells treated with AT13148 affected metabolites which are in a gene protein metabolite network associated with Nitric oxide synthases (NOS). In mice bearing the human tumour xenografts BT474 and PC3, AT13148 treatment did not produce a common robust tumour specific metabolite change. However, AT13148 treatment of non-tumour bearing mice revealed 45 metabolites that were different from non-treated mice. These changes were also observed in patients at doses where biomarker modulation was observed. Further network analysis of these metabolites indicated enrichment for genes associated with the NOS pathway. The impact of AT13148 on the metabolite changes and the involvement of NOS-AT13148- Asymmetric dimethylarginine (ADMA) interaction were consistent with hypotension observed in patients in higher dose cohorts (160-300 mg).

Conclusion
AT13148 affects metabolites associated with NOS in cells, mice and patients which is consistent with the clinical dose-limiting hypotension.
Adapting to the Challenges of Chronic Non-communicable Diseases: Evidence from Russia
Authors: Gerry Christopher J , Kaneva Maria 
Published: April 2020

AbstractAs life expectancies increase and healthcare improves, increasing numbers of the population can expect to live with combinations of two or more chronic non-communicable diseases (NCDs). Population studies suggest that more than half of older-aged adults report having multiple chronic NCDs (multimorbidities) and two-thirds of total health spending in high-income countries is accounted for by patients with multimorbidities. Beyond the need to obviate the growing burden on healthcare systems, the increasing incidence and prevalence of multimorbidity and its effects requires further investigation. Using nationally representative data from a Russian population survey, we examine the impact of chronic NCDs on self-assessed health, explore the prevalence of multimorbidity and, applying an iterative partial proportional odds estimator, examine how different combinations of chronic NCDs interact to influence self-assessed health. Confirming that there are high levels of chronic NCDs and associated multimorbidities, we find that the impact of these on self-assessed health is greater than previous estimates suggested but that, where there are dual morbidities, the effect of the additional disease is weaker than it would have been if experienced as a single condition. We conclude that individuals possess critical adaptive psychological mechanisms which attenuate the incremental health impact of additional chronic NCDs. These are important for understanding the relationship between illness and the quality of life.
Heterogeneity in relation to electrical and mineralogical properties of hematitic sandstone samples
Authors: Gomaa Mohamed Mahmoud 
Published: April 2020

AbstractElectrical properties of mixtures of composite materials are sensitive to texture between grains. Electrical measurements of hematite and sandstone composite mixture were performed in the frequency range (5 × 10−4 Hz–105 Hz). This study is a trial to give more detailed information upon the effect of electrical properties and their relation to the ore composite mixture, its geochemical and spectrographic analyses. The composite mixture of the samples displays some similarity in the frequency-dependent response of the electrical properties that follow Jonscher’s universal law. The frequency dependence of electrical conductivity indicates that the sample behaves as a semiconductor material at relatively high frequencies. The spectra of the measured electrical properties vary strongly with the change of the concentration of the conductive elements and the texture of the specimens. The main change of the electrical properties is related to the conductor (saturation) concentration. This change does not increase monotonically with the increase in the conductor (saturation) concentration which may be attributed to the degree of heterogeneity between the grains (and texture). The interface between the grains controls the relatively low frequencies, whereas the bulk grain dominates the relatively high frequencies. The heterogeneity of the samples is an effective component in controlling the electrical properties of the composite mixtures.