bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Yaoita Nobuhiro , Satoh Kimio , Satoh Taijyu , Shimizu Toru , Saito Sakae , Sugimura Koichiro , Tatebe Shunsuke , Yamamoto Saori , Aoki Tatsuo , Kikuchi Nobuhiro , Kurosawa Ryo , Miyata Satoshi , Nagasaki Masao , Yasuda Jun , Shimokawa Hiroaki 
Published: October 2020

Background
Although chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds.

Methods and Results

Whole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of
F5
, which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of
THBD
, which encodes thrombomodulin. Moreover, thrombin‐activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of
THBD
compared with those without it.

Conclusions
These results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.
Recovery-oriented intersectoral care between mental health hospitals and community mental health services: An integrative review
Authors: Jørgensen Kim , Rasmussen Tonie , Hansen Morten , Andreasson Kate 
Published: October 2020

Background: Recovery-oriented intersectoral care is described as an aim in mental healthcare to create a holistic framework for planning that provides integration of treatment and rehabilitation. Existing studies show that nurses and other professionals do not take responsibility for the collaborative element of intersectoral care between mental health hospitals and community mental health services. The users of mental healthcare do not experience their patient journey as a cohesive process when they are discharged from a mental health hospital to community mental health services. Aim: The integrative review aims to examine the professionals’ experience with recovery-oriented intersectoral care between mental health hospitals and community mental health services. Design: Since the aim was to review user experience, we chose an integrative review as an obvious choice for design. Ethical approval: Not applicable. Findings: Seven studies met the inclusion criteria. The interactive inductive and deductive analysis generated four themes, which clarify the experience of professionals with recovery-oriented intersectoral care between the mental health hospitals and community mental health services, namely ‘structurally routine care’, ‘unequal balance of power between the sectors’, ‘bureaucracy as a barrier to recovery-oriented intersectoral care’ and ‘flexible mental healthcare approaches’. Conclusion: This review achieves specific knowledge of recovery-oriented intersectoral care. The studies included show that recovery-oriented intersectoral care is not clearly defined. It is challenging to transfer intersectoral care to an organisation with different structural and linguistic barriers.
The support needs of parent caregivers of children with a life-limiting illness and approaches used to meet their needs: A scoping review
Authors: Gill Fenella J , Hashem Zahraa , Stegmann Roswitha , Aoun Samar M 
Published: October 2020

Background: Provision of paediatric palliative care is complex and optimally covers meeting the individual needs of a heterogenous population of children and their parent caregivers throughout a life-limiting illness. It is unclear whether existing approaches comprehensively address parent caregivers’ needs. Aim: To examine support needs of parents caring for children with life limiting illnesses and identify specific approaches used to identify and address needs. Design: A scoping review Data sources: MEDLINE, EMBASE, PsycINFO, CINAHL and ProQuest Central, were searched for peer reviewed English language full text research published from 2008 to 2019. Study quality appraisal was undertaken. Fourteen quantitative, 18 qualitative and 12 mixed methods studies were synthesised and themed using summative content analysis and mapped to the Parent Supportive Care Needs Framework (PSCNF). Results: Themes were communication, choice, information, practical, social, psychological, emotional and physical. Communication and choice were central and additional to domains of the PSCNF. Unmet were needs for supporting siblings, for respite care, out of hours, psychological, home and educational support. Six articles reported using instruments to identify parent carer support needs. Conclusion: Support needs of parent caregivers of children with life limiting illnesses are substantial and heterogenous. While studies report evidence of burden and distress in parent caregivers, this rarely translates into improvements in practice through the development of interventions. A systematic and regular assessment of individual parent caregiver support needs is required by using instruments appropriate to use in clinical practice to move the focus to palliative care interventions and improved services for parents.
Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice
Authors: Leibold Nicole K , van den Hove Daniel LA , Weidner Magdalena T , Buchanan Gordon F , Steinbusch Harry WM , Lesch Klaus-Peter , Schruers Koen RJ 
Published: October 2020

Background: Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the SLC6A4 gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model. Aim: The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide. Methods: Based on our previous work, wildtype and serotonin transporter deficient (+/–, –/–) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/– mice, also cardio-respiration was assessed. Results: For most behavioral measures under air exposure, wildtype and serotonin transporter +/– mice did not differ, while serotonin transporter –/– mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter –/– mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype. Conclusion: Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.
Dissociable contributions of mediodorsal and anterior thalamic nuclei in visual attentional performance: A comparison using nicotinic and muscarinic cholinergic receptor antagonists
Authors: Mantanona Craig P , Božič Tadej , Chudasama Yogita , Robbins Trevor W , Dalley Jeffrey W , Alsiö Johan , Pienaar Ilse S 
Published: October 2020

Background: Thalamic subregions mediate various cognitive functions, including attention, inhibitory response control and decision making. Such neuronal activity is modulated by cholinergic thalamic afferents and deterioration of such modulatory signaling has been theorised to contribute to cognitive decline in neurodegenerative disorders. However, the thalamic subnuclei and cholinergic receptors involved in cognitive functioning remain largely unknown. Aims: We investigated whether muscarinic or nicotinic receptors in the mediodorsal thalamus and anterior thalamus contribute to rats’ performance in the five-choice serial reaction time task, which measures sustained visual attention and impulsive action. Methods: Male Long-Evans rats were trained in the five-choice serial reaction time task then surgically implanted with guide cannulae targeting either the mediodorsal thalamus or anterior thalamus. Reversible inactivation of either the mediodorsal thalamus or anterior thalamus were achieved with infusions of the γ-aminobutyric acid-ergic agonists muscimol and baclofen prior to behavioural assessment. To investigate cholinergic mechanisms, we also assessed the behavioural effects of locally administered nicotinic (mecamylamine) and muscarinic (scopolamine) receptor antagonists. Results: Reversible inactivation of the mediodorsal thalamus severely impaired discriminative accuracy and response speed and increased omissions. Inactivation of the anterior thalamus produced less profound effects, with impaired accuracy at the highest dose. In contrast, blocking cholinergic transmission in these regions did not significantly affect five-choice serial reaction time task performance. Conclusions/interpretations: These findings show the mediodorsal thalamus plays a key role in visuospatial attentional performance that is independent of local cholinergic neurotransmission.
Effects of caffeine on ethanol-elicited place preference, place aversion and ERK phosphorylation in CD-1 mice
Authors: Porru Simona , Maccioni Riccardo , Bassareo Valentina , Peana Alessandra T , Salamone John D , Correa Mercè , Acquas Elio 
Published: October 2020

Background: Epidemiological studies indicate a rise in the combined consumption of caffeinated and alcoholic beverages, which can lead to increased risk of alcoholic-beverage overconsumption. However, the effects of the combination of caffeine and ethanol in animal models related to aspects of drug addiction are still underexplored. Aims: To characterize the pharmacological interaction between caffeine and ethanol and establish if caffeine can affect the ability of ethanol (2 g/kg) to elicit conditioned place preference and conditioned place aversion, we administered caffeine (3 or 15 mg/kg) to male CD-1 mice before saline or ethanol. Moreover, we determined if these doses of caffeine could affect ethanol (2 g/kg) elicited extracellular signal-regulated kinase phosphorylation in brain areas, nucleus accumbens, bed nucleus of stria terminalis, central nucleus of the amygdala, and basolateral amygdala, previously associated with this type of associative learning. Results: In the place-conditioning paradigm, caffeine did not have an effect on its own, whereas ethanol elicited significant conditioned-place preference and conditioned-place aversion. Caffeine (15 mg/kg) significantly prevented the acquisition of ethanol-elicited conditioned-place preference and, at both doses, also prevented the acquisition of ethanol-elicited conditioned-place aversion. Moreover, both doses of caffeine also prevented ethanol-elicited extracellular signal-regulated kinase phosphorylation expression in all brain areas examined. Conclusions: The present data indicate a functional antagonistic action of caffeine and ethanol on associative learning and extracellular signal-regulated kinase phosphorylation after an acute interaction. These results could provide exciting grounds for further studies, also in a translational perspective, of their pharmacological interaction modulating other processes involved in drug consumption and addiction.
Immunoreactivity of ICAM-1, MMP-2, and Nesfatin-1 in lens epithelial cells of patients with diabetes mellitus with or without diabetic retinopathy
Authors: Turan Meydan , Turan Gulay 
Published: October 2020

Purpose: The aim of this study was to evaluate the immunoreactivity of matrix metalloproteinases-2 (MMP-2), intercellular adhesion molecule-1 (ICAM-1), and nesfatin-1 in cataract lens epithelial cells (LECs) of patients with diabetes mellitus (DM) and to investigate the relationship of these markers with DM cataract and diabetic retinopathy (DR). Materials and methods: Ninety patients were included in the study. The patients were divided into three groups ( n = 30): Group 1 (control; patients without DM or DR); Group 2 (patients with DM only), and Group 3 (patients with both DM and DR). Lens capsule samples were collected during intraoperative cataract surgery. Samples were immunohistochemically stained for MMP-2, ICAM-1, and nesfatin-1 and their immunoreactivity was evaluated. The number of immunoreactive cells was determined with a microscope at ×400 magnification. Results: Increased MMP-2 and ICAM-1 immunoreactivity was detected in the LECs of patients with DM, and especially in patients with DR ( p < 0.001, p < 0.001, respectively). Nesfatin-1 immunoreactivity was significantly lower in LECs of diabetic patients ( p < 0.001). The mean of MMP-2 immunoreactive cells were 7.47 ± 8.18, 22.80 ± 15.70, and 34.80 ± 20.85 in Groups 1, 2, and 3, respectively. The mean of ICAM-1 immunoreactive cells were 17.10 ± 9.83, 38.50 ± 23.55, and 56.93 ± 20.94 in Groups 1, 2, and 3, respectively. Conclusion: Nesfatin-1, MMP-2, and ICAM-1 and could potentially play important roles in the pathogenesis of cataracts in patients with DM.
One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study
Authors: Schrezenmeier Hubert , Kulasekararaj Austin , Mitchell Lindsay , Sicre de Fontbrune Flore , Devos Timothy , Okamoto Shinichiro , Wells Richard , Rottinghaus Scott T. , Liu Peng , Ortiz Stephan , Lee Jong Wook , Socié Gérard 
Published: October 2020

Background: Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in complement inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results with up to 52 weeks of treatment. Methods: Patients assigned to ravulizumab every 8 weeks (q8w) or eculizumab every 2 weeks during the randomized primary evaluation period received ravulizumab q8w during the 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization, transfusion avoidance, breakthrough hemolysis (BTH), LDH levels, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and stabilized hemoglobin. Serum free C5 levels and safety were assessed. Outcomes as of the data cut-off (4 September 2018) were summarized using descriptive statistics. Results: Overall, 124 patients continued ravulizumab, and 119 switched from eculizumab to ravulizumab. During the extension, 43.5% and 40.3% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved LDH normalization; 76.6% and 67.2% avoided transfusion. BTH decreased in the eculizumab–ravulizumab arm; no events were associated with free C5 ⩾0.5 μg/mL while receiving ravulizumab. Overall, 73.4% and 65.5% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved stabilized hemoglobin. Similar proportions of patients achieved ⩾3-point improvement in FACIT-Fatigue at week 52 (ravulizumab–ravulizumab, 64.5%; eculizumab–ravulizumab, 57.1%). All patients maintained free C5 <0.5 μg/mL during the ravulizumab extension, including those who experienced C5 excursions ⩾0.5 μg/mL while receiving eculizumab during the primary evaluation period. Adverse events were comparable between groups and decreased over time. Conclusion: In adult, complement inhibitor–naïve patients with PNH, ravulizumab q8w for up to 52 weeks demonstrated durable efficacy and was well tolerated, with complete and sustained free C5 inhibition and a decreased incidence of BTH with no events associated with loss of free C5 control. Trial registration: ClinicalTrials.gov identifier, NCT02946463
Laminar analysis of the cerebellar cortex shows widespread damage in early MS patients: A pilot study at 7T MRI
Authors: Galbusera Riccardo , Parmar Katrin , Boillat Yohan , Fartaria Mario Joao , Todea Alexandra-Ramona , Brien Kieran O’ , Smolinski Anna , Kappos Ludwig , Zwaag Wietske van der , Granziera Cristina 
Published: October 2020

Background To date, little is known about the presence and extent of cerebellar cortical pathology in early stages of MS. Objective The aims of this study were to (i) investigate microstructural changes in the normal-appearing cerebellar cortex of early MS patients by using 7 T MRI and (ii) evaluate the influence of those changes on clinical performance. Methods Eighteen RRMS patients and nine healthy controls underwent quantitative T1 and T2* measurement at 7 T MRI using high-resolution MP2RAGE and multi-echo gradient-echo imaging. After subtracting lesion masks, average T1 and T2* maps were computed for three layers in the cerebellar cortex and compared between groups using mixed effects models. Results The volume of the cerebellar cortex and its layers did not differ between patients and controls. In MS patients, significantly longer T1 values were observed in all vermis cortical layers and in the middle and external cortical layer of the cerebellar hemispheres. No between-group differences in T2* values were found. T1 values correlated with EDSS, SDMT and PASAT. Conclusions We found MRI evidence of damage in the normal-appearing cerebellar cortex at early MS stages and before volumetric changes. This microstructural alteration appears to be related to EDSS and cognitive performance.
Evaluation of Changes in Temperature of Zirconia Frameworks During Grinding Under Different Chair-Side Conditions: An In Vitro Study
Authors: S¸ivet Özgecan , Malkondu Özlem , Küçükkurt Sercan , Kazazoglu Ender 
Published: October 2020

Aim: To evaluate the changes in the temperature of zirconia during grinding under different clinical conditions. Materials and Methods: A total of 60 zirconia framework specimens were fabricated and divided into groups of 10 specimens each. Two different handpieces, namely, a high-speed handpiece (HSH) and a low-speed handpiece (LSH), were used for grinding with and without water cooling. Fine- and coarse-grit diamond burrs were used with the HSH, separately. The following six groups were created: (a) HSH fine-grit with water cooling, (b) HSH coarse grit with water cooling, (c) HSH fine grit without water cooling, (d) HSH coarse grit without water cooling, (e) LSH with water cooling, and (f) LSH without water cooling. Each zirconia framework was ground until 1 mm3 of the material was removed. Temperature values corresponding to the grinding techniques were compared and statistically analyzed. One-way analysis of variance was used to compare the group parameters, while the Tukey honest significant difference test was used to detect significant differences between the groups. The significance level was set at P <.05. Results: The highest mean temperature was measured in the case of grinding with the LSH without water cooling (54.7 °C ± 11.6 °C), while the lowest mean temperature was observed in the case of grinding with the HSH using the coarse-grit diamond rotary instrument under water cooling (22.6 °C ± 0.6 °C). Conclusions: The grinding of zirconia must be performed with an HSH under water cooling. Further, when water cooling is used, neither the type of handpiece nor the grain type of the rotary instrument used as it has a significant effect on the temperature.
Calculating the most likely intron splicing orders in S. pombe, fruit fly, Arabidopsis thaliana, and humans
Authors: Li Meng 
Published: October 2020

Abstract
Background
Introns have been shown to be spliced in a defined order, and this order influences both alternative splicing regulation and splicing fidelity, but previous studies have only considered neighbouring introns. The detailed intron splicing order remains unknown.

Results
In this work, a method was developed that can calculate the intron splicing orders of all introns in each transcript. A simulation study showed that this method can accurately calculate intron splicing orders. I further applied this method to real S. pombe, fruit fly, Arabidopsis thaliana, and human sequencing datasets and found that intron splicing orders change from gene to gene and that humans contain more not in-order spliced transcripts than S. pombe, fruit fly and Arabidopsis thaliana. In addition, I reconfirmed that the first introns in humans are spliced slower than those in S. pombe, fruit fly, and Arabidopsis thaliana genome-widely. Both the calculated most likely orders and the method developed here are available on the web.

Conclusions
A novel computational method was developed to calculate the intron splicing orders and applied the method to real sequencing datasets. I obtained intron splicing orders for hundreds or thousands of genes in four organisms. I found humans contain more number of not in-order spliced transcripts.