bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants
Authors: Lenz Dominic , Stahl Mirjam , Seidl Elias , Schöndorf Dominik , Brennenstuhl Heiko , Gesenhues Florian , Heinzmann Tina , Longerich Thomas , Mendes Marisa I. , Prokisch Holger , Salomons Gajja S. , Schön Carola , Smith Desirée E. C. , Sommerburg Olaf , Wagner Matias , Westhoff Jens H. , Reiter Karl , Staufner Christian , Griese Matthias 
Published: August 2020

AbstractBackgroundPulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited.MethodsThe clinical course of two brothers with pathogenic variants in the methionyl‐tRNA synthetase (MARS)1 gene was compared to previously published patients. Functional studies in patient‐derived fibroblasts were performed and therapeutic options evaluated.ResultsThe younger brother was diagnosed with PAP at the age of 1 year. Exome sequencing revealed the homozygous MARS1 variant p.(Arg598Cys), leading to interstitial lung and liver disease (ILLD). At 2 years of age, following surgery hypoglycemia was detected, the pulmonary condition deteriorated, and the patient developed multiorgan failure. Six therapeutic whole lung lavages (WLL) were necessary to improve respiratory insufficiency. Methionine supplementation was started and a high protein diet ensured, leading to complete respiratory recovery. The older brother, homozygous for the same MARS1 variant, had a long‐known distinct eating preference of methionine‐rich food and showed a less severe clinical phenotype. Decreased aminoacylation activity confirmed the pathogenicity of p.(Arg598Cys) in vitro. In agreement with our review of currently published ILLD patients, the presence of hepatopathy, developmental delay, muscular hypotonia, and anemia support the multisystemic character of the disease.ConclusionsCatabolic events can provoke a severe deterioration of the pulmonary situation in ILLD with a need for repetitive WLL. Although the precise role of oral methionine supplementation and high protein intake are unknown, we observed an apparent treatment benefit, which needs to be evaluated systematically in controlled trials.
Sliding mode tracking control using finite‐time differentiator in high‐orders nonlinear systems with output stochastic signals
Authors: Ma Ruizi , Yan Tianhong 
Published: August 2020

SummaryThis article presents sliding mode tracking control using finite‐time nonlinear differentiator (FND) to the high‐orders nonlinear systems that states are unknown and the output measurement signals involves stochastic disturbances. The FND using singular perturbation technique is applied to estimate the unknown states in the tracking system, and not rely on the model information under the condition of output stochastic signals. The stochastic noises involved in the output measurement signals are restrained sufficiently by the FNDs. The design of sliding mode tracking controller using FND reduces the chattering phenomenon efficiently. The analysis of systems stability and differentiator robustness is demonstrated. The comparative simulation results show that the sliding mode controller using FND track the desired trajectory in high accuracy with tracking errors fast convergence.
On the scalability of battery‐aware contact plan design for LEO satellite constellations
Authors: Fraire Juan A. , Gerstacker Carsten , Hermanns Holger , Nies Gilles , Bisgaard Morten , Bay Kristian 
Published: August 2020

SummarySize and weight limitations of low‐Earth orbit (LEO) small satellites make their operation rest on a fine balance between solar power infeed and power demands of supporting communication technologies, buffered by on‐board battery storage. As a result, the problem of planning battery‐powered intersatellite communication is a very difficult one. Nevertheless, there is a growing trend toward constellations and mega‐constellations that are to be managed using sophisticated software support. In earlier work, we have discussed how the effective construction of contact plans in delay‐tolerant satellite networking can profit from a refined model of the on‐board battery behavior. This paper presents a profound study of the scalability of the approach and discusses how to tailor it to the needs arising in the management of mega‐constellations, together with a variety of improvements to the base approach. Results show that efficient mega‐constellation operations are compromised, encouraging further research on the area.
Accelerating forest tree breeding by integrating genomic selection and greenhouse phenotyping
Authors: Alves Filipe C. , Balmant Kelly M. , Resende Marcio F. R. , Kirst Matias , de los Campos Gustavo 
Published: August 2020

AbstractBreeding forest species can be a costly and slow process because of the extensive areas needed for field trials and the long periods (e.g., five years) that are required to measure economically and environmentally relevant phenotypes (e.g., adult plant biomass or plant height). Genomic selection (GS) and indirect selection using early phenotypes (e.g., phenotypes collected in greenhouse conditions) are two ways by which tree breeding can be accelerated. These approaches can both reduce the costs of field‐testing and the time required to make selection decisions. Moreover, these approaches can be highly synergistic. Therefore, in this study, we used a data set comprising DNA genotypes and longitudinal measurements of growth collected from a population of Populus deltoides W. Bartram ex Marshall (eastern cottonwood) in the greenhouse and the field, to evaluate the potential impact of integrating large‐scale greenhouse phenotyping with conventional GS. We found that the integration of greenhouse phenotyping and GS can deliver very early selection decisions that are moderately accurate. Therefore, we conclude that the adoption of these approaches, in conjunction with reproductive techniques that shorten the generation interval, can lead to an unprecedented acceleration of selection gains in P. deltoides and, potentially, other commercially planted tree species.
Mild cognitive impairment in Aboriginal Australians
Authors: Derrig Hannah , Lavrencic Louise M. , Broe Gerald A. , Draper Brian , Cumming Robert G , Garvey Gail , Hill Thi Yen , Daylight Gail , Chalkley Simon , Mack Holly , Lasschuit Danielle , Delbaere Kim , Radford Kylie 
Published: August 2020

AbstractIntroductionAboriginal Australians have among the highest rates of dementia worldwide, yet no study has investigated the subtypes, risk factors, or longer term outcomes of mild cognitive impairment (MCI) in this population.MethodsA total of 336 community‐dwelling Aboriginal Australians aged ≥60 years participated in a longitudinal study, completing a structured interview at baseline. MCI (amnestic subtype, aMCI; non‐amnestic subtype, naMCI) and dementia were diagnosed via cognitive screening, medical assessment, and clinical consensus. Associations between life‐course factors and baseline MCI subtypes were examined using logistic regression. Conversion to dementia was assessed at 6‐year follow‐up.ResultsPrevalent aMCI (n = 24) was associated with older age (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 1.12 to 2.53), head injury (OR = 3.19, 95% CI: 1.35 to 7.56), symptoms of depression (OR = 1.52, 95% CI: 1.04 to 2.24), and lower blood pressure (OR = 0.53, 95% CI: 0.33 to 0.86). Prevalent naMCI (n = 29) was associated with low education (OR = 4.46, 95% CI: 1.53 to 13.05), unskilled work history (OR = 5.62, 95% CI: 2.07 to 13.90), higher body mass index (OR = 1.99, 95% CI: 1.30 to 3.04), and moderate to severe hearing loss (OR = 2.82, 95% CI: 1.06 to 7.55). A small proportion of MCI cases reverted to intact at follow‐up (15%), but most remained stable (44%), developed dementia and/or died (41%).DiscussionSociodemographic and clinical factors both contributed to baseline MCI and were distinct for MCI subtypes, with similar patterns of conversion to dementia for amnestic and non‐amnestic MCI.
Application of fracture mechanics for the characterization of PVC pipes. I. Evaluation of the applicability of the EWF technique in specimens produced directly from pipes
Authors: Rodolfo Antonio 
Published: August 2020

AbstractUnplasticized (U‐PVC) and modified (M‐PVC) pipes used in irrigation and infrastructure applications in Brazil (nominal diameter DN 300, outside diameter 326 mm), were evaluated according to various fracture mechanics methodologies, including essential work of fracture (EWF), C‐ring toughness and fracture toughness parameters (stress intensity factor KC and energy release rate GC, both at plastic collapse). These pipes were also evaluated for the quality of processing (degree of gelation) via DSC and tensile strength. Results show that the differences in behavior against fracture propagation are sensitive, depending on the technique, when comparing the results between the different types of pipes, opening up new possibilities for testing this product. This possibility is particularly interesting in the case of the evaluation of the degree of gelation in industrial process controls, since the dichloromethane (DCMT) solvent immersion method still in use tends to be replaced in the future by alternative methodologies due to chemical exposure factors.
Chirurgische Rekonstruktionen beim Larynxkarzinom
Authors: Arens C. , Schwemmle C. , Voigt-Zimmermann S. 
Published: August 2020

ZusammenfassungTumoren des Kehlkopfes können sowohl die Stimmfunktion und die Atmung als auch den Schluckvorgang erheblich beeinträchtigen. Das übergeordnete Ziel der rekonstruktiven chirurgischen Behandlung von laryngealen Tumoren ist, den Tumor suffizient zu resezieren und gleichzeitig die Auswirkungen der Behandlung auf Stimme, Atmung und Schlucken zu minimieren. Allgemein haben primäre Rekonstruktionen im Rahmen der primären Larynxoperation viele Vorteile. Das Gewebe ist zu diesem Zeitpunkt weich, weil der Vernarbungsprozess noch nicht eingesetzt hat. Auch kann durch den sofort hergestellten Stimmlippenvolumenausgleich eine bessere Voraussetzung für einen suffizienten Glottisschluss erwartet werden. Die rekonstruktive Behandlung kann jedoch auch sekundär erfolgen. Unterschiedliche Methoden der rekonstruktiven Chirurgie beim Larynxkarzinom werden vorgestellt und erörtert.
Need for a precise molecular diagnosis in Beckwith-Wiedemann and Silver-Russell syndrome: what has to be considered and why it is important
Authors: Eggermann Thomas , Brück Johanna , Knopp Cordula , Fekete György , Kratz Christian , Tasic Velibor , Kurth Ingo , Elbracht Miriam , Eggermann Katja , Begemann Matthias 
Published: August 2020

Abstract
Molecular diagnostic testing of the 11p15.5-associated imprinting disorders Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS) is challenging due to the broad spectrum of molecular defects and their mosaic occurrence. Additionally, the decision on the molecular testing algorithm is hindered by their clinical heterogeneity. However, the precise identification of the type of defect is often a prerequisite for the clinical management and genetic counselling. Four major molecular alterations (epimutations, uniparental disomies, copy number variants, single nucleotide variants) have been identified, but their frequencies vary between SRS and BWS. Due to their molecular aetiology, epimutations in both disorders as well as upd(11)pat in BWS are particular prone to mosaicism which might additionally complicate the interpretation of testing results. We report on our experience of molecular analysis in a total cohort of 1448 patients referred for diagnostic testing of BWS and SRS, comprising a dataset from 737 new patients and from 711 cases from a recent study. Though the majority of positively tested patients showed the expected molecular results, we identified a considerable number of clinically unexpected molecular alterations as well as not yet reported changes and discrepant mosaic distributions. Additionally, the rate of multilocus imprinting disturbances among the patients with epimutations and uniparental diploidies could be further specified. Altogether, these cases show that comprehensive testing strategies have to be applied in diagnostic testing of SRS and BWS. The precise molecular diagnosis is required as the basis for a targeted management (e.g. ECG (electrocardiogram) and tumour surveillance in BWS, growth treatment in SRS). The molecular diagnosis furthermore provides the basis for genetic counselling. However, it has to be considered that recurrence risk calculation is determined by the phenotypic consequences of each molecular alteration and mechanism by which the alteration arose.

Key messages

The detection rates for the typical molecular defects of Beckwith-Wiedemann syndrome or Silver-Russell syndrome (BWS, SRS) are lower in routine cohorts than in clinically well-characterised ones.

A broad spectrum of (unexpected) molecular alterations in both disorders can be identified.

Multilocus imprinting disturbances (MLID) are less frequent in SRS than expected.

The frequency of MLID and uniparental diploidy in BWS is confirmed.

Mosaicism is a diagnostic challenge in BWS and SRS.

The precise determination of the molecular defects affecting is the basis for a targeted clinical management and genetic counselling.
A systematic approach for introduction of novel treatments to a chronic patient group: sacubitril-valsartan as a case study
Authors: Norberg Helena , Bergdahl Ellinor , Ängerud Karin Hellström , Lindmark Krister 
Published: August 2020

Abstract
Purpose
To develop a model for systematic introduction and to test the feasibility in a chronic disease population. We also investigated how the approach was received by the patients.

Methods and results
The systematic introduction approach is a seven-step procedure: step 1, define a few main criteria; step 2, primary scan patients with the one or two main criteria using computerized medical records/databases/clinical registries; step 3, identify patients applying the other predefined criteria; step 4, evaluate if any examinations/laboratory test updates are required; step 5, summon identified patients to the clinic with an information letter; step 6, discuss treatment with the patient and prescribe if appropriate; and step 7, follow up on initiated therapy and evaluate the applied process. The model was tested in a case study during introduction of the new drug sacubitril-valsartan in a heart failure population. In total, 76 out of 1924 patients were identified to be eligible for sacubitril-valsartan and summoned to the clinic to discuss treatment. Patient experiences with the approach were investigated in an interview study with general inductive approach using qualitative content analysis. This resulted in three final categories: a good approach, role of the information letter, and trust in care.

Conclusions
The systematic introduction approach ensures that strict criteria are used in the selection process and that a treatment can be implemented in eligible patients within a specified population with limited resources and time. The model was effective in our case study and maintained the patient’s confidence in healthcare.
Power in the Council of the EU: organizing theory, a new index, and Brexit
Authors: Grech Philip D. 
Published: August 2020

AbstractWe aim to estimate the power distribution in the Council of the European Union—both a priori and a posteriori. With respect to the latter, our analysis suggests that several previously used indices are ill-suited for this application. By introducing minimal modifications, we propose a new index and compare it with previous constructions in a unified framework. Empirically, we find that that all countries gain a priori voting power in the Council as a result of Brexit. We rely on data from the Chapel Hill Expert survey to compute a posteriori power and find that it is more unequally distributed than a priori power. Specifically, a posteriori power is almost exclusively held by relatively few rather populous states (yet not the United Kingdom). As regards Brexit, France appears as the main benefactor in terms of gaining a posteriori power; Poland loses substantive power in several areas but remains one of the most powerful EU member states.
Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies?
Authors: Klotz Daniel Martin , Wimberger Pauline 
Published: August 2020

Abstract
Purpose
Ovarian cancer is the most lethal gynaecological malignancy. Despite the introduction of bevacizumab, standard chemotherapy has remained largely unchanged and the vast majority of patients will relapse within the first two years of diagnosis. However, results from recent clinical trials demonstrating clinical benefits of PARP inhibitor treatment are rapidly changing therapeutic options for many patients with ovarian cancer.

Methods
Given the introduction of new therapeutic options in the treatment of ovarian cancer, we critically review key clinical trials, areas of scientific research and its clinical relevance.

Results
Most notably, patients with BRCA1/2 mutant ovarian cancer benefit from maintenance treatment with PARP inhibitors after (complete or partial) response to platinum-based chemotherapy. Here, we discuss the mechanism of PARP inhibition, multiple drug resistance mechanisms, including BRCA reverse mutations, altered PARP expression, changes in DNA repair pathways, kinase activation and additional drug targets that may augment PARP inhibition.

Conclusion
Although the use of PARP inhibitors is a huge step forward, it is apparent that patients, both with and without BRCA-mutant ovarian cancer, will eventually become resistant to PARP inhibitors. Therefore, novel combination therapies may enhance PARP inhibitor efficacy and overcome resistance mechanisms.
Forensic age estimation via magnetic resonance imaging of knee in the Turkish population: use of T1-TSE sequence
Authors: Ekizoglu Oguzhan , Er Ali , Bozdag Mustafa , Basa Can Doruk , Kacmaz Ismail Eralp , Moghaddam Negahnaz , Grabherr Silke 
Published: August 2020

AbstractThe evaluation of epiphyseal areas by magnetic resonance imaging (MRI) for forensic age estimation is an important supportive diagnostic method to prevent repeated radiation exposure without a valid medical reason. There are still not enough individuals being analyzed with MRI for age estimation. The aim of this study was to investigate the utility of T1-weighted turbo spin echo (T1-TSE) MRI sequences in determining the degree of ossification of the distal femoral and proximal tibial epiphyses in a Turkish population. In this study, images from 649 patients (335 males and 314 females) aged 10–30 years were retrospectively evaluated with sagittal T1-weighted turbo spin echo (T1-TSE) MRI sequences of the knee. Proximal tibial and distal femoral epiphysis were scored by two different observers twice using the combined staging system described by Schmeling and Kellinghaus. Spearman’s rank correlation analysis indicated a significant positive relationship between age and ossification stages of the distal femoral and proximal tibial epiphyses (p < 0.001). The intra- and inter-observer reliabilities in evaluating the femur and tibia were separately determined and gave promising results and Cohen’s kappa statistics ranged from κ = 0.886 and κ = 0.961. The minimal ages of patients with stage 4 ossification were 15.1 years for females and 15.8 years for males for the distal tibial epiphysis and 15.4 years for females and 17 years for males for the distal femoral epiphysis. This study show that (T1-TSE) MRI and the applicability and Schmeling and Kellinghaus staging method of the knee can be performed for living 14- to 17-year-old individuals in need of a supportive noninvasive method for estimating forensic age.
Mechanisms of nonalcoholic fatty liver disease and implications for surgery
Authors: Kaufmann Benedikt , Reca Agustina , Wang Baocai , Friess Helmut , Feldstein Ariel E. , Hartmann Daniel 
Published: August 2020

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in both adults and children worldwide. Understanding the pathogenic mechanisms behind NAFLD provides the basis for identifying risk factors, such as metabolic syndrome, pancreatoduodenectomy, and host genetics, that lead to the onset and progression of the disease. The progression from steatosis to more severe forms, such as steatohepatitis, fibrosis, and cirrhosis, leads to an increased number of liver and non-liver complications.

Purpose
NAFLD-associated end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) often require surgery as the only curative treatment. In particular, the presence of NAFLD together with the coexisting metabolic comorbidities that usually occur in these patients requires careful preoperative diagnosis and peri-/postoperative management. Bariatric surgery, liver resection, and liver transplantation (LT) have shown favorable results for weight loss, HCC, and ESLD in patients with NAFLD. The LT demand and the increasing spread of NAFLD in the donor pool reinforce the already existing lack of donor organs.

Conclusion
In this review, we will discuss the diverse mechanisms underlying NAFLD, its implications for surgery, and the challenges for patient management.
Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study
Authors: Myrdal Ole Henrik , Diep Phoi Phoi , Ruud Ellen , Brinch Lorentz , Massey Richard John , Edvardsen Elisabeth , Kongerud Johny , Lund May B. , Sikkeland Liv Ingunn 
Published: August 2020

AbstractPurposeSurvivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O2peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function.MethodsIn a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17–54) years, 56% females] were examined, 17 (6–26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test.ResultsChronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DLCO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O2peak was 36.4 (34.7–38.0) mL/min/kg [89 (85–93)% of predicted]. V̇O2peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O2peak was associated with low DLCO, low LVEF, BOS, overweight, and inactivity.ConclusionHalf of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.