bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated pulmonary valve endocarditis with rapid progression: a case report and literature review
Authors: Zhang Ming-Xuan , Zhang Wei-Min , Yu Chan , Zhao Bo-Wen , Chen Ran , Pan Mei , Wang Bei 
Published: January 2021

Abstract
Background
Isolated pulmonary valve endocarditis (IPE) is rare, accounting for 1.5–2% of all cases of infective endocarditis. Herein, we describe a case of isolated pulmonary valve endocarditis with rapid progression in a 28-year-old male. Unlike most patients reported previously who were cured with only anti-infective therapy, without surgery at an early stage, multiple complications occurred in this patient in less than 2 weeks.

Case presentation
The patient was diagnosed with pulmonary valve endocarditis with blood cultures showing Staphylococcus aureus and echocardiography revealing 2 masses (measuring 14*13 mm、11*16 mm in size). Only 12 days later, acute massive pulmonary embolism occurred. Then, repeated echocardiography revealed multiple masses attached to the pulmonary valve with severe pulmonary insufficiency and the possibility of pulmonary valve destruction. Finally, pulmonary valve replacement, vegetation removal, and right pulmonary thromboendarterectomy together with resection of the middle and lower lobes of the right lung were performed.

Conclusions
The role of surgery at an early stage might need to be reconsidered, and it may be viable to combine medical and surgical approaches.
Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later
Authors: Isgut Monica , Sun Jimeng , Quyyumi Arshed A. , Gibson Greg 
Published: January 2021

Abstract
Background
Several polygenic risk scores (PRS) have been developed for cardiovascular risk prediction, but the additive value of including PRS together with conventional risk factors for risk prediction is questionable. This study assesses the clinical utility of including four PRS generated from 194, 46K, 1.5M, and 6M SNPs, along with conventional risk factors, to predict risk of ischemic heart disease (IHD), myocardial infarction (MI), and first MI event on or before age 50 (early MI).

Methods
A cross-validated logistic regression (LR) algorithm was trained either on ~ 440K European ancestry individuals from the UK Biobank (UKB), or the full UKB population, including as features different combinations of conventional established-at-birth risk factors (ancestry, sex) and risk factors that are non-fixed over an individual’s lifespan (age, BMI, hypertension, hyperlipidemia, diabetes, smoking, family history), with and without also including PRS. The algorithm was trained separately with IHD, MI, and early MI as prediction labels.

Results
When LR was trained using risk factors established-at-birth, adding the four PRS significantly improved the area under the curve (AUC) for IHD (0.62 to 0.67) and MI (0.67 to 0.73), as well as for early MI (0.70 to 0.79). When LR was trained using all risk factors, adding the four PRS only resulted in a significantly higher disease prevalence in the 98th and 99th percentiles of both the IHD and MI scores.

Conclusions
PRS improve cardiovascular risk stratification early in life when knowledge of later-life risk factors is unavailable. However, by middle age, when many risk factors are known, the improvement attributed to PRS is marginal for the general population.
Ixekizumab, with or without concomitant methotrexate, improves signs and symptoms of PsA: week 52 results from Spirit-P1 and Spirit-P2 studies
Authors: Combe Bernard , Tsai Tsen-Fang , Huffstutter J. Eugene , Sprabery Aubrey Trevelin , Lin Chen-Yen , Park So Young , Kronbergs Andris , Hufford Matthew M. , Nash Peter 
Published: January 2021

AbstractBackgroundThe efficacy and safety of ixekizumab (IXE) with and without continuous concomitant methotrexate (MTX), for up to 52 weeks of treatment, were evaluated in patients with active psoriatic arthritis (PsA).MethodsPatients with active PsA who were biologic-naive (SPIRIT-P1) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2) were randomized to 80 mg IXE every 4 (IXE Q4W) or 2 weeks (IXE Q2W), after a 160-mg initial dose. In this post hoc analysis, efficacy and safety were assessed up to week 52 in the subgroups of patients who received (i) IXE as monotherapy and (ii) IXE along with a stable dose of MTX (no dose tapering or increase). Efficacy outcomes included, but were not limited to, the percentage of patients achieving the American College of Rheumatology (ACR) responses.ResultsOut of 455 patients initially randomized to IXE, 177 (38.9%) received monotherapy, 230 (50.5%) had concomitant MTX use, and 48 (10.5%) had other concomitant medication. Overall, 183 (40.2%) received IXE with a stable dose of concomitant MTX for 1 year. At week 52, the percentage of patients achieving ACR20/50/70 responses in IXE Q4W monotherapy versus concomitant MTX groups were 66.3% versus 55.3%, 48.4% versus 38.8%, and 35.8% versus 27.1%, respectively; these responses were generally similar with IXE Q2W. The safety profiles were similar between patients receiving IXE with or without concomitant MTX.ConclusionsIn this post hoc analysis, treatment with IXE demonstrated sustained efficacy in patients with PsA up to 1 year of treatment, with or without concomitant MTX therapy.Trial registrationClinicalTrials.govNCT01695239andNCT02349295.
Loss of H3K27 methylation identifies poor outcomes in adult-onset acute leukemia
Authors: van Dijk A. D. , Hoff F. W. , Qiu Y. H. , Chandra J. , Jabbour E. , de Bont E. S. J. M. , Horton T. M. , Kornblau S. M. 
Published: January 2021

Abstract
Background
Acute leukemia is an epigenetically heterogeneous disease. The intensity of treatment is currently guided by cytogenetic and molecular genetic risk classifications; however these incompletely predict outcomes, requiring additional information for more accurate outcome predictions. We aimed to identify potential prognostic implications of epigenetic modification of histone proteins, with a focus on H3K4 and H3K27 methylation marks in relation to mutations in chromatin, splicing and transcriptional regulators in adult-onset acute lymphoblastic and myeloid leukemia.

Results
Histone 3 lysine 4 di- and trimethylation (H3K4me2, H3K4me3) and lysine 27 trimethylation (H3K27me3) mark expression was evaluated in 241 acute myeloid leukemia (AML), 114 B-cell acute lymphoblastic leukemia (B-ALL) and 14T-cell ALL (T-ALL) patient samples at time of diagnosis using reverse phase protein array. Expression levels of the marks were significantly lower in AML than in B and T-ALL in both bone marrow and peripheral blood, as well as compared to normal CD34+ cells. In AML, greater loss of H3K27me3 was associated with increased proliferative potential and shorter overall survival in the whole patient population, as well as in subsets with DNA methylation mutations. To study the prognostic impact of H3K27me3 in the context of cytogenetic aberrations and mutations, multivariate analysis was performed and identified lower H3K27me3 level as an independent unfavorable prognostic factor in all, as well as in TP53 mutated patients. AML with decreased H3K27me3 demonstrated an upregulated anti-apoptotic phenotype. In ALL, the relative quantity of histone methylation expression correlated with response to tyrosine kinase inhibitor in patients who carried the Philadelphia cytogenetic aberration and prior smoking behavior.

Conclusion
This study shows that proteomic profiling of epigenetic modifications has clinical implications in acute leukemia and supports the idea that epigenetic patterns contribute to a more accurate picture of the leukemic state that complements cytogenetic and molecular genetic subgrouping. A combination of these variables may offer more accurate outcome prediction and we suggest that histone methylation mark measurement at time of diagnosis might be a suitable method to improve patient outcome prediction and subsequent treatment intensity stratification in selected subgroups.
Inflammation scores as prognostic biomarkers in small cell lung cancer: a systematic review and meta-analysis
Authors: Winther-Larsen Anne , Aggerholm-Pedersen Ninna , Sandfeld-Paulsen Birgitte 
Published: January 2021

Abstract
Background
Inflammation scores based on general inflammation markers as leucocyte count or C-reactive protein have been evaluated as prognostic markers of inferior survival in several cancers. In small cell lung cancer (SCLC), however, inflammation scores are less studied. In the present study, we set out to perform a systematic review and meta-analysis investigating reported associations between inflammation scores and overall survival (OS) in SCLC.

Methods
A literature search was performed in PubMed, Embase, Scopus, and Web of Science following the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines. Of the identified publications, only studies in English containing original data evaluating inflammation scores as a prognostic factor in SCLC patients were included. Hazard ratios (HRs) for OS were pooled in a random-effects model.

Results
In total, 33 articles were included evaluating eight different inflammation scores in 7762 SCLC patients. Seven of the identified scores were based on leucocyte count. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio were the most frequently evaluated scores (NLR: n = 23; PLR: n = 22). For NLR, a meta-analysis including 16 studies demonstrated that patients with a high NLR had a significantly shorter OS compared to patients with a low NLR (pooled HR = 1.39 (95% CI, 1.23–1.56)). For PLR, an association with survival could not be confirmed in a meta-analysis performed based on eight studies (pooled HR = 1.20 (95% CI, 0.96–1.51)).

Conclusions
This review identifies that inflammation scores based on general inflammation markers have some potential as prognostic biomarkers in SCLC. The meta-analyses indicated that NLR is associated with inferior OS, whereas an association between PLR and OS could not be confirmed. Thus, NLR could be a useful biomarker of OS in SCLC patients.

Systematic review registration
The protocol for the study was submitted to the PROSPERO database (registration number CRD42020188553).
Adaptive synchronization for fractional stochastic neural network with delay
Authors: Junxiang Lu , Xue Hong 
Published: January 2021

AbstractUnder the Brownian motion environment, adaptive synchronization is mainly studied in this paper for fractional-order stochastic neural networks (FSNNs) with time delays and discontinuous activation functions. Firstly, an existence theorem of solutions is established and global solutions of FNNs are obtained under the definition of Filippov solution by using the fixed-point theorem for a condensing map. Secondly, an adaptive controller is designed to ensure the synchronization between FNNs and the corresponding fractional-order FSNNs. Finally, a numerical example is given to illustrate the given results.
Multi-objective workflow optimization strategy (MOWOS) for cloud computing
Authors: Konjaang J. Kok , Xu Lina 
Published: January 2021

AbstractWorkflow scheduling involves mapping large tasks onto cloud resources to improve scheduling efficiency. This has attracted the interest of many researchers, who devoted their time and resources to improve the performance of scheduling in cloud computing. However, scientific workflows are big data applications, hence the executions are expensive and time consuming. In order to address this issue, we have extended our previous work ”Cost Optimised Heuristic Algorithm (COHA)” and presented a novel workflow scheduling algorithm named Multi-Objective Workflow Optimization Strategy (MOWOS) to jointly reduce execution cost and execution makespan. MOWOS employs tasks splitting mechanism to split large tasks into sub-tasks to reduce their scheduling length. Moreover, two new algorithms called MaxVM selection and MinVM selection are presented in MOWOS for task allocations. The design purpose of MOWOS is to enable all tasks to successfully meet their deadlines at a reduced time and budget. We have carefully tested the performance of MOWOS with a list of workflow inputs. The simulation results have demonstrated that MOWOS can effectively perform VM allocation and deployment, and well handle incoming streaming tasks with a random arriving rate. The performance of the proposed algorithm increases significantly in large and extra-large workflow tasks than in small and medium workflow tasks when compared to the state-of-art work. It can greatly reduce cost by 8%, minimize makespan by 10% and improve resource utilization by 53%, while also allowing all tasks to meet their deadlines.
A preliminary exploration of the effect of concurrent antidepressant medication on responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) in severe, enduring anorexia nervosa
Authors: Dalton Bethan , McClelland Jessica , Bartholdy Savani , Kekic Maria , Campbell Iain C. , Schmidt Ulrike 
Published: January 2021

Abstract
Background
Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment option for people with severe, enduring anorexia nervosa (SE-AN). As depression is often comorbid with AN, antidepressant medication is commonly prescribed to this patient group. Concurrent antidepressant medications may affect the rTMS treatment response. Therefore, in a secondary analysis of data from a feasibility trial, we explored the effect of antidepressant medication on responses to rTMS in people with SE-AN.

Methods
Twenty-six participants with SE-AN received 20 sessions (over 4 weeks) of neuronavigated high-frequency real rTMS to the left dorsolateral prefrontal cortex. Eating disorder (ED) and general psychopathology symptoms were assessed at baseline, post-treatment and at a 4-month follow-up.

Results
Participants taking antidepressants (n = 16) for the duration of the rTMS treatment had a greater reduction in ED symptoms at the 4-month follow-up, compared to those not taking antidepressants (n = 10). Antidepressant status was not however associated with significant changes in mood outcomes.

Conclusions
In people with SE-AN receiving rTMS treatment, preliminary findings suggest a potential synergistic effect of antidepressant medication in reducing ED symptomatology. There was however no associated reduction in affective symptoms i.e., the effect does not seem to be related to changes in mood. The sample in this exploratory study was small and heterogenous. However, the preliminary results provide a basis for hypothesis generation for future studies.
Tau-proximity ligation assay reveals extensive previously undetected pathology prior to neurofibrillary tangles in preclinical Alzheimer’s disease
Authors: Bengoa-Vergniory Nora , Velentza-Almpani Elisavet , Silva Ana Maria , Scott Connor , Vargas-Caballero Mariana , Sastre Magdalena , Wade-Martins Richard , Alegre-Abarrategui Javier 
Published: January 2021

AbstractBackgroundMultimerization is a key process in prion-like disorders such as Alzheimer’s disease (AD), since it is a requirement for self-templating tau and beta-amyloid amyloidogenesis. AT8-immunohistochemistry for hyperphosphorylated tau is currently used for the diagnosis and staging of tau pathology. Given that tau–tau interactions can occur in the absence of hyperphosphorylation or other post-translational modifications (PTMs), the direct visualization of tau multimerization could uncover early pathological tau multimers.MethodsHere, we used bimolecular fluorescent complementation, rapamycin-dependent FKBP/FRB-tau interaction and transmission electron microscopy to prove the in vitro specificity of tau-proximity ligation assay (tau-PLA). We then analyzedMAPTKO and P301S transgenic mice, and human hippocampus and temporal isocortex of all Braak stages with tau-PLA and compared it with immunohistochemistry for the diagnostic antibody AT8, the early phosphorylation-dependent AT180, and the conformational-dependent antibody MC1. Finally, we performed proteinase-K treatment to infer the content of amyloidogenic beta-sheet fold.ResultsOur novel tau-proximity ligation assay (tau-PLA) directly visualized tau–tau interactions in situ, and exclusively recognized tau multimers but not monomers. It elicited no signal inMAPTKO mouse brains, but extensively labelled P301S transgenic mice and AD brain. Two groups of structures were detected, a previously unreported widespread small-sized diffuse pathology and large, neurofibrillary-like lesions. Tau-PLA-labelled diffuse pathology appeared from the earliest Braak stages, mostly unaccompanied by tangle-like tau-immunohistochemistry, being significantly more sensitive than any small-sized dot-/thread-like pathology labelled by AT180-, AT8- and MC1-immunohistochemistry in most regions quantified at stages 0-II. Tau-PLA-labelled diffuse pathology was extremely sensitive to Proteinase-K, in contrast to large lesions.ConclusionsTau-PLA is the first method to directly visualize tau multimers both in vitro and in situ with high specificity. We find that tau multimerization appears extensively from the earliest presymptomatic Braak stages as a previously unreported type of diffuse pathology. Importantly, in our study multimerization is the earliest detectable molecular event of AD tau pathology. Our findings open a new window to the study of early tau pathology, with potential implications in early diagnosis and the design of therapeutic strategies.
Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid
Authors: Islam Mahjabin , Hoggard Nigel , Hadjivassiliou Marios 
Published: January 2021

Abstract
Background
Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability.

Methods
A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years.

Results
Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia.

Conclusion
A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.
A randomized, open-label, multicentre, comparative study of therapeutic efficacy, preventive potential and tolerability of BNO 1030 extract, containing Althea root, Chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years
Authors: Popovych Vasyl , Koshel Ivana , Malofiichuk Oleksandr , Pyletska Lubov , Semenyuk Oleksandr , Martynnyk Oksana , Orlovska Ruslana 
Published: January 2021

Abstract
Acute tonsillitis tends to recur. In cases where patients do not meet the Paradise criteria, the possibilities of non-surgical treatment are more often considered. The objective of this study was to evaluate the therapeutic efficacy during the long-term follow-up and the effect on the recurrence of the phytoneering extract BNO 1030 (Imupret®) in patients with acute non-bacterial tonsillitis.

Methods
In this Randomized, Open-Label, Multicentre, Comparative Study, 238 outpatients aged 6–18 years were randomized to receive either BNO 1030 (Imupret®) for 4 weeks in addition to standard symptomatic treatment, or to receive standard treatment. Evaluation criteria: reduction in the symptom severity less than 1 point, the number of tonsillitis recurrences at each control point after 3, 6 and 12 months during the one-year follow-up.

Results
A significant reduction in the severity of local symptoms and the general condition at each control point within the year of follow-up and a significant decrease (by 66.56%) in the recurrence rate of tonsillitis were noted. The anti-recurrent action was manifested during within the year of follow-up. All patients tolerated phytotherapy well; no adverse reactions were noted.

Conclusions
BNO 1030 (Imupret®) is a safe and effective medicinal product for acute non-bacterial tonsillitis in children aged 6–18 years. In addition to the main symptomatic treatment, it leads to a significant reduction in the clinical manifestations and the number of recurrences of tonsillitis within the year of follow-up.

Trial registration
This trial was registered in German Clinical Trials Register retrospectively on June 27, 2018.
Trial Acronym: ATi-1
DRKS-ID: DRKS00015020
“By women, for women, and with women”: on the integration of highly qualified female refugees into the labour Markets of Berlin and Brandenburg
Authors: Hillmann Felicitas , Toğral Koca Burcu 
Published: January 2021

AbstractThis article focuses on the labour market integration of highly qualified female refugees in cosmopolitan Berlin and smaller towns in the county of Brandenburg. Based on interviews with civil society organisations designed mainly for female refugees, universities, employees of the job agency and government administrations, the gendered pathways of stratified access of this group to the labour markets of the two areas were analysed. Special attention was given to the role of emerging intermediary actors and their powers to influence stratified access to the labour markets. As this research shows, a variety of new approaches have evolved, and a web of migration-related jobs to support these women has been created – with marked regional differences.
Well leg compartment syndrome following robot-assisted radical cystectomy in the lithotomy position: a case report
Authors: Fukuda Masataka , Kawagoe Izumi , Kochiyama Tsukasa , Ando Nozomi , Kudoh Osamu , Satoh Daizoh , Hayashida Masakazu 
Published: January 2021

Abstract
Background
The indications for robot-assisted urologic surgeries have expanded due to their low invasiveness. However, complicated surgical procedures lead to prolonged surgical duration, requiring patients to remain in the lithotomy position for an extended time. Well leg compartment syndrome (WLCS) is a known severe postoperative complication related to the lithotomy position.

Case presentation
We report a case of WLCS after robot-assisted radical cystectomy (RARC), in which the patient recovered without neurological sequelae. A 55-year-old, obese male who underwent RARC complained of right leg pain and paresthesia 3 h after the surgery that lasted for 481 min. Emergency evaluation revealed unilateral WLCS in the anterior and lateral compartments. Urgent fasciotomy was performed 4 h after symptom onset. He thereafter recovered completely and was discharged without any neuromuscular dysfunction.

Conclusions
Early detection of WLCS, surgical treatment, and additional measures are crucial to prevent its life-threatening and/or disabling outcomes.