bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood transcriptome sequencing identifies biomarkers able to track disease stages in spinocerebellar ataxia type 3
Authors: Raposo Mafalda , Hübener-Schmid Jeannette , Ferreira Ana F , Vieira Melo Ana Rosa , Vasconcelos João , Pires Paula , Kay Teresa , Garcia-Moreno Hector , Giunti Paola , Santana Magda M , Pereira de Almeida Luis , Infante Jon , van de Warrenburg Bart P , de Vries Jeroen J , Faber Jennifer , Klockgether Thomas , Casadei Nicolas , Admard Jakob , Schöls Ludger ,   European Spinocerebellar ataxia type 3/Machado-Joseph disease Initiative (ESMI) study group, Krahe Janna , Reetz Kathrin , González José , Gonzalez Carlos , Baptista Carlos , Lemos João , Giordano Ilaria , Grobe-Einsler Marcus , Önder Demet , Silva Patrick , Januário Cristina , Ribeiro Joana , Cunha Inês , Lemos João , Pinto Maria M , Timmann Dagmar , Steiner Katharina M , Thieme Andreas , Ernst Thomas M , Jacobi Heike , Solanky Nita , Gonzalez-Robles Cristina , Van Gaalen Judith , Pelayo-Negro Ana Lara , Manrique Leire , Hengel Holger , Synofzik Matthis , Ilg Winfried , Riess Olaf , Lima Manuela 
Published: April 2023

Abstract
Transcriptional dysregulation has been described in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant ataxia caused by a polyglutamine expansion in the ataxin-3 protein. As ataxin-3 is ubiquitously expressed, transcriptional alterations in blood may reflect early changes that start before clinical onset and might serve as peripheral biomarkers in clinical and research settings. Our goal was to describe enriched pathways and report dysregulated genes, which can track disease onset, severity or progression in carriers of the ATXN3 mutation (pre-ataxic subjects and patients).
Global dysregulation patterns were identified by RNA sequencing of blood samples from 40 carriers of ATXN3 mutation and 20 controls and further compared with transcriptomic data from post-mortem cerebellum samples of MJD patients and controls. Ten genes—ABCA1, CEP72, PTGDS, SAFB2, SFSWAP, CCDC88C, SH2B1, LTBP4, MEG3 and TSPOAP1—whose expression in blood was altered in the pre-ataxic stage and simultaneously, correlated with ataxia severity in the overt disease stage, were analysed by quantitative real-time PCR in blood samples from an independent set of 170 SCA3/MJD subjects and 57 controls.
Pathway enrichment analysis indicated the Gαi signalling and the oestrogen receptor signalling to be similarly affected in blood and cerebellum. SAFB2, SFSWAP and LTBP4 were consistently dysregulated in pre-ataxic subjects compared to controls, displaying a combined discriminatory ability of 79%. In patients, ataxia severity was associated with higher levels of MEG3 and TSPOAP1.
We propose expression levels of SAFB2, SFSWAP and LTBP4 as well as MEG3 and TSPOAP1 as stratification markers of SCA3/MJD progression, deserving further validation in longitudinal studies and in independent cohorts.
Spike-microstates correlate with interictal epileptogenic discharges: a marker for hidden epileptic activity
Authors: Rochas Vincent , Gschwind Markus , Nedeltchev Krassen , Seeck Margitta 
Published: April 2023

Abstract
Objectively estimating disease severity and treatment success is a main problem in outpatient managing of epilepsy. Self-reported seizures diaries are well-known to underestimate the actual seizure count, and repeated EEGs might not show interictal epileptiform discharges (IEDs), although patients suffer from seizures. In this prospective study, we investigate the potential of microstate analysis to monitor epilepsy patients independently of their IED count.
From our databank of candidates for epilepsy surgery, we included 18 patients who underwent controlled resting EEG sessions (with eyes closed, 30 min), at around the same time of the day, during at least four days (range: 4–8 days; mean: 5). Nine patients with temporal foci, six with extratemporal foci, and three with generalized epilepsy were included. Each patient’s IEDs were marked and the topographic voltage maps of the IED peaks were averaged, and an individual average spike topography (AST) was created. The AST was then backfitted to each timepoint of the whole EEG resulting in the Spike-Microstate (SMS). The presence of the SMS in the residual EEG outside of the short IEDs epochs was determined for each recording session in each patient and correlated with the occurrence of the IEDs across all recording session, as well as with the drug charge of each day.
Overall, SMS was much more represented in the routine EEG than the IEDs: they were identified 262 times more often than IEDs. The SMS time coverage correlated significantly with the IED occurrence rate (rho = 0.56; P &lt; 0.001). If only patients with focal epilepsy were considered, this correlation was even higher rho = 0.69 (P &lt; 0.001). Drug charge per day did not correlate with SMS.
In this proof-of-concept study, the time coverage of SMS correlated strongly with the occurrence rate of the IEDs, they can be retrieved in the scalp EEG at a much higher occurrence rate. We conclude that SMS, once obtained for a given patient, are a more abundant marker of hidden epileptic activity than IEDs, in particular in focal epilepsy, and can be used also in absence of IEDs. Future larger studies are needed to verify its potential as monitoring tool and to determine cut-off values when drug protection becomes imperfect.
Parasagittal dural space hypertrophy and amyloid-β deposition in Alzheimer’s disease
Authors: Song Alexander K , Hett Kilian , Eisma Jarrod J , McKnight Colin D , Elenberger Jason , Stark Adam J , Kang Hakmook , Yan Yan , Considine Ciaran M , Donahue Manus J , Claassen Daniel O 
Published: April 2023

AbstractOne of the pathological hallmarks of Alzheimer’s and related diseases is the increased accumulation of protein amyloid-β in the brain parenchyma. As such, recent studies have focused on characterizing protein and related clearance pathways involving perivascular flow of neurofluids, but human studies of these pathways are limited owing to limited methods for evaluating neurofluid circulation non-invasively in vivo. Here, we utilize non-invasive MRI methods to explore surrogate measures of CSF production, bulk flow and egress in the context of independent PET measures of amyloid-β accumulation in older adults. Participants (N = 23) were scanned at 3.0 T with 3D T2-weighted turbo spin echo, 2D perfusion-weighted pseudo-continuous arterial spin labelling and phase-contrast angiography to quantify parasagittal dural space volume, choroid plexus perfusion and net CSF flow through the aqueduct of Sylvius, respectively. All participants also underwent dynamic PET imaging with amyloid-β tracer 11C-Pittsburgh Compound B to quantify global cerebral amyloid-β accumulation. Spearman’s correlation analyses revealed a significant relationship between global amyloid-β accumulation and parasagittal dural space volume (rho = 0.529, P = 0.010), specifically in the frontal (rho = 0.527, P = 0.010) and parietal (rho = 0.616, P = 0.002) subsegments. No relationships were observed between amyloid-β and choroid plexus perfusion nor net CSF flow. Findings suggest that parasagittal dural space hypertrophy, and its possible role in CSF-mediated clearance, may be closely related to global amyloid-β accumulation. These findings are discussed in the context of our growing understanding of the physiological mechanisms of amyloid-β aggregation and clearance via neurofluids.
The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype
Authors: Muir Andrew , Bennett Alex , Smith Hannah , Logunova Larisa , Wolfenden Andrew , Fenn Jonathan , Lowe Ann E , Brass Andy , Grainger John R , Konkel Joanne E , Bradley Janette E , Mair Iris , Else Kathryn J 
Published: April 2023

Abstract
The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a human-homologous, genetically manipulable and reproducible model that has enabled an immeasurable volume of high-quality immunological research. However, recent research has questioned the translatability of laboratory mouse research into humans and proposed that the exposure of mice to their wild and natural environment may hold the key to further immunological breakthroughs. To date, there have been no studies providing an in-depth cellular analysis of the wild mouse bone marrow. This study utilized wild mice from an isolated island population (Isle of May, Scotland, UK) and performed flow cytometric and histological analysis to characterize the myeloid, lymphoid, hematopoietic progenitor, and adipocyte compartments within the wild mouse bone marrow. We find that, compared to laboratory mouse bone marrow, the wild mouse bone marrow differs in every cell type assessed. Some of the major distinctions include; a smaller B cell compartment with an enriched presence of plasma cells, increased proportions of KLRG1+ CD8+ T cells, diminished CD11b expression in the myeloid lineage and a five-fold enlargement of the eosinophil compartment. We conclude that the wild mouse bone marrow is dramatically distinct from its laboratory counterparts, with multiple phenotypes that to our knowledge have never been observed in laboratory models. Further research into these unique features may uncover novel immunological mechanisms and grant a greater understanding of the role of the immune system in a natural setting.
Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron
Authors: Meloni Antonella , Pistoia Laura , Positano Vincenzo , Martini Nicola , Borrello Rita Laura , Sbragi Sara , Spasiano Anna , Casini Tommaso , Bitti Pier Paolo , Putti Maria Caterina , Cuccia Liana , Allò Massimo , Massei Francesco , Sanna Paola Maria Grazia , De Caterina Raffaele , Quaia Emilio , Cademartiri Filippo , Pepe Alessia 
Published: April 2023

Abstract

Aims
We measured myocardial T2 values by a segmental approach in thalassaemia major (TM) patients, comparing such values against T2* values for the detection of myocardial iron overload (MIO), evaluating their potential in detecting subclinical inflammation, and correlating with clinical status.

Methods and results
One-hundred and sixty-six patients (102 females, 38.29 ± 11.49years) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent magnetic resonance imaging for the assessment of hepatic, pancreatic, and cardiac iron overload (T2* technique), of biventricular function (cine images), and of replacement myocardial fibrosis [late gadolinium enhancement (LGE)]. T2 and T2* values were quantified in all 16 myocardial segments, and the global value was the mean of all segments. Global heart T2 values were significantly higher in TM than in a cohort of 80 healthy subjects. T2 and T2* values were significantly correlated. Out of the 25 patients with a decreased global heart T2* value, 11 (44.0%) had reduced T2 values. No patient with a normal T2* value had a decreased T2 value.
Eleven (6.6%) patients had a decreased global heart T2 value, 74 (44.6%) a normal global heart T2 value, and 81 (48.8%) an increased global heart T2 value. Biventricular function was comparable amongst the three groups, whilst LGE was significantly more frequent in patients with reduced vs. increased global heart T2 value. Compared with the other two groups, patients with reduced T2 values had significantly higher hepatic and pancreatic iron deposition.

Conclusion
In TM, T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment but detects subclinical myocardial inflammation.
Utility of cardiac magnetic resonance imaging for pre-operatively evaluating the degree of caseous calcification of the mitral annulus infiltration within the left ventricular myocardium: a case report
Authors: Hishikawa Takanori , Ohashi Takeki , Kageyama Soichiro , Kojima Akinori 
Published: April 2023

AbstractBackgroundDepending on the degree of infiltration of dry mitral annulus calcification (MAC) into the left ventricular myocardium, calcification removal may cause thinning of the left ventricular wall and increase the risk of post-operative left ventricular rupture. Therefore, the degree of pre-operative infiltration into the left ventricular myocardium should be assessed as accurately as possible. We report a case of caseous calcification of the mitral annulus (CCMA), a subtype of MAC, in an 84-year-old woman; cardiac magnetic resonance imaging (MRI) was useful in assessing the degree of left ventricular infiltration of calcification.Case summaryThe patient was referred to our hospital for surgery due to respiratory distress and severe mitral insufficiency. Echocardiography revealed a mass under the posterior mitral annulus adjacent to the mitral valve ring, suspected to be a CCMA. Cardiac MRI was performed to assess the risk of left ventricular rupture. Pre-operatively, no valve ring or left ventricular myocardium infiltration was confirmed. Surgical caseous calcification removal and artificial valve implantation within the preserved valve annulus were then performed. The patient had an uneventful post-operative course and was discharged without complications on the 21st post-operative day.DiscussionIn this CCMA case, a pre-operative cardiac MRI was useful for evaluating the degree of the valve annulus and left ventricular myocardial involvement and estimating the risk of left ventricular rupture.
Unraveling Firms: Demand, Productivity and Markups Heterogeneity
Authors: Forlani Emanuele , Martin Ralf , Mion Giordano , Muûls Mirabelle 
Published: April 2023

Abstract
We develop a novel framework that simultaneously allows recovering heterogeneity in demand, quantity total factor productivity and markups across firms while leaving the correlation between the three dimensions unrestricted. We accomplish this by explicitly introducing demand heterogeneity and systematically exploiting assumptions used in previous productivity estimation approaches. In doing so, we provide an exact decomposition of revenue productivity in terms of the underlying heterogeneities, thus bridging the gap between quantity and revenue productivity estimations. We use Belgian firms’ production data to quantify total factor productivity, demand and markups, and show how they are correlated with each other across time and with measures obtained from other approaches. In doing so, we find quantity total factor productivity and demand to be strongly negatively correlated with each other, so suggesting a trade-off between the quality of a firm’s products and their production cost. We also show how our framework provides deeper and sharper insights on the response of firms to increasing import competition from China. In particular, we find that changes in revenue productivity materialise as the outcome of complex and sometimes offsetting changes in quantity total factor productivity, demand, markups and production scale.
Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study
Authors: Xing Lucas Yixi , Diederichsen Søren Zöga , Højberg Søren , Krieger Derk W , Graff Claus , Olesen Morten S , Nielsen Jonas Bille , Brandes Axel , Køber Lars , Haugan Ketil Jørgen , Svendsen Jesper Hastrup 
Published: April 2023

Abstract

Aims
Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters.

Methods and results
We included AF-naïve individuals aged 70–90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2–1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51–0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02–3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration.

Conclusion
We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.
Bayesian optimization for demographic inference
Authors: Noskova Ekaterina , Borovitskiy Viacheslav 
Published: April 2023

Abstract
Inference of demographic histories of species and populations is one of the central problems in population genetics. It is usually stated as an optimization problem: find a model’s parameters that maximize a certain log-likelihood. This log-likelihood is often expensive to evaluate in terms of time and hardware resources, critically more so for larger population counts. Although genetic algorithm-based solution has proven efficient for demographic inference in the past, it struggles to deal with log-likelihoods in the setting of more than three populations. Different tools are therefore needed to handle such scenarios. We introduce a new optimization pipeline for demographic inference with time consuming log-likelihood evaluations. It is based on Bayesian optimization, a prominent technique for optimizing expensive black box functions. Comparing to the existing widely used genetic algorithm solution, we demonstrate new pipeline’s superiority in the limited time budget setting with four and five populations, when using the log-likelihoods provided by the moments tool.
Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus
Authors: Howell Abigail A , Terbot John W , Soni Vivak , Johri Parul , Jensen Jeffrey D , Pfeifer Susanne P 
Published: April 2023

Abstract
Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable interhost and intrahost diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically and clinically. Herein, we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration—including mutation and recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization—and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.
Four Past Path-Builders Incorporated the Humanities and Arts Into Gerontology’s Scientific Frontiers
Authors: Achenbaum W Andrew 
Published: April 2023

AbstractScholars and practitioners in the humanities and arts are collaborating with bio-medico-psycho-social scientists and clinicians in projects that illuminate current understandings of how “aging” processes unfold and what they may mean in creating the future of the Gerontological Society of America. Moving ahead by connecting backwards, we should emulate past path-builders who imagined an interdisciplinary agenda that incorporated humanistic perspectives as they imparted scientific age-based insights to experts and lay audiences. Elie Metchnikoff, G. Stanley Hall, Robert N. Butler, and Gene D. Cohen demonstrated critical humanist thinking about aging and dying in advancing gerontology’s scientific frontiers.
Dynamic rupture simulations based on interseismic locking models—taking the Suoerkuli section of the Altyn Tagh fault as an example
Authors: Gu Yuhao , Zhang Zhenguo , Wang Wenqiang , Wang Zijia 
Published: April 2023

SUMMARYFor simulating the dynamic rupture process in earthquake scenarios, the stress distribution along the fault remains unclear owing to a lack of direct measurements. Regional stress fields are often resolved onto the fault plane to determine the stress distribution along it. To overcome this limitation, we considered different interseismic locking models to better constrain the actual stress distribution. Specifically, we took the Suoerkuli section in the middle of the Altyn Tagh fault, China, and conducted dynamic rupture simulations to obtain possible earthquake scenarios. The surface rupture length and moment magnitude obtained from the simulations were consistent with those of historical earthquakes. Compared with the traditional stress field resolution method, our approach led to better constrained fault rupture extent and distribution characteristics of regional intensity, thereby avoiding overestimations of earthquake damage. We conclude that examining regional seismic hazards and risks based on seismic dynamic rupture simulations that account for the locking ratio of the fault plane is advantageous, and should be encouraged.
Raman spectroscopy in crop quality assessment: focusing on sensing secondary metabolites: a review
Authors: Park Miri , Somborn Annette , Schlehuber Dennis , Keuter Volkmar , Deerberg Görge 
Published: April 2023

Abstract
As a crop quality sensor, Raman spectroscopy has been consistently proposed as one of the most promising and non-destructive methods for qualitative and quantitative analysis of plant substances, because it can measure molecular structures in a short time without requiring pretreatment along with simple usage. The sensitivity of the Raman spectrum to target chemicals depends largely on the wavelength, intensity of the laser power, and exposure time. Especially for plant samples, it is very likely that the peak of the target material is covered by strong fluorescence effects. Therefore, methods using lasers with low energy causing less fluorescence, such as 785 nm or near-infrared, are vigorously discussed. Furthermore, advanced techniques for obtaining more sensitive and clear spectra, like surface-enhanced Raman spectroscopy, time-gated Raman spectroscopy or combination with thin-layer chromatography, are being investigated. Numerous interpretations of plant quality can be represented not only by the measurement conditions but also by the spectral analysis methods. Up to date, there have been attempted to optimize and generalize analysis methods. This review summarizes the state of the art of micro-Raman spectroscopy in crop quality assessment focusing on secondary metabolites, from in vitro to in vivo and even in situ, and suggests future research to achieve universal application.