bluuebunny/crossref_metadata_2025_split huggingface dataset:
Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration
Authors: Tonietto Matteo , Poirion Emilie , Lazzarotto Andrea , Ricigliano Vito , Papeix Caroline , Bottlaender Michel , Bodini Benedetta , Stankoff Bruno 
Published: September 2022

Abstract
In multiple sclerosis, spontaneous remyelination is generally incomplete and heterogeneous across patients. A high heterogeneity in remyelination may also exist across lesions within the same individual, suggesting the presence of local factors interfering with myelin regeneration. In this study we explored in vivo the regional distribution of myelin repair and investigated its relationship with neurodegeneration. We first took advantage of the myelin binding property of the amyloid radiotracer 11C-PiB to conduct a longitudinal 11C-PiB PET study in an original cohort of 19 participants with a relapsing–remitting form of multiple sclerosis, followed-up over a period of 1–4 months. We then replicated our results on an independent cohort of 40 people with multiple sclerosis followed-up over 1 year with magnetization transfer imaging, an MRI metrics sensitive to myelin content. For each imaging method, voxel-wise maps of myelin content changes were generated according to modality-specific thresholds.
We demonstrated a selective failure of remyelination in periventricular white matter lesions of people with multiple sclerosis in both cohorts. In both the original and the replication cohort, we estimated that the probability of demyelinated voxels to remyelinate over the follow-up increased significantly as a function of the distance from ventricular CSF. Enlarged choroid plexus, a recently discovered biomarker linked to neuroinflammation, was found to be associated with the periventricular failure of remyelination in the two cohorts (r = −0.79, P = 0.0018; r = −0.40, P = 0.045, respectively), suggesting a role of the brain–CSF barrier in affecting myelin repair in surrounding tissues. In both cohorts, the failure of remyelination in periventricular white matter lesions was associated with lower thalamic volume (r = 0.86, P &lt; 0.0001; r = 0.33; P = 0.069, respectively), an imaging marker of neurodegeneration. Interestingly, we also showed an association between the periventricular failure of remyelination and regional cortical atrophy that was mediated by the number of cortex-derived tracts passing through periventricular white matter lesions, especially in patients at the relapsing–remitting stage.
Our findings demonstrate that lesion proximity to ventricles is associated with a failure of myelin repair and support the hypothesis that a selective periventricular remyelination failure in combination with the large number of tracts connecting periventricular lesions with cortical areas is a key mechanism contributing to cortical damage in multiple sclerosis.
Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study
Authors: Amiri Moshgan , Fisher Patrick M , Raimondo Federico , Sidaros Annette , Cacic Hribljan Melita , Othman Marwan H , Zibrandtsen Ivan , Albrechtsen Simon S , Bergdal Ove , Hansen Adam Espe , Hassager Christian , Højgaard Joan Lilja S , Jakobsen Elisabeth Waldemar , Jensen Helene Ravnholt , Møller Jacob , Nersesjan Vardan , Nikolic Miki , Olsen Markus Harboe , Sigurdsson Sigurdur Thor , Sitt Jacobo D , Sølling Christine , Welling Karen Lise , Willumsen Lisette M , Hauerberg John , Larsen Vibeke Andrée , Fabricius Martin , Knudsen Gitte Moos , Kjaergaard Jesper , Møller Kirsten , Kondziella Daniel 
Published: September 2022

Abstract
Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study ‘Consciousness in neurocritical care cohort study using EEG and fMRI’ (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77–0.80) and 0.71 (95% CI 0.77–0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71–0.86) and 0.83 (95% CI 0.75–0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.
Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States
Authors: Zanni Markella V , Foldyna Borek , McCallum Sara , Burdo Tricia H , Looby Sara E , Fitch Kathleen V , Fulda Evelynne S , Autissier Patrick , Bloomfield Gerald S , Malvestutto Carlos D , Fichtenbaum Carl J , Overton Edgar T , Aberg Judith A , Erlandson Kristine M , Campbell Thomas B , Ellsworth Grant B , Sheth Anandi N , Taiwo Babafemi , Currier Judith S , Hoffmann Udo , Lu Michael T , Douglas Pamela S , Ribaudo Heather J , Grinspoon Steven K 
Published: September 2022

Abstract

Background
Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein.

Methods
REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)–treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score.

Results
The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P &lt; .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P &lt; .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055).

Conclusions
Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters.
Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).
A Phase 1, open-label, crossover study evaluating the effect of a single dose of sodium zirconium cyclosilicate on the pharmacokinetics of tacrolimus and cyclosporin
Authors: Någård Mats , Choudhury Nurul , Al-Shurbaji Ayman , Lisovskaja Vera , Mackillop Neil 
Published: September 2022

ABSTRACT

Background
Sodium zirconium cyclosilicate (SZC) is an oral, highly selective potassium binder approved for the treatment of hyperkalaemia in adults. SZC may change the absorption of co-administered drugs that exhibit pH-dependent bioavailability. This study evaluated whether the pharmacokinetic (PK) profiles of tacrolimus and cyclosporin were altered by concomitant SZC administration in healthy participants.

Methods
This was an open-label, randomised sequence, two-cohort crossover, single-centre study. Healthy adults were assigned to one of two cohorts: Cohort 1 (tacrolimus) received a single dose of tacrolimus 5 mg and tacrolimus 5 mg + SZC 15 g in a random order; Cohort 2 (cyclosporin) received a single dose of cyclosporin 100 mg and cyclosporin 100 mg + SZC 15 g in a random order. Primary PK endpoints were maximum observed blood concentration (Cmax) and area under the concentration–time curve (AUC) from time zero to infinity (AUCinf). Differences in mean Cmax and AUCinf were analysed using a mixed effects model.

Results
Thirty participants in Cohort 1 and 29 in Cohort 2 completed the study. Tacrolimus exposure was lower with tacrolimus + SZC versus tacrolimus alone: Cmax geometric mean ratio (GMR) 71.10% [90% confidence interval (CI) 65.44–77.24], AUCinf 62.91% (55.64–71.13). Cyclosporin exposure was similar with cyclosporin + SZC compared with cyclosporin alone: Cmax GMR 102.9% (90% CI 96.11–110.10), AUCinf 97.23% (92.93–101.70).

Conclusions
Tacrolimus exposure was lower when co-administered with SZC 15 g and should be administered ≥2 h before or after SZC. The PK profile of cyclosporin was not affected by SZC co-administration.
Incidence, causes, correlates, and outcome of bioprosthetic valve dysfunction and failure following transcatheter aortic valve implantation
Authors: Nitsche Christian , Koschutnik Matthias , Donà Carolina , Mutschlechner David , Halavina Kseniya , Spinka Georg , Dannenberg Varius , Mascherbauer Katharina , Sinnhuber Leah , Kammerlander Andreas , Winter Max-Paul , Bartko Philipp , Goliasch Georg , Pibarot Philippe , Hengstenberg Christian , Mascherbauer Julia 
Published: September 2022

Abstract

Aims
Bioprosthetic valve dysfunction (BVD) is a major concern regarding transcatheter aortic valve implantation (TAVI) durability. We aimed to assess incidence, correlates, causes, and outcome of early to mid-term BVD after TAVI in relation to patient’s life expectancy.

Methods and results
Consecutive TAVI recipients (2007–20) with a follow-up ≥1 year were prospectively included. BVD and bioprosthetic valve failure (BVF) were assessed according to Valve-Academic-Research-Consortium-3. BVD/BVF and all-cause death served as endpoints. Average life expectancy was calculated from National Open Health Data and patients were stratified according to tertiles (1st: &lt;6.85 years, 2nd: 6.85–9.7 years, 3rd: &gt;9.7 years). Of 1047 patients (81.6 ± 6.8 years old, EuroSCORE II 4.5 ± 2.5), ≥2 follow ups were available from 622 (serial echo cohort). After a median echo follow up of 12.2 months, incidence rates of BVD/BVF were 8.4% (95% confidence interval 6.7–10.3), and 3.5% (2.5–4.9) per valve-year, respectively, without differences between life expectancy tertiles. The incidence of BVD was two-fold higher within the first year of implant (9.9% per valve-year) vs. beyond (4.8% per valve-year). Valve-in-valve procedure and residual stenosis, but not age/life expectancy predisposed for BVD. BVD/BVF were independently associated with outcome for patients in the first [adjusted hazard ratio (AHR) 1.72 (1.06–2.88)/2.97 (1.72–6.22)] and second [AHR 1.96 (1.02–3.73)/2.31 (1.00–5.30)], but not the third tertile of life expectancy (P = n.s.)

Conclusions
In this large prospective observational cohort, early to mid-term BVD after TAVI occurred at the same rate across the spectrum of life expectancy and was associated with increased mortality in patients with short but not in those with the longest life expectancy.
Successful treatment of recurrent thoracic aortic prosthetic graft infection after omentopexy by free latissimus dorsi and rectus abdominis muscle flap
Authors: Miura Shuhei , Shichinohe Ryuji , Iba Yutaka 
Published: September 2022

Abstract
A 50-year-old patient who underwent total aortic arch replacement for acute type A aortic dissection developed recurrent thoracic prosthetic graft infection after omentopexy for the treatment of initial postoperative graft infection of the ascending aorta and transverse aortic arch. We report the successful treatment of the disastrous complication by covering the prosthetic graft with a free latissimus dorsi muscle flap coupled with a pedicled rectus abdominis myocutaneous flap for the reduction of mediastinal dead space, following surgical disinfection with partial graft reconstruction.
TheFoxGene Repertoire in the AnnelidOwenia fusiformisReveals Multiple Expansions of thefoxQ2Class in Spiralia
Authors: Seudre Océane , Martín-Zamora Francisco M , Rapisarda Valentina , Luqman Imran , Carrillo-Baltodano Allan M , Martín-Durán José M 
Published: September 2022

AbstractFox genes are a large and conserved family of transcription factors involved in many key biological processes, including embryogenesis and body patterning. Although the role of Fox genes has been studied in an array of model systems, comprehensive comparative studies in Spiralia—a large clade of invertebrate animals including molluscs and annelids—are scarce but much needed to better understand the evolutionary history of this gene family. Here, we reconstruct and functionally characterize the Fox gene complement in the annelid Owenia fusiformis, a slow evolving species and member of the sister group to all remaining annelids. The genome of O. fusiformis contains at least a single ortholog for 20 of the 22 Fox gene classes that are ancestral to Bilateria, including an ortholog of the recently discovered foxT class. Temporal and spatial expression dynamics reveal a conserved role of Fox genes in gut formation, mesoderm patterning, and apical organ and cilia formation in Annelida and Spiralia. Moreover, we uncover an ancestral expansion of foxQ2 genes in Spiralia, represented by 11 paralogs in O. fusiformis. Notably, although all foxQ2 copies have apical expression in O. fusiformis, they show variable spatial domains and staggered temporal activation, which suggest cooperation and sub-functionalization among foxQ2 genes for the development of apical fates in this annelid. Altogether, our study informs the evolution and developmental roles of Fox genes in Annelida and Spiralia generally, providing the basis to explore how regulatory changes in Fox gene expression might have contributed to developmental and morphological diversification in Spiralia.
Genomic selection with fixed-effect markers improves the prediction accuracy for Capsaicinoid contents in Capsicum annuum
Authors: Kim Geon Woo , Hong Ju-Pyo , Lee Hea-Young , Kwon Jin-Kyung , Kim Dong-Am , Kang Byoung-Cheorl 
Published: September 2022

ABSTRACT
Capsaicinoids provide chili peppers (Capsicum spp.) with their characteristic pungency. Several structural and transcription factor genes are known to control capsaicinoid contents in pepper. However, many other genes also regulating capsaicinoid contents remain unknown, making it difficult to develop pepper cultivars with different levels of capsaicinoids. Genomic selection (GS) uses genome-wide random markers (including many in undiscovered genes) for a trait to improve selection efficiency. In this study, we predicted the capsaicinoid contents of pepper breeding lines using several GS models trained with genotypic and phenotypic data from a training population. We used a core collection of 351 Capsicum accessions and 96 breeding lines as training and testing populations, respectively. To obtain the optimal number of single nucleotide polymorphism (SNP) markers for GS, we tested various numbers of genome-wide SNP markers based on linkage disequilibrium. We obtained the highest mean prediction accuracy (0.550) for different models using 3294 SNP markers. Using this marker set, we conducted GWAS and selected 25 markers that were associated with capsaicinoid biosynthesis genes and quantitative trait loci for capsaicinoid contents. Finally, to develop more accurate prediction models, we obtained SNP markers from GWAS as fixed-effect markers for GS, where 3294 genome-wide SNPs were employed. When four to five fixed-effect markers from GWAS were used as fixed effects, the RKHS and RR-BLUP models showed accuracies of 0.696 and 0.689, respectively. Our results lay the foundation for developing pepper cultivars with various capsaicinoid levels using GS for capsaicinoid contents.
Tomato receptor-like cytosolic kinase RIPK confers broad-spectrum disease resistance without yield penalties
Authors: Wang Ran , Li Chenying , Li Qinghong , Ai Yingfei , Huang Zeming , Sun Xun , Zhou Jie , Zhou Yanhong , Liang Yan 
Published: September 2022

AbstractProduction of reactive oxygen species (ROS) is an important immune response in plant multilayer defense mechanisms; however, direct modification of ROS homeostasis to breed plants with broad-spectrum resistance to disease has not yet been successful. In Arabidopsis, the receptor-like cytosolic kinase AtRIPK regulates broad-spectrum ROS signaling in multiple layers of the plant immune system. Upon treatment with immune elicitors, AtRIPK is activated and phosphorylates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which leads to ROS production. In this study, we identified an AtRIPK ortholog in tomatoes and generated knockdown mutants using CRISPR/Cas9 technology. Slripk mutants displayed reduced ROS production in response to representative immune elicitors and were susceptible to pathogenic bacteria and fungi from different genera, including Ralstonia solanacearum, Pectobacterium carotovorum, Botrytis cinerea, and Fusarium oxysporum, which are leaf and root pathogens with hemibiotrophic and necrotrophic infection strategies. In contrast, transgenic tomato plants overexpressing SlRIPK are more resistant to these pathogens. Remarkably, the slripk mutants and SlRIPK-overexpressing transgenic plants did not exhibit significant growth retardation or yield loss. These results suggest that overexpression of SlRIPK confers broad-spectrum disease resistance without a yield penalty in tomato plants. Our findings suggest that modifying ROS homeostasis by altering the regulatory components of ROS production in plant immunity could contribute to engineering or breeding broad-spectrum disease-resistant crops without yield penalty.
Short Proofs of Rainbow Matchings Results
Authors: Correia David Munh , Pokrovskiy Alexey , Sudakov Benny 
Published: September 2022

Abstract
A subgraph of an edge-coloured graph is called rainbow if all its edges have distinct colours. The study of rainbow subgraphs goes back to the work of Euler on Latin squares and has been the focus of extensive research ever since. Many conjectures in this area roughly say that “every edge coloured graph of a certain type contains a rainbow matching using every colour.” In this paper we introduce a versatile “sampling trick,” which allows us to asymptotically solve some well-known conjectures and to obtain short proofs of old results. In particular:
$\bullet $ We give the first asymptotic proof of the “non-bipartite” Aharoni–Berger conjecture, solving two conjectures of Aharoni, Berger, Chudnovsky, and Zerbib.
$\bullet $ We give a very short asymptotic proof of Grinblat’s conjecture (first obtained by Clemens, Ehrenmüller, and Pokrovskiy). Furthermore, we obtain a new asymptotically tight bound for Grinblat’s problem as a function of edge multiplicity of the corresponding multigraph.
$\bullet $ We give the first asymptotic proof of a 30-year-old conjecture of Alspach.
$\bullet $ We give a simple proof of Pokrovskiy’s asymptotic version of the Aharoni–Berger conjecture with greatly improved error term.
Bridging of a Liquid Chromatography–Tandem Mass Spectrometry Method for Oxytetracycline, Chlortetracycline, and Tetracycline in Bovine Kidney with the Official Microbial Growth Inhibition Assay
Authors: Girard Lauren , Li Hui , Feng Charles , Kijak Philip J , Sklenka Sara , Smith Shani , Rasmussen Sharon , Pugh Carol , McDermott Shawn , Chiesa O Alberto , Ward Jeffrey , Hasbrouck Elizabeth , Smith Elizabeth , Lancaster Vicki , Qiu Junshan 
Published: September 2022

Abstract

Background
Oxytetracycline (OTC), chlortetracycline (CTC), and tetracycline (TC) are approved antibiotics used to treat bacterial infections in cattle. To ensure human food safety, a tolerance has been established for the sum of these three TC residues as 12 parts per million in bovine kidney in the United States The current official regulatory method for quantifying these antibiotics in the target organ is a labor-intensive microbiological assay.

Objective
Our laboratory developed and validated a fast, selective, and less laborious method utilizing LC–tandem mass spectrometry for the determination and confirmation of the three tetracyclines (TET) in bovine kidney.

Methods
Briefly, homogenized kidney tissue was spiked with an internal standard (ISTD), and then was extracted with 1% phosphate buffer. The crude extract was cleaned up using solid-phase extraction cartridges before instrumental analysis.

Results
Accuracies for quantifying these three drugs in fortified kidney homogenate were between 99.9 and 110% at multiple concentrations, with respective CVs all below 9.5%. Quantitative correlation between the two methods (bridging) was evaluated with incurred bovine kidney samples for each of the three tetracyclines separately. The results were statistically evaluated using a measurement model called Functional Relationship Estimation by Maximum Likelihood.

Conclusion
A linear quantitative relationship was demonstrated between the two methods within the concentration range of regulatory relevance.

Highlights
This instrumental method is in addition to the established microbial assay for the detection of tetracyclines residue in beef kidney to ensure the food safety of cattle products.