bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses
Authors: Spatola Marianna , Nziza Nadège , Jung Wonyeong , Deng Yixiang , Yuan Dansu , Dinoto Alessandro , Bozzetti Silvia , Chiodega Vanessa , Ferrari Sergio , Lauffenburger Douglas A , Mariotto Sara , Alter Galit 
Published: May 2023

Abstract
Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the CNS, can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations and persistence of SARS-CoV-2 reservoirs.
In this prospective cohort study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common coronaviruses: 229E, HKU1, NL63 and OC43) in the serum and CSF from 112 infected individuals who developed (n = 18) or did not develop (n = 94) neuroPASC.
Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC compared with serum responses. All antibody isotypes (IgG, IgM, IgA) and subclasses (IgA1–2, IgG1–4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favour of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood–brain barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Compared to individuals who did not develop post-acute complications following infection, individuals with neuroPASC had similar demographic features (median age 65 versus 66.5 years, respectively, P = 0.55; females 33% versus 44%, P = 0.52) but exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fcγ receptors. However, surprisingly, neuroPASC individuals showed significantly expanded antibody responses to other common coronaviruses, including 229E, HKU1, NL63 and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting an ‘original antigenic sin’ (or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to the current infection, as a key prognostic marker of neuroPASC disease.
Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection.
GAA-FGF14 ataxia (SCA27B): phenotypic profile, natural history progression and 4-aminopyridine treatment response
Authors: Wilke Carlo , Pellerin David , Mengel David , Traschütz Andreas , Danzi Matt C , Dicaire Marie-Josée , Neumann Manuela , Lerche Holger , Bender Benjamin , Houlden Henry ,   RFC1 study group, Faber Jennifer , Roxburgh Richard , Pedroso José Luiz , Alvez Paula Camila , Barsottini Orlando , Pane Chiara , Saccà Francesco , Filla Alessandro , Santorelli Filippo M , Ricca Ivana , Züchner Stephan , Schöls Ludger , Brais Bernard , Synofzik Matthis 
Published: May 2023

Abstract
Ataxia due to an autosomal dominant intronic GAA repeat expansion in FGF14 [GAA-FGF14 ataxia, spinocerebellar ataxia 27B (SCA27B)] has recently been identified as one of the most common genetic late-onset ataxias. We here aimed to characterize its phenotypic profile, natural history progression, and 4-aminopyridine (4-AP) treatment response.
We conducted a multi-modal cohort study of 50 GAA-FGF14 patients, comprising in-depth phenotyping, cross-sectional and longitudinal progression data (up to 7 years), MRI findings, serum neurofilament light (sNfL) levels, neuropathology, and 4-AP treatment response data, including a series of n-of-1 treatment studies.
GAA-FGF14 ataxia consistently presented as late-onset [60.0 years (53.5–68.5), median (interquartile range)] pancerebellar syndrome, partly combined with afferent sensory deficits (55%) and dysautonomia (28%). Dysautonomia increased with duration while cognitive impairment remained infrequent, even in advanced stages. Cross-sectional and longitudinal assessments consistently indicated mild progression of ataxia [0.29 Scale for the Assessment and Rating of Ataxia (SARA) points/year], not exceeding a moderate disease severity even in advanced stages (maximum SARA score: 18 points). Functional impairment increased relatively slowly (unilateral mobility aids after 8 years in 50% of patients). Corresponding to slow progression and low extra-cerebellar involvement, sNfL was not increased relative to controls. Concurrent second diseases (including progressive supranuclear palsy neuropathology) represented major individual aggravators of disease severity, constituting important caveats for planning future GAA-FGF14 trials. A treatment response to 4-AP with relevance for everyday living was reported by 86% of treated patients. A series of three prospective n-of-1 treatment experiences with on/off design showed marked reduction in daily symptomatic time and symptom severity on 4-AP.
Our study characterizes the phenotypic profile, natural history progression, and 4-AP treatment response of GAA-FGF14 ataxia. It paves the way towards large-scale natural history studies and 4-AP treatment trials in this newly discovered, possibly most frequent, and treatable late-onset ataxia.
Peripheral blood lymphopenia in sarcoidosis associates with HLA-DRB1 alleles but not with lung immune cells and organ involvement
Authors: Darlington Pernilla , Melin Jonas , Rivera Natalia , Grunewald Johan , Eklund Anders , Kullberg Susanna 
Published: May 2023

Abstract
Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Peripheral blood (PB) lymphopenia is reported as more common in sarcoidosis patients with worse prognosis. The mechanisms behind are unrecognized but a PB depletion due to lymphocytes migrating to lung and/or extra pulmonary organs has been suggested. Insights into associations between HLA alleles, lung immune cells, clinical phenotype including extra pulmonary manifestations (EPM), and PB lymphopenia may provide mechanistic clues and enable adequate intervention in this patient group. In this situdy,141 treatment naïve, newly diagnosed patients were retrospectively identified in a Swedish cohort of sarcoidosis patients. Data on HLA-DRB1 alleles, lung immune cells from bronchoalveolar lavage fluid (BALF), PB lymphocytes and clinical parameters including treatment and disease course (chronic vs. resolving) were collected. The patients were followed for 2 years. PB lymphopenia associated with male sex, development of non-resolving disease, a need for first- and second-line systemic immunosuppressant treatment and HLA- DRB1*07. No correlation between BALF and PB lymphocytes, and no difference in EPM was detected between patients with and without PB lymphopenia. In conclusion, PB lymphopenia is associated with a more severe disease phenotype and carriage of the HLA-DRB1*07 allele. The results do not lend support to the hypothesis about sarcoidosis PB lymphopenia being due to a migration of PB lymphocytes to other organs. Rather, they provide a basis for future studies on the connection between HLA-DRB1*07 and PB lymphopenia mechanisms.
Discrepancy in clinical and laboratory profiles of NMOSD patients between AQP4 antibody positive and negative: can NMOSD be diagnosed without AQP4 antibody?
Authors: Chu Fengna , Shi Mingchao , Liu Canyun , Zhu Jie 
Published: May 2023

AbstractAQP4-IgG has been considered as the pathogenic factor leading to NMOSD. However, about 20–30% of patients lack AQP4-IgG. So far, all therapeutic medicines are ineffective for NMOSD patients without AQP4 IgG. Thus AQP4-IgG is the pathogenic factor of NMOSD has been suspected and challenged. In addition, lack of efficacy of immunotherapy in NMOSD without AQP4 IgG has been a serious problem in the neurology. Identifying the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG can be helpful to further explore the pathogenesis of NMOSD and guide clinical treatment. This is a single-centre retrospective study in The First Hospital of Jilin University, China including 92 patients diagnosed as NMOSD from January 2013 to January 2015. The characteristics of clinic, blood, cerebrospinal fluid (CSF), and image between AQP4-IgG negative (AQP4-IgG−) and AQP4-IgG positive (AQP4-IgG+) NMOSDs were compared. Our results showed that in the AQP4-IgG+ group, the ratio of women to men was 5.55, while in AQP4-IgG− group was 1.54 (P = 0.0092). In the AQP4-IgG+ patients, the expanded disability status scale (EDSS) was from 0 to 8.5, with an average of 5.550 ± 0.25, and the AQP4-IgG− patients had the EDSS score from 0 to 9, with an average of 4.032 ± 0.36 (P = 0.0006), which mainly affected movement system (P &lt; 0.05) and superficial sensory impairment (P &lt; 0.05). In the AQP4-IgG+ group, the blood brain barrier (BBB) permeability (P = 0.0210) and myelin basic protein (MBP) were increased (P = 0.0310) when compared to AQP4-IgG− group. Higher level IL-17 was seen in AQP4-IgG+ group than AQP4-IgG− group (P= 0.0066). Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. The differences in clinical and laboratory profiles between NMOSD with and without AQP4-IgG indicate the heterogeneity of NMOSD, in which AQP4-IgG may not be the only pathogenic molecule. It is necessary to find more pathogenic factors and to explore the new pathogenesis of NMOSD and therapeutic methods in the future.
Endothelial mechanobiology in atherosclerosis
Authors: Wang Xiaoli , Shen Yang , Shang Min , Liu Xiaoheng , Munn Lance L 
Published: May 2023

AbstractCardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit ‘disturbed’ flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis.
The impact of antiplatelet therapy on the descending thoracic aorta fate and long-term prognosis of extensive repaired type A aortic dissection
Authors: Zhang Bowen , Dun Yaojun , Liu Yanxiang , Ren Jie , Gao Haoyu , Wang Luchen , Zhou Sangyu , Xie Mingxin , Sun Xiaogang 
Published: May 2023

Abstract

OBJECTIVES
To evaluate the impact of antiplatelet therapy on the long-term descending thoracic aorta (DTA) fate and prognosis of extensive repaired type A aortic dissection (TAAD).

METHODS
1147 eligible TAAD patients from January 2010 to December 2019 were stratified into non-antiplatelet (n = 754) and antiplatelet groups (n = 393). The primary end points were overall survival, and DTA remodelling, including false lumen (FL) thrombosis and aortic redilation. The secondary end points were DTA reintervention or rupture and major bleeding events (MBEs).

RESULTS
The 5-year overall survival rates were 95.6% and 94.3% in the non-antiplatelet and antiplatelet groups (P = 0.53), respectively. In the stent covering segment, the 1-year FL complete thrombosis rates were 92.1% and 92.4% in the non-antiplatelet and antiplatelet groups (P = 0.27), respectively, while in the stent uncovering segment, the 5-year FL complete thrombosis rates were 47.1% and 56.5% in the non-antiplatelet and antiplatelet groups (P = 0.12), respectively. Antiplatelet therapy was not an independent predictor of aortic redilation at the pulmonary artery bifurcation (β±SE = –0.128 ± 0.203, P = 0.53), diaphragm (β±SE = 0.143 ± 0.152, P = 0.35) or coeliac artery (β±SE = 0.049 ± 0.136, P = 0.72) levels. With death as a competing risk, the cumulative incidences of DTA reintervention or rupture at 5 years were 4.6% and 4.0% in the non-antiplatelet and antiplatelet groups (sHR = 0.85, 95% CI, 0.49∼1.19; P = 0.58), respectively, and the 5-year cumulative incidences of MBEs were 2.1% and 2.3% in the non-antiplatelet and antiplatelet groups (sHR = 0.82, 95% CI, 0.56∼2.67; P = 0.62), respectively.

CONCLUSIONS
Antiplatelet therapy did not impact long-term DTA FL thrombosis, redilation, reintervention or rupture, MBEs or overall survival on extensive repaired TAAD. Thus, antiplatelet therapy can be administered as indicated on extensive repaired TAAD.
The effect of tooth borne versus skeletally anchored Alt-RAMEC protocol in early treatment of Class III malocclusion: a single-centre randomized clinical trial
Authors: Alzoubi Emad Eddin , Camilleri Simon , Al Muzian Mohammed , Attard Nikolai 
Published: May 2023

Summary

Trial design
This was a randomized, controlled trial designed to compare outcomes between the use of dental and skeletal anchorage, using the Face mask/Alternate Rapid Maxillary Expansion and Contraction (FM/Alt-RAMEC) protocol.

Methods and participants
The study was carried out at Mater Dei Hospital, Malta and included prepubertal skeletal Class III malocclusion patients where the aetiology was primarily maxillary hypoplasia.

Interventions
Two groups were assigned. Group I was treated with FM/Alt-RAMEC and group II was treated with skeletally anchored FM/Alt-RAMEC. Wear-time (WT) of the FM was monitored using TheraMon microsensors. Patients were instructed to wear the FM for 12–14 hours/day for 9 months. Changes were evaluated with lateral cephalograms and analysed with Wilcoxon and Mann–Whitney U tests. ANOVA was used to analyse the effect of gender on compliance parameters. Spearman’s correlation coefficient was used to assess the correlation between compliance and skeletal changes.

Objective
To compare the skeletal and dentoalveolar changes in patients treated with these two protocols.

Outcomes
The primary outcome was to assess skeletal and dentoalveolar outcomes in patients treated with skeletally anchored FM/RME and tooth-borne FM/RME; utilizing Alt-RAMEC protocol. The secondary outcome was compliance rate and adherence to FM wear among patients.

Randomization
Randomizer software and the sealed envelope technique were used to randomly allocate patients 1:1 into either group I (tooth-borne FM/Alt-RAMEC) or group II (skeletally anchored FM/Alt-RAMEC).

Blinding
It was not possible to blind to treatment allocation, but blinding was used when assessing the outcomes.

Results
Numbers randomized and analysed. Thirty-five patients were allocated. Group I consisted of 18 subjects and group II consisted of 17 subjects. One patient in group I dropped out due to illness, so 17 subjects in each group completed the study.

Outcomes
Post-treatment changes in group I showed significant increases in SNA (2.10°), ANB (3.90°), Wits (4.70 mm), and overjet (5.40 mm). Group II showed significant increases in ANB (3.10°), Wits (3.20 mm), and overjet (4.50 mm). Wearing time for group I patients was 7.87 ± 2.88 hours/day and for group II was 6.98 ± 2.68 hours/day, with no significant difference between the groups.

Limitations
Lack of long-term follow-up post-treatment, making the conclusion applicable only in the short term.

Harms
No harm was observed in both groups

Conclusion
Despite the large difference between the measured and the patient-reported daily WT, both tooth-borne and skeletally anchored FM/Alt-RAMEC showed positive, similar, skeletal and dental effects.

Clinical trial registration
ISRCTN12197405.
Atrial substrate characterization based on bipolar voltage electrograms acquired with multipolar, focal and mini-electrode catheters
Authors: Knecht Sven , Schlageter Vincent , Badertscher Patrick , Krisai Philipp , Jousset Florian , Küffer Thomas , Madaffari Antonio , Schaer Beat , Osswald Stefan , Sticherling Christian , Kühne Michael 
Published: May 2023

Abstract

Background
Bipolar voltage (BV) electrograms for left atrial (LA) substrate characterization depend on catheter design and electrode configuration.

Aims
The aim of the study was to investigate the relationship between the BV amplitude (BVA) using four catheters with different electrode design and to identify their specific LA cutoffs for scar and healthy tissue.

Methods and results
Consecutive high-resolution electroanatomic mapping was performed using a multipolar-minielectrode Orion catheter (Orion-map), a duo-decapolar circular mapping catheter (Lasso-map), and an irrigated focal ablation catheter with minielectrodes (Mifi-map). Virtual remapping using the Mifi-map was performed with a 4.5 mm tip-size electrode configuration (Nav-map). BVAs were compared in voxels of 3 × 3 × 3 mm3. The equivalent BVA cutoff for every catheter was calculated for established reference cutoff values of 0.1, 0.2, 0.5, 1.0, and 1.5 mV. We analyzed 25 patients (72% men, age 68 ± 15 years). For scar tissue, a 0.5 mV cutoff using the Nav corresponds to a lower cutoff of 0.35 mV for the Orion and of 0.48 mV for the Lasso. Accordingly, a 0.2 mV cutoff corresponds to a cutoff of 0.09 mV for the Orion and of 0.14 mV for the Lasso. For healthy tissue cutoff at 1.5 mV, a larger BVA cutoff for the small electrodes of the Orion and the Lasso was determined of 1.68 and 2.21 mV, respectively.

Conclusion
When measuring LA BVA, significant differences were seen between focal, multielectrode, and minielectrode catheters. Adapted cutoffs for scar and healthy tissue are required for different catheters.
Beyond fitness: the nature of selection acting through the constructive steps of lifecycles
Authors: Smith Eric 
Published: May 2023

Abstract
We address the problem of defining selection and extracting the adaptive part of evolutionary change, originally formalized by Fisher and Price. Conventionally, selection and adaptation are defined through fitness attributed to genes or genotypes chosen as units of selection. The construction through fitness is known to suffer ambiguities and omissions as a theory of change due to selection. We construct an alternative framing in which units of selection and fitness are replaced as the main abstractions by formal lifecycle models and reproduction rates through genetically distinct lifecycle realizations. Graphical representations of lifecycles express relations among reproductive stages that cannot be assigned to any one unit of selection. The lifecycle partition refines the statistics of overall reproductive success and resolves modes of selection that fitness either excludes or distorts through additive projections. We derive the Price equation in the basis of lifecycle realizations and compare it to the conventional Price equation for additive fitness of organisms. We show how the lifecycle approach recovers fitnesses acting concurrently at multiple levels, or contrasts forms of competition within and between levels that are invisible to additive fitness. Defining selection through lifecycles recasts population genetics from an object-focused to a construction- and process-focused representation.
Impulse controllability for the heat equation with inverse square potential and dynamic boundary conditions
Authors: Baroun Mahmoud , El Baggari Hind , Ouled Driss Ilham , Boulite Said 
Published: May 2023

Abstract
In this paper, we investigate the null approximate impulse controllability of the heat equation with an inverse square potential subject to dynamic boundary conditions in the ball $B(0, R_{0})$ of radius $R_{0}=\left (\frac{4}{3}\right )^{\frac{3}{2}}$. To that purpose, we use the Carleman commutator approach to show a logarithmic convexity estimate traducing an observability inequality at one instant of time.
Age-Dependent Risk of Respiratory Syncytial Virus Infection: A Systematic Review and Hazard Modeling From Serological Data
Authors: Nakajo K , Nishiura H 
Published: May 2023

Abstract

Background
There is no immunization campaign that currently exist for respiratory syncytial virus (RSV). Seroprevalence studies are critical for assessing epidemiological dynamics before and during an immunization program. A systematic literature review was conducted to summarize the evidence from seroprevalence studies on RSV.

Methods
A systematic search of age-dependent RSV seroprevalence was conducted using the PubMed database and EMBASE. Age-dependent force of infections (FoI) and the decay rate of immunity were estimated. A mixture finite model was used, estimating the age-dependent disease state and the antibody concentrations in susceptible and infected or recovered populations.

Results
Twenty-one studies were identified from 15 countries, with studies using enzyme-linked immunosorbent assay being the most represented. Using a catalytic model, the age-dependent force of infection was estimated to be the lowest in infants aged 6 months to 1 year and increased in older age groups. The proportion ever-infected/recovered was estimated to be above 90% by 3 years of age.

Conclusions
The number of seroprevalence studies covering a broad range of ages are limited. The age-dependent FoI indicated that the risk of infection was greatest among those aged &gt;5 years. Additional data using valid assays are required to describe the transmission dynamics of RSV infection.