bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of spastic paraplegia in a family with a novelPSEN1mutation
Authors: Ringman John M , Dorrani Naghmeh , Fernández Sara Gutiérrez , Signer Rebecca , Martinez-Agosto Julian , Lee Hane , Douine Emilie D , Qiao Yuchuan , Shi Yonggang , D’Orazio Lina , Pawar Sanjay , Robbie Leah , Kashani Amir H , Singer Maxwell , Byers Joshua T , Magaki Shino , Guzman Sam , Sagare Abhay , Zlokovic Berislav , Cederbaum Stephen , Nelson Stanley , Sheikh-Bahaei Nasim , Chui Helena C , Chávez-Gutiérrez Lucía , Vinters Harry V 
Published: February 2023

AbstractSpastic paraparesis has been described to occur in 13.7% of PSEN1 mutations and can be the presenting feature in 7.5%. In this paper, we describe a family with a particularly young onset of spastic paraparesis due to a novel mutation in PSEN1 (F388S). Three affected brothers underwent comprehensive imaging protocols, two underwent ophthalmological evaluations and one underwent neuropathological examination after his death at age 29. Age of onset was consistently at age 23 with spastic paraparesis, dysarthria and bradyphrenia. Pseudobulbar affect followed with progressive gait problems leading to loss of ambulation in the late 20s. Cerebrospinal fluid levels of amyloid-β, tau and phosphorylated tau and florbetaben PET were consistent with Alzheimer’s disease. Flortaucipir PET showed an uptake pattern atypical for Alzheimer’s disease, with disproportionate signal in posterior brain areas. Diffusion tensor imaging showed decreased mean diffusivity in widespread areas of white matter but particularly in areas underlying the peri-Rolandic cortex and in the corticospinal tracts. These changes were more severe than those found in carriers of another PSEN1 mutation, which can cause spastic paraparesis at a later age (A431E), which were in turn more severe than among persons carrying autosomal dominant Alzheimer’s disease mutations not causing spastic paraparesis. Neuropathological examination confirmed the presence of cotton wool plaques previously described in association with spastic parapresis and pallor and microgliosis in the corticospinal tract with severe amyloid-β pathology in motor cortex but without unequivocal disproportionate neuronal loss or tau pathology. In vitro modelling of the effects of the mutation demonstrated increased production of longer length amyloid-β peptides relative to shorter that predicted the young age of onset. In this paper, we provide imaging and neuropathological characterization of an extreme form of spastic paraparesis occurring in association with autosomal dominant Alzheimer’s disease, demonstrating robust diffusion and pathological abnormalities in white matter. That the amyloid-β profiles produced predicted the young age of onset suggests an amyloid-driven aetiology though the link between this and the white matter pathology remains undefined.
Low QRS voltages and left ventricular hypertrophy: a risky association
Authors: Pelliccia Antonio , Tatangelo Mario , Borrazzo Cristian , Zampaglione Domenico , Mango Federica , Fedele Elisa , Lanzillo Chiara , Martino Annamaria , Crescenzi Cinzia , Maestrini Viviana , Zorzi Alessandro , Corrado Domenico , Calò Leonardo 
Published: February 2023

Abstract

Aims
Low QRS voltages (LQRSV) are an unexpected finding in left ventricular hypertrophy, i.e. hypertrophic cardiomyopathy (HCM) or athlete’s heart.

Methods and results
Prevalence and clinical correlates of LQRSV were investigated in 197 consecutive HCM patients, aged 58 ± 13 years and comparatively in 771 Olympic athletes, aged 23 ± 4. Clinical characterization included family/personal history, symptoms, New York Heart Association (NYHA) functional class, electrocardiographic pattern, ventricular arrhythmias, and cardiac magnetic resonance (CMR). Twenty-two (11%) of HCM and 18 (2.3%) of athletes presented LQRSV. At initial evaluation, in HCM, LQRSV showed no differences vs. non-LQRSV for functional class (90% vs. 91%, in Classes I and II; P = 0.983), symptoms (27% vs. 18%; P = 0.478), and ventricular arrhythmias (40% vs. 39%; P = 857) but showed larger extent of late gadolinium enhancement (LGE) at CMR (4.1 ± 1.5 vs. 1.5 ± 0.7 affected segments; P &lt; 0.001). In athletes, LQRSV was associated with larger prevalence of inverted T-waves (22% vs. 9%; P &lt; 0.001) and ventricular arrhythmias (28% vs. 8%; P = 0.005). In one LQRSV athlete, arrhythmogenic cardiomyopathy was identified. Over 4.5 ± 2.6-year follow-up, presence of LQRSV in HCM was associated with larger incidence of functional deterioration (31% vs. 14%; P = 0.038), stroke (22% vs. 6%; P = 0.008), and implantable cardioverter defibrillator (ICD) implant (27% vs. 10%; P = 0.015). No clinical events occurred in LQRSV athletes without initial evidence of cardiac disease.

Conclusion
LQRSV are relatively common (11%) in HCM and have clinical relevance, being predictive over a medium term for a worsening functional class, incidence of stroke, and ICD implant. Instead, LQRSV are rare (2.3%) in athletes but may occasionally be a marker that raises suspicion for underlying cardiac disease at risk.
Recombination and selection against introgressed DNA
Authors: Veller Carl , Edelman Nathaniel B , Muralidhar Pavitra , Nowak Martin A 
Published: February 2023

AbstractIntrogressed DNA is often deleterious at many loci in the recipient species’ genome, and is therefore purged by selection. Here, we use mathematical modeling and whole-genome simulations to study the influence of recombination on this process. We find that aggregate recombination controls the genome-wide rate of purging in the early generations after admixture, when purging is most rapid. Aggregate recombination is influenced by the number of chromosomes and heterogeneity in their size, and by the number of crossovers and their locations along chromosomes. A comparative prediction is that species with fewer chromosomes should purge introgressed ancestry more profoundly, and should therefore exhibit weaker genomic signals of historical introgression. Turning to within-genome patterns, we show that, in species with autosomal recombination in both sexes, more purging is expected on sex chromosomes than autosomes, all else equal. The opposite prediction holds for species without autosomal recombination in the heterogametic sex. Finally, positive correlations between recombination rate and introgressed ancestry have recently been observed within the genomes of several species. We show that these correlations are likely driven not by recombination’s effect in unlinking neutral from deleterious introgressed alleles, but by recombination’s effect on the rate of purging of deleterious introgressed alleles themselves.
The analytic extension of solutions to initial-boundary value problems outside their domain of definition
Authors: Farkas Matthew , Cisneros Jorge , Deconinck Bernard 
Published: February 2023

AbstractWe examine the analytic extension of solutions of linear, constant-coefficient initial-boundary value problems outside their spatial domain of definition. We use the Unified Transform Method or Method of Fokas, which gives a representation for solutions to half-line and finite-interval initial-boundary value problems as integrals of kernels with explicit spatial and temporal dependence. These solution representations are defined within the spatial domain of the problem. We obtain the extension of these representation formulae via Taylor series outside these spatial domains and find the extension of the initial condition that gives rise to a whole-line initial-value problem solved by the extended solution. In general, the extended initial condition is not differentiable or continuous unless the boundary and initial conditions satisfy compatibility conditions. We analyse dissipative and dispersive problems, and problems with continuous and discrete spatial variables.
Scalar Curvature, Entropy, and Generalized Ricci Flow
Authors: Streets Jeffrey 
Published: February 2023

AbstractWe derive a family of weighted scalar curvature monotonicity formulas for generalized Ricci flow, involving an auxiliary dilaton field evolving by a certain reaction–diffusion equation motivated by renormalization group flow. These scalar curvature monotonicities are dual to a new family of Perelman-type energy and entropy monotonicity formulas by coupling to a solution of the associated weighted conjugate heat equation. In the setting of Ricci flow, we further obtain a new family of convex Nash entropies and pseudolocality principles.
Selective reporting of antibiotic susceptibility testing results for urine cultures: feasibility and acceptability by general practitioners and laboratory professionals in France
Authors: Le Dref Gaëlle , Simon Maïa , Bocquier Aurélie , Fougnot Sébastien , Kivits Joëlle , Duda Alain , Pulcini Céline , Thilly Nathalie ,   ANTIBIO-ciblés Scientific Committee‡, CHARMILLON Alexandre , CHOPARD Virginie , DE MONCHY Patrice , DELPUECH Marion , FAGOT-CAMPAGNA Anne , LOZNIEWSKI Alain , LUC Amandine , MAUFFREY Violaine , RABAUD Christian , VARON Emmanuelle 
Published: February 2023

Abstract

Background
Selective reporting of antibiotic susceptibility testing (AST) is a recommended antibiotic stewardship strategy, aiming at reducing inappropriate antibiotic prescriptions.

Objectives
Our objectives were to evaluate (i) the feasibility of the implementation of selective reporting of AST for urine cultures for laboratory professionals; and (ii) its acceptability by prescribers and laboratory professionals, to explore facilitators and barriers to its potential implementation on a national scale.

Methods
As part of the ‘ANTIBIO-ciblés’ interventional study (north-eastern France, August 2018–December 2019), we prospectively collected quantitative data on all resources dedicated by the laboratories of the intervention group to implement selective reporting of AST for Escherichia coli-positive urine cultures, and on the numbers and reasons of complete reporting of AST the prescribers requested to the laboratories. We also collected qualitative data using semi-structured interviews and focus groups of GPs and laboratory professionals.

Results
The implementation of selective reporting of AST required around 80 h and cost 23 000 euros. All interviewed professionals were favourable toward the principle of this tool. Most of them found it clear, simple and useful to improve the appropriateness of antibiotic prescriptions and reduce antibiotic resistance. Its major constraint was the necessity for GPs to call the laboratory to obtain the complete reporting of AST, but the number of requests was actually low (1.2% of all selective reporting of AST).

Conclusions
Selective reporting of AST resulted in reasonable human and financial costs, and was well accepted by both GPs and laboratory professionals.
Obligations to ‘Strangers’
Authors: Owiso Owiso 
Published: February 2023

Abstract
Proceeding from the assumption that international criminal justice is a cosmopolitan project, the article advances a reconceptualized understanding of cosmopolitanism as a theoretical basis for collective action in ensuring accountability for international crimes. The article examines the building blocks of cosmopolitanism, and how the concept’s emphasis on equality and unity of the human family can guarantee its fundamental values of human dignity and shared humanity. Based on the understanding that international crimes assault humanity’s fundamental and cosmopolitan value of human dignity, and that accountability for such crimes is a cosmopolitan objective, the article advances the argument that while accountability for international crimes is primarily the obligation of individual sovereign states, this responsibility is ultimately residually one of humanity as a whole, exercisable through humanity’s collective action such as through regional intergovernmental organizations where an individual state is unable or unwilling by itself to do so.
Comparative analysis of histopathological parameters, genome-wide copy number alterations, and variants in genes involved in cell cycle regulation in chordomas of the skull base and sacrum
Authors: Salle Henri , Durand Stéphanie , Durand Karine , Bourthoumieu Sylvie , Lemnos Leslie , Robert Sandrine , Pollet Justine , Passeri Thibault , Khalil Wassim , Froelich Sébastien , Adle-Biassette Homa , Labrousse François 
Published: February 2023

Abstract
Chordomas are rare tumors of the axial skeleton that are refractory to conventional therapy. Few studies have compared the morphological and molecular characteristics of chordomas according to the skull base and sacral locations. Histopathological data and changes revealed by array comparative genomic hybridization (CGH) and next-generation sequencing (NGS) of cell cycle regulation genes were analyzed for 28 skull base (SBCs) and 15 sacral (SC) chordomas. All cases were conventional chordomas. SBCs were significantly more frequent in patients aged &lt;40 years and SCs predominated in patients aged &gt;60 years. Mitotic indices ≥2 mitoses/10 high-power fields were correlated with high degrees of nuclear atypia and Ki67 labeling indices ≥6%. We identified 321 genomic positions, and copy number variation losses were more frequent than gain. Moreover, we report a panel of 85 genetic variants of cell cycle genes and the presence of molecular clusters for chordoma as well in CGH as in NGS. These new data strengthen the view that the chordoma should not be considered as a single molecular entity.
Dynamical non-Gaussian modelling of spatial processes
Authors: Fonseca Thaís C O , Lobo Viviana G R , Schmidt Alexandra M 
Published: February 2023

AbstractEnvironmental data are often assumed to follow a spatio-temporal Gaussian process, possibly after transformation. However, heterogeneity might have a pattern not accommodated by transformation and modelling the variance laws is an appealing alternative. This work extends the multivariate dynamic Gaussian model by defining the process as a scale mixture with the scale depending on covariates. State-space equations define the temporal dynamics, resulting in feasible inference and prediction. Various simulations studies show that the parameters are identifiable and our proposal recovers simpler structures. The analyses of temperature and ozone illustrate the improvement in quantifying the uncertainty of predictions.
The Secretary: Enslaved Workers, Stenography, and the Production of Early Christian Literature
Authors: Moss Candida R 
Published: February 2023

Abstract
This article examines the evidence for the role of enslaved and formerly enslaved secretaries in the production of the New Testament. While secretaries have formed part of the conversation around the authorship of the Pauline epistles, secretaries and ancient literary culture have not featured in conversations about the composition of early Christian literature in general. Drawing upon recent scholarship in Classics (Reay, Blake, Howley, Johnson, and Geue), this paper traces the reasons why secretaries have been marginalized in ancient and modern conversations about authorship. It further suggests that, rather than unwittingly rehearsing ancient slaveholder discourses that seek to erase enslaved contributions, we should take seriously the ways in which a broader range of actors was involved in the production of ancient literature. Using the technologies of shorthand and theological abbreviations as examples, it tentatively suggests that enslaved workers contributed to the formation of early Christian texts and theology far beyond the mistakes that are sometimes attributed to them. The reasons for entertaining these possibilities, it argues, are both historical and ethical: the distribution of agency across a wider range of characters invites us to reflect upon the ethics of reading and the communities with whom we read.
Kinetics of the Antibody Response to Symptomatic SARS-CoV-2 Infection in Vaccinated and Unvaccinated Individuals in the Blinded Phase of the mRNA-1273 COVID-19 Vaccine Efficacy Trial
Authors: Follmann Dean , Janes Holly E , Chu Eric , Jayashankar Lakshmi , Petropoulos Christos J , Serebryannyy Leonid , Carroll Robin , Jean-Baptiste Naz , Narpala Sandeep , Lin Bob C , McDermott Adrian , Novak Richard M , Graciaa Daniel S , Rolsma Stephanie , Magaret Craig A , Doria-Rose Nicole , Corey Lawrence , Neuzil Kathleen M , Pajon Rolando , Miller Jacqueline M , Donis Ruben O , Koup Richard A , Baden Lindsey R , El Sahly Hana M 
Published: February 2023

AbstractBackgroundHybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals.MethodsThe 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28 days later (DD29).ResultsThe primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post–first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post–disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group.ConclusionsFollowing COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.
Feasibility of a Geriatric Oncology Longitudinal End to End (GOLDEN) Program in a Tertiary Cancer Center in Singapore
Authors: Ho Francis , Kow Alfred , Lim Wan Chin , Chen Matthew Zhixuan , Mohd Rais Nydia Camelia , Ling Natalie Mun Wai , Ooi Melissa , Ng Jing Yu , Ng Yean Shin , Chun Meiling , Yao Yao , Mohd Said Noorhanah , Eng Wan Nghee , Chen Wen Meei , Luah Vivian , Loy Yijun , Ong Jiexin , Wong Wei Yee , Korc-Grodzicki Beatriz , Lichtman Stuart M , Pang Angela 
Published: February 2023

AbstractIntroductionIn the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship.Methods and MaterialsOlder adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes.ResultsThere were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN.ConclusionMore than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out.
Planets Everywhere and the Search for Extraterrestrial Life
Authors: Ostlie Dale A. 
Published: February 2023

Abstract
Planets Everywhere and the Search for Extraterrestrial Life begins with an overview of the types of exoplanets that have been detected so far beyond our Solar System. Statistical studies provide information about their distances from their parent stars, their masses, radii, and other characteristics. Exoplanets also inform our understanding of our Solar System. Models of planetary system formation that include the migration of planets due to the scattering of smaller planetary system bodies and orbital resonances have been developed. Of course, all physical laws must be obeyed, and all evidence must be included. The chapter and Part II conclude with the consideration of possible life beyond Earth. With evidence of amino acids and other complex molecules throughout the Solar System and in interstellar space, is it possible that sophisticated molecules like RNA and DNA could form elsewhere? Drake’s equation and the search for extraterrestrial intelligence is also explored.
Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis
Authors: Lewis Caitlin V. , Sellak Hassan , Sawan Mariem A. , Joseph Giji , Darby Trevor M. , VanInsberghe David , Naudin Crystal R. , Archer David R. , Jones Rheinallt M. , Taylor W. Robert 
Published: February 2023

AbstractThe intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3‐fold increase in intestinal permeability as assessed via FITC‐dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice (n = 4, p < 0.05). This was associated with 25 to 50% decreases in claudin‐1, 3, and 15 and zonula occludens‐1 gene expression (n = 8–10, p < 0.05) in the small intestine. Increased Ly6G staining demonstrated more neutrophils in the SS small intestine (3‐fold, n = 5, p < 0.05) associated with increased expression of TNFα, IL‐17A, CXCL1, and CD68 (2.5 to 5‐fold, n = 7–10, p < 0.05). In addition, we observed 30 to 55% decreases in superoxide dismutase‐1, glutathione peroxidase‐1, and catalase antioxidant enzyme expression (n = 7–8, p < 0.05) concomitant to an increase in superoxide (2‐fold, n = 4, p < 0.05). Importantly, all significant observations of a leaky gut phenotype and inflammation were limited to the small intestine and not observed in the colon. Finally, characterization of the composition of the microbiome within the small intestine revealed dysbiosis in SS mice compared to their AA littermates with 47 phyla to species‐level significant alterations in amplicon sequence variants. We conclude that the intestinal barrier is compromised in SCD, associated with decreased gene expression of tight junction proteins, enhanced inflammation, oxidative stress, and gut microbiome dysbiosis, all specific to the small intestine.