julilili42/papers huggingface dataset:
Multiword units in multilingual speakers
2023-10-14

Aims and objectives: This introductory article aims to set the scene for the special issue by discussing existing and future research directions on multiword units (MWUs) in multilingual speakers. It also outlines the purpose and structure of the special issue and presents the individual contributions. Design, data and analysis: The introductory article reviews the most relevant theoretical and methodological issues as well as the main research gaps related to the processing, learning, and use of MWUs in both mono- and multilingual speakers. In addition, it introduces the contributions to this volume and briefly presents the types of MWUs, the types of multilingual speakers and the data and methodologies that are in focus. Conclusions, originality and implications: The contributions in this special issue on different types of MWUs in different groups of multilingual speakers using different methodologies shed new light on open questions in various areas of multilingualism research, including psycholinguistic approaches to second-language learning and processing, contact linguistics as well as research on heritage speakers and language attrition. In this regard, the special issue contributes to a more complete and differentiated picture of the role of MWUs in multilingual speakers but also in language processing, learning, and use in general.
S3 guideline „actinic keratosis and cutaneous squamous cell carcinoma“ – update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention
2023-10-15

Summary Actinic keratosis (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.
Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease
2023-10-15

Abstract RFC1 disease, caused by biallelic repeat expansion in RFC1 , is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson’s coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multi-variate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset (smaller allele HR=2.06, p&lt;0.001; larger allele HR=1.53, p&lt;0.001) and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR=3.40, p&lt;0.001; larger allele HR=1.71, p=0.002) or loss of independent walking (smaller allele HR=2.78, p&lt;0.001; larger allele HR=1.60; p&lt;0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions (smaller allele: complex neuropathy RR=1.30, p=0.003; CANVAS RR=1.34, p&lt;0.001; larger allele: complex neuropathy RR=1.33, p=0.008; CANVAS RR=1.31, p=0.009). Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V β=-1.06, p&lt;0.001; lobules VI-VII β=-0.34, p=0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype, and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.
Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease
2023-10-16

Importance Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [ P = .001]; ADNI: t = 2.7 [ P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [ P = .002]; ADNI: t = −5.6 [ P &amp;amp;lt; .001]; HABS: t = −2.2 [ P = .03]), greater in older individuals (DIAN: t = 6.8 [ P &amp;amp;lt; .001]; ADNI: t = 9.1 [ P &amp;amp;lt; .001]; HABS: t = 5.4 [ P &amp;amp;lt; .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [ P = .40]; ADNI: t = 0.6 [ P = .50]; HABS: t = 1.8 [ P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P &amp;amp;lt; .001). Conclusions and Relevance The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.
Getting into the Flow: Towards Better Type Error Messages for Constraint-Based Type Inference
2023-10-16

Creating good type error messages for constraint-based type inference systems is difficult. Typical type error messages reflect implementation details of the underlying constraint-solving algorithms rather than the specific factors leading to type mismatches. We propose using subtyping constraints that capture data flow to classify and explain type errors. Our algorithm explains type errors as faulty data flows, which programmers are already used to reasoning about, and illustrates these data flows as sequences of relevant program locations. We show that our ideas and algorithm are not limited to languages with subtyping, as they can be readily integrated with Hindley-Milner type inference. In addition to these core contributions, we present the results of a user study to evaluate the quality of our messages compared to other implementations. While the quantitative evaluation does not show that flow-based messages improve the localization or understanding of the causes of type errors, the qualitative evaluation suggests a real need and demand for flow-based messages.
From Capabilities to Regions: Enabling Efficient Compilation of Lexical Effect Handlers
2023-10-16

Effect handlers are a high-level abstraction that enables programmers to use effects in a structured way. They have gained a lot of popularity within academia and subsequently also in industry. However, the abstraction often comes with a significant runtime cost and there has been intensive research recently on how to reduce this price. A promising approach in this regard is to implement effect handlers using a CPS translation and to provide sufficient information about the nesting of handlers. With this information the CPS translation can decide how effects have to be lifted through handlers, i.e., which handlers need to be skipped, in order to handle the effect at the correct place. A structured way to make this information available is to use a calculus with a region system and explicit subregion evidence. Such calculi, however, are quite verbose, which makes them impractical to use as a source-level language. We present a method to infer the lifting information for a calculus underlying a source-level language. This calculus uses second-class capabilities for the safe use of effects. To do so, we define a typed translation to a calculus with regions and evidence and we show that this lift-inference translation is typability- and semantics-preserving. On the one hand, this exposes the precise relation between the second-class property and the structure given by regions. On the other hand, it closes a gap in a compiler pipeline enabling efficient compilation of the source-level language. We have implemented lift inference in this compiler pipeline and conducted benchmarks which indicate that the approach is indeed working.
Mental association of time and valence
2023-10-16

Abstract Five experiments investigated the association between time and valence. In the first experiment, participants classified temporal expressions (e.g., past, future) and positively or negatively connotated words (e.g., glorious, nasty) based on temporal reference or valence. They responded slower and made more errors in the mismatched condition (positive/past mapped to one hand, negative/future to the other) compared with the matched condition (positive/future to one hand, negative/past to the other hand). Experiment 2 confirmed the generalization of the match effect to nonspatial responses, while Experiment 3 found no reversal of this effect for left-handers. Overall, the results of the three experiments indicate a robust match effect, associating the past with negative valence and the future with positive valence. Experiment 4 involved rating the valence of time-related words, showing higher ratings for future-related words. Additionally, Experiment 5 employed latent semantic analysis and revealed that linguistic experiences are unlikely to be the source of this time–valence association. An interactive activation model offers a quantitative explanation of the match effect, potentially arising from a favorable perception of the future over the past.
EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project
2023-10-16

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. Methods This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. Discussion The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. Trial registration The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.
ACOX1 Gain-of-Function Variant in Two German Pediatric Patients, in One Case Mimicking Autoimmune Inflammatory Disease
2023-10-16

Abstract Mitchell syndrome is a very rare genetic disorder due to a specific de novo gain-of-function variant in acyl-CoA oxidase 1 (ACOX1). So far, only five patients with this disease have been described worldwide. We present here two additional unrelated German patients found to carry the same heterozygous ACOX1 N237S variant through exome sequencing (ES). Both patients showed neurodegenerative clinical features starting from ∼4 to 5 years of age including progressive hearing loss, ataxia, ichthyosis, as well as progressive visual impairment leading to amaurosis, and died at the ages of 16 and 8 years, respectively. The first patient was clinically suspected to have anti–myelin oligodendrocyte glycoprotein-antibody-associated myelitis, but the disease course overall deteriorated despite extensive immunomodulatory therapy. The second patient was originally suspected to have a mitochondrial disorder due to intermittent elevated blood lactate. Since Mitchell syndrome has only been identified in 2020, the diagnosis in this second patient was only established through re-evaluation of ES data years after the original analysis. Comparison of all seven reported patients suggests that Mitchell syndrome often (but not always) clinically mimics autoimmune-inflammatory disease. Therefore, in patients with autoimmune central nervous system disease who do not respond adequately to standard therapies, re-evaluation of this diagnosis is needed and genetic analyses such as trio ES should be considered.
Measuring the acuity of the approximate number system in young children
2023-10-16

The approximate number system (ANS) is a hypothesized mechanism responsible for the representation and processing of numerical information in an imprecise fashion. According to the predominant theory, the ANS is essential in solving simple numerical tasks such as comparing which of two quantities is numerically larger, and some research has indicated that individual differences in its acuity influence higher-level mathematical performance. Because of this far-reaching role of the ANS, it is essential to assess its acuity with measures that are reliable, and valid. The present work reviews and synthesizes many of the methodological problems that are relevant for measuring ANS acuity in young children. We discuss issues related to task comprehension, the role of non-numerical perceptual properties of the stimuli, the role of inhibition, and the appropriateness and reliability of the ANS acuity indices. Recommendations and open questions are summarized.
Artificial Vision: The High-Frequency Electrical Stimulation of the Blind Mouse Retina Decay Spike Generation and Electrogenically Clamped Intracellular Ca2+ at Elevated Levels
2023-10-16

Background: The electrical stimulation (stim) of retinal neurons enables blind patients to experience limited artificial vision. A rapid response outage of the stimulated ganglion cells (GCs) allows for a low visual sensation rate. Hence, to elucidate the underlying mechanism, we investigated different stim parameters and the role of the neuromodulator calcium (Ca2+). Methods: Subretinal stim was applied on retinal explants (blind rd1 mouse) using multielectrode arrays (MEAs) or single metal electrodes, and the GC activity was recorded using Ca2+ imaging or MEA, respectively. Stim parameters, including voltage, phase polarity, and frequency, were investigated using specific blockers. Results: At lower stim frequencies (&lt;5 Hz), GCs responded synaptically according to the stim pulses (stim: biphasic, cathodic-first, −1.6/+1.5 V). In contrast, higher stim frequencies (≥5 Hz) also activated GCs directly and induced a rapid GC spike response outage (&lt;500 ms, MEA recordings), while in Ca2+ imaging at the same frequencies, increased intracellular Ca2+ levels were observed. Conclusions: Our study elucidated the mechanisms involved in stim-dependent GC spike response outage: sustained high-frequency stim-induced spike outage, accompanied by electrogenically clamped intracellular Ca2+ levels at elevated levels. These findings will guide future studies optimizing stim paradigms for electrical implant applications for interfacing neurons.
Protective effects of Gαi3 deficiency in a murine heart-failure model of β1-adrenoceptor overexpression
2023-10-16

Abstract We have shown that in murine cardiomyopathy caused by overexpression of the β 1 -adrenoceptor, Gα i2 -deficiency is detrimental. Given the growing evidence for isoform-specific Gα i -functions, we now examined the consequences of Gα i3 deficiency in the same heart-failure model. Mice overexpressing cardiac β 1 -adrenoceptors with (β 1 -tg) or without Gα i3 -expression (β 1 -tg/Gα i3 −/− ) were compared to C57BL/6 wildtypes and global Gα i3 -knockouts (Gα i3 −/− ). The life span of β 1 -tg mice was significantly shortened but improved when Gα i3 was lacking (95% CI: 592–655 vs. 644–747 days). At 300 days of age, left-ventricular function and survival rate were similar in all groups. At 550 days of age, β 1 -tg but not β 1 -tg/Gα i3 −/− mice displayed impaired ejection fraction (35 ± 18% vs. 52 ± 16%) compared to wildtype (59 ± 4%) and Gα i3 −/− mice (60 ± 5%). Diastolic dysfunction of β 1 -tg mice was prevented by Gα i3 deficiency, too. The increase of ANP mRNA levels and ventricular fibrosis observed in β 1 -tg hearts was significantly attenuated in β 1 -tg/Gα i3 −/− mice. Transcript levels of phospholamban, ryanodine receptor 2, and cardiac troponin I were similar in all groups. However, Western blots and phospho-proteomic analyses showed that in β 1 -tg, but not β 1 -tg/Gα i3 −/− ventricles, phospholamban protein was reduced while its phosphorylation increased. Here, we show that in mice overexpressing the cardiac β 1 -adrenoceptor, Gα i3 deficiency slows or even prevents cardiomyopathy and increases shortened life span. Previously, we found Gα i2 deficiency to aggravate cardiac dysfunction and mortality in the same heart-failure model. Our findings indicate isoform-specific interventions into G i -dependent signaling to be promising cardio-protective strategies.
Comment on bg-2023-147
2023-10-16

<strong class="journal-contentHeaderColor">Abstract.</strong> Scientific drilling expeditions offer a unique opportunity to characterize the microbial communities in the subsurface that have been long-term isolated from the surface. With subsurface microbial biomass being low in general, biological contamination from the drilling fluid, sample processing, or molecular work is a major concern. To address this, characterization of the contaminant populations in the drilling fluid and negative extraction controls are essential for assessing and evaluating such sequencing data. Here, crystalline rock cores down to 2250 m depth, groundwater-bearing fractures, and the drilling fluid were sampled for DNA to characterize the microbial communities using a broad genomic approach. However, even after removing potential contaminant populations present in the drilling fluid, notorious contaminants were abundant and mainly affiliated with the bacterial order Burkholderiales. These contaminant microorganisms likely originated from the reagents used for isolating and amplifying DNA despite stringent quality standards during the molecular work. The detection of strictly anaerobic sulfate reducers such as <em>Candidatus</em> Desulforudis audaxviator suggested the presence of autochthonous deep biosphere taxa in the sequenced libraries, yet these clades represented only a minor fraction of the sequence counts (&lt; 0.1 %), hindering further ecological interpretations. The described methods and findings emphasize the importance of sequencing extraction controls and can support experimental design for future microbiological studies in conjunction with continental drilling operations.