bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome
Authors: Serpieri Valentina , Mortarini Giulia , Loucks Hailey , Biagini Tommaso , Micalizzi Alessia , Palmieri Ilaria , Dempsey Jennifer C , D’Abrusco Fulvio , Mazzotta Concetta , Battini Roberta , Bertini Enrico Silvio , Boltshauser Eugen , Borgatti Renato , Brockmann Knut , D'Arrigo Stefano , Nardocci Nardo , Fischetto Rita , Agolini Emanuele , Novelli Antonio , Romano Alfonso , Romaniello Romina , Stanzial Franco , Signorini Sabrina , Strisciuglio Pietro , Gana Simone , Mazza Tommaso , Doherty Dan , Valente Enza Maria 
Published: February 2023

BackgroundJoubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the ‘molar tooth sign’. Over 40 JS-associated genes are known, accounting for two-thirds of cases.MethodsWhile most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known ‘founder variants’ in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in ~550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of ~600 JS probands from the USA.ResultsAll variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216c.218G>T) was significantly enriched in American compared with European patients with JS, whileMKS1c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes.Two recurrent variants (MKS1c.1476T>G andKIAA0586c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from aMKS1c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from aKIAA0586c.428delG healthy homozygote.ConclusionThis study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants.
A better self-efficacy is predictive of better health-related quality of life (HRQoL) in patients with systemic lupus erythematosus: data from the Almenara Lupus Cohort
Authors: Ugarte-Gil Manuel Francisco , Gamboa-Cardenas Rocio Violeta , Reátegui-Sokolova Cristina , Pimentel-Quiroz Victor Román , Medina Mariela , Elera-Fitzcarrald Claudia , Rodriguez-Bellido Zoila , Pastor-Asurza Cesar Augusto , Perich-Campos Risto Alfredo , Alarcón Graciela S 
Published: February 2023

ObjectiveTo determine the possible predictive value of self-efficacy on health-related quality of life (HRQoL) in patients with SLE.MethodsPatients with SLE from the Almenara Lupus Cohort were included. Self-efficacy was ascertained with the six domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) self-efficacy for managing chronic conditions. For PROMIS domains, a score of 50 is the average for a clinical population (people with a chronic condition), a higher score indicates that the respondent has greater self-efficacy. HRQoL was ascertained with the physical and mental component summary (PCS and MCS) measures of the Short-Form 36 (SF-36). Generalised estimating equations were performed, using as outcome the PCS or MCS in the subsequent visit, and the self-efficacy domain in the previous visit; multivariable models were adjusted for possible confounders. The confounders were measured in the same visit as the self-efficacy domain.ResultsTwo-hundred and nine patients for a total of 564 visits were included; 194 (92.8%) patients were women and mean age at diagnosis was 36.4 (14.0) years. In the multivariable models, a better PCS was predicted by a better self-efficacy for managing symptoms, managing medications and treatments and managing social interactions and general self-efficacy; a better MCS was predicted by a better self-efficacy for managing daily activities, managing symptoms, managing medications and treatments and managing social interactions.ConclusionA better self-efficacy is predictive of subsequent better HRQoL, even after adjustment for possible confounders. These results should encourage clinicians to develop strategies to improve self-efficacy in patients with SLE.
Holographic dark energy through Kaniadakis entropy in non flat universe
Authors: Kumar P. Suresh , Pandey Bramha Dutta , Sharma Umesh Kumar , Pankaj  
Published: February 2023

AbstractBy extending the standard holographic principle to a cosmological framework and combining the non-flat condition with the Kaniadakis entropy, we construct the non-flat Kaniadakis holographic dark energy (KHDE) model. The model employs Kaniadakis parameter K and a parameter c. Derivation of the differential equation for KHDE density parameter to describe the evolutionary behavior of the universe is obtained. Such a differential equation could explain both the open as well as closed universe models. The classification based on matter and dark energy (DE) dominated regimes show that the KHDE scenario may be used to specify the universe’s thermal history and that a quintom regime can be encountered. For both open and closed, we find the expressions for the deceleration parameter and the equation of state (EoS) parameter. Also, by varying the associated parameters, classical stability of the method is established. On considering the curvature to be positive, the universe favors the quintom behavior for substantially smaller values as opposed to the flat condition, when only quintessence is attained for such K values. Additionally, we see a similar behavior while considering the negative curvature for such K values. Therefore, adding a little bit of spatial geometry that isn’t flat to the KHDE enhances the phenomenology while maintaining K values at lower levels. To validate the model parameters, the most recent $$30\;H(z)$$

30

H
(
z
)

dataset, in the redshift range $$0.07 \le z \le 1.965$$

0.07
≤
z
≤
1.965

are utilized. In addition, the distance modulus from the current Union 2.1 data set of type SNIa are employed.
Low TCR Binding Strength Results in Increased Progenitor-like CD8+ Tumor-Infiltrating Lymphocytes
Authors: Hay Zachary L.Z. , Knapp Jennifer R. , Magallon Roman E. , O'Connor Brian P. , Slansky Jill E. 
Published: February 2023

Abstract
T-cell receptor (TCR) binding strength to peptide-MHC antigen complex influences numerous T-cell functions. However, the vast diversity of a polyclonal T-cell repertoire for even a single antigen greatly increases the complexity of studying the impact of TCR affinity on T-cell function. Here, we determined how TCR binding strength affected the protein and transcriptional profile of an endogenous, polyclonal T-cell response to a known tumor-associated antigen (TAA) within the tumor microenvironment (TME). We confirmed that the staining intensity by flow cytometry and the counts by sequencing from MHC-tetramer labeling were reliable surrogates for the TCR-peptide-MHC steady-state binding affinity. We further demonstrated by single-cell RNA sequencing that tumor-infiltrating lymphocytes (TIL) with high and low binding affinity for a TAA can differentiate into cells with many antigen-specific transcriptional profiles within an established TME. However, more progenitor-like phenotypes were significantly biased towards lower affinity T cells, and proliferating phenotypes showed significant bias towards high-affinity TILs. In addition, we found that higher affinity T cells advanced more rapidly to terminal phases of T-cell exhaustion and exhibited better tumor control. We confirmed the polyclonal TIL results using a TCR transgenic mouse possessing a single low-affinity TCR targeting the same TAA. These T cells maintained a progenitor-exhausted phenotype and exhibited impaired tumor control. We propose that high-affinity TCR interactions drive T-cell fate decisions more rapidly than low-affinity interactions and that these cells differentiate faster. These findings illustrate divergent forms of T-cell dysfunction based on TCR affinity which may impact TIL therapies and antitumor responses.
Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling
Authors: Ye Shiju , Huang He , Han Xue , Luo Wu , Wu Lili , Ye Yang , Gong Yingchao , Zhao Xia , Huang Weijian , Wang Yi , Long Xiaohong , Fu Guosheng , Liang Guang 
Published: February 2023

Background:
Cardiac remodeling in heart failure involves macrophage-mediated immune responses. Recent studies have shown that a PRR (pattern recognition receptor) called dectin-1, expressed on macrophages, mediates proinflammatory responses. Whether dectin-1 plays a role in pathological cardiac remodeling is unknown. Here, we identified a potential role of dectin-1 in this disease.

Methods:
To model aberrant cardiac remodeling, we utilized mouse models of chronic Ang II (angiotensin II) infusion. In this model, we assessed the potential role of dectin-1 through using D1KO (dectin-1 knockout) mice and bone marrow transplantation chimeric mice. We then used cellular and molecular assays to discover the underlying mechanisms of dectin-1 function.

Results:
We found that macrophage dectin-1 is elevated in mouse heart tissues following chronic Ang II administration. D1KO mice were significantly protected against Ang II–induced cardiac dysfunction, hypertrophy, fibrosis, inflammatory responses, and macrophage infiltration. Further bone marrow transplantation studies showed that dectin-1 deficiency in bone marrow–derived cells prevented Ang II–induced cardiac inflammation and dysfunction. Through detailed molecular studies, we show that Ang II binds directly to dectin-1, causing dectin-1 homodimerization and activating the downstream Syk (spleen tyrosine kinase)/NF-κB (nuclear factor kappa B) signaling pathway to induce expression of inflammatory and chemoattractant factors. Mutagenesis studies identified R184 in the C-type lectin domain to interact with Ang II. Blocking dectin-1 in macrophages suppresses Ang II–induced inflammatory mediators and subsequent intercellular cross talk with cardiomyocytes and fibroblasts.

Conclusions:
Our study has discovered dectin-1 as a new nonclassical receptor of Ang II and a key player in cardiac remolding and dysfunction. These studies suggest that dectin-1 may be a new target for treating hypertension-related heart failure.
Perspectives on Computation in Plants
Authors: Del Dottore Emanuela , Mazzolai Barbara 
Published: February 2023

Abstract
Plants thrive in virtually all natural and human-adapted environments and are becoming popular models for developing robotics systems because of their strategies of morphological and behavioral adaptation. Such adaptation and high plasticity offer new approaches for designing, modeling, and controlling artificial systems acting in unstructured scenarios. At the same time, the development of artifacts based on their working principles reveals how plants promote innovative approaches for preservation and management plans and opens new applications for engineering-driven plant science. Environmentally mediated growth patterns (e.g., tropisms) are clear examples of adaptive behaviors displayed through morphological phenotyping. Plants also create networks with other plants through subterranean roots–fungi symbiosis and use these networks to exchange resources or warning signals. This article discusses the functional behaviors of plants and shows the close similarities with a perceptron-like model that could act as a behavior-based control model in plants. We begin by analyzing communication rules and growth behaviors of plants; we then show how we translated plant behaviors into algorithmic solutions for bioinspired robot controllers; and finally, we discuss how those solutions can be extended to embrace original approaches to networking and robotics control architectures.
Dire Straits-Education Reforms
Authors: Gomendio Montserrat , Wert José Ignacio 
Published: February 2023

Responding to an ‘educational emergency’ generated largely by the difficulties of implementing education reforms, this book compares education policies around the world in order to understand what works where.
To address the key question of why education reforms are so difficult, the authors take into account a broad range of relevant factors, such as governance, ideology, and stakeholder conflicts of interest, and their interactions with one another.
Drawing on their experiences as policymakers in the Spanish government and as governmental advisors worldwide, Montserrat Gomendio and Jose Ignacio Wert produce a publication like no other, shifting the usual Eurocentric narrative and shedding light on frequently overlooked educational policies from elsewhere. In this context, they dive deeper into details of educational failures and successes, the processes of implementation and investment priorities in different countries. They provide revealing accounts of stakeholder conflicts of interest and the challenges of implementing educational reform during a financial crisis.
The authors also investigate why the evidence from international large-scale assessments (ILSAs) has, contrary to expectation, not generated improvements in most education systems. Gomendio and Wert investigate the evolution of different education systems, closely examining their advances or declines. Gomendio and Wert’s expert voices illuminate the current state of global education systems and the necessary changes to ensure long-awaited improvements. This is a revelatory and informative resource for policymakers, teachers and academics alike.
Causal Forcing Analysis on the Low-Frequency Variations of Eddy Kinetic Energy in the Kuroshio Extension Region
Authors: Wang Qiang , Pierini Stefano 
Published: February 2023

Abstract
The eddy kinetic energy (EKE) in the Kuroshio Extension (KE) region may be affected by two factors: EKE in the Kuroshio large meander (KLM) region and the North Pacific Gyre Oscillation (NPGO). Previous studies reported that the Kuroshio path variations south of Japan may affect the low-frequency variability of the KE jet and related EKE, but the linear correlation between these phenomena derived from long time series is low and not significant, implying that the linkage between EKE in the KLM and KE regions is still unclear. Besides, whether NPGO has a causal effect on the KE EKE remains under debate. In this study, we investigate the causal forcing of the KLM EKE and NPGO on the KE EKE using the convergent cross mapping (CCM) approach based on satellite sea surface height observations. The analysis shows that the KLM EKE affects the EKE only in the KE upstream area (west of 146°E), with no significant causal effect on the EKE in the downstream area; the NPGO plays, instead, a remarkable role on the EKE in both areas. The effect of the KLM EKE on the KE EKE is found to depend on the Kuroshio latitudinal position over the Izu Ridge. Changes in the KLM EKE affect the downstream advection of eddies and induce changes in the Kuroshio position over the ridge, which cause different EKE levels in the KE upstream region. The NPGO affects the KE EKE through the westward propagation of sea surface height anomalies remotely forced by wind stress anomalies associated with the North Pacific Oscillation.
What is ‘successful rehabilitation’? A multi-stakeholder nominal group technique study to inform rehabilitation outcome measurement
Authors: Wallace Sarah J , Barnett Amandine , Cheng Bonnie BY , Lowe Joshua , Campbell Katrina L , Young Adrienne M 
Published: February 2023

Objective To explore how stakeholders in rehabilitation conceptualise ‘successful rehabilitation’, to inform the development of a minimum dataset and core outcomes for sub-acute rehabilitation. Design Qualitative consensus study using the nominal group technique. Setting Online focus groups. Participants Consumer representatives ( n = 7), clinicians ( n = 15), and health service managers ( n = 9) from Australia. Intervention Participants responded to the question, ‘What does successful rehabilitation look like?’. Following item generation, they prioritised their top five responses, allocating 100 points across items to denote relative importance. Main measures Prioritised responses were analysed across stakeholder groups using qualitative content analysis. Results Ten themes were identified. ‘Successful rehabilitation’ is: (1) person and family centred; (2) effective; (3) inter-professional; (4) accessible; (5) goal oriented with meaningful outcomes; (6) connected to the continuum of care; (7) evidence-based and supportive of innovation and research; (8) appropriately funded and skilled; (9) satisfying and engaging; and (10) safe. Conclusions Stakeholder-defined ‘successful rehabilitation’ aligned with principles of value-based care and evidence-based rehabilitation. Provision and receipt of person and family centred care was the most important indicator of successful rehabilitation. Measures of success should include indicators of structure, process, outcome, and experience, and be conducted at multiple time-points.
DNA-methylation and immunological response in medication overuse headache
Authors: Carlsen Louise Ninett , Hansen Christine Søholm , Kogelman Lisette J. A. , Werge Thomas Mears , Ullum Henrik , Bybjerg-Grauholm Jonas , Hansen Thomas Folkmann , Jensen Rigmor Højland 
Published: February 2023

Objective To investigate whether medication-overuse headache patients have differential DNA-methylation pattern. Methods We collected blood samples from 120 medication-overuse headache-patients, 57 controls (29 episodic migraine patients and 28 healthy controls) in a hypothesis-generating cross-sectional case-control pilot study; 100 of the medication-overuse headache-patients were followed for six months and samples were collected at two and six months for the longitudinal methylation analyses. Blood cell proportions of leucocytes (neutrophils, NK-cells, monocytes, CD8+ and CD4+ T-cells, and B-cells) and the neutrophile-lymphocyte ratio were estimated using methylation data as a measure for immunological analysis and a cell type-specific epigenome wide association study was conducted between medication-overuse headache-patients and controls, and longitudinally for reduction in headache days/month among medication-overuse headache-patients. Results We found a higher neutrophile-lymphocyte ratio in medication-overuse headache-patients compared to controls, indicating a higher immunological response in medication-overuse headache-patients (false discovery rate (adjusted p-value)<0.001). Reduction in headache days/month (9.8; 95% CI 8.1–11.5) was associated with lower neutrophile-lymphocyte ratio (false discovery rate adjusted p-value = 0.041). Three genes ( CORIN, CCKBR and CLDN9) were hypermethylated in specific cell types in medication-overuse headache-patients compared to controls. No methylation differences were associated with reduction in headache days in medication-overuse headache-patients after six months. Conclusion This pilot study was consistent with higher immunological response in medication-overuse headache-patients which decreased with a reduction in headache days in longitudinal analysis. medication-overuse headache-patients exhibited differential methylation in innate immune cells but did not exhibit longitudinal differences with alterations in headache days. Our study creates hypotheses for further biomarker searches. ClinicalTrials.gov Identifier: NCT02993289
The Role of Salivary C-Reactive Protein in Diagnosis of Neonatal Sepsis
Authors: Abed Neveen Tawfik , Behiry Eman Gamal , El-Aty Basima Fawzy Abd 
Published: February 2023

Background Neonatal sepsis remains one of the leading causes of morbidity and mortality among neonates. Objective to evaluate the role of salivary C-reactive protein (CRP) as a diagnostic marker in neonatal sepsis. Methods This case-control study was carried out on 90 neonates including 45 neonates with symptoms and signs suggestive of neonatal sepsis and 45 healthy neonates as controls. All neonates were subjected to full history taking, thorough clinical examination, laboratory investigations including complete blood count (CBC), serum CRP, blood culture, and salivary CRP. Results Septic neonates showed significantly higher salivary CRP compared to controls; it was significantly associated with positive serum CRP, blood culture, and hematological scoring system (HSS). It was significantly higher in neonates who died compared to those who survived. Twenty one cases with positive salivary CRP showed significant positive correlations with the length of the neonatal intensive care unit stay, total white blood cell (WBC) count, mean platelet volume (MPV), neutrophils to lymphocytes ratio (NLR), serum CRP, HSS, significant negative correlations with gestational age, birth weight, APGAR at 1, 5 min, and platelet count. Receiver operating characteristic (ROC) curve for salivary CRP showed that at cut-off value of 0.135 mg/L, the sensitivity was (81.8%) and the specificity was (75.6%) for detecting neonatal sepsis. Conclusion Salivary CRP was significantly higher in the septic group, and was associated with positive serum CRP. Hence, salivary CRP could be considered a novel non-invasive biomarker for diagnosing neonatal sepsis.
The economic burden of diseases in the Nordic countries: A systematic review
Authors: Mayntz Stephan Krog , Peronard Cecilie Rose Fossar , Søgaard Jes , Chang Angela Y. 
Published: February 2023

Background: Economic burden studies can provide insights into the drivers leading to increasing healthcare costs. It can also provide a more holistic view of how diseases impact the welfare of patients and their families. Having concrete estimates of the economic burden across multiple diseases can help policymakers determine which diseases are economically more burdensome. This study aimed to review and summarise comprehensively economic burden studies across multiple diseases in the Nordic countries between 2000 and 2020. Methods: According to the 2020 PRISMA statement, a systematic literature review was conducted in PubMed, CINAHL, Academic Search Premier and Global Health databases using key terms related to the economic burden of any disease in Denmark, Finland, Greenland, Iceland, Norway and Sweden. Grey literature was also reviewed. Results: A total of 10,050 potential titles and abstracts were identified and screened, and 254 full-text papers that met the inclusion criteria were evaluated by two independent reviewers. Of these, 119 articles were included in a qualitative synthesis. Twenty-nine had clearly defined comparison groups, thus able to attribute the costs to the disease. Large variations concerning methodology and cost components were noted. Across diseases, the economic burden ranged from EUR 1668 per patient annually for chronic obstructive pulmonary disease to EUR 93,041 for multiple sclerosis. However, estimates varied widely, even within each disease. Conclusions: Our review highlights the need for more comparable economic burden studies. Future studies should focus on applying robust methodology and homogeneous cost-reporting methods to inform policymakers about which diseases are economically more burdensome.