bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Validation for the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) Hebrew Battery in Adolescents and Young Adults With Typical Development
Authors: Fussman Shanie , Mashal Nira 
Published: January 2022

Currently there is no validated battery to assess pragmatic abilities in Hebrew. The use of such battery has great importance, as it may provide norms to the assessment of impaired pragmatic skills across several populations, such as ASD, schizophrenia, specific learning disorders and intellectual disabilities. In order to validate the battery, the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) was translated to Hebrew. The APACS battery was previously validated and found high reliability and validity for ages 19–89 years. The battery includes six tasks, focusing on two main domains: pragmatic production and pragmatic comprehension. The assessment of pragmatic production will be conducted by the use of interview and description tasks, whereas pragmatic comprehension will be assessed by narratives, two figurative language, and humor tasks. The translated battery, APACS-Heb is currently the most comprehensive and the first validated battery for pragmatic tests in Hebrew. Forty Hebrew-speaking adolescents ages 16–20 participated in the study. All participants performed screening tests assessing vocabulary, Theory of Mind and social responsiveness. In addition, the validity and test-retest reliability of APACS-Heb were assessed. Furthermore, the effect of vocabulary, Theory of Mind and social responsiveness on performance was evaluated. High internal consistency, content validity and test-retest reliability was found for most APACS-Heb tasks and all composite scores. Furthermore, an effect of age and gender was found for most tasks with females outperformed males. In addition, a contribution of Theory of Mind to pragmatic production, pragmatic comprehension and APACS total scores was found. Lastly, a factor analysis revealed two factors, in which the first factor correlates with most tasks, and the second factor correlates only to humor. The results thus suggest that humor is a separate skill among the other pragmatic skills. In conclusion, normative data was collected for the APACS-Heb battery, and it was found that it is a valid and reliable measure of pragmatic skills. Since APACS is a comprehensive battery assessing the various aspects of figurative language, it can identify the specific deficits in figurative language and therefore may pinpoint the appropriate intervention program for each individual.
Different Rates of Bioprosthetic Aortic Valve Failure With Perimount™ and Trifecta™ Bioprostheses
Authors: Lange Rüdiger , Alalawi Zahra , Voss Stephanie , Boehm Johannes , Krane Markus , Vitanova Keti 
Published: January 2022

ObjectivesThe use of bioprostheses in surgical aortic valve replacement (SAVR) has increased in younger patients. Comparative analysis of different types of bioprostheses is lacking. We aimed to compare two proprietary bioprostheses with different designs, i.e., internally and externally mounted leaflets, focusing on the long-term durability and survival.MethodsWe conducted a large single-center retrospective analysis of all consecutive patients who underwent SAVR with either Perimount™ or Trifecta™ bioprostheses between 2001 and 2019. The patient groups were further subdivided by age &lt;65 and &gt;65. Endpoints of the study were all-cause mortality and reoperation due to bioprosthetic valve failure (BVF).ResultsSelection criteria resulted in a total sample of 5,053 patients; 2,630 received a Perimount prosthesis (internally mounted leaflets) and 2,423 received a Trifecta prosthesis (externally mounted leaflets). The mean age at surgery was similar (69 ± 11 y, PM, and 68 ± 10 y, TF, p = 0.9), as was estimated survival at 8 years (76.1 ± 1.3%, PM, and 63.7 ± 1.9% TF; p=0.133). Patients in the Trifecta group had a significantly higher cumulative reoperation rate at 8 years compared to those in the Perimount group (16.9 ± 1.9% vs. 3.8 ± 0.4%; p &lt; 0.01). This difference persisted across age groups (&lt;65 y, 13.3% TF vs. 8.6% PM; &gt;65 y, 12% TF vs. 7% PM).ConclusionBioprostheses for SAVR with externally mounted leaflets (Trifecta) showed significantly higher long-term reoperation rates compared to those with internally mounted leaflets (Perimount), regardless of the patient's age at SAVR. Survival was similar with both bioprostheses.
Brown Adipose Tissue Rescues Bone Loss Induced by Cold Exposure
Authors: Du Jingke , He Zihao , Xu Mingming , Qu Xinhua , Cui Junqi , Zhang Shuangyan , Zhang Shuhong , Li Hanjun , Yu Zhifeng 
Published: January 2022

Cold temperature activates the sympathetic nervous system (SNS) to induce bone loss by altering bone remodeling. Brown adipose tissue (BAT) is influenced by the SNS in cold environments. Many studies have confirmed a positive relationship between BAT volume and bone mass, but the influence and mechanism of BAT on bone in vivo and in vitro is still unknown. Two-month-old C57/BL6j male mice were exposed to cold temperature (4°C) to induce BAT generation. BAT volume, bone remodeling and microstructure were assessed after 1 day, 14 days and 28 days of cold exposure. CTX-1, P1NP and IL-6 levels were detected in the serum by ELISA. To determine the effect of BAT on osteoclasts and osteoblasts in vitro, brown adipocyte conditional medium (BAT CM) was collected and added to the differentiation medium of bone marrow-derived macrophages (BMMs) and bone marrow mesenchymal stem cells (BMSCs). Micro-CT results showed that the bone volume fraction (BV/TV, %) significantly decreased after 14 days of exposure to cold temperature but recovered after 28 days. Double labeling and TRAP staining in vivo showed that bone remodeling was altered during cold exposure. BAT volume enlarged after 14 days of cold stimulation, and IL-6 increased. BAT CM promoted BMSC mineralization by increasing osteocalcin (Ocn), RUNX family transcription factor 2 (Runx2) and alkaline phosphatase (Alp) expression, while bone absorption was inhibited by BAT CM. In conclusion, restoration of bone volume after cold exposure may be attributed to enlarged BAT. BAT has a beneficial effect on bone mass by facilitating osteogenesis and suppressing osteoclastogenesis.
Yearly Height Gain Is Dependent on the Truly Received Dose of Growth Hormone and the Duration of Periods of Poor Adherence: Practical Lessons From the French Easypod™ Connect Multicenter Observational Study
Authors: Coutant Régis , Nicolino Marc , Cammas Benoit , de Buyst Valérie , Tauber Maïthé , Hamel Jean-François 
Published: January 2022

ObjectiveTo study the impact of the true mean daily dose and the true mean number of injections per week on the yearly height gain in short children treated with recombinant human growth hormone (rhGH).Design and Methods220 children from the French Easypod™ Connect Observational Study (ECOS) used the Easypod™ electronic device to record rhGH injections. The mean daily rhGH dose (the sum of the doses truly received divided by the number of days) and mean number of injections per week (the number of injections truly performed divided by the number of weeks) were calculated. Linear mixed models were used to study the impact of short (3-month) and long (1-year) variations in rhGH administration on the yearly height change [as a standard deviation score (SDS)], with time on treatment as a covariate. For each patient, several periods of 3 or 12 months were considered and designated as poorly adherence or fully adherence. We studied the impact of each of period on the height change.ResultsAt treatment initiation, the mean ± SD age was 9.8 ± 3.7 years (females: 47%, prepubertal: 86%) and the mean height was -2.28 ± 0.92 SDS. The mean treatment duration was 3.2 ± 1.1 years (685.2 patient years). 122 patients were GH-deficient, 79 were small for gestational age, and 19 had Turner syndrome. When treatment was computed over 12-month periods, receiving a mean daily dose &lt;0.03 mg/kg.d was associated with a 20% lower mean yearly height gain SDS when&lt;3 injections/week were received (vs.&gt;5 injections/week), whereas maintaining a mean daily dose &gt;0.03 mg/kg.d with&lt;3 injections/week was not associated with a lower yearly height gain SDS (vs.&gt;5 injections/week). For 3-month periods, changes in the daily rhGH dose or the number of injections per week over such short period did not influence the yearly height gain SDS.ConclusionThe 12-month treatment model showed that when poor adherence leads to a low true daily GH dose, the yearly height gain is low. The 3-month treatment model showed that poor adherence for short periods (&lt;3 months) had no impact on the height SDS.
Systematic Analysis of Expression and Prognostic Values of Lysyl Oxidase Family in Gastric Cancer
Authors: Wang Li , Cao Shan , Zhai Rujun , Zhao Yang , Song Guodong 
Published: January 2022

Background: Gastric cancer (GC) remains the fifth most commonly diagnosed malignancy worldwide, with a poor prognosis. The lysyl oxidase (LOX) family, a type of secreted copper-dependent amine oxidases, is comprised of LOX and four LOX-like (LOXL) 1–4 isoforms and has been reported to be dysregulated in a number of different type cancers. However, the diverse expression patterns and prognostic values of LOX family in GC have yet to be systematically analyzed.Methods: ONCOMINE, GEPIA, UALCAN, Kaplan–Meier Plotter, LOGpc, cBioPortal, GeneMANIA and Metascape databases were utilized in this study to analyze the expression, prognostic values, mutations and functional networks of LOX family in GC.Results: The mRNA expression levels of LOX, LOXL1 and LOXL2 were significantly higher in GC, the expression level of LOXL3 was contrary in different databases, while the expression level of LOXL4 made no difference; the expression levels of LOX, LOXL1 and LOXL3 were higher in stages 2–4 than that of normal tissues and stage 1, while the mRNA level of LOXL2 in stage 1–4 was higher than normal tissues; patients with high expression of LOX and LOXL 2-4 had poor OS; the genes correlated with LOX and LOXL2 were enriched in extracellular matrix organization, vasculature development and skeletal system development.Conclusion: Our results indicated that the LOX family, especially LOX and LOXL2, might play an important role in GC oncogenesis, and they may become biomarkers for predicting tumor prognosis and potential targets for tumor therapy.
Shared Genetic Architecture and Causal Relationship Between Asthma and Cardiovascular Diseases: A Large-Scale Cross-Trait Analysis
Authors: Zhou Yi , Liang Zhi-Sheng , Jin Yinzi , Ding Jiayuan , Huang Tao , Moore Jason H. , Zheng Zhi-Jie , Huang Jie 
Published: January 2022

Background: Accumulating evidence has suggested that there is a positive association between asthma and cardiovascular diseases (CVDs), implying a common architecture between them. However, the shared genetic architecture and causality of asthma and CVDs remain unclear.Methods: Based on the genome-wide association study (GWAS) summary statistics of recently published studies, our study examined the genetic correlation, shared genetic variants, and causal relationship between asthma (N = 127,669) and CVDs (N = 86,995–521,612). Statistical methods included high-definition likelihood (HDL), cross-trait meta-analyses of large-scale GWAS, transcriptome-wide association studies (TWAS), and Mendelian randomization (MR).Results: First, we observed a significant genetic correlation between asthma and heart failure (HF) (Rg = 0.278, P = 5 × 10−4). Through cross-trait analyses, we identified a total of 145 shared loci between asthma and HF. Fifteen novel loci were not previously reported for association with either asthma or HF. Second, we mapped these 145 loci to a total of 99 genes whose expressions are enriched in a broad spectrum of tissues, including the seminal vesicle, tonsil, appendix, spleen, skin, lymph nodes, breast, cervix and uterus, skeletal muscle, small intestine, lung, prostate, cardiac muscle, and liver. TWAS analysis identified five significant genes shared between asthma and HF in tissues from the hemic and immune system, digestive system, integumentary system, and nervous system. GSDMA, GSDMB, and ORMDL3 are statistically independent genetic effects from all shared TWAS genes between asthma and HF. Third, through MR analysis, genetic liability to asthma was significantly associated with heart failure at the Bonferroni-corrected significance level. The odds ratio (OR) is 1.07 [95% confidence interval (CI): 1.03–1.12; p = 1.31 × 10−3] per one-unit increase in loge odds of asthma.Conclusion: These findings provide strong evidence of genetic correlations and causal relationship between asthma and HF, suggesting a shared genetic architecture for these two diseases.
Case Report: Eosinophilic Esophagitis in a Patient With a Novel STAT1 Gain-of-Function Pathogenic Variant
Authors: Scott Ori , Sharfe Nigel , Dadi Harjit , Vong Linda , Garkaby Jenny , Abrego Fuentes Laura , Willett Pachul Jessica , Nelles Sandra , Nahum Amit , Roifman Chaim M. 
Published: January 2022

BackgroundSTAT1 gain-of-function (GOF) is a primary immune dysregulatory disorder marked by wide infectious predisposition (most notably chronic mucocutaneous Candidiasis), autoimmunity, vascular disease and malignant predisposition. While atopic features have been described in some STAT1 GOF patients, they are not considered a predominant feature of the disease. Additionally, while eosinophilic gastrointestinal infiltration has been reported in some cases, this has always been described in the context of pre-existing oropharyngeal and/or esophageal Candidiasis.Clinical casesHerein, we report 3 members of a multi-generational family diagnosed with STAT1 GOF caused by a novel mutation in the N-terminal domain, c.194A&gt;C (p.D65A). The proband presented initially with a long-standing history of treatment-refractory eosinophilic esophagitis (EoE) without preceding gastrointestinal tract fungal infections, and her mother was diagnosed with esophagitis as well.ConclusionEoE has been previously associated with alterations to STAT6 and STAT3 signaling pathways. The current report expands the possible association between JAK/STAT-related disorders and EoE, suggesting that EoE could be a primary disease manifestation of STAT1 GOF, even in the absence of oropharyngeal and/or esophageal Candidiasis.
Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival
Authors: Yu Yang , Tang Huiwen , Franceschi Debora , Mujagond Prabhakar , Acharya Aneesha , Deng Yupei , Lethaus Bernd , Savkovic Vuk , Zimmerer Rüdiger , Ziebolz Dirk , Li Simin , Schmalz Gerhard 
Published: January 2022

ObjectiveThis study aimed to identify the programmed death ligand-1 (PDL1, also termed as CD274) and its positively correlated immune checkpoint genes (ICGs) and to determine the immune subtypes of CD274-centered ICG combinations in oral and squamous cell carcinoma (OSCC).Materials and MethodsFirstly, the 95 ICGs obtained via literature reviews were identified in the Cancer Genome Atlas (TCGA) database in relation to OSCC, and such 88 ICG expression profiles were extracted. ICGs positively correlated with CD274 were utilized for subsequent analysis. The relationship between ICGs positively correlated with CD274 and immunotherapy biomarkers (tumor mutation burden (TMB), and adaptive immune resistance pathway genes) was investigated, and the relationships of these genes with OSCC clinical features were explored. The prognostic values of CD274 and its positively correlated ICGs and also their associated gene pairs were revealed using the survival analysis.ResultsEight ICGs, including CTLA4, ICOS, TNFRSF4, CD27, B- and T-lymphocyte attenuator (BTLA), ADORA2A, CD40LG, and CD28, were found to be positively correlated with CD274. Among the eight ICGs, seven ICGs (CTLA4, ICOS, TNFRSF4, CD27, BTLA, CD40LG, and CD28) were significantly negatively correlated with TMB. The majority of the adaptive immune resistance pathway genes were positively correlated with ICGs positively correlated with CD274. The survival analysis utilizing the TCGA-OSCC data showed that, although CD274 was not significantly associated with overall survival (OS), the majority of ICGs positively correlated with CD274 (BTLA, CD27, CTLA4, CD40LG, CD28, ICOS, and TNFRSF4) were significantly correlated with OS, whereby their low-expression predicted a favorable prognosis. The survival analysis based on the gene pair subtypes showed that the combination subtypes of CD274_low/BTLA_low, CD274_low/CD27_low, CD274_low/CTLA4_low, CD8A_high/BTLA_low, CD8A_high/CD27_low, and CD8A_high/CTLA4_low predicted favorable OS.ConclusionThe results in this study provide a theoretical basis for prognostic immune subtyping of OSCC and highlight the importance of developing future immunotherapeutic strategies for treating oral cancer.
Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction
Authors: Kwapong William Robert , Jiang Shuai , Yan Yuying , Wan Jincheng , Wu Bo 
Published: January 2022

PurposeTo assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients.MethodsForty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants.ResultsRSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P &lt; 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients.ConclusionsOur report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.
Tinnitus: Characteristics, Need for Therapy, and Therapeutic Outcomes; Results of an International Patient Initiated Platform
Authors: Smit Adriana L. , Vesala Markku , Goedhart Hazel , Eijden Job van , Wempe Christiaan , Stegeman Inge 
Published: January 2022

IntroductionSo far, there is a gap of knowledge about factors influencing the impact of tinnitus, the need for treatment, as well as the experienced effect of regular and alternative tinnitus therapies. In this study, we analyzed the need for treatment and the outcomes of these treatments in an international patient initiated in tinnitus platform.Materials and MethodsTwo surveys were undertaken at an online tinnitus patient support community (www.tinnitustalk.com). The surveys were aimed at (1) using tinnitus treatment and outcomes and (2) the factors that influence tinnitus. Univariable logistic and linear regression were used to calculate the relation between the factors and the tinnitus impact as well as the relation with the used tinnitus treatments and the outcomes.ResultsOf the participants to the first survey (n = 5,017), 2,914 (58.1%) used one or more tinnitus therapies, whereas others most commonly self-administered sound therapy [n = 1,562 (31.1%)] and supplements/herbal medicines [n = 1,157 (23.1 %)]. Being female [odds ratio (OR) 0.83 (95% CI 0.74–0.93, p &lt; 0.01)], tinnitus impact, and some degrees of hearing loss and hyperacusis were all statistically significantly associated with higher odds of having tinnitus treatment. Out of the second survey (n = 6,115), it was found that patient physical and psychological factors were statistically significantly related to tinnitus impact.ConclusionIn this study, we demonstrated the usage and experience of (multiple) tinnitus therapy in patients. Several patient physical and psychological characteristics were found to be related to tinnitus impact and therapy usage. These outcomes might function as the next step to find a personalized treatment and to improve the tinnitus health care.
Blood-Based Markers of Neuronal Injury in Adult-Onset Myotonic Dystrophy Type 1
Authors: van der Plas Ellen , Long Jeffrey D. , Koscik Timothy R. , Magnotta Vincent , Monckton Darren G. , Cumming Sarah A. , Gottschalk Amy C. , Hefti Marco , Gutmann Laurie , Nopoulos Peggy C. 
Published: January 2022

IntroductionThe present study had four aims. First, neuronal injury markers, including neurofilament light (NF-L), total tau, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), were compared between individuals with and without adult-onset myotonic dystrophy type 1 (DM1). Second, the impact of age and CTG repeat on brain injury markers was evaluated. Third, change in brain injury markers across the study period was quantified. Fourth, associations between brain injury markers and cerebral white matter (WM) fractional anisotropy (FA) were identified.MethodsYearly assessments, encompassing blood draws and diffusion tensor imaging on a 3T scanner, were conducted on three occasions. Neuronal injury markers were quantified using single molecule array (Simoa).ResultsThe sample included 53 patients and 70 controls. NF-L was higher in DM1 patients than controls, with individuals in the premanifest phases of DM1 (PreDM1) exhibiting intermediate levels (χ(2)2=38.142, P &lt; 0.001). Total tau was lower in DM1 patients than controls (Estimate = −0.62, 95% confidence interval [CI] −0.95: −0.28, P &lt; 0.001), while GFAP was elevated in PreDM1 only (Estimate = 30.37, 95% CI 10.56:50.19, P = 0.003). Plasma concentrations of UCH-L1 did not differ between groups. The age by CTG interaction predicted NF-L: patients with higher estimated progenitor allelege length (ePAL) had higher NF-L at a younger age, relative to patients with lower CTG repeat; however, the latter exhibited faster age-related change (Estimate = −0.0021, 95% CI −0.0042: −0.0001, P = 0.045). None of the markers changed substantially over the study period. Finally, cerebral WM FA was significantly associated with NF-L (Estimate = −42.86, 95% CI −82.70: −3.02, P = 0.035).InterpretationWhile NF-L appears sensitive to disease onset and severity, its utility as a marker of progression remains to be determined. The tau assay may have low sensitivity to tau pathology associated with DM1.