bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis
Authors: Wang X , Sun L , He N , An Z , Yu R , Li C , Li Y , Li Y , Liu X , Fang X , Zhao J 
Published: October 2020

SummaryAnti-citrullinated protein/peptide antibodies (ACPA) play important roles in the pathogenesis of rheumatoid arthritis (RA). ACPA-positive (ACPA+) and ACPA-negative (ACPA−) RA were suggested to be different disease subsets, with distinct differences in genetic variation and clinical outcomes. The aims of the present study were to compare gene expression profiles in ACPA+ and ACPA− RA, and to identify novel candidate gene signatures that might serve as therapeutic targets. Comprehensive transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from ACPA+ and ACPA− RA patients and healthy controls was performed via RNA sequencing. A validation cohort was used to further investigate differentially expressed genes via polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Spearman's correlation test was used to evaluate the correlation of differentially expressed genes and the clinical and laboratory data of the patients. The role of differentially expressed genes in osteoclastogenesis was further investigated. Expression of C-X-C motif chemokine ligand 2 (CXCL2) was significantly increased in ACPA+ RA than in ACPA− RA, which was validated in PBMCs and serum. CXCL2 promoted the migration of CD14+ monocytes and increased osteoclastogenesis in RA patients. RAW264.7 macrophages were used to investigate specific mechanisms, and the results suggested that CXCL2 stimulated osteoclastogenesis via extracellular receptor kinase (ERK) mitogen-activated protein kinase (MAPK) and nuclear factor kappa B pathways. In conclusion, CXCL2 was highly expressed in ACPA+ RA than in ACPA− RA. CXCL2 promoted osteoclastogenesis and was related to bone erosion in RA, which suggests that the blockade of CXCL2 might be a novel strategy for the treatment of RA.
Heterozygous de novo variants in CSNK1G1 are associated with syndromic developmental delay and autism spectrum disorder
Authors: Gold Nina B. , Li Dong , Chassevent Anna , Kaiser Frank J. , Parenti Ilaria , Strom Tim M. , Ramos Feliciano J. , Puisac Beatriz , Pié Juan , McWalter Kirsty , Guillen Sacoto Maria J. , Cui Hong , Saadeh‐Haddad Reem , Smith‐Hicks Constance , Rodan Lance , Blair Edward , Bhoj Elizabeth 
Published: October 2020

AbstractThe gamma‐1 isoform of casein kinase 1, the protein encoded by CSNK1G1, is involved in the growth and morphogenesis of cells. This protein is expressed ubiquitously among many tissue types, including the brain, where it regulates the phosphorylation of N‐methyl‐D‐aspartate receptors and plays a role in synaptic transmission. One prior individual with a de novo variant in CSNK1G presenting with severe developmental delay and early‐onset epilepsy has been reported. Here we report an updated clinical history of this previously published case, as well as four additional individuals with de novo variants in CSNK1G1 identified via microarray‐based comparative genomic hybridization, exome, or genome sequencing. All individuals (n = 5) had developmental delay. At least three individuals had diagnoses of autism spectrum disorder. All participants were noted to have dysmorphic facial features, although the reported findings varied widely and therefore may not clearly be recognizable. None of the participants had additional major malformations. Taken together, our data suggest that CSNK1G1 may be a cause of syndromic developmental delay and possibly autism spectrum disorder.
Copy number alterations involving 59 ACMG‐recommended secondary findings genes
Authors: Yatsenko Svetlana A. , Aarabi Mahmoud , Hu Jie , Surti Urvashi , Ortiz Damara , Madan‐Khetarpal Suneeta , Saller Devereux N. , Bellissimo Daniel , Rajkovic Aleksandar 
Published: October 2020

AbstractIn clinical exome/genome sequencing, the American College of Medical Genetics and Genomics (ACMG) recommends reporting of secondary findings unrelated to a patient's phenotype when pathogenic single‐nucleotide variants (SNVs) are observed in one of 59 genes associated with a life‐threatening, medically actionable condition. Little is known about the incidence and sensitivity of chromosomal microarray analysis (CMA) for detection of pathogenic copy number variants (CNVs) comprising medically‐actionable genes. Clinical CMA has been performed on 8865 individuals referred for molecular cytogenetic testing. We retrospectively reviewed the CMA results to identify patients with CNVs comprising genes included in the 59‐ACMG list of secondary findings. We evaluated the clinical significance of these CNVs in respect to pathogenicity, phenotypic manifestations, and heritability. We identified 23 patients (0.26%) with relevant CNV either deletions comprising the entire gene or intragenic alterations involving one or more secondary findings genes. A number of patients and/or their family members with pathogenic CNVs manifest or expected to develop an anticipated clinical phenotype and would benefit from preventive management similar to the patients with pathogenic SNVs. To improve patients' care standardization should apply to reporting of both sequencing and CNVs obtained via clinical genome‐wide analysis, including chromosomal microarray and exome/genome sequencing.
Novel GZF1 pathogenic variants identified in two Chinese patients with Larsen syndrome
Authors: Zeng Lanlan , Li Zhibin , Pan Lijuan , Li Hongyan , Wu Jiayu , Yuan Xiying , Li Zhuo , Liang Desheng , Wu Lingqian 
Published: October 2020

AbstractGZF1 was recently reported as a genetic factor associated with Larsen syndrome. Two patients presenting hip dislocation, scoliosis and severe myopia, as well as hearing loss and other abnormal features, were found to carry two novel compounds heterozygous variants in GZF1 (c.397400del, p. Leu133fs; and c.1474del, p. Met492fs) through whole‐exome sequencing. The mRNA expression level of L133fs‐GZF1 did not significantly differ from that of WT‐GZF1. However, no HA‐conjugated mutant protein was detected by western blotting, which was also confirmed by immunofluorescence staining. In addition, both mRNA transcription and protein expression levels of M492fs‐GZF1 were significantly lower than those of wild type, and HA‐tagged M492fs‐GZF1 was mainly distributed in the cytoplasm of HEK 293 T cells. These results suggested that the two variants could lead to loss of function of GZF1. Our study was the second to report the association between GZF1 variants and Larsen syndrome. We also provided functional evidence for the pathogenicity of GZF1 variants, which expands the mutation spectrum and offers a basis for functional research on the role of GZF1 in the development of Larsen syndrome.
Obesity and activity patterns before and during COVID‐19 lockdown among youths in China
Authors: Yang Shujuan , Guo Bing , Ao Linjun , Yang Chao , Zhang Lei , Zhou Junmin , Jia Peng 
Published: October 2020

SummaryThis study aim to assess changes in obesity and activity patterns among youths in China during the COVID‐19 lockdown. We used the COVID‐19 Impact on lifestyle change survey (COINLICS), a national retrospective survey distributed via social media platforms in early May 2020 where more than 10 000 youth participants in China have voluntarily reported their basic sociodemographic information, weight status, and routine lifestyles in the months before and during COVID‐19 lockdown. The extended IOTF and WHO standards were used to define overweight and obesity of the participants. We used paired t‐tests or χ2 tests and non‐parametric methods to evaluate the significance of differences in weight‐related outcomes and lifestyles across education levels, between sexes, and before and during COVID‐19 lockdown. The mean body mass index of all participating youths has significantly increased (21.8‐22.6) and in all education subgroups during COVID‐19 lockdown. Increases also occurred in the prevalence of overweight/obesity (21.3%‐25.1%, P < .001) and obesity (10.5% to 12.9%, P < .001) in overall youths, especially in high school and undergraduate students. Their activity patterns had also significantly changed, including the decreased frequency of engaging in active transport, moderate−/vigorous‐intensity housework, leisure‐time moderate−/vigorous‐intensity physical activity, and leisure‐time walking, and the increased sedentary, sleeping, and screen time. Our findings would inform policy‐makers and clinical practitioners of these changes in time, for better policy making and clinical practice. School administrators should also be informed of these changes, so in‐class and/or extracurricular physical activity programs could be designed to counteract them.
Metastasizing basal cell carcinoma: A clinicopathologic and immunohistochemical study of 22 cases
Authors: Mochel Mark C. , Liaquat Samia , Moore Johanna B. , Hoang Mai P. 
Published: October 2020

AbstractBasal cell carcinomas metastasize rarely, and there have been limited studies of potential drivers for this metastasis. Epithelial‐mesenchymal transition (EMT) may play a role, although this has not been investigated in detail. We reviewed clinicopathologic features of 22 patients with metastasizing basal cell carcinoma (MBCC). Immunohistochemical markers of EMT, including CD44, E‐cadherin, claudin, smooth muscle actin, beta‐catenin, Twist1, and Oct 3/4, were evaluated on 10 MBCC (primary and metastases) and 18 non‐metastasizing BCC. Primary sites included the head and neck, trunk, and extremity, while metastatic sites included lymph nodes, lung, bone, and soft tissue. Of 19 cases with follow‐up, the range of follow‐up after diagnosis of metastasis was 5 to 248 months (median: 50 months). Two cases were of unknown primary, nine metastases were diagnosed concurrently with primary tumors, and remaining cases showed a median latency between diagnosis of primary and metastatic tumors of 27.5 months (range: 3‐81 months). Median survival was 66 months. Compared to non‐metastasizing BCC, MBCC demonstrated reduced CD44 expression (primary [P = .0036], metastatic [P = .011]) and increased Twist1 expression (primary, P = .0017). MBCC shows variably aggressive behavior, and reduced CD44 and increased Twist1 expression may indicate significant EMT in metastasizing tumors and signify a metastatic phenotype.
Comparison of Afirma Gene Expression Classifier with Gene Sequencing Classifier in indeterminate thyroid nodules: A single‐institutional experience
Authors: Geng Yipeng , Aguilar‐Jakthong Josephine S. , Moatamed Neda A. 
Published: October 2020

AbstractIntroductionThe Afirma test has been used in the diagnosis of cytologically indeterminate thyroid nodules to reduce diagnostic uncertainty and unnecessary surgeries. Gene Sequencing Classifier (GSC) was developed to improve the positive predictive value and overall test performance of Gene Expression Classifier (GEC). Here we present our experience comparing the performance of first‐generation assay of Afirma (GEC) with the new assay (GSC).MethodsRetrospective analysis was performed on all Bethesda III and IV cytology thyroid nodules tested with GEC and GSC. Test performance was evaluated by surgical pathology outcomes.ResultsIn total, 167 cases were tested with GEC, of which 49% were reported as benign. Fourteen cases had surgical follow‐up with 11 benign, one non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) and two malignant diagnoses. Of the 167 cases, 51% had suspicious GEC result. Fifty‐seven of these suspicious GEC cases had surgical follow‐up with 28 benign, nine NIFTP and 20 malignant histology. There 133 cases tested with GSC, of which 61% were reported as benign. Ten cases had surgical follow‐up, all of which showed benign results and 32% of the cases were tested as suspicious. Thirty‐six cases with suspicious GSC had surgical follow‐up. Fourteen of them had benign, five NIFTP, and 17 malignant surgical pathology. Based on molecular testing, surgical resection could have been be prevented 61% with GSC, compared to 49% with GEC test.ConclusionOur experience shows that GSC has a better test performance than GEC. Also, our data support that GSC identify more cases as benign and reduces the number of unnecessary surgeries compared to GEC.
Manifestations, clinical course and prognostic markers in cutaneous polyarteritis nodosa
Authors: Munera‐Campos Mónica , Bielsa Isabel , Martínez‐Morillo Melania , Aparicio Gloria , Olivé Alejandro , Ferrándiz Carlos 
Published: October 2020

SummaryBackground and objectivesCutaneous polyarteritis nodosa (CPAN) is a comparatively rare form of vasculitis that affects small arteries and arterioles in the panniculus and dermo‐subcutaneous junction. Limited information is available regarding its course in the European population. The aim of this study is to characterize the manifestations and prognostic markers of recurrence in CPAN.Patients and methodsWe report a retrospective study of patients with clinical and histopathologic evidence of CPAN, which was treated at two tertiary referral centers in Spain between 1989 and 2019.Results31 patients were included. The most frequent manifestation was subcutaneous nodules (90.3 %); ulcers were frequent at diagnosis (35.5 %). Two thirds of the patients had at least one extracutaneous manifestation. Seventeen patients (54.8 %) experienced relapse. The strongest predictor of recurrence was ulceration in the initial episode (OR 18.6; 95 % CI 2.73–38; p < 0.01). The pre‐treatment results of laboratory parameters associated with inflammation (such as C‐reactive protein and neutrophil‐to‐lymphocyte ratio) were significantly higher in the relapsing group. There were no disease‐related deaths and none of the patients developed systemic PAN.ConclusionsAlthough CPAN is a vasculitis limited to the skin, symptoms may involve adjacent skeletal muscle or peripheral nerves. While the condition is not life‐threatening, the presence of ulceration and elevation of certain laboratory parameters predicts a worse prognosis.
Patient preferences for treatment of advanced melanoma: impact of comorbidities
Authors: Weilandt Juliane , Diehl Katharina , Schaarschmidt Marthe‐Lisa , Kiecker Felix , Sasama Bianca , Pronk Melanie , Ohletz Jan , Könnecke Andreas , Müller Verena , Utikal Jochen , Hillen Uwe , Harth Wolfgang , Peitsch Wiebke K. 
Published: October 2020

SummaryBackground and objectivesChoice of treatment for advanced melanoma is crucially influenced by comorbidities and patient preferences. Our study aimed to investigate the impact of comorbidities on preferences.Patients and methods150 patients with melanoma stage IIC–IV completed a discrete choice experiment to determine preferences for outcome (overall response rate [ORR], 2‐year survival, progression‐free survival [PFS], time to response [TTR], kind of adverse events [AE], AE‐related treatment discontinuation) and process attributes (frequency and route of administration [RoA], frequency of consultations) of systemic melanoma treatments. The impact of comorbidities was assessed by analysis of variance and multivariate regression.ResultsParticipants with hypertension and other cardiovascular diseases attached significantly greater importance to TTR and RoA than others. Respondents with arthropathy cared more about TTR (β = 0.179, P = 0.047) and RoA, but less about ORR (β = –0.209, P = 0.021). Individuals with diabetes considered AE (β = 0.185, P = 0.039) and frequency of consultations more essential, but ORR less relevant. Those with other malignancies were particularly worried about treatment discontinuation (β = 0.219, P = 0.008), but less about ORR (β = –0.202, P = 0.015). Participants with depression focused more on PFS (β = 0.201, P = 0.025) and less on TTR (β = –0.201, P = 0.023) and RoA (β = –0.167, P = 0.050).ConclusionsTreatment preferences of melanoma patients vary significantly dependent on comorbidities.
Trends in the detection of aquatic non‐indigenous species across global marine, estuarine and freshwater ecosystems: A 50‐year perspective
Authors: Bailey Sarah A. , Brown Lyndsay , Campbell Marnie L. , Canning‐Clode João , Carlton James T. , Castro Nuno , Chainho Paula , Chan Farrah T. , Creed Joel C. , Curd Amelia , Darling John , Fofonoff Paul , Galil Bella S. , Hewitt Chad L. , Inglis Graeme J. , Keith Inti , Mandrak Nicholas E. , Marchini Agnese , McKenzie Cynthia H. , Occhipinti‐Ambrogi Anna , Ojaveer Henn , Pires‐Teixeira Larissa M. , Robinson Tamara B. , Ruiz Gregory M. , Seaward Kimberley , Schwindt Evangelina , Son Mikhail O. , Therriault Thomas W. , Zhan Aibin 
Published: October 2020

AbstractAimThe introduction of aquatic non‐indigenous species (ANS) has become a major driver for global changes in species biogeography. We examined spatial patterns and temporal trends of ANS detections since 1965 to inform conservation policy and management.LocationGlobal.MethodsWe assembled an extensive dataset of first records of detection of ANS (1965–2015) across 49 aquatic ecosystems, including the (a) year of first collection, (b) population status and (c) potential pathway(s) of introduction. Data were analysed at global and regional levels to assess patterns of detection rate, richness and transport pathways.ResultsAn annual mean of 43 (±16 SD) primary detections of ANS occurred—one new detection every 8.4 days for 50 years. The global rate of detections was relatively stable during 1965–1995, but increased rapidly after this time, peaking at roughly 66 primary detections per year during 2005–2010 and then declining marginally. Detection rates were variable within and across regions through time. Arthropods, molluscs and fishes were the most frequently reported ANS. Most ANS were likely introduced as stowaways in ships’ ballast water or biofouling, although direct evidence is typically absent.Main conclusionsThis synthesis highlights the magnitude of recent ANS detections, yet almost certainly represents an underestimate as many ANS go unreported due to limited search effort and diminishing taxonomic expertise. Temporal rates of detection are also confounded by reporting lags, likely contributing to the lower detection rate observed in recent years. There is a critical need to implement standardized, repeated methods across regions and taxa to improve the quality of global‐scale comparisons and sustain core measures over longer time‐scales. It will be fundamental to fill in knowledge gaps given that invasion data representing broad regions of the world's oceans are not yet readily available and to maintain knowledge pipelines for adaptive management.
Arthropod abundance modulates bird community responses to urbanization
Authors: Planillo Aimara , Kramer‐Schadt Stephanie , Buchholz Sascha , Gras Pierre , von der Lippe Moritz , Radchuk Viktoriia 
Published: October 2020

AbstractAimWe analysed the role of species interactions in wildlife community responses to urbanization. Specifically, we investigated non‐trophic associations within a bird community and the role of trophic interactions in the responses of bird species to the urbanization gradient.LocationCity‐state of Berlin, Central Europe.MethodsArthropod and bird abundances were sampled across the study area and analysed using hierarchical joint species distribution models (JSDMs). Urbanization gradient was defined by environmental predictors reflecting anthropogenic disturbances, for example noise level and human population density, as well as nature‐like features, for example tree cover and open green area. Relevant environmental predictors for each group and relevant spatial resolution were selected a priori using AICc. Arthropod abundances were modelled for the bird sampling transects and included as additional predictor variable in the bird community model. In this model, we used abundances and traits of 66 breeding bird species as response variables.ResultsBird species responses to urbanization were captured by the interaction between invertebrate abundance and environmental predictors. We identified three groups of birds: the urban group (12 species) showed no decrease in abundance along the urbanization gradient and were not related to arthropods abundance; the woodland group (18 species) were positively related to tree cover and arthropod abundance, also in areas with high anthropogenic disturbance; and the nature group (36 species) were positively related to arthropod abundance, but the species abundance decreased sharply with increasing anthropogenic disturbance. All the non‐trophic associations found within the bird community were positive.Main conclusionsArthropod abundance clearly modulated birds’ responses to the urbanization gradient for most species. Especially at moderate levels of anthropogenic disturbance, the abundance of arthropods is key for the occurrence and abundance of bird species in urban areas. To maintain bird diversity in urban green areas, management measures should focus on maintaining and increasing invertebrate abundance.
Puberty and menarche in young females with cerebral palsy and intellectual disability: a qualitative study of caregivers’ experiences
Authors: Gray Susan H , Wylie Molly , Christensen Sinead , Khan Anqa , Williams David , Glader Laurie 
Published: October 2020

AimTo explore experiences of parents of young females with cerebral palsy (CP) and intellectual disability at the onset of puberty.MethodThis was a phenomenological qualitative study. We conducted phone interviews of parents of young females with CP and intellectual disability who had been seen in the CP center at a freestanding children's hospital within the prior 2 years. Inclusion criteria were English‐speaking parents of young females who had combined diagnoses of CP and intellectual disability. Interviews were coded and analyzed by the research team facilitated by Dedoose software.ResultsNine interviews were conducted with parents of daughters aged 14 to 24 years. All daughters used wheelchairs for mobility and augmentative technology for communication. Despite homogeneity in functional ability, there was marked variation in parental perception of the significance of puberty for their daughters. Families often learned about reproductive health from informal social networks. Although families acknowledged the need for sexual abuse screening, there was little consensus about how to do it, and most denied that their own daughter could ever be abused.InterpretationParents of young females with CP and intellectual disability have diverse reproductive health beliefs that health care providers must explore in order to provide appropriate recommendations for management of puberty.What this paper adds

Parents of young females with cerebral palsy (CP) and intellectual disability have diverse reproductive health beliefs.

Approaches to menstrual management in this population must be individualized.

Families discounted the likelihood of abuse, despite acknowledging their daughters’ risk.