bluuebunny/crossref_metadata_2025_split huggingface dataset:
WWOXdevelopmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk
Authors: Oliver Karen L. , Trivisano Marina , Mandelstam Simone A. , De Dominicis Angela , Francis David I. , Green Timothy E. , Muir Alison M. , Chowdhary Apoorva , Hertzberg Christoph , Goldhahn Klaus , Metreau Julia , Prager Christine , Pinner Jason , Cardamone Michael , Myers Kenneth A. , Leventer Richard J. , Lesca Gaetan , Bahlo Melanie , Hildebrand Michael S. , Mefford Heather C. , Kaindl Angela M. , Specchio Nicola , Scheffer Ingrid E. 
Published: February 2023

AbstractObjectiveWWOXis an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX‐DEE), also known as WOREE (WWOX‐related epileptic encephalopathy). We analyzed the epileptology and imaging features ofWWOX‐DEE, and investigated genotype–phenotype correlations, particularly with regard to survival.MethodsWe studied 13 patients from 12 families withWWOX‐DEE. Information regarding seizure semiology, comorbidities, facial dysmorphisms, and disease outcome were collected. Electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) data were analyzed. PathogenicWWOXvariants from our cohort and the literature were coded as either null or missense, allowing individuals to be classified into one of three genotype classes: (1) null/null, (2) null/missense, (3) missense/missense. Differences in survival outcome were estimated using the Kaplan–Meier method.ResultsAll patients experienced multiple seizure types (median onset = 5 weeks, range = 1 day–10 months), the most frequent being focal (85%), epileptic spasms (77%), and tonic seizures (69%). Ictal EEG recordings in six of 13 patients showed tonic (n = 5), myoclonic (n = 2), epileptic spasms (n = 2), focal (n = 1), and migrating focal (n = 1) seizures. Interictal EEGs demonstrated slow background activity with multifocal discharges, predominantly over frontal or temporo‐occipital regions. Eleven of 13 patients had a movement disorder, most frequently dystonia. Brain MRIs revealed severe frontotemporal, hippocampal, and optic atrophy, thin corpus callosum, and white matter signal abnormalities. Pathogenic variants were located throughoutWWOXand comprised both missense and null changes including five copy number variants (four deletions, one duplication). Survival analyses showed that patients with two null variants are at higher mortality risk (p‐value = .0085, log‐rank test).SignificanceBiallelicWWOXpathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome. The most common seizure types are focal seizures and epileptic spasms. Mortality risk is associated with mutation type; patients with biallelic nullWWOXpathogenic variants have significantly lower survival probability compared to those carrying at least one presumed hypomorphic missense pathogenic variant.
Oral self‐care among dependent older New Zealanders
Authors: Xue Cindy , Al‐Jassasi Noor , Thomson William M. , Adam Lee , Smith Moira B. 
Published: February 2023

ObjectivesThe objective of the study was to describe the occurrence and associations of oral self‐care by dependent older New Zealanders.BackgroundDependent older adults who require some level of assisted daily care have been shown to have poorer oral health than their independent counterparts, yet national estimates are lacking.Materials and methodsA secondary analysis was conducted of data from New Zealand's 2012 Older People's Oral Health Survey, a national survey that interviewed and examined a representative sample of 2,218 dependent older adults living in aged residential care or receiving home‐based care. Survey data were weighted for statistical analyses, and modelling was carried out using a modified Poisson approach.ResultsOverall, 59.5% (95% CI: 55.1, 63.7) of participants brushed their teeth twice a day, with this rate higher among women, Asians and those without cognitive or physical impairment. Cleaning interdentally at least once a week was less common than brushing, at 25.9% (95% CI: 21.5, 30.9), and that proportion was significantly lower among those with higher dependency or who were cognitively or physically impaired. Almost 9 in 10 (87.8%; 95% CI 83.1, 91.4) used fluoride toothpaste, and adults of high socio‐economic status had lower rates of fluoride toothpaste use. Only 15.0% (95% CI 12.4, 18.0) used mouthwash, with this being most prevalent in Pasifika. More than half of those who wore dentures also wore them at night.ConclusionOral self‐care was sub‐optimal among dependent older New Zealanders. Improving the situation should be a high priority.
When the chickens come home to roost: The short‐ versus long‐term performance implications of government contracting and supplier network structure
Authors: Falcone Ellie C. , Carnovale Steven , Fugate Brian S. , Williams Brent D. 
Published: February 2023

AbstractThe old adage “it is not what you know, but who you know” suggests that in connection(s) lies the key(s) to success. But what does success mean, and for how long will it last? What does the choice of partner, and network connections say about the performance implications of contracting, particularly in the case of a public–private partnership? With countries such as the United States accounting for the world's largest buyer (of any and everything), several suppliers eagerly await their opportunity to contract with large government entities, but is it always a wise decision? Such questions remain largely unexplored and require answers. This research provides answers to these questions by integrating congruence, and network theory to investigate how government contracting impacts private suppliers' financial performance and how suppliers' supply chain network connections moderate this relationship. Results using panel data over several years suggest that while contracting with government bolsters' short‐term financial performance (ROA), it negatively affects long‐term supplier performance (Tobin's Q). In addition, the prominence of a firm's connections (i.e., who they know) and the composition of these connections enhances the performance gains, highlighting the critical role of a firm's network structure on their performance within the contracting relationship. We therefore find that the power of supply chain network connections enhances the short‐term positive effects and mitigates the long‐term adverse effects when contracting with government buyers, as the relationship is not always universally positive.
Health‐related quality of life in patients with primary sclerosing cholangitis: A longitudinal population‐based cohort study
Authors: Mol Bregje , van Munster Kim N. , Bogaards Johannes A. , Weersma Rinse K. , Inderson Akin , de Groof E. Joline , Rossen Noortje G. M. , Ponsioen Willemijn , Turkenburg Maud , van Erpecum Karel J. , Poen Alexander C. , Spanier B. W. Marcel , Beuers Ulrich H. W. , Ponsioen Cyriel Y. ,   the EpiPSC2 study group
Published: February 2023

AbstractBackground & AimsData regarding health‐related quality of life (HRQoL) in primary sclerosing cholangitis (PSC) are sparse and have only been studied cross‐sectionally in a disease which runs a fluctuating and unpredictable course. We aim to describe HRQoL longitudinally by using repeated measurements in a population‐based cohort.MethodsEvery 3 months from May 2017 up to August 2020, patients received digital questionnaires at home. These included the EQ‐5D, 5‐D Itch, patient‐based SCCAI and patient‐based HBI. The SF‐36, measuring HRQoL over eight dimensions as well as a physical component summary (PCS) and mental component summary (MCS) score, was sent annually. Data were compared with Dutch reference data and a matched IBD disease control from the population‐based POBASIC cohort. Mixed‐effects modelling was performed to identify factors associated with HRQoL.ResultsThree hundred twenty‐eight patients completed 2576 questionnaires. A significant reduction of small clinical relevance in several mean HRQoL scores was found compared with the Dutch reference population: 46.4 versus 48.0, p = .018 for PCS and 47.5 versus 50.5, p = .004 for MCS scores. HRQoL outcomes were significantly negatively associated with coexisting active IBD (PCS −12.2, p < .001 and MCS −12.0, p < .001), which was not the case in case of quiescent IBD. Decreasing HRQoL scores were also negatively associated with increasing age (PCS −0.1 per 10 years, p = .002), female sex (PCS ‐2.8, p < .001), diagnosis of AIH overlap (PCS ‐3.7, p = .059), end‐stage liver disease (PCS ‐3.7, p = .015) and presence of itch (PCS ‐9.2, p < .001 and MCS −3.1, p = .078). The odds of reporting a clinically relevant reduction in EQ‐5D scores showed seasonal variation, being lowest in summer (OR = 0.48 relative to spring, p = .037). In patients with liver transplant, HRQoL outcomes were comparable to the Dutch general population.ConclusionsPSC patients report impaired HRQoL of small clinical relevance compared with the general population. After liver transplantation, HRQoL scores are at comparable levels to the general population. HRQoL scores are associated with potentially modifiable factors such as itch and IBD activity.
Clues for inflammatory diseases in the differential diagnosis of a child with sacroiliitis
Authors: Karagöl Cüneyt , Güngörer Vildan , Ekici Tekin Zahide , Çelikel Elif , Aydın Fatma , Kurt Tuba , Tekgöz Nilüfer , Sezer Müge , Coşkun Serkan , Kaplan Melike Mehveş , Öner Nimet , Polat Merve Guler , Tiftik Mehmet , Tıgrak Sefa , Dereci Selim , Hızlı Şamil , Acar Banu Çelikel 
Published: February 2023

AbstractBackgroundThe purpose of this study was to compare the demographic, clinical and laboratory characteristics of patients with enthesitis‐related arthritis (ERA), familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), which are inflammatory diseases that may develop sacroiliitis. Thus, it was aimed to reveal various findings that may indicate primary disease in patients with sacroiliitis.MethodsPediatric patients aged 6–18 years, who were being followed with a diagnosis of ERA (n = 62), FMF (n = 590), and IBD (n = 56) over the period 2013–2021 were included in the study. Sacroiliitis (n = 55) was diagnosed by magnetic resonance imaging of the sacroiliac joint, obtained from clinically suspected patients.ResultsSacroiliitis was detected in 54.8% of ERA patients, 2.3% of FMF patients, and 12.5% of IBD patients. The mean follow‐up period was 4.1 ± 2.8 years (10 months‐8 years) for the entire study group. The most common MRI finding for sacroiliitis was bone marrow edema. Peripheral joint involvement (73.5%) and HLA B27 positivity (64.7%) was significantly higher in ERA patients, and ERA was diagnosed more frequently in patients presenting with sacroiliitis. Non‐steroidal anti‐inflammatory drugs (NSAIDs) were the first choice of treatment agent when sacroiliitis developed in all three patient groups.ConclusionsThe clinical and laboratory findings of ERA, FMF and IBD can sometimes be intertwined or can even coexist. Treatment may differ depending on the disease associated with sacroiliitis, although NSAIDs may be used in the first‐line treatment of all three diseases. Sacroiliitis patients with HLA B27 positivity and peripheral arthritis may need to be addressed as ERA.
Circ_0068631 sponges miR‐139‐5p to promote the growth and metastasis of cutaneous squamous cell carcinoma by upregulating HOXB7
Authors: Ji Jun , Xiong Chengcheng , Peng Jing , Zhang Niannian , Zhang Yan , Yang Honghong , Zhu Wenwen 
Published: February 2023

AbstractBackgroundCircular RNAs (circRNAs) are often dysregulated in cancers and closely related to cancer progression, including cutaneous squamous cell carcinoma (CSCC). However, the role and mechanism of circ_0068631 in CSCC progression have not been reported.MethodsThe expression of circ_0068631, microRNA‐139‐5p (miR‐139‐5p), and homeobox B7 (HOXB7) was measured by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell counting kit‐8 (CCK‐8) assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, and colony formation assay were used to measure cell proliferation. Cell apoptosis was assessed by flow cytometry. Cell migration was detected by transwell assay. The interaction between miR‐139‐5p and circ_0068631 or HOXB7 was confirmed by dual‐luciferase reporter assay. A xenograft tumor model was established to confirm the function of circ_0068631 in vivo.ResultsCirc_0068631 was upregulated in CSCC tissues and cells, and its silencing could inhibit CSCC cell proliferation and metastasis while promoting apoptosis in vitro, as well as restrain CSCC tumor growth in vivo. Circ_0068631 acted as a sponge of miR‐139‐5p, and miR‐139‐5p inhibition reversed the repressive effect of circ_0068631 knockdown on CSCC cell progression. Furthermore, HOXB7 was a target of miR‐139‐5p, and miR‐139‐5p inhibited the malignant behaviors by downregulating HOXB7 expression in CSCC cells. Further, circ_0068631 sponged miR‐139‐5p to regulate HOXB7 expression.ConclusionCirc_0068631 functioned as a novel oncogene in CSCC progression by regulating miR‐139‐5p/HOXB7 axis, suggesting that circ_0068631 may be a potential target for CSCC treatment.Highlights
Circ_0068631 was overexpressed in CSCC tissues and cells.
Circ_0068631 downregulation suppressed CSCC progression via miR‐139‐5p.
Circ_0068631 regulated HOXB7 via sponging miR‐139‐5p.
Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer
Authors: Blatti Charles , de la Fuente Jesús , Gao Huanyao , Marín-Goñi Irene , Chen Zikun , Zhao Sihai D. , Tan Winston , Weinshilboum Richard , Kalari Krishna R. , Wang Liewei , Hernaez Mikel 
Published: February 2023

AbstractSurvival rates of patients with metastatic castration-resistant prostate cancer (mCRPC) are low due to lack of response or acquired resistance to available therapies, such as abiraterone (Abi). A better understanding of the underlying molecular mechanisms is needed to identify effective targets to overcome resistance. Given the complexity of the transcriptional dynamics in cells, differential gene expression analysis of bulk transcriptomics data cannot provide sufficient detailed insights into resistance mechanisms. Incorporating network structures could overcome this limitation to provide a global and functional perspective of Abi resistance in mCRPC. Here, we developed TraRe, a computational method using sparse Bayesian models to examine phenotypically driven transcriptional mechanistic differences at three distinct levels: transcriptional networks, specific regulons, and individual transcription factors (TF). TraRe was applied to transcriptomic data from 46 patients with mCRPC with Abi-response clinical data and uncovered abrogated immune response transcriptional modules that showed strong differential regulation in Abi-responsive compared with Abi-resistant patients. These modules were replicated in an independent mCRPC study. Furthermore, key rewiring predictions and their associated TFs were experimentally validated in two prostate cancer cell lines with different Abi-resistance features. Among them, ELK3, MXD1, and MYB played a differential role in cell survival in Abi-sensitive and Abi-resistant cells. Moreover, ELK3 regulated cell migration capacity, which could have a direct impact on mCRPC. Collectively, these findings shed light on the underlying transcriptional mechanisms driving Abi response, demonstrating that TraRe is a promising tool for generating novel hypotheses based on identified transcriptional network disruptions.Significance:The computational method TraRe built on Bayesian machine learning models for investigating transcriptional network structures shows that disruption of ELK3, MXD1, and MYB signaling cascades impacts abiraterone resistance in prostate cancer.
The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study
Authors: Karanth Shama D. , Akinyemiju Tomi , Walker Courtney J. , Yang Danting , Migliorati Cesar A. , Yoon Hyung-Suk , Hong Young-Rock , Washington Caretia J. , Lattimore Chayil , Fredenburg Kristianna M. , Braithwaite Dejana 
Published: February 2023

AbstractBackground:Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES.Methods:Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated.Results:76,095 patients were included in the analysis: 63.2% were &lt;65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups.Conclusions:NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities.Impact:The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.
Genomic and Transcriptomic Characteristics of Metastatic Thyroid Cancers with Exceptional Responses to Radioactive Iodine Therapy
Authors: Boucai Laura , Saqcena Mahesh , Kuo Fengshen , Grewal Ravinder K. , Socci Nicholas , Knauf Jeffrey A. , Krishnamoorthy Gnana P. , Ryder Mabel , Ho Alan L. , Ghossein Ronald A. , Morris Luc G.T. , Seshan Venkatraman , Fagin James A. 
Published: February 2023

AbstractPurpose:The determinants of response or resistance to radioiodine (RAI) are unknown. We aimed to identify genomic and transcriptomic factors associated with structural responses to RAI treatment of metastatic thyroid cancer, which occur infrequently, and to test whether high MAPK pathway output was associated with RAI refractoriness.Experimental Design:Exceptional response to RAI was defined as reduction of tumor volume based on RECIST v1.1. We performed a retrospective case–control study of genomic and transcriptomic characteristics of exceptional responders (ER; n = 8) versus nonresponders (NR; n = 16) matched by histologic type and stage at presentation on a 1:2 ratio.Results:ER are enriched for mutations that activate MAPK through RAF dimerization (RAS, class 2 BRAF, RTK fusions), whereas NR are associated with BRAFV600E, which signals as a monomer and is unresponsive to negative feedback. ER have a lower MAPK transcriptional output and a higher thyroid differentiation score (TDS) than NR (P &lt; 0.05). NR are enriched for 1q-gain (P &lt; 0.05) and mutations of genes regulating mRNA splicing and the PI3K pathway. BRAFV600E tumors with 1q-gain have a lower TDS than BRAFV600E/1q-quiet tumors and transcriptomic signatures associated with metastatic propensity.Conclusions:ER tumors have a lower MAPK output and higher TDS than NR, whereas NR have a high frequency of BRAFV600E and 1q-gain. Molecular profiling of thyroid cancers and further functional validation of the key findings discriminating ER from NR may help predict response to RAI therapy.
Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity
Authors: Kansikas Minttu , Vähätalo Laura , Kantelinen Jukka , Kasela Mariann , Putula Jaana , Døhlen Anni , Paloviita Pauliina , Kärkkäinen Emmi , Lahti Niklas , Arnez Philippe , Kilpinen Sami , Alcala-Repo Beatriz , Pylvänäinen Kirsi , Pöyhönen Minna , Peltomäki Päivi , Järvinen Heikki J. , Seppälä Toni T. , Renkonen-Sinisalo Laura , Lepistö Anna , Mecklin Jukka-Pekka , Nyström Minna 
Published: February 2023

Lynch syndrome (LS) is the most common hereditary cancer syndrome. Early diagnosis improves prognosis and reduces health care costs, through existing cancer surveillance methods. The problem is finding and diagnosing the cancer predisposing genetic condition. The current workup involves a complex array of tests that combines family cancer history and clinical phenotypes with tumor characteristics and sequencing data, followed by a challenging task to interpret the found variant(s). On the basis of the knowledge that an inherited mismatch repair (MMR) deficiency is a hallmark of LS, we have developed and validated a functional MMR test, DiagMMR, that detects inherited MMR deficiency directly from healthy tissue without need of tumor and variant information. The validation included 119 skin biopsies collected from clinically pathogenic MMR variant carriers (MSH2, MSH6) and controls, and was followed by a small clinical pilot study. The repair reaction was performed on proteins extracted from primary fibroblasts and the interpretation was based on the MMR capability of the sample in relation to cutoff, which distinguishes MMR proficient (non-LS) from MMR deficient (LS) function. The results were compared with the reference standard (germline NGS). The test was shown to have exceptional specificity (100%) with high sensitivity (89%) and accuracy (97%). The ability to efficiently distinguish LS carriers from controls was further shown with a high area under the receiving operating characteristic (AUROC) value (0.97). This test offers an excellent tool for detecting inherited MMR deficiency linked to MSH2 or MSH6 and can be used alone or with conventional tests to recognize genetically predisposed individuals.Significance:Clinical validation of DiagMMR shows high accuracy in distinguishing individuals with hereditary MSH2 or MSH6 MMR deficiency (i.e., LS). The method presented overcomes challenges faced by the complexity of current methods and can be used alone or with conventional tests to improve the ability to recognize genetically predisposed individuals.