bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features of Chinese patients with relapsing polychondritis
Authors: Yang Peizeng , Yuan Wen , Du Liping , Zhou Qingyun , Wang Chaokui , Ye Zi , Kijlstra Aize 
Published: October 2018

PurposeTo characterise the ocular and extraocular findings in patients with relapsing polychondritis (RP) patients.DesignRetrospective, longitudinal study.MethodsA total number of 16 patients with ocular RP, seen in our tertiary uveitis referral centre over a time period of 10 years were included in this study. Routine ocular examinations such as best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, ophthalmoscopy and auxiliary examinations including ultrasound biomicroscopy, B-scanultrasonography, fundus fluorescein angiography and optical coherence tomography were performed. Ocular and systemic manifestations of these 16 patients were analysed and compared with those presented by others. The patients were treated by corticosteroids or in combination with immunosuppressive agents.ResultsEleven male and five female patients were included with a mean age of 40.4 years. Ocular involvement was bilateral in 75% of the patients and manifested as scleritis (n=10) or uveitis (n=6). Generalised, anterior and posterior uveitis was found in three, two and one patients, respectively. The frequencies of inner ear involvement and arthritis were lower in Chinese patients compared with that observed in Caucasians. Nine patients had a follow-up of 2–44 months, and in these individuals a better visual prognosis was observed in female patients compared with males.ConclusionsOur study shows that uveitis associated with RP may manifest as generalised, anterior or posterior uveitis. The incidence of inner ear involvement and arthritis in these patients was lower than that in Caucasians. Female patients seem to have milder inflammation and a better visual prognosis.
Medical nutrition therapy for gestational diabetes mellitus based on Mediterranean Diet principles: a subanalysis of the St Carlos GDM Prevention Study
Authors: Assaf-Balut Carla , Garcia de la Torre Nuria , Durán Alejandra , Fuentes Manuel , Bordiú Elena , del Valle Laura , Valerio Johanna , Familiar Cristina , Jiménez Inés , Herraiz Miguel Angel , Izquierdo Nuria , Torrejón Maria José , Runkle Isabelle , de Miguel Maria Paz , Moraga Inmaculada , Montañez Maria Carmen , Barabash Ana , Cuesta Martín , Rubio Miguel A , Calle-Pascual Alfonso Luis 
Published: October 2018

ObjectivesTo assess whether Mediterranean Diet (MedDiet)-based medical nutrition therapy facilitates near-normoglycemia in women with gestational diabetes mellitus (GDMw) and observe the effects on adverse pregnancy outcomes.Research design and methodsThis is a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clínico San Carlos (Madrid, Spain). One thousand consecutive women with normoglycemia were included before 12 gestational weeks (GWs), with 874 included in the final analysis. Of these, 177 women were diagnosed with gestational diabetes mellitus (GDM) and 697 had normal glucose tolerance. All GDMw received MedDiet-based medical nutrition therapy with a recommended daily extra virgin olive oil intake ≥40 mL and a daily handful of nuts. The primary goal was comparison of hemoglobin A1c (HbA1c) levels at 36–38 GWs in GDMw and women with normal glucose tolerance (NGTw).ResultsGDMw as compared with NGTw had higher HbA1clevels at 24–28 GWs (5.1%±0.3% (32±0.9 mmol/mol) vs 4.9%±0.3% (30±0.9 mmol/mol), p=0.001). At 36–38 GWs values were similar between the groups. Similarly, fasting serum insulin and homeostatic model assessment insulin resitance (HOMA-IR) were higher in GDMw at 24–28 GWs (p=0.001) but became similar at 36–38 GWs. 26.6% of GDMw required insulin for glycemic control. GDMw compared with NGTw had higher rates of insufficient weight gain (39.5% vs 22.0%, p=0.001), small for gestational age (6.8% vs 2.6%, p=0.009), and neonatal intensive care unit admission (5.6% vs 1.7%, p=0.006). The rates of macrosomia, large for gestational age, pregnancy-induced hypertensive disorders, prematurity and cesarean sections were comparable with NGTw.ConclusionsUsing a MedDiet-based medical nutrition therapy as part of GDM management is associated with achievement of near-normoglycemia, subsequently making most pregnancy outcomes similar to those of NGTw.
Drivers of potentially avoidable emergency admissions in Ireland: an ecological analysis
Authors: Lynch Brenda , Fitzgerald Anthony P , Corcoran Paul , Buckley Claire , Healy Orla , Browne John 
Published: October 2018

BackgroundMany emergency admissions are deemed to be potentially avoidable in a well-performing health system.ObjectiveTo measure the impact of population and health system factors on county-level variation in potentially avoidable emergency admissions in Ireland over the period 2014–2016.MethodsAdmissions data were used to calculate 2014–2016 age-adjusted emergency admission rates for selected conditions by county of residence. Negative binomial regression was used to identify which a priori factors were significantly associated with emergency admissions for these conditions and whether these factors were also associated with total/other emergency admissions. Standardised incidence rate ratios (IRRs) associated with a 1 SD change in risk factors were reported.ResultsNationally, potentially avoidable emergency admissions for the period 2014–2016 (266 395) accounted for 22% of all emergency admissions. Of the population factors, a 1 SD change in the county-level unemployment rate was associated with a 24% higher rate of potentially avoidable emergency admissions (IRR: 1.24; 95% CI 1.04 to 1.41). Significant health system factors included emergency admissions with length of stay equal to 1 day (IRR: 1.20; 95% CI 1.11 to 1.30) and private health insurance coverage (IRR: 0.92; 95% CI 0.89 to 0.96). The full model accounted for 50% of unexplained variation in potentially avoidable emergency admissions in each county. Similar results were found across total/other emergency admissions.ConclusionThe results suggest potentially avoidable emergency admissions and total/other emergency admissions are primarily driven by socioeconomic conditions, hospital admission policy and private health insurance coverage. The distinction between potentially avoidable and all other emergency admissions may not be as useful as previously believed when attempting to identify the causes of regional variation in emergency admission rates.
SWI/SNF component ARID1A restrains pancreatic neoplasia formation
Authors: Wang Sam C , Nassour Ibrahim , Xiao Shu , Zhang Shuyuan , Luo Xin , Lee Jeon , Li Lin , Sun Xuxu , Nguyen Liem H , Chuang Jen-Chieh , Peng Lan , Daigle Scott , Shen Jeanne , Zhu Hao 
Published: October 2018

ObjectiveARID1A is commonly mutated in pancreatic ductal adenocarcinoma (PDAC), but the functional effects of ARID1A mutations in the pancreas are unclear. Understanding the molecular mechanisms that drive PDAC formation may lead to novel therapies.DesignConcurrent conditional Arid1a deletion and Kras activation mutations were modelled in mice. Small-interfering RNA (siRNA) and CRISPR/Cas9 were used to abrogate ARID1A in human pancreatic ductal epithelial cells.ResultsWe found that pancreas-specific Arid1a loss in mice was sufficient to induce inflammation, pancreatic intraepithelial neoplasia (PanIN) and mucinous cysts. Concurrent Kras activation accelerated the development of cysts that resembled intraductal papillary mucinous neoplasm. Lineage-specific Arid1a deletion confirmed compartment-specific tumour-suppressive effects. Duct-specific Arid1a loss promoted dilated ducts with occasional cyst and PDAC formation. Heterozygous acinar-specific Arid1a loss resulted in accelerated PanIN and PDAC formation with worse survival. RNA-seq showed that Arid1a loss induced gene networks associated with Myc activity and protein translation. ARID1A knockdown in human pancreatic ductal epithelial cells induced increased MYC expression and protein synthesis that was abrogated with MYC knockdown. ChIP-seq against H3K27ac demonstrated an increase in activated enhancers/promoters.ConclusionsArid1a suppresses pancreatic neoplasia in a compartment-specific manner. In duct cells, this process appears to be associated with MYC-facilitated protein synthesis.
Immediate verbal recall and familial dementia risk: population-based study of over 4000 twins
Authors: Lindgren Noora , Kaprio Jaakko , Rinne Juha O , Vuoksimaa Eero 
Published: October 2018

ObjectiveTo investigate the effect of familial risk for dementia on verbal learning by comparing cognitively healthy twins who had demented co-twins with cognitively healthy twins who had cognitively healthy co-twins.Methods4367 twins aged ≥65 years including 1375 twin pairs (533 monozygotic (MZ), 823 dizygotic (DZ) and 19 unknown zygosity pairs) from a population-based Finnish Twin Cohort participated in a cross-sectional telephone assessment for dementia and in a single free recall trial of a 10-item word list.ResultsCognitively healthy twins with demented co-twins (n=101 pairs) recalled less words than cognitively healthy twins with cognitively healthy co-twins (n=770 pairs) after adjusting for age, sex and education, B=− 0.44, 95%  CI (−0.73 to −0.14), p=0.003. The effect size was similar in MZ (n=31) twins (3.88 vs 4.29 words, B=−0.41, 95%  CI (−0.96 to 0.13)) and DZ (n=66) twins (3.70 vs 4.17 words, B=−0.47, 95%  CI (−0.84 to −0.10)). The heritability estimate of immediate recall (IR) was 0.37, 95%  CI (0.21 to 0.43).ConclusionsThe results demonstrate that familial risk for dementia is reflected in the IR performance of cognitively healthy older persons. The finding of poorer IR performance in non-affected siblings compared with the general population, together with substantial heritability of IR, supports IR as a useful endophenotype for molecular genetic studies of dementia.
Decreasing incidence of subarachnoid hemorrhage
Authors: Nicholson Patrick , O’Hare Alan , Power Sarah , Looby Seamus , Javadpour Mohsen , Thornton John , Brennan Paul 
Published: October 2018

ObjectiveTo determine the incidence and trends in subarachnoid hemorrhage in Ireland using data from a national database.Materials and methodsWe performed a retrospective nationwide query of the Irish Hospital In-patient Enquiry System (HIPE). This is a national database of all in-patient activity in acute public hospitals in Ireland. Each HIPE entry records one episode of in-patient care. The study period ranged from 1997 to 2015. Population data was obtained from the Irish Central Statistics Office, and the annual prevalence of smoking from the Irish National Tobacco Control Office. We were therefore able to calculate both crude annual acute subarachnoid hemorrhage (SAH) incidence rates, as well as population-standardized rates, and compared them with trends in the annual smoking rates.ResultsThe mean number of SAH cases per year is 549, with 465 cases in 1997 and 517 in 2015 (range: 465–624). The absolute incidence of SAH, therefore, remained relatively stable. Due to population increases over time, the population-adjusted rate of SAH therefore decreased, from 126.9/million people/year in 1997 to 111.5/million people/year in 2015. Nationally, there was a decrease in smoking prevalence, from 31% in 1998 to 19.2% in 2015. There was a statistically significant correlation between decreasing smoking rates and decreasing population-adjusted incidence of SAH (P=<0.0001).ConclusionsOur data suggests that the incidence of non-traumatic subarachnoid hemorrhage in our population appears to be decreasing, a decrease which is correlated with decreasing smoking rates. This provides important data both in terms of the epidemiology of SAH, as well as the possible role of public-health interventions in tackling both smoking and declining rates of SAH.
Sensitivity and specificity of normalized truncated navicular height in assessment of static foot posture in children aged 6–12 years
Authors: Aboelnasr Emad A. , El-Talawy Hoda A. , Abdelazim Faten H. , Hegazy Fatma A. 
Published: October 2018

Background: Normalized truncated navicular height (NTNH) is a non-invasive, easy to perform, and simple clinical measure of static foot posture. However, its sensitivity and specificity in evaluation of the static foot posture in children have not been investigated yet. Objective: To investigate the intra-rater reliability, sensitivity, and specificity of NTNH in evaluation of the static foot posture in children using radiographic measure as a gold standard measure. Methods: A cross-sectional study of a random sample of 300 school children aged 6–12 years old. Intra-rater reliability, minimal detectable change, sensitivity, and specificity of NTNH were investigated. NTNH as a clinical measure of static foot posture was calculated and compared to the radiographic measure and displayed on the receiver operating characteristic (ROC) curve. Results: NTNH demonstrated an intra-rater reliability of [Formula: see text]. The sensitivity and specificity of NTNH were 88.1% and 99.5%, respectively. The optimal cutoff point for the diagnosis of flat foot using NTNH in children aged 6–12 years is NTNH [Formula: see text]. Conclusion: NTNH is a sensitive and specific measure of static foot posture in the children aged 6–12 years. It is recommended to be used as a screening measure of static foot posture in children as it is easy, simple to perform, and a non-invasive clinical measure.
Prognostic Value of Cancer Stem Cell Markers in Potentially Malignant Disorders of Oral Mucosa: A Meta-analysis
Authors: Saluja Tajindra Singh , Ali Murtaza , Mishra Prabhaker , Kumar Vijay , Singh Satyendra Kumar 
Published: October 2018

Abstract

Background:
Oral squamous cell carcinoma (OSCC) is usually preceded by clinically visible changes on oral mucosa categorized as oral potentially malignant disorders (OPMD). The progression of OPMD to OSCC is a multistep process that provides an opportunity for early cancer detection and interception. Recent research suggests that cancer stem cells (CSC) hold the key to unlocking effective strategies to curb initiation and growth of several malignant neoplasms, including OSCC. In this meta-analysis, we evaluated the efficacy of CSC markers CD133, podoplanin, ALDH1, and others in predicting risk of malignant transformation of OPMDs.

Methods:
The PubMed database was systematically reviewed for relevant articles. Quality of eligible studies was assessed as per reporting recommendations for tumor marker (REMARK) criteria. A total of 18 investigations from 12 studies evaluated clinical or prognostic significance of CSC markers in OPMDs. A reasonable number of patients (1,659) were included in this analysis.

Results:
Positive expression of CSC markers in OPMDs is significantly associated with progression to OSCC [risk ratio (RR), 3.31; 95% confidence interval (CI), 2.72–4.02]. Variability in CSC population makes it difficult to understand exact biology of OPMDs based on single CSC marker investigation.

Conclusions:
Identifying CSC population is a reliable prognostic indicator in OPMDs with or without dysplasia. Multi-marker panel investigation for CSCs in OPMDs may assist in curtailing new cases of oral cancer to a great extent.

Impact:
The study illustrates that evaluating CSC marker expression in OPMDs is a key tool in identifying high-risk cases to prevent development of OSCC.
Combined Blockade of Activating ERBB2 Mutations and ER Results in Synthetic Lethality of ER+/HER2 Mutant Breast Cancer
Authors: Croessmann Sarah , Formisano Luigi , Kinch Lisa N. , Gonzalez-Ericsson Paula I. , Sudhan Dhivya R. , Nagy Rebecca J. , Mathew Aju , Bernicker Eric H. , Cristofanilli Massimo , He Jie , Cutler Richard E. , Lalani Alshad S. , Miller Vincent A. , Lanman Richard B. , Grishin Nick V. , Arteaga Carlos L. 
Published: October 2018

Abstract

Purpose:
We examined the role of ERBB2-activating mutations in endocrine therapy resistance in estrogen receptor positive (ER+) breast cancer.

Experimental Design:
ERBB2 mutation frequency was determined from large genomic databases. Isogenic knock-in ERBB2 mutations in ER+ MCF7 cells and xenografts were used to investigate estrogen-independent growth. Structural analysis was used to determine the molecular interaction of HERL755S with HER3. Small molecules and siRNAs were used to inhibit PI3Kα, TORC1, and HER3.

Results:
Genomic data revealed a higher rate of ERBB2 mutations in metastatic versus primary ER+ tumors. MCF7 cells with isogenically incorporated ERBB2 kinase domain mutations exhibited resistance to estrogen deprivation and to fulvestrant both in vitro and in vivo, despite maintaining inhibition of ERα transcriptional activity. Addition of the irreversible HER2 tyrosine kinase inhibitor neratinib restored sensitivity to fulvestrant. HER2-mutant MCF7 cells expressed higher levels of p-HER3, p-AKT, and p-S6 than cells with wild-type HER2. Structural analysis of the HER2L755S variant implicated a more flexible active state, potentially allowing for enhanced dimerization with HER3. Treatment with a PI3Kα inhibitor, a TORC1 inhibitor or HER3 siRNA, but not a MEK inhibitor, restored sensitivity to fulvestrant and to estrogen deprivation. Inhibition of mutant HER2 or TORC1, when combined with fulvestrant, equipotently inhibited growth of MCF7/ERBB2V777L xenografts, suggesting a role for TORC1 in antiestrogen resistance induced by ERBB2 mutations.

Conclusions:
ERBB2 mutations hyperactivate the HER3/PI3K/AKT/mTOR axis, leading to antiestrogen resistance in ER+ breast cancer. Dual blockade of the HER2 and ER pathways is required for the treatment of ER+/HER2 mutant breast cancers.
Peripheral Stem Cell Apheresis is Feasible Post 131Iodine-Metaiodobenzylguanidine-Therapy in High-Risk Neuroblastoma, but Results in Delayed Platelet Reconstitution
Authors: Kraal Kathelijne C.J.M. , Timmerman Ilse , Kansen Hannah M. , van den Bos Cor , Zsiros Jozsef , van den Berg Henk , Somers Sebastiaan , Braakman Eric , Peek Annemarie M.L. , van Noesel Max M. , van der Schoot C. Ellen , Fiocco Marta , Caron Huib N. , Voermans Carlijn , Tytgat Godelieve A.M. 
Published: October 2018

AbstractPurpose:Targeted radiotherapy with 131iodine-meta-iodobenzylguanidine (131I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment is being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront 131I-MIBG-therapy.Experimental Design:In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of 131I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34+ cell) harvest yield, required number of apheresis sessions, and time to neutrophil (&gt;0.5 × 109/L) and platelet (&gt;20 × 109/L) reconstitution after ASCT were analyzed and compared with “chemotherapy-only”–treated patients. Moreover, harvested CD34+ cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41, and CD62L) tested before cryopreservation (n = 44) and/or after thawing (n = 19).Results:Thirty-eight patients (47%) were treated with 131I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative 131I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34+ cell harvest yield and apheresis days were comparable in both groups. Post ASCT, neutrophil recovery was similar (11 days vs. 10 days), whereas platelet recovery was delayed in 131I-MIBG- compared with chemotherapy-only–treated patients (29 days vs. 15 days, P = 0.037). Testing of harvested CD34+ cells revealed a reduced post-thaw viability in the 131I-MIBG-group. Moreover, the viable CD34+ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery.Conclusions:Harvesting of CD34+ cells is feasible after 131I-MIBG. Platelet recovery after ASCT was delayed in 131I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34+ cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront 131I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of 131I-MIBG-treated patients contained lower viable CD34+ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of 131I-MIBG after apheresis is preferred.
Genetically Determined Platelet Count and Risk of Cardiovascular Disease
Authors: Gill Dipender , Monori Grace , Georgakis Marios K. , Tzoulaki Ioanna , Laffan Mike 
Published: October 2018

Objective—
Cardiovascular disease, including coronary artery disease (CAD) and ischemic stroke, is the leading cause of death worldwide. This Mendelian randomization study uses genetic variants as instruments to investigate whether there is a causal effect of genetically determined platelet count on CAD and ischemic stroke risk.

Approach and Results—

A genome-wide association study of 166 066 subjects was used to identify instruments and genetic association estimates for platelet count. Genetic association estimates for CAD and ischemic stroke were obtained from genome-wide association studies, including 60 801 CAD cases and 123 504 controls, and 60 341 ischemic stroke cases and 454 450 controls, respectively. The inverse-variance weighted meta-analysis of ratio method Mendelian randomization estimates was the main method used to obtain estimates for the causal effect of genetically determined platelet count on risk of cardiovascular outcomes. We found no significant Mendelian randomization effect of genetically determined platelet count on risk of CAD (odds ratio of CAD per SD unit increase in genetically determined platelet count, 1.01; 95% CI, 0.98–1.04;
P
=0.60). However, higher genetically determined platelet count was causally associated with an increased risk of ischemic stroke (odds ratio, 1.07; 95% CI, 1.04–1.11;
P
<1×10
−5
), including all major ischemic stroke subtypes. Similar results were obtained in sensitivity analyses more robust to the inclusion of pleiotropic genetic variants.

Conclusions—
This Mendelian randomization study found evidence that higher genetically determined platelet count is causally associated with higher risk of ischemic stroke.