bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification
Authors: Kleeman Sam O , Koelzer Viktor H , Jones Helen JS , Vazquez Ester Gil , Davis Hayley , East James E , Arnold Roland , Koppens Martijn AJ , Blake Andrew , Domingo Enric , Cunningham Chris , Beggs Andrew D , Pestinger Valerie , Loughrey Maurice B , Wang Lai-Mun , Lannagan Tamsin RM , Woods Susan L , Worthley Daniel , Tomlinson Ian , Dunne Philip D , Maughan Timothy , Leedham Simon J 
Published: September 2019

ObjectivePathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (Adenomatous polyposis coli, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (RNF43,RSPO-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours.DesignWe undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups.ResultsWnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation ofRSPOmay compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (AXIN2,NKD1) occurring even in CIMP-negative LD cancers.AXIN2mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93).ConclusionsEpigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differentialAXIN2expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.
Multiplex fluorescence in situ hybridisation to detect anaplastic lymphoma kinase and ROS proto-oncogene 1 receptor tyrosine kinase rearrangements in lung cancer cytological samples
Authors: Zito Marino Federica , Rossi Giulio , Cozzolino Immacolata , Montella Marco , Micheli Mariacarolina , Bogina Giuseppe , Munari Enrico , Brunelli Matteo , Franco Renato 
Published: September 2019

AimsSeveral predictive biomarkers of response to specific inhibitors have become mandatory for the therapeutic choice in non-small-cell lung cancer (NSCLC). In most lung cancer patients, the biological materials available to morphological and molecular diagnosis are exclusively cytological samples and minimum tumour wastage is necessary. Multiplex fluorescence in situ hybridisation (mFISH) to detect simultaneouslyALK-rearrangement andROS1-rearrangement on a single slide could be useful in clinical practice to save cytological samples for further molecular analysis. In this study, we aim to validate diagnostic performance of multiplex ALK/ROS1 fluorescence in situ hybridisation (FISH) approach in lung adenocarcinoma cytological series compared with classic single break apart probes.MethodsWe collected a series of 61 lung adenocarcinoma cytological specimens enriched in tumours harbouringALK-rearrangement andROS1-rearrangement.ALKandROS1status were previously assessed by classic FISH test using single break apart probes and immunohistochemistry. Study population was composed of 6ALK-positive, 2ROS1-positive and 53ALK/ROS1-wild type. All specimens were analysed by multiplex FISH assay using FlexISH ALK/ROS1 DistinguISH Probe Zytovision.ResultsThe dual ALK/ROS1 FISH probe test results were fully concordant with the results of previous single ALK and ROS1 FISH tests on two different slides. 6ALK-positive and 2ROS1-positive were confirmed through multiplex FISH test, without false-positive and false-negative results. Multiplex ALK/ROS1 FISH test results agreed with immunohistochemistry assay staining results.ConclusionMultiplex ALK/ROS1 FISH probe test is a useful tool to detect simultaneouslyALK-rearrangement andROS1-rearrangement on a single slide in cytological specimens with a small amount of biomaterial.
Onset of type 1 diabetes mellitus in rural areas of the USA
Authors: Rogers Mary A M 
Published: September 2019

BackgroundIn the USA, the epidemiologic features of type 1 diabetes are not well-defined across all 50 states. However, the advent of large nationwide insurance databases enables the investigation of where type 1 diabetes cases occur throughout the country.MethodsAn integrated database from a large nationwide health insurer in the USA (Clinformatics Data Mart Database) was used, from 2001 to 2017. The database contained longitudinal information on approximately 77 million people.ResultsThe incidence of type 1 diabetes was greatest in areas of low population density across the 50 states. Individuals in the lowest population density areas had rates that were 2.28 times (95% CI 2.08 to 2.50) that of persons living in high-density areas. This association was consistent across various measures of rural status (p<0.001 for population density; p<0.001 for per cent rural as defined by the US Census Bureau; p=0.026 for farmland). The association between rural areas and the incidence of type 1 diabetes was evident across all four general regions of the USA.ConclusionsThe predilection of type 1 diabetes in rural areas provides clues to potential factors associated with the onset of this autoimmune disease.
Undiagnosed and untreated chronic kidney disease and its impact on renal outcomes in the Japanese middle-aged general population
Authors: Yamada Yukari , Ikenoue Tatsuyoshi , Saito Yoshiyuki , Fukuma Shingo 
Published: September 2019

BackgroundThe effectiveness of identifying and monitoring early-stage chronic kidney disease (CKD) is not fully recognised. This study quantified people with undiagnosed CKD among the middle-aged Japanese population and clarified potential risks of untreated CKD.MethodsWe included 71 233 individuals who underwent annual health check-ups (AHC) in 2014 for both baseline and follow-up proteinuria and serum creatine measurements. CKD was identified by AHC data as proteinuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We differentiated undiagnosed from diagnosed CKD using the medical claims database. In undiagnosed CKD, we assessed risk differences for disease progression, defined as an eGFR decline slope >3 mL/min/1.73 m2/year or proteinuria incidence over 3 years, between those who visited a physician for CKD treatment within 6 months after AHC and those who did not.ResultsCKD prevalence was 5.7% (5.2% undiagnosed and 0.5% diagnosed). Only 2.1% of the patients with undiagnosed CKD visited a physician for CKD treatment within 6 months after AHC. Between-group risk differences in instrumental variable adjustment models showed that those left untreated progressed to kidney diseases 16.3% more often than those who visited physicians for CKD treatment.ConclusionCKD was undiagnosed in 5.2% of the middle-aged general population. Only a few people visited physicians for CKD treatment. Visiting physicians for CKD treatment during the first 6 months after screening may be associated with a lower risk of kidney disease progression.
THUR 072 A service evaluation of patients attending A&E with seizures
Authors: Navindi Fernandopulle , Mahinda Yogarajah 
Published: September 2019

BackgroundEpilepsy is the most common, chronic neurological condition with a prevalence of 0.5% and an incidence of 3 to 5%. Despite anticonvulsant use, there are approximately 60,000 A&E attendances and 40,000 hospital admissions.MethodUsing A&E triage records a list of all patients attending St George’s Hospital A&E department with a seizure within a six month period was derived. By referring to clinical records, management in A&E and beyond was audited according to NICE guidelines.Results382 adults with seizures were identified. 33% attended A&E in the previous 12 months with a seizure. Of those with epilepsy (n=187), 9% were on no drug. In all seizure cases, documentation was often incomplete and a collateral history was only obtained in 44% cases. 44% of patients were admitted, and of these, 15% were unnecessary according to criteria outlined by Iyer et al. Only 8% were asked if they were a driver and alcohol intake was not documented in 44%. Only 37% were referred to a neurologist or epilepsy specialist.ConclusionSeeing as a third of the patients attended A&E in the previous 12 months, it is clear that thorough history taking and better management in the community is necessary.
THUR 038 Encephalopathy with MRI cortical ribbon and reversible white matter hyperintensities
Authors: Morrison Hamish , Morgan Dafydd , Smith Matthew , Mclauchlan Duncan , Johnston Ann 
Published: September 2019

We present an unusual case of encephalopathy with profound MR white matter and cortical abnormalities secondary to, and responsive to treatment for, hepatic encephalopathy alone.A 52-year-old man with known alcohol related liver disease (now abstinent), previous intravenous drug abuse and treated Hepatitis C presented over 18 months with discrete episodes of fluctuating confusion, and altered consciousness progressing to coma.Neuroimaging demonstrated symmetrical confluent white matter T2/ FLAIR hyperintensities in the posterior frontal and parietal lobes with symmetrical dWI cortical ribboning in the precentral gyrus. Due to his clinical state and the unusual neuroimaging findings he was transferred for further neurological investigation and management.On admission a serum ammonia was 111 µmol/L (normal range 16 – 60 µmol/L). Further to this a detailed systemic blood, imaging and CSF analysis did not yield an alternative diagnosis. Electroencephalography revealed generalised slowing.Serial imaging showed persistent, fluctuating, confluent, and symmetrical white matter T2/ FLAIR hyperintensities. Fluctuations in his clinical state correlated with serum ammonia levels, bowel motions, neuroimaging and the EEG findings. He was treated for hepatic encephalopathy alone, on one occasion in intensive care, with lactulose, phosphate enemas and diuretics. He was discharged home independently after a period of sustained clinical improvement.
Effects of first pass recanalization on outcomes of contact aspiration thrombectomy
Authors: Kang Dong-Hun , Kim Byung Moon , Heo Ji Hoe , Nam Hyo Suk , Kim Young Dae , Hwang Yang Ha , Kim Yong-Won , Kim Dong Joon , Kim Joon Whi , Baek Jang-Hyun , Kim Yong-Sun 
Published: September 2019

BackgroundFirst pass recanalization (FPR, defined as achieving a modified Thrombolysis in Cerebral Ischemia (mTICI) grade 2c/3 with a single pass of a thrombectomy device) effect has not yet been evaluated in contact aspiration thrombectomy (CAT). We evaluated FPR effect on clinical outcomes and FPR predictors in CAT.MethodsAll consecutive patients who underwent frontline CAT for anterior circulation large vessel occlusion with recanalization (mTICI 2b–3) were identified from registries at six stroke centers. The patients were dichotomized into FPR and non-FPR groups. Clinical features and outcomes were compared between the groups. Multivariate analyses were performed to determine whether FPR was independently associated with clinical outcomes and to identify predictors of FPR.ResultsOf the 429 patients who underwent frontline CAT, recanalization was successful in 344 patients (80.2%; mean age 68.7±11.0 years; M:F ratio 179:165). The FPR group had a higher rate of good outcome (modified Rankin Scale score 0–2) than the non-FPR group. Furthermore, the good outcome rate was higher in the FPR group than in patients who achieved mTICI 2c/3 with multiple passes or rescue treatment. FPR (OR 2.587; 95% CI 1.237 to 5.413) remained independently associated with good outcomes, in addition to age, baseline National Institute Health Stroke Scale, and coronary artery disease. The use of a balloon guide catheter (OR 3.071; 95% CI 1.699 to 5.550) was the only predictor of FPR.ConclusionsPatients in the FPR group had better clinical outcomes than the non-FPR group in CAT. FPR was independently associated with a good outcome. The use of a balloon guide catheter was the only predictor of FPR.
Microcatheter shaping using three-dimensional printed models for intracranial aneurysm coiling
Authors: Xu Y , Tian W , Wei Z , Li Y , Gao X , Li W , Dong B 
Published: September 2019

Background and purposeMicrocatheterization is an important, but also difficult, technique used for the embolization of intracranial aneurysms. The purpose of this study was to investigate the application of three-dimensional (3D) printing technology in microcatheter shaping.MethodsNine cases of internal carotid artery posterior communicating artery aneurysm diagnosed by CT angiography were selected, and 3D printing technology was used to build a 3D model including the aneurysm and the parent artery. The hollow and translucent model had certain flexibility; it was immersed in water and the microcatheter was introduced into the water to the target position in the aneurysm, followed by heating the water temperature to 50°C. After soaking for 5 min, the microcatheter was taken out and the shaping was completed. After sterilization, the shaped microcatheter was used for arterial aneurysm embolization and evaluation was conducted.ResultsNine cases of microcatheter shaping were satisfactory and shaping the needle was not necessary; no rebound was observed. The microcatheter was placed in an ideal position, and the stent-assisted method was used in three cases of wide-neck aneurysm. There were no complications related to surgery.ConclusionA new microcatheter shaping method using 3D printing technology makes intracranial artery aneurysm embolization more stable and efficient.
Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy
Authors: Smpokou Evangelia-Theano , González-Quiroz Marvin , Martins Carla , Alvito Paula , Le Blond Jennifer , Glaser Jason , Aragón Aurora , Wesseling Catharina , Nitsch Dorothea , Pearce Neil , Norman Jill , Lindh Christian H , Morton Jackie , Caplin Ben 
Published: September 2019

ObjectivesThere is an epidemic of Mesoamerican nephropathy (MeN) in Central America, where sugarcane production is prominent. Numerous causes are proposed, but to date limited evidence supports any one hypothesis. A nested case–control study using biosamples from a rural, community-based follow-up study of 350 young adults from Northwest Nicaragua at risk of MeN was conducted with the aim of characterising the associations between urinary concentrations of metals, pesticides and mycotoxins from samples collected in the first 6 months and decline in kidney function over 2 years.MethodsUrine samples collected at baseline (pre-sugarcane harvest) and the first 6 month follow-up (post-sugarcane harvest) visit were tested. Twelve metals and metalloids (aluminium, total arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, selenium, silicon and strontium) were analysed by inductively coupled plasma-mass spectrometry. Twelve pesticides or their metabolites (2,4-dichlorophenoxyacetic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, chloro-3,3,3-trifluoro-1-propen-1-yl-2,2-dimethylcyclopropanecarboxylic acid, cis/trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, ethylenethiourea, glyphosate, 4-chloro-2-methylphenoxy acetic acid, 3-hydroxy-pyrimetanil, 5-hydroxytiabendazole, hydroxy-tebuconazole and 3,5,6-trichloro-2-pyridinol) and two mycotoxins (ochratoxin A (OTA) and citrinin (CIT)) were analysed by liquid chromatography coupled-mass spectrometry. Differences in the creatinine-corrected urinary concentrations of the measured exposures between outcome groups (participants with stable vs declining kidney function) were examined.ResultsElevated levels of aluminium and total arsenic as well as metabolites of several pesticides were detected across the population. No differences were identified between the declining and stable groups in the levels of metals or pesticides tested. OTA and CIT were below the limit of detection.ConclusionsThe tested metals, metalloids, pesticides and mycotoxins were not associated with loss of kidney function in participants at-risk of MeN.
Association of adiponectin and adiponectin receptor gene polymorphisms with rheumatoid arthritis in a Chinese population
Authors: Zhao Yu-Lan , Zhang Tian-Ping , Wu Jun , Li Bao-Zhu , Li Xiao-Mei , Pan Hai-Feng , Ye Dong-Qing 
Published: September 2019

AbstractPurposeTo explore the association of adiponectin (AD) and adiponectin receptor (ADR) gene single-nucleotide polymorphisms (SNPs) with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population.Study designFive AD SNPs (rs266729, rs2241766, rs1063537, rs2082940 and rs1063539) and two ADR SNPs (rs7539542 and rs12342) were genotyped in a cohort of 617 patients with RA and 639 healthy controls. Seven SNPs were genotyped using TaqMan genotyping assays on the Fluidigm 192.24 system. The concentration of AD in plasma was examined by ELISA.ResultsPatients with RA showed a considerably lower plasma level of AD than healthy controls (p=0.002). No significant differences were observed for the distribution of allele and genotype frequencies of rs266729, rs2241766, rs2082940, rs1063539, rs7539542 and rs12342 SNPs between patients with RA and controls. The genotype effects of recessive and dominant models were also analysed, but no marked evidence for association was found. However, further analysis in female patients with RA showed that the frequency of the AD gene rs1063539 GG genotype was nominally significantly higher in patients who were anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (p=0.040). No significant differences in serum AD level were observed in patients with RA with different genotypes.Conclusionsrs266729, rs2241766, rs2082940 and rs1063539 in the AD gene and rs7539542 and rs12342 in the ADR gene are possibly not associated with genetic susceptibility to RA, but the AD gene rs1063539 locus was possibly associated with anti-CCP in RA female patients.
Factors influencing pharmacists’ over-the-counter drug recommendations
Authors: Grebenar Darija , Nham Eric , Likic Robert 
Published: September 2019

AbstractBackgroundSelf-care is a growing trend all over the world, and pharmacists have a major role in it since they are the most easily accessible medical experts.ObjectivesOur aim was to investigate factors influencing pharmacists’ over-the-counter (OTC) drugs recommendations in Croatia.SettingA random sample of 565 (50%) of all pharmacies in Croatia.MethodsA cross-sectional study with a five-point Likert scale online questionnaire covering medical and non-medical factors influencing OTC drug recommendation was distributed in October 2017 to a random sample of pharmacies.Results206/565 (response rate 36.5%) responses were collected. The most important factors influencing pharmacists’ recommendation were: composition of the OTC product and its active component (4.76±0.47), scientific evidence of effectiveness (4.54±0.60), feedback from the patients (4.32±0.61) and information from professional journals (4.22±0.67). On average, medical factors had greater importance (4.5±0.58) for pharmacists’ OTC recommendation than marketing (3.18±0.84) and social factors (3.15±0.79). Female pharmacists appeared less inclined to recommend an OTC product based on advice of other pharmacists (OR=0.61, CI=0.43 to 0.86, p=0.005) and pharmacists working directly in a pharmacy attached more importance to active components of OTC products during their OTC product counselling (OR=2.28, CI=0.92 to 5.65, p=0.03).ConclusionIt is vital to know that pharmacists’ OTC recommendations are mainly influenced by medical factors and to a lesser degree by marketing and social factors.
Prospective cohort study examining the use of regional anesthesia for early pain management after combat-related extremity injury
Authors: Gallagher Rollin M , Polomano Rosemary C , Giordano Nicholas A , Farrar John T , Guo Wensheng , Taylor Lynn , Oslin David , Goff Brandon J , Buckenmaier Chester C 
Published: September 2019

Background
No studies have examined the long-term benefits of regional anesthesia (RA) for pain management after combat-related injury. The objective of this prospective cohort study was to examine the relationship between RA administration and patient-reported pain-related outcomes among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) service members sustaining a combat-related extremity injury.

Methods
Between 2007 and 2013, n=358 American military personnel injured in OEF/OIF were enrolled at two military treatment facilities. Individuals were followed for up to 2 years after injury. Cohorts were defined based on whether participants were administered RA within 7 days after sustaining a combat-related injury, or not. Linear mixed effects models examined the association between RA and average pain intensity. Secondary outcomes included pain relief, pain interference, neuropathic pain symptoms, treatment outcomes related to pain management, and mental health symptoms.

Results
Receiving early RA was associated with improved average pain over the first 6 months after injury (β=−0.57; p=0.012) adjusting for injury severity and length of stay at the primary treatment facility. This difference was observed up to 24 months after injury (β=−0.36; p=0.046). Individuals receiving early RA reported greater pain relief, improved neuropathic pain intensity, and higher satisfaction with pain outcomes; however, by 24 months, mean scores did not significantly differ between cohorts.

Conclusion
Findings indicate that when administered soon after traumatic injury, RA is a valuable pain management intervention. Future longitudinal studies investigating the timely delivery of RA for optimal pain management in civilian trauma settings are needed.

Trial registration number

NCT00431847
Bolus epidural infusion improves spread compared with continuous infusion in a cadaveric porcine spine model
Authors: Cole Jacob , Hughey Scott 
Published: September 2019

Background
The administration of epidural anesthesia during labor is a common technique used to reduce the pain of childbirth. We sought to compare standard infusion strategies of continuous epidural infusions (CEI) with programmed intermittent epidural bolus (PIEB) to assess the length of spread in terms of vertebral body length. Based on previous clinical data in humans, the PIEB was associated with improved pain control and decreased total dose of local anesthetic. We hypothesized that the PIEB was associated with increased spread when compared with CEI.

Methods
Thirty female Yorkshire-cross swine cadavers were used to compare three infusion strategies, continuous infusion (CEI) 10 mL/hour programmed continuously, multiple bolus (MB) 2 mL given every 12 min for 10 mL total and 10 mL delivered in a single bolus (SB). Radiographs were used to identify the spread of the radiopaque contrast dye, and a number of vertebral bodies covered were measured to assess spread.

Results
Overall, the CEI had an average spread of 5.6 levels, MB 7.9 and SB 10.4. The differences between SB and MB (p=0.011), SB and CEI (p<0.001) and MB and CEI (p=0.028) were all found to be significant.

Conclusions
We demonstrated increased spread of epidural contrast with programmed intermittent bolus strategies. This supports previous evidence of improved patient outcomes with PIEB strategy compared with CEI, and encourages the use of PIEB in the appropriate patient population.