bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novel risk stratification algorithm for relapsed multiple myeloma
Authors: Hájek Roman , Delforge Michel , Raab Marc S. , Schoen Paul , DeCosta Lucy , Spicka Ivan , Radocha Jakub , Pour Ludek , Gonzalez‐McQuire Sebastian , Bouwmeester Walter 
Published: August 2019

SummaryMultiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease‐related factors change between diagnosis and the initiation of second‐line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K‐adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)–4 (highest risk) were 61·6, 29·6, 14·2 and 5·9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations.
Three‐dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores
Authors: Porpiglia Francesco , Amparore Daniele , Checcucci Enrico , Manfredi Matteo , Stura Ilaria , Migliaretti Giuseppe , Autorino Riccardo , Ficarra Vincenzo , Fiori Cristian 
Published: August 2019

ObjectivesTo apply the standard PADUA and RENAL nephrometry score variables to three‐dimensional (3D) virtual models (VMs) produced from standard bi‐dimensional imaging, thereby creating three‐dimensional (3D)‐based (PADUA and RENAL) nephrometry scores/categories for the reclassification of the surgical complexity of renal masses, and to compare the new 3D nephrometry score/category with the standard 2D‐based nephrometry score/category, in order to evaluate their predictive role for postoperative complications.Materials and MethodsAll patients with localized renal tumours scheduled for minimally invasive partial nephrectomy (PN) between September 2016 and September 2018 underwent 3D and 2D nephrometry score/category assessments preoperatively. After nephrometry score/category evaluation, all the patients underwent surgery. Chi‐squared tests were used to evaluate the individual patients’ grouping on the basis of the imaging tool (3D VMs and 2D imaging) used to assess the nephrometry score/category, while Cohen's κ coefficient was used to test the concordance between classifications. Receiver‐operating characteristic curves were produced to evaluate the sensitivity and specificity of the 3D nephrometry score/category vs the 2D nephrometry score/category in predicting the occurrence of postoperative complications. A general linear model was used to perform multivariable analyses to identify predictors of overall and major postoperative complications.ResultsA total of 101 patients were included in the study. The evaluation of PADUA and RENAL nephrometry scores via 3D VMs showed a downgrading in comparison with the same scores evaluated with 2D imaging in 48.5% and 52.4% of the cases. Similar results were obtained for nephrometry categories (29.7% and 30.7% for PADUA risk and RENAL complexity categories, respectively). The 3D nephrometry score/category demonstrated better accuracy than the 2D nephrometry score/category in predicting overall and major postoperative complications (differences in areas under the curve for each nephrometry score/category were statistically significant comparing the 3D VMs with 2D imaging assessment). Multivariable analyses confirmed 3D PADUA/RENAL nephrometry category as the only independent predictors of overall (P = 0.007; P = 0.003) and major postoperative complications (P = 0.03; P = 0.003).ConclusionsIn the present study, we showed that 3D VMs were more precise than 2D standard imaging in evaluating the surgical complexity of renal masses according to nephrometry score/category. This was attributable to a better perception of tumour depth and its relationships with intrarenal structures using the 3D VM, as confirmed by the higher accuracy of the 3D VM in predicting postoperative complications.
Oncogenic splicing abnormalities induced by DEAD‐Box Helicase 56 amplification in colorectal cancer
Authors: Kouyama Yuta , Masuda Takaaki , Fujii Atsushi , Ogawa Yushi , Sato Kuniaki , Tobo Taro , Wakiyama Hiroaki , Yoshikawa Yukihiro , Noda Miwa , Tsuruda Yusuke , Kuroda Yousuke , Eguchi Hidetoshi , Ishida Fumio , Kudo Shin‐ei , Mimori Koshi 
Published: August 2019

AbstractAlternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1.
How to correct the odds ratio for lack of sensitivity and specificity
Authors: Antunes José Leopoldo Ferreira 
Published: August 2019

AbstractThis commentary explains and exemplifies a method to estimate the Odds Ratio—OR with a correction for possible errors in diagnosis. This procedure allows reassessing hypotheses of association between health outcomes and exposures when the database entails lack of accuracy, and the estimates of sensitivity and specificity of the diagnostic tool are available. Misclassification is not uncommon in dental public health research. Classification errors should not be ignored; they should instead be subject of measurement and adjustment. However, the lack of diagnostic validity is an elusive error, which cannot be entirely controlled. The method described here is solely an attempt to explore further the assessment of factors impacting on health outcomes.
Identification of a dominant MYH11 causal variant in chronic intestinal pseudo‐obstruction: Results of whole‐exome sequencing
Authors: Dong Weilai , Baldwin Clinton , Choi Jungmin , Milunsky Jeff M. , Zhang Junhui , Bilguvar Kaya , Lifton Richard P. , Milunsky Aubrey 
Published: August 2019

AbstractChronic Intestinal Pseudo‐Obstruction (CIPO) is a rare gastrointestinal disorder, which affects the smooth muscle contractions of the gastrointestinal tract. Dominant mutations in the smooth muscle actin gene, ACTG2, accounts for 44%‐50% of CIPO patients. Other recessive or X‐linked genes, including MYLK, LMOD1, RAD21, MYH11, MYL9, and FLNA were reported in single cases. In this study, we used Whole‐Exome Sequencing (WES) to study 23 independent CIPO families including one extended family with 13 affected members. A dominantly inherited rare mutation, c.5819delC (p.Pro1940HisfsTer91), in the smooth muscle myosin gene, MYH11, was found in the extended family, shared by 7 affected family members but not by 3 unaffected family members with available DNA, suggesting a high probability of genetic linkage. Gene burden analysis indicates that additional genes, COL4A1, FBLN1 and HK2, may be associated with the disease. This study expanded our understanding of CIPO etiology and provided additional genetic evidence to physicians and genetic counselors for CIPO diagnosis.
Colorectal cancer patients under the age of 50 experience delays in primary care leading to emergency diagnoses: a population‐based study
Authors: Arhi C. S. , Ziprin P. , Bottle A. , Burns E. M. , Aylin P. , Darzi A. 
Published: August 2019

AbstractAimThe incidence of colorectal cancer in the under 50s is increasing. In this national population‐based study we aim to show that missed opportunities for diagnosis in primary care are leading to referral delays and emergency diagnoses in young patients.MethodWe compared the interval before diagnosis, presenting symptom(s) and the odds ratio (OR) of an emergency diagnosis for those under the age of 50 with older patients sourced from the cancer registry with linkage to a national database of primary‐care records.ResultsThe study included 7315 patients, of whom 508 (6.9%) were aged under 50 years, 1168 (16.0%) were aged 50–59, 2294 (31.4%) were aged 60–69 and 3345 (45.7%) were aged 70–79 years. Young patients were more likely to present with abdominal pain and via an emergency, and had the lowest percentage of early stage cancer. They experienced a longer interval between referral and diagnosis (12.5 days) than those aged 60–69, reflecting the higher proportion of referrals via the nonurgent pathway (33.3%). The OR of an emergency diagnosis did not differ with age if a red‐flag symptom was noted at presentation, but increased significantly for young patients if the symptom was nonspecific.ConclusionYoung patients present to primary care with symptoms outside the national referral guidelines, increasing the likelihood of an emergency diagnosis.
Designing a global mechanism for intergovernmental biodiversity financing
Authors: Droste Nils , Farley Joshua , Ring Irene , May Peter H. , Ricketts Taylor H. 
Published: August 2019

AbstractThe Convention on Biological Diversity and the Nagoya Protocol display a broad international consensus for biodiversity conservation and equitable benefit sharing. Yet, the Aichi biodiversity targets show a lack of progress and thus indicate a need for additional action such as enhanced and better targeted financial resource mobilization. To date, no global financial burden‐sharing instrument has been proposed. Developing a global‐scale financial mechanism to support biodiversity conservation through intergovernmental transfers, we simulate three allocation designs: ecocentric, socioecological, and anthropocentric. We analyze the corresponding incentives needed to reach the Aichi target of terrestrial protected area coverage by 2020. Here we show that the socioecological design would provide the strongest median incentive for states which are farthest from achieving the target. Our proposal provides a novel concept for global biodiversity financing, which can serve as a starting point for more specific policy dialogues on intergovernmental burden and benefit‐sharing mechanisms to halt biodiversity loss.
China's Overinvestment and International Trade Conflicts
Authors: Schnabl Gunther 
Published: August 2019

AbstractFor a long time, China's impressive growth performance has been driven by investment and high productivity gains. Based on a discussion of possible overcapacities and overinvestment in China, this paper investigates the sustainability of China's investment and export‐driven growth model. Since the turn of the millennium, buoyant capital inflows and low interest rates have been at the root of overinvestment and misallocation of capital, which necessitated export subsidies to clear markets. The overinvestment boom is argued to have ended around 2014. Since then, the overcapacities have weakened China's bargaining position in the US–Chinese trade conflict and have tempted Chinese authorities to postpone the restructuring of the Chinese economy by providing low‐interest credit. The gradual reemergence of quasi‐soft budget constraints is seen to undermine China's long‐term growth potential.
Cardiac sarcoidosis in monozygotic twins: An opportunity for early surveillance and treatment
Authors: Pierson Doris , Kozak Patrick M. , Maradey Joan A. , Paterson Robert , Pu Min 
Published: August 2019

AbstractGenetic factors play an important role in the development of cardiac sarcoidosis and may determine disease pattern, severity, and prognosis. A 55‐year‐old African American male presented with new onset of congestive heart failure. This patient was diagnosed with pulmonary sarcoidosis eleven years prior and initially treated with prednisone. He was lost to follow‐up until this index admission. He had a monozygotic twin brother who was diagnosed with pulmonary and cardiac sarcoidosis, and passed away from severe biventricular dysfunction. Surveillance, with echocardiography or cardiac MRI, in siblings at high risk of sarcoidosis may allow for early detection and treatment.
Evolution of resource specialisation in competitive metacommunities
Authors: Wickman Jonas , Diehl Sebastian , Brännström Åke 
Published: August 2019

AbstractSpatial environmental heterogeneity coupled with dispersal can promote ecological persistence of diverse metacommunities. Does this premise hold when metacommunities evolve? Using a two‐resource competition model, we studied the evolution of resource‐uptake specialisation as a function of resource type (substitutable to essential) and shape of the trade‐off between resource uptake affinities (generalist‐ to specialist‐favouring). In spatially homogeneous environments, evolutionarily stable coexistence of consumers is only possible for sufficiently substitutable resources and specialist‐favouring trade‐offs. Remarkably, these same conditions yield comparatively low diversity in heterogeneous environments, because they promote sympatric evolution of two opposite resource specialists that, together, monopolise the two resources everywhere. Consumer diversity is instead maximised for intermediate trade‐offs and clearly substitutable or clearly essential resources, where evolved metacommunities are characterised by contrasting selection regimes. Taken together, our results present new insights into resource‐competition‐mediated evolutionarily stable diversity in homogeneous and heterogeneous environments, which should be applicable to a wide range of systems.
The influence of American mink odour on the spatial distribution and behaviour of water voles
Authors: Brzeziński Marcin , Pyrlik Joanna , Churski Marcin , Komar Ewa , Zalewski Andrzej 
Published: August 2019

AbstractThe perception and assessment of predation risk often cause changes in the activities of animals and induce behavioural responses that may in turn affect their movements and distribution. To simulate high predation risk in a midfield pond riparian habitat, we used fresh faeces from ranch American mink Neovison vison and recorded behavioural responses of water voles Arvicola amphibius. In areas where mink odour was deployed, the numbers of captured vole individuals and their trappability were significantly lower than in control areas. Several voles migrated from the zones with deployed mink faeces to the areas without faeces, thus proving that increased predation risk affects the distribution of individuals in a population. The response to mink odour was much more pronounced in females than in males; in areas with deployed mink faeces, not a single female was trapped. We conclude that although American mink is a non‐native, invasive predator, water voles respond to mink odour by reducing their activity and/or by avoiding places with higher predation risk.
Chronic severe pyloric lesions in horses: 47 cases
Authors: Bezdekova B. , Wohlsein P. , Venner M. 
Published: August 2019

SummaryBackgroundThe clinical findings and outcome associated with chronic severe equine pyloric lesions have not been well described previously.ObjectivesTo describe the history, clinical signs, endoscopic and ultrasound results, laboratory data, treatment, pathological findings and survival of horses with chronic severe pyloric lesions.Study designRetrospective case series.MethodsMedical records from horses treated at clinics in Czech Republic and Germany in which chronic severe pyloric lesions were confirmed endoscopically and/or on post‐mortem examination were reviewed.ResultsForty‐seven horses were identified, median age 3 years (range 0.8–16 years). There were 3 geldings, 23 mares and 19 stallions and the majority were Warmbloods (60%). The most common presenting signs were poor body condition (40; 87%), slow eating (39; 83%), recurrent colic (35; 74%) and selective appetite (30; 64%). The most consistent laboratory abnormality was hypoalbuminaemia (10; 36%). Slow gastric emptying was confirmed in 29 individuals during gastroscopy and/or ultrasonography. Endoscopy revealed distal oesophagitis in 9 of 47 horses, and severe equine squamous gastric disease in all cases. Pyloric lesions were depressed, flat or raised fibrinosuppurative pyloric ulcers and were seen in 45 (2 pylori were not seen endoscopically). Thirty‐two cases were treated, with 28 responding well initially. All treated cases received anti‐ulcer medication and four underwent gastrojejunostomy. Clinical signs recurred after medical treatment in at least 11 cases. Only 18 of 44 cases (41%) survived long term (3 were lost to follow‐up). Horses diagnosed at 3 years of age or younger were significantly less likely to survive more than 6 months than older horses (27.8% vs. 72.2%, P<0.001).Main limitationsThe study is retrospective, some records were incomplete and case identification was subjective.ConclusionsChronic severe pyloric lesions can be associated with delayed gastric emptying identified with ultrasonography and/or endoscopy. The prognosis is poor in young horses.
Interior induced fatigue of surface‐strengthened steel under constant and variable loading: Failure mechanism and damage modeling
Authors: Li W. , Sun R. , Gao N. , Wang P. , Sakai T. 
Published: August 2019

AbstractPulsating tension tests with constant amplitude (CA) and variable amplitude (VA) were conducted to investigate the interior failure mechanisms of a carburized Cr steel, and a cumulative damage model with the fine granular area (FGA) formation process was proposed in this study. Such a steel represents the continuously descending S‐N (stress‐number of cycles) curve characteristics associated with inclusion‐FGA‐fisheye induced failure even under variable amplitude. Due to crack growth retardations and accelerations resulted from the interaction effect between stepwise resets of the applied stress, the crack morphology under variable amplitude loading is much rougher. The interior failure mechanism was elucidated in combination with the determination of stress intensity factor values at different crack tips. Based on proposed damage model, the agreement between the predicted and experimental results is fairly good within the factor‐of‐two range.
Chemical efficacy of several NaOCl concentrations on biofilms of different architecture: new insights on NaOCl working mechanisms
Authors: Petridis X. , Busanello F. H. , So M. V. R. , Dijkstra R. J. B. , Sharma P. K. , van der Sluis L. W. M. 
Published: August 2019

AbstractAimTo investigate the anti‐biofilm efficacy and working mechanism of several NaOCl concentrations on dual‐species biofilms of different architecture as well as the changes induced on the architecture of the remaining biofilms.MethodologyStreptococcus oralis J22 and Actinomyces naeslundii T14V‐J1 were co‐cultured under different growth conditions on saliva‐coated hydroxyapatite discs. A constant‐depth film fermenter (CDFF) was used to grow steady‐state, four‐day mature biofilms (dense architecture). Biofilms were grown under static conditions for 4 days within a confined space (less dense architecture). Twenty microlitres of buffer, 2‐, 5‐, and 10% NaOCl were applied statically on the biofilms for 60 s. Biofilm disruption and dissolution, as well as bubble formation, were evaluated with optical coherence tomography (OCT). The viscoelastic profile of the biofilms post‐treatment was assessed with low load compression testing (LLCT). The bacteria/extracellular polysaccharide (EPS) content of the biofilms was examined through confocal laser scanning microscopy (CLSM). OCT, LLCT and CLSM data were analysed through one‐way analysis of variance (ANOVA) and Tukey’s HSD post‐hoc test. Linear regression analysis was performed to test the correlation between bubble formation and NaOCl concentration. The level of significance was set at a < 0.05.ResultsThe experimental hypothesis according to which enhanced biofilm disruption, dissolution and bubble formation were anticipated with increasing NaOCl concentration was generally confirmed in both biofilm types. Distinct differences between the two biofilm types were noted with regard to NaOCl anti‐biofilm efficiency as well as the effect that the several NaOCl concentrations had on the viscoelasticity profile and the bacteria/EPS content. Along with the bubble generation patterns observed, these led to the formulation of a concentration and biofilm structure‐dependent theory of biofilm removal.ConclusionsBiofilm architecture seems to be an additional determining factor of the penetration capacity of NaOCl, and consequently of its anti‐biofilm efficiency.
Influence of root maturity or periodontal involvement on dentinal collagen changes following NaOCl irrigation: an ex vivo study
Authors: Browne J. T. , Ng Y.‐L. , Odlyha M. , Gulabivala K. , Bozec L. 
Published: August 2019

AbstractAimTo refine a FTIR protocol for detection of NaOCl‐induced dentinal collagen changes using an ex vivo irrigation model, and to apply it to determine the collagen change within 0.5 mm of canal or root surfaces, with or without mature roots or periodontal involvement.MethodologyThe root canals of extracted human roots were irrigated with control saline (n = 3) or 5% NaOCl (n = 3) and sectioned into transverse disks for FTIR analyses, 0.5 mm from both the canal lumen and root surface, before and after surface treatment with 17% EDTA. Amide I/phosphate and amide II/phosphate absorbance ratios were compared using the Wilcoxon sign rank test. Mature roots without periodontal involvement were irrigated with: saline (n = 7), 5% NaOCl (n = 7) or 5% NaOCl + 17% EDTA (n = 7); those with periodontal involvement (n = 7) or immature roots (n = 7) were irrigated with 5% NaOCl. Dentine disks were then prepared for FTIR analyses. The effects of irrigant/root maturity/periodontal involvement were analysed using linear mixed models.ResultsFTIR analyses of the irrigated samples revealed a significant (P < 0.05) reduction in collagen bands near the canal lumen after NaOCl irrigation using surface EDTA‐treated samples. Irrigation with the test solutions resulted in significant (P < 0.0001) dentinal collagen changes in the mature roots, whilst those in the immature roots were significantly (P < 0.05) greater compared with the mature roots with or without periodontal involvement; but there was no difference between the latter groups.ConclusionEDTA surface treatment of polished dentine surfaces enhanced FTIR detection of NaOCl‐induced collagen changes. Both root maturity and irrigation protocol influenced the ability of NaOCl to alter dentinal collagen up to 0.5 mm from the canal lumen.