bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in calculated percentage improvement versus patient-reported percentage improvement in pain scores: a review of spinal cord stimulation trials
Authors: Hagedorn Jonathan M , Deer Timothy R , Canzanello Nicholas C , Covington Stephen M , Schroeder Darrell R , Bendel Markus A , Moeschler Susan M , Hooten W Michael 
Published: January 2021

IntroductionSpinal cord stimulation is frequently used for the treatment of intractable chronic pain conditions. Trialing of the spinal cord stimulator device is recommended to assess the patient’s response to neurostimulation before permanent implantation. The trial response is often assessed by Numeric Rating Scale changes and patient-reported percentage pain improvement. Using number rating scale changes between prespinal and postspinal cord stimulation trial, a calculated percentage pain improvement can be obtained. The aim of this study was to assess the difference between calculated and patient-reported percentage improvement in pain scale during spinal cord stimulation trials.MethodsThis study was a retrospective single center review of all spinal cord stimulation trials from January 1 2017 to July 1 2019. A total of 174 patients were included. The paired t-test was used to compare numeric pain scores obtained prestimulation versus poststimulation. The mean difference between methods (patient-reported minus calculated) was compared with zero using the 1-sample t-test. Lin’s concordance correlation coefficient was computed with a 95% CI, calculated using Fisher z-transformation; and a bootstrapping approach was used to compare the concordance correlation coefficient between groups. In all cases, two-tailed tests were used with p<0.05 considered statistically significant.ResultsBased on prestimulation and poststimulation numeric rating scale scores, the mean±SD calculated percentage improvement in pain scale was 54±28. The mean±SD patient-reported percentage improvement in pain scale was 59±25. The overall 95% limits of agreement for the two methods are −30% to +41%. The overall concordance correlation coefficient was 0.76 (95% CI 0.69 to 0.81).ConclusionAlthough the two methods are highly correlated, there is substantial lack of agreement between patient-reported and calculated percentage improvement in pain scale, suggesting that these measures should not be used interchangeably for spinal cord stimulator trial outcome assessment. This emphasizes the need for improved metrics to better measure patient response to neuromodulation therapies. Additionally, patient-reported percentage improvement in pain was found to be higher than calculated percentage improvement in pain, potentially highlighting the multidimensional experience of pain and the unpredictability of solely using Numeric Rating Scale scores to assess patient outcomes.
Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: a prospective study
Authors: Hansen Martin Rune Hassan , Jørs Erik , Sandbæk Annelli , Sekabojja Daniel , Ssempebwa John C , Mubeezi Ruth , Staudacher Philipp , Fuhrimann Samuel , Sigsgaard Torben , Burdorf Alex , Bibby Bo Martin , Schlünssen Vivi 
Published: January 2021

Introduction and aimExposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders.MethodsIn a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome.ResultsLow AChE/Hb was significantly associated with low FEV1Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50thpercentile, reference), those with lower AChE/Hb 24.50 U/g (35thpercentile) had mean FEV1Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65thpercentile) had a mean FEV1Z-score 0.043 (−0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC.ConclusionExposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure.
Academic criteria for promotion and tenure in faculties of medicine: a cross-sectional study of the Canadian U15 universities
Authors: Rice Danielle B. , Raffoul Hana , Ioannidis John P.A. , Moher David 
Published: January 2021

Background: The objective of this study was to determine the presence of a set of prespecified criteria used to assess scientists for promotion and tenure within faculties of medicine among the U15 Group of Canadian Research Universities. Methods: Each faculty guideline for assessing promotion and tenure was reviewed and the presence of five traditional (peer-reviewed publications, authorship order, journal impact factor, grant funding, and national/international reputation) and seven nontraditional (citations, data sharing, publishing in open access mediums, accommodating leaves, alternative ways for sharing research, registering research, using reporting guidelines) criteria were collected by two reviewers. Results: Among the U15 institutions, four of five traditional criteria (80.0%) were present in at least one promotion guideline, whereas only three of seven nontraditional incentives (42.9%) were present in any promotion guidelines. When assessing full professors, there were a median of three traditional criteria listed, versus one nontraditional criterion. Conclusion: This study demonstrates that faculties of medicine among the U15 Group of Canadian Research Universities base assessments for promotion and tenure on traditional criteria. Some of these metrics may reinforce problematic practices in medical research. These faculties should consider incentivizing criteria that can enhance the quality of medical research.
Stability and improved physical characteristics of relativistic compact objects arising from the quadratic term in $$p_r = \alpha \rho ^2 + \beta \rho - \gamma $$
Authors: Thirukkanesh S. , Bogadi Robert S. , Govender Megandhren , Moyo Sibusiso 
Published: January 2021

AbstractWe investigate the stability and enhancement of the physical characteristics of compact, relativistic objects which follow a quadratic equation of state. To achieve this, we make use of the Vaidya–Tikekar metric potential. This gravitational potential has been shown to be suitable for describing superdense stellar objects. Pressure anisotropy is also a key feature of our model and is shown to play an important role in maintaining stability. Our results show that the combination of the Vaidya–Tikekar gravitational potential used together with the quadratic equation of state provide models which are favourable. In comparison with other equations of state, we have shown that the quadratic equation of state mimics the colour-flavour-locked equation of state more closely than the linear equation of state.
The challenges and possibilities of earthquake predictions using non-seismic precursors
Authors: Bhardwaj A. , Sam L. , Martin-Torres F. J. 
Published: January 2021

AbstractThe catastrophic magnitude of life and monetary losses associated with earthquakes deserve serious attention and mitigation measures. However, in addition to the pre-earthquake and post-earthquake alleviation actions, the scientific community indeed needs to reconsider the possibilities of earthquake predictions using non-seismic precursors. A significant number of studies in the recent decades have reported several possible earthquake precursors such as anomalies in electric field, magnetic field, gas/aerosol emissions, ionospheric signals, ground water level, land surface temperature, surface deformations, animal behaviour, thermal infrared signals, atmospheric gravity waves, and lightning. Such substantial number of scientific articles and reported anomalous signals cannot be overlooked without a thoughtful appraisal. Here, we provide an opinion on the way forward for earthquake prediction in terms of challenges and possibilities while using non-seismic precursors. A general point of concern is the widely varying arrival times and the amplitudes of the anomalies, putting a question mark on their universal applicability as earthquake markers. However, a unifying concept which does not only define the physical basis of either all or most of these anomalies but which also streamlines their characterisation procedure must be the focus of future earthquake precursory research. Advancements in developing the adaptable instrumentation for in-situ observations of the claimed non-seismic precursors must be the next step and the satellite observations should not be taken as a replacement for field-based research. We support the need to standardise the precursor detection techniques and to employ a global-scale monitoring system for making any possible earthquake predictions reliable.
Critical zone of the branching crack model for earthquakes: Inherent randomness, earthquake predictability, and precursor modelling
Authors: Zhuang Jiancang , Matsu’ura Mitsuhiro , Han Peng 
Published: January 2021

Abstract
The branching crack model for earthquakes was developed by Vere-Jones and Kagan in the 1970s and the 1980s, respectively. With some simple and rational assumptions, its simulation results explain the Gutenberg-Richter magnitude-frequency relationship and the Omori-Utsu aftershock decay formula. By introducing the concept of the critical zone, this model can be connected with the asperity model, the barrier model, and the nucleation model through a parameter – criticality. Particularly, the size of the critical zone determines the maximum magnitude of potential earthquakes and the source of their anomalies. The key to earthquake forecasting is to determine whether the concerned area is in a critical state and how large the critical zone is. We discuss what kinds of anomalies are meaningful as candidates of earthquake precursors. Finally, we outline modelling strategies for earthquake precursors with low probability gains that are due to the inherent randomness of earthquake source processes.
Digital Image DNA Cytometry: A Useful Tool for the Evaluation of Malignancy in Biliary Strictures
Authors: Osterheld M. C. , Andrejevic Blant S. , Caron L. , Braunschweig R. , Dorta G. , Bouzourene H. , Mihaescu A. 
Published: January 2021

Background: Cytologic evaluation of the biliary tract strictures is nowadays widely used for distinguishing between benign and malignant lesions but remains a challenge for some problematic cases. Digital Image cytometry (DNA‐cytometry) helps cytopathologists to resolve some unclear situations.Methods: We have analysed 41 specimens of bile duct brushings obtained from patients during ERCP (11 benign cases, 7 suspicious for malignancy cases and 23 malignant cases) by DNA‐cytometry and correlated them with the histological biopsy counterpart.Results: All eleven cytological and histological benign cases were DNA‐diploid and among 22 patients with malignant cytological and histological diagnosis 21 were DNA‐aneuploid. One case considered malignant by the cytopathologist revealed DNA‐aneuploid but malignancy could not be confirmed by histology. The analysis of the suspicious for malignancy cases revealed that all DNA‐aneuploid cases were malignant and all DNA‐diploid cases were benign referring to the follow‐up of the patients.The comparison between cytology alone and cytology combined with DNA‐cytometry related to the histological diagnosis (gold standard) resulted in a sensitivity of 100% and a specificity of 79% for cytology alone; a specificity of 94% and a sensitivity 92% for DNA‐cytometry and a specificity of 93% and a sensitivity of 100% with combined analyses. The positive predictive value was 90% for cytology, 96% for DNA‐cytometry and for both analyses. The negative predictive value showed 100% for cytology, 89% for DNA‐cytometry and 100% for combined studies.Conclusions: Despite the limited number of patients involved in the study, the Results obtained indicate an increased of specificity and of positive predictive value using DNA‐cytometry. These Results confirm the pertinence of these method for challenging cases, in conjunction with other available diagnostic tools.
Immunohistochemical Detection and Localization of Somatostatin Receptor Subtypes in Prostate Tissue from Patients with Bladder Outlet Obstruction
Authors: Montironi Rodolfo , Cheng Liang , Mazzucchelli Roberta , Morichetti Doriana , Stramazzotti Daniela , Santinelli Alfredo , Moroncini Gianluca , Galosi Andrea B. , Muzzonigro Giovanni , Comeri Giancarlo , Lovisolo Jon , Cosciani-Cunico Sergio , Bono Aldo V. 
Published: January 2021

Background and Aim of the Study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate.Materials: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated.Results: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively).Conclusions: Our immunohistochemical study on the SSTRs expands our knowledge in the distribution of these subtypes in the
various tissue components in the prostate. Such an information may prove useful in developing further non-surgical strategies for the prevention and treatment of benign prostatic hyperplasia and, in particular, of preneoplastic and neoplastic lesions of the prostate.
MLPAnalyzer: Data Analysis Tool for Reliable Automated Normalization of MLPA Fragment Data
Authors: Coffa Jordy , van de Wiel Mark A. , Diosdado Begoña , Carvalho Beatriz , Schouten Jan , Meijer Gerrit A. 
Published: January 2021

Background: Multiplex Ligation dependent Probe Amplification (MLPA) is a rapid, simple, reliable and customized method for detection of copy number changes of individual genes at a high resolution and allows for high throughput analysis. This technique is typically applied for studying specific genes in large sample series. The large amount of data, dissimilarities in PCR efficiency among the different probe amplification products, and sample-to-sample variation pose a challenge to data analysis and interpretation. We therefore set out to develop an MLPA data analysis strategy and tool that is simple to use, while still taking into account the above-mentioned sources of variation.Materials and Methods: MLPAnalyzer was developed in Visual Basic for Applications, and can accept a large number of file formats directly from capillary sequence systems. Sizes of all MLPA probe signals are determined and filtered, quality control steps are performed, and variation in peak intensity related to size is corrected for. DNA copy number ratios of test samples are computed, displayed in a table view and a set of comprehensive figures is generated. To validate this approach, MLPA reactions were performed using a dedicated MLPA mix on 6 different colorectal cancer cell lines. The generated data were normalized using our program and results were compared to previously performed array-CGH results using both statistical methods and visual examination.Results and Discussion: Visual examination of bar graphs and direct ratios for both techniques showed very similar results, while the average Pearson moment correlation over all MLPA probes was found to be 0.42. Our results thus show that automated MLPA data processing following our suggested strategy may be of significant use, especially when handling large MLPA data sets, when samples are of different quality, or interpretation of MLPA electropherograms is too complex. It remains, however, important to recognize that automated MLPA data processing may only be successful when a dedicated experimental setup is also considered.
HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines
Authors: Heikaus Sebastian , van den Berg Linda , Kempf Tobias , Mahotka Csaba , Gabbert Helmut Erich , Ramp Uwe 
Published: January 2021

Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms. Sensitivity to TRAIL-induced apoptosis correlated with cleavage of the initiator caspase-8, but the mitochondrial apoptosis pathway was not induced. Similarly, etoposide and betulinic acid could not induce mitochondrial damage. In contrast, HA14-1 was able to activate mitochondrial apoptosis, thereby demonstrating functionally inducible signalling pathways downstream of the mitochondria. The intactness of the pathways upstream of the mitochondria was shown by pretreatment of TRAIL-sensitive cell lines with HA14-1, which could reconstitute TRAIL-induced mitochondrial damage and resulted in a synergistic apoptosis induction.Our results demonstrate that the apoptotic pathways upstream and downstream of the mitochondria are intact and inducible in renal cell carcinoma cell lines. However, resistance towards mitochondrial apoptosis is located on the level of the mitochondria themselves.
A Fast, Sensitive and Accurate High Resolution Melting (HRM) Technology-Based Assay to Screen for Common K-ras Mutations
Authors: Kramer D. , Thunnissen F. B. , Gallegos-Ruiz M. I. , Smit E. F. , Postmus P. E. , Meijer C. J. L. M. , Snijders P.J.F. , Heideman D. A. M. 
Published: January 2021

Background: Increasing evidence points to a negative correlation between K-ras mutations and patient’s response to, or survival benefit after, treatment with EGFR-inhibitors. Therefore, rapid and reliable assays for mutational analysis of the K-ras gene are strongly needed.Methods: We designed a high resolution melting (HRM) technology-based approach followed by direct sequencing to determine K-ras exon 1 (codons 12/13) tumour genotype.Results: Reconstruction experiments demonstrated an analytical sensitivity of the K-ras exon 1 HRM assay following sequencing of 1.5–2.5% of mutated DNA in a background of wild-type DNA. Assay reproducibility and accuracy were 100%. Application of the HRM assay following sequencing onto genomic DNA isolated from formalin-fixed paraffin-embedded tumour specimens of non-small cell lung cancer (n=91) and colorectal cancer (n=7) patients revealed nucleotide substitutions at codons 12 or 13, including a homozygous mutation, in 33 (34%) and 5 (5%) cases, respectively. Comparison to conventional nested-PCR following cycle-sequencing showed an overall high agreement in genotype findings (kappa value of 0.96), with more mutations detected by the HRM assay following sequencing.Conclusion: HRM allows rapid, reliable and sensitive pre-screening of routine diagnostic specimens for subsequent genotyping of K-ras mutations, even if present at low abundance or homozygosity, and may considerably facilitate personalized therapy planning.
LOH at 1p31 (ARHI) and Proliferation in Lymph Node-Negative Breast Cancer
Authors: Janssen Emiel A. M. , Øvestad Irene T. , Skaland Ivar , Søiland Håvard , Gudlaugsson Einar , Kjellevold Kjell H. , Nysted Arne , Søreide Jon-Arne , Baak Jan P. A. 
Published: January 2021

Background: The mitotic activity index (MAI) is a strong prognosticator in node-negative invasive breast cancer patients. Recently, a correlation between the MAI and specific chromosomal aberrations at chromosome 1p was described.Methods: Analysis of MAI, immunohistochemical staining patterns for proliferation-associated phosphohistone H3 (PPH3), phosphorylated ERK1/2, p21, cyclin E, Ki67 and cyclin D1 proteins; and prognosis in 158 adjuvant chemotherapy-treated T1-2N0M0 invasive breast cancer patients, analysis of LOH at 1p31 (including ARHI) using the dinucleotide repeats D1S207, D1S430 and D1S464 in 76 patients. Single and multivariate survival analysis was used to evaluate the importance of the various markers tested.Results: LOH at 1p31 did not correlate with MAI nor provide prognostic information. Phosphohistone H3 was the best prognosticator for patients in all age groups with 20 year distant metastasis free survival of distant metastases 93% vs. 72% respectively (p = 0.004, HR = 4.5). In multivariate analysis, phosphohistone H3 < 13 vs. ≥13 exceeded the prognostic value of the mitotic activity index.Conclusions: LOH at 1p31 is common in breast cancer, and correlates with loss of proliferation-associated proteins, but not with MAI, PPH3 or prognosis. PPH3 is the best prognosticator in this study group of adjuvant chemotherapy-treated lymph node-negative breast cancer patients.