bluuebunny/crossref_metadata_2025 huggingface dataset:
How the COVID‐19 Pandemic Impacted Oncological Molecular Diagnosis: A Picture from a National Reference Center for Molecular Pathology
Authors: Daniel Pinto  , Cirnes Luís , Regina Pinto  , Pina Maria João , Troncone Giancarlo , Schmitt Fernando
Published: October 2020

Introduction. The Portuguese healthcare system had to adapt at short notice to the COVID‐19 pandemic. We implemented workflow changes to our molecular pathology laboratory, a national reference center, to maximize safety and productivity. We assess the impact this situation had on our caseload and what conclusions can be drawn about the wider impact of the pandemic in oncological therapy in Portugal. Material and Methods. We reviewed our database for all oncological molecular tests requested between March and April of 2019 and 2020. For each case, we recorded age, sex, region of the country, requesting institution, sample type, testing method, and turnaround time (TAT). A comparison between years was made. Results. The total number of tests decreased from 421 in 2019 to 319 in 2020 (p = 0.0027). The greatest reduction was in clinical trial‐related cases. Routine cases were similar between years (267 vs. 256). TAT was higher in 2019 (mean 15 days vs. 12.3 days; p = 0.0003). Medium‐ to large‐sized public hospitals in the north of the country were mostly responsible for the reduction in cases (p = 0.0153). Conclusions. Case reduction was observed at hospitals that have mostly been involved in the treatment of COVID‐19 and in the north of the country, the region worst‐hit by the pandemic. Similar to other studies, our TAT decreased, even with a similar number of routine cases. Thus, we conclude that it is possible to successfully adapt the workflow of a molecular pathology laboratory to new safety standards without losing efficiency.
Hepatocellular Carcinoma in a 24-Year-Old Female with Beckwith–Wiedemann Syndrome: A Case Report and Review of the Literature
Authors: Ahlers Carolyn G. , Trinh Quoc-Huy , Montenovo Martin
Published: October 2020

In this report, the case of a 24-year-old female with Beckwith–Wiedemann Syndrome (BWS) who was diagnosed with well-differentiated hepatocellular carcinoma (HCC) is described. While BWS has been associated with childhood embryonal tumors, most commonly Wilms tumors and hepatoblastomas, this is the first case report to describe HCC in an adult with BWS. Although HCC typically occurs in elderly adults or those with underlying liver disease, in this case, we show that HCC can occur in a young adult with BWS without any underlying liver disease.
The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis
Authors: Zhang Li , Cheng Yan-Li , Xue Shuai , Xu Zhong-Gao
Published: October 2020

Background. Diabetic nephropathy is a common and serious complication of diabetes mellitus (DM) and is one of the leading causes of end-stage renal disease worldwide. Although there have been many investigations on biomarkers for DN, there is no consistent conclusion about reliable biomarkers. The purpose of this study was to perform a systematic review and meta-analysis of the role of circulating retinol-binding protein 4 (RBP4) in the type 2 diabetes mellitus (T2DM) patients with kidney diseases.Materials and Methods. We searched the PubMed, MEDLINE, EMBASE, and Web of Science databases for publications. For the 12 cross-sectional studies that we included in the review, we calculated standard mean differences (SMD) with 95% confidence intervals (CI) for continuous data when the applied scales were different. Risk of bias of included trials was assessed by using the Newcastle-Ottawa Scale.Results. RBP4 concentrations in the micro-, macro-, or micro+macroalbuminuria groups were significantly higher than those in the normal albuminuria group of T2DM patients [P=0.001, SMD 1.07, 95% CI (0.41, 1.73)]. The estimated glomerular filtration rate (eGFR) was negatively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher’sZ=−0.48, 95% CI (-0.69, -0.26),P<0.0001]. The albumin-to-creatinine ratio (ACR) was positively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher’sZ=0.20, 95% CI (0.08, 0.32),P=0.001].Conclusion. The levels of circulating RBP4 were significantly higher both in T2DM subjects with micro/macroalbuminuria and in T2DM subjects with declined eGFR. The levels of circulating RBP4 were positively correlated with ACR but negatively correlated with eGFR. Circulating RBP4 could be a reliable biomarker for kidney diseases in T2DM.
Air Pollution Concentration Forecast Method Based on the Deep Ensemble Neural Network
Authors: Guo Canyang , Liu Genggeng , Chen Chi-Hua
Published: October 2020

The global environment has become more polluted due to the rapid development of industrial technology. However, the existing machine learning prediction methods of air quality fail to analyze the reasons for the change of air pollution concentration because most of the prediction methods take more focus on the model selection. Since the framework of recent deep learning is very flexible, the model may be deep and complex in order to fit the dataset. Therefore, overfitting problems may exist in a single deep neural network model when the number of weights in the deep neural network model is large. Besides, the learning rate of stochastic gradient descent (SGD) treats all parameters equally, resulting in local optimal solution. In this paper, the Pearson correlation coefficient is used to analyze the inherent correlation of PM2.5 and other auxiliary data such as meteorological data, season data, and time stamp data which are applied to cluster for enhancing the performance. Extracted features are helpful to build a deep ensemble network (EN) model which combines the recurrent neural network (RNN), long short-term memory (LSTM) network, and gated recurrent unit (GRU) network to predict the PM2.5 concentration of the next hour. The weights of the submodel change with the accuracy of them in the validation set, so the ensemble has generalization ability. The adaptive moment estimation (Adam) an algorithm for stochastic optimization is used to optimize the weights instead of SGD. In order to compare the overall performance of different algorithms, the mean absolute error (MAE) and mean absolute percentage error (MAPE) are used as accuracy metrics in the experiments of this study. The experiment results show that the proposed method achieves an accuracy rate (i.e., MAE=6.19 and MAPE=16.20%) and outperforms the comparative models.
Experimental Study on the Fractal Features and Permeability Characteristics of Low Metamorphic Coal Pore Structure under Thermal Damage
Authors: Liu Zhen , Zhang Mingrui , Yu Shijian , Xin Lin , Wang Gang , Sun Liutao
Published: October 2020

Underground coal gasification and exploitation of geothermal mine resources can effectively improve coal conversion and utilization efficiency, and the basic theory of the above technologies generally relies on the change law of the coal pore structure under thermal damage. Therefore, the influence mechanism of the development of the coal pore structure under thermal damage is analyzed by the nuclear magnetic resonance experiment, and the temperature-permeability fractal model is created. The results show that compared with microtransitional pores, the volume of meso-macropores in the coal body is more susceptible to an increase in temperature, which was most obvious at 200-300°C. During the heating process, the measured fractal dimension based on the T2 spectral distribution is between 2 and 3, indicating that the fractal characteristics did not disappear upon a change in external temperature. The temperature has a certain negative correlation with DmNMR, DMNMR, and DNMR, indicating that the complexity of the pore structure of the coal body decreased gradually with the increase of the temperature. Compared with the permeability calculated based on the theoretical permeability fractal model, the permeability obtained from the temperature-permeability fractal model has a similar increasing trend as the permeability measured by the NMR experiment when the temperature increases. The experimental study on pore structure and permeability characteristics of the low metamorphic coal under thermal damage provides a scientific theory for underground coal gasification and geothermal exploitation.
Epithelial-Myoepithelial Carcinoma of the Breast with Rhabdoid Features
Authors: Grenier Karl , Altinel Gulbeyaz , Dastani Zari , Omeroglu Atilla
Published: October 2020

Epithelial-myoepithelial carcinoma of the breast is a rare biphasic tumor composed of intermixed malignant epithelial and myoepithelial components. Myoepithelial cells are known to adopt varied morphologies, including spindle, chondroid, clear cell, and rhabdoid morphologies, and can represent a diagnostic challenge when isolated on biopsy. Rhabdomyosarcoma, phyllodes tumor, metaplastic carcinoma, and myoepithelial carcinoma are primary breast tumors that all have been shown to exhibit rhabdoid features, whether representing true differentiation or morphological mimic. We here report an epithelial-myoepithelial carcinoma of the breast with rhabdoid features in a 76-year-old woman. The rhabdoid-appearing myoepithelial cells are negative for myogenin, consistent with a rhabdoid-like morphology rather than a true rhabdoid differentiation, comparably to previously described myoepithelial carcinoma with rhabdoid features. To our knowledge, this is the first reported case of epithelial-myoepithelial carcinoma of the breast with rhabdoid features and thus adds another entity to the differential diagnosis of breast lesions with rhabdoid features.
The Histone Demethylase KDM3B Promotes Osteo-/Odontogenic Differentiation, Cell Proliferation, and Migration Potential of Stem Cells from the Apical Papilla
Authors: Zhang Chen , Han Xiao , Liang Yuncun , Liu Huina , Fan Zhipeng , Zhang Jianpeng
Published: October 2020

Understanding the regulation mechanisms of mesenchymal stem cells (MSCs) can assist in tissue regeneration. The histone demethylase (KDM) family has a crucial role in differentiation and cell proliferation of MSCs, while the function of KDM3B in MSCs is not well understood. In this study, we used the stem cells from the apical papilla (SCAPs) to test whether KDM3B could regulate the function of MSCs. By an alkaline phosphatase (ALP) activity assay, Alizarin red staining, real-time RT-PCR, and western blot analysis, we found that KDM3B enhanced the ALP activity and mineralization of SCAPs and promoted the expression of runt-related transcription factor 2 (RUNX2), osterix (OSX), dentin sialophosphoprotein (DSPP), and osteocalcin (OCN). Additionally, the CFSE, CCK-8, and flow cytometry assays revealed that KDM3B improved cell proliferation by accelerating cell cycle transition from the G1 to S phase. Scratch and transwell migration assays displayed that KDM3B promoted the migration potential of SCAPs. Mechanically, microarray results displayed that 98 genes were upregulated, including STAT1, CCND1, and FGF5, and 48 genes were downregulated after KDM3B overexpression. Besides, we found that the Toll-like receptor and JAK-STAT signaling pathway may be involved in the regulating function of KDM3B in SCAPs. In brief, we discovered that KDM3B promoted the osteo-/odontogenic differentiation, cell proliferation, and migration potential of SCAPs and provided a novel target and theoretical basis for regenerative medicine.
Parental Reported Bullying among Saudi Schoolchildren: Its Forms, Effect on Academic Abilities, and Associated Sociodemographic, Physical, and Dentofacial Features
Authors: Alabdulrazaq Raghad S. , Al-Haj Ali Sanaa N.
Published: October 2020

Context. Bullying among schoolchildren is a serious phenomenon and a leading health concern. Aim. To determine the prevalence of bullying, its forms, and its effect on academic abilities and school attendance, as well as associated sociodemographic, physical, and dentofacial features among Saudi schoolchildren. Methods. This cross-sectional study recruited a sample of 1131 parents of schoolchildren 8-18 years old and requested them to complete internationally accepted questionnaires for their children. Chi-squared test and logistic regression analysis were used to analyze the data (p<0.05). Results. A majority (89.2%) of schoolchildren were bully victims. Physical bullying (48.9%) was the most common form of bullying. The youngest schoolchildren (8-11 years) and those who disliked school classes or neither liked nor hated them, as well as those who were truant from school, were more likely to be victims. In addition, those who had worse grades because of bullying and those who were very often bullied because of good grades or because they showed an interest in school were more likely to be victims. With regard to targeted physical features, teeth were the number one target, followed by the shape of the lips and strength, while tooth shape and color were the most common dentofacial targets, followed by anterior open bite and protruded anterior teeth. Boys and the youngest schoolchildren were more often subjected to bullying because of these features (p<0.05). Conclusions. The prevalence of bullying, mainly in a physical form, was high among Saudi schoolchildren, with a negative influence on students’ academic abilities. Problems related to teeth, in particular, which can be treated, were targets, mainly for boys and the youngest schoolchildren. More studies are required in Saudi Arabia to explore the issue further among schoolchildren themselves.
First Report of a Low-Grade Pseudomyxoma peritonei Originating from Gall Bladder
Authors: Prabhu Aruna , Brandl Andreas , Wakama Satoshi , Sako Shouzou , Ishibashi Haruki , Nishino Eisei , Yonemura Yutaka
Published: October 2020

Pseudomyxoma peritonei (PMP) refers to accumulation of mucinous ascites with or without neoplastic cells in the peritoneal cavity. It most commonly originates from a low or a high grade primary appendiceal mucinous neoplasm. Though adenocarcinoma of gall bladder has been reported to give rise to PMP, to the best of our knowledge, this is the first report of a PMP arising from a low grade mucinous tumour of the gall bladder. A 72-year-old patient was diagnosed with PMP 1.5 years after a cholecystectomy. After initial oral TS1 (combination of tegafur, gimeracil and oteracil) and later intraperitoneal (IP) chemotherapy with docetaxel and cisplatin, the patient was operated with the goal of tumour debulking, including removal of 5.5 L of mucinous ascites, an appendectomy, and ovariectomy. The histopathologic report showed a normal appendix and metastasis of PMP to the right ovary. After the exclusion of the 2 most common sites of origin (appendix and ovary), the specimen of the cholecystectomy was reviewed. It showed low grade mucinous tumour in the gall bladder, with immuno-histochemical markers (IHCs) suggestive of CK7, CDX2, MUC 2 positive and CK20, MUC5AC negative. MIB-1 index was 12%. The pathologic report of cytoreductive surgery performed after 7 cycles of IP chemotherapy confirmed the diagnosis of PMP originating from low grade mucinous tumour of the gall bladder. Our case report illustrates a rare disease and highlights that, though peritoneal metastasis from gall bladder cancers are known to have a poor prognosis, the peritoneal dissemination from a low grade mucinous neoplasm of gall bladder (PMP) has a significantly better prognosis due to a better disease biology and improved treatment options currently available for the treatment of PMP.
Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies
Authors: Keup Corinna , Kimmig Rainer , Kasimir-Bauer Sabine
Published: October 2020

Background: Despite the assumption of breast cancer (BC) as a cold, non-immunogenic tumor, immune checkpoint inhibitor (ICI) therapy is favorable for a subgroup of patients. Immunohistochemical assessment of the programmed cell death ligand 1 (PD-L1) is the only approved companion diagnostic for anti-PD-L1 therapy in metastatic triple-negative BC; however, challenges regarding the standardization of PD-L1 scoring in tumor tissue still remain. Consequently, to select patients most likely to respond to ICI, blood-based biomarkers are urgently needed. Summary and Key Messages: Liquid biopsy, comprising circulating immune cells, circulating tumor cells and extracellular vesicles, as well as their surface proteins, is of high potential, and these analytes were already shown to be molecular correlates or regulators of the evasion from antitumoral immune reaction. Liquid biopsy, also enabling the evaluation of tumor mutational burden (TMB), microsatellite instability, and the T-cell receptor repertoire, allows serial sampling for monitoring purposes and reflects intra-tumoral heterogeneity which qualifies as marker for immunogenicity. Only a very few studies have already elucidated the potential of these analytes as biomarkers under ICI therapy. Nonetheless, the topic is of growing interest and has high relevance for the future. However, for clinical implementation, these multifarious analytes first need to pass robust standardization and validation procedures.
Validation of the Simplified Modified Rankin Scale Questionnaire
Authors: Isaksson Eva , Wester Per , Laska Ann Charlotte , Näsman Per , Lundström Erik
Published: October 2020

Introduction: The modified Rankin scale (mRS) is the most common assessment tool for measuring overall functional outcome in stroke studies. The traditional way of using mRS face-to-face is time- and cost-consuming. The aim of this study was to test the validity of the Swedish translation of the simplified modified Rankin scale questionnaire (smRSq) as compared with the mRS assessed face-to-face 6 months after a stroke. Methods: Within the ongoing EFFECTS trial, smRSq was sent out to 108 consecutive stroke patients 6 months after a stroke. The majority, 90% (97/108), of the patients answered the questionnaire; for the remaining 10%, it was answered by the next of kin. The patients were assessed by face-to-face mRS by 7 certified healthcare professionals at 4 Swedish stroke centres. The primary outcome was assessed by Cohen’s kappa and weighted kappa. Results: There was good agreement between postal smRSq, answered by the patients, and the mRS face-to-face; Cohen’s kappa was 0.43 (CI 95% 0.31–0.55), weighted kappa was 0.64 (CI 95% 0.55–0.73), and Spearman rank correlation was 0.82 (p < 0.0001). In 55% (59/108), there was full agreement, and of the 49 patients not showing exact agreement, 44 patients differed by 1 grade and 5 patients had a difference of 2 grades. Discussion/Conclusion: Our results show good validity of the postal smRSq, answered by the patients, compared with the mRS carried out face-to-face at 6 months after a stroke. This result could help trialists in the future simplify study design and make multicentre trials and quality registers with a large number of patients more feasible and time-saving.
High Prevalence of Moyamoya Syndrome in Appalachia
Authors: Nisiewicz Michael John , Roberts Jill M. , Dobbs Michael R. , Ajadi Ebunoluwa A. , Kitzman Patrick , Wolfe Marc , Elkins Kelley , Dugan Adam J. , Fraser Justin F.
Published: October 2020

Introduction: Moyamoya is a chronic cerebrovascular condition of unclear etiology characterized by progressive occlusion of 1 or both internal carotid arteries with neovascular collateral formation. With both an idiopathic form (moya­moya disease) and congenital condition-associated form (moyamoya syndrome), it can cause ischemic and hemorrhagic stroke. Recent findings in Kentucky have challenged traditional estimates of its incidence in US populations. Using the Kentucky Appalachian Stroke Registry (KApSR), our aim was to further characterize its incidence as a cause of stroke and to understand the patient population in Appalachia. Methods: A retrospective review of moyamoya patients was performed using the KApSR database. Data collected included demographics, county location, risk factors, comorbidities, and health-care encounters from January 1, 2012, to December 31, 2016. Results: Sixty-seven patients were identified; 36 (53.7%) resided in Appalachian counties. The cohort accounted for 125 of 6,305 stroke admissions, representing an incidence of 1,983 per 100,000 stroke admissions. Patients presented with ischemic strokes rather than hemorrhagic strokes (odds ratio 5.50, 95% CI: 2.74–11.04, p < 0.01). Eleven patients (16.4%) exhibited autoimmune disorders. Compared to the general population with autoimmune disorder prevalence of 4.5%, the presence of autoimmunity within the cohort was significantly higher (p < 0.01). Compared to non-Appalachian patients, Appalachian patients tended to present with lower frequencies of tobacco use (p = 0.08), diabetes mellitus (p = 0.13), and hypertension (p = 0.16). Conclusions: Moyamoya accounts for a substantial number of stroke admissions in Kentucky; these patients were more likely to develop an ischemic stroke rather than a hemorrhagic stroke. Autoimmune disorders were more prevalent in moyamoya patients than in the general population. The reduced frequency of traditional stroke risk factors within the Appalachian group suggests an etiology distinct to the population.
John Cunningham Virus Status, Seroconversion Rate, and the Risk of Progressive Multifocal Leukoencephalopathy in Polish John Cunningham Virus-Seronegative Patients with Relapsing-Remitting Multiple Sclerosis
Authors: Kapica-Topczewska Katarzyna , Collin Francois , Tarasiuk Joanna , Czarnowska Agata , Chorąży Monika , Mirończuk Anna , Kochanowicz Jan , Kułakowska Alina
Published: October 2020

Introduction: Presence of anti-JC-virus antibodies (JCVAbs) is associated with the increased risk of natalizumab (NAT)-related progressive multifocal leukoencephalopathy (PML). Little is known about seroconversion rate and time to seroconversion in relapsing-remitting multiple sclerosis (RRMS) patients treated with NAT in Poland. The aim of the study was to assess the true risk of PML, seroconversion rate, and time to seroconversion in all JCVAb-negative RRMS patients treated with NAT in Poland. Methods: Demographic and clinical data of all Polish RRMS patients treated with NAT reimbursed by National Health Fund (NFZ) were prospectively collected in electronic files using the Therapeutic Programme Monitoring System provided by NFZ. The assessment of JCVAb presence (without collection of JCVAb index value) in serum (Unilabs, STRATIFY JCV: anti-JCV antibody ELISA) was done at the beginning of therapy and then repeated every 6 months. The maximum follow-up time was 4 years. In Poland, since 2013, according to the NFZ drug program guidance, only patients with negative JCVAb test have started treatment with NAT. Results: In all Polish multiple sclerosis centers, 210 negative JCVAb RRMS patients with at least 9 (±3) months of observation (146 females, 64 males, and the median age at baseline: 33 years) were included in the study. During the follow-up period, JCVAb status changed from negative to positive in 34 patients (16.2%). For half of the patients, the seroconversion was diagnosed 1 year after starting NAT treatment. In 4 patients (1.9%) during follow-up, JCVAb status changed again from positive to negative. In Poland, before establishment of NFZ drug program, 4 cases of PML in patients treated with NAT in clinical trials were diagnosed. In the NFZ drug program, since 2013, no patient treated with NAT has been diagnosed with PML. Conclusions: NAT therapy in JCV-seronegative RRMS patients is safe and results in the absence of PML cases. In Poland, JCV seroconversion rate is similar to that observed in other European countries.
Why *if or notbut ✓whether or not
Authors: Wu Danfeng
Published: October 2020

This squib provides an account of a contrast between whether and if in English, manifested in the contrast between the grammaticality of I don’t know whether or not Pat will arrive and the ungrammaticality of *I don’t know if or not Pat will arrive. I argue that this contrast can be explained if we assume that whether can pied-pipe, but there is no pied-piping in if-questions. Strikingly, once the pied-piping parse for whether is eliminated, it behaves like if. Then I show that this contrast exists crosslinguistically: Polish alternative questions behave like whether-questions because pied-piping is possible, and Bengali alternative questions behave like if-questions because pied-piping is not possible.
A contribution to the genus Sphaeroplotina Miyatake (Coleoptera, Coccinellidae, Plotinini)
Authors: TONG JUNBO , CHEN JIANJUN , ZHANG XIAONING , CHEN XIAOSHENG , WANG XINGMIN
Published: October 2020

The genus Sphaeroplotina Miyatake, 1969 is reviewed. Sphaeroplotina hainanensis Miyatake, 1969 is redescribed and Sphaeroplotina varimarginata Tong & Wang sp. nov. is described as new to science. Both species are illustrated. A diagnosis of the genus is provided. A key and a distribution map of the known species are also presented.
Three new species of free-living marine nematodes (Nematoda: Enoplida) from the Clarion-Clipperton Fracture Zone (CCFZ), North Pacific
Authors: SHIMADA DAISUKE , TAKEDA NAOYA , TSUNE AKIRA , MURAKAMI CHISATO
Published: October 2020

Three new species of free-living marine nematodes, Phanodermopsis dordi sp. nov., Halalaimus shinkai sp. nov., and Oxystomina hakureiae sp. nov. are described from the abyssal sediments of the Clarion-Clipperton Fracture Zone, North Pacific. Phanodermopsis dordi sp. nov. differs from the congeners by having papilliform anterior sensilla and a long conical tail with an acute tip. Halalaimus shinkai sp. nov., belonging to Keppner’s group 2 based on the presence of caudal alae and the absence of precloacal sensillum or pore, can be distinguished from all of the members of this group by the presence of lateral pieces of gubernacula. Oxystomina hakureiae sp. nov. differs from the congeners by the short setiform anterior sensilla, the amphid located posterior to cephalic sensilla, the conico-cylindrical tail in both sexes, the spicules with a velum and a capitulum, the presence of the gubernacula and the precloacal setae, and the diorchic and monodelphic reproductive systems. The amended dichotomous keys to the species of Phanodermopsis, Halalaimus group 2, and Oxystomina are provided. A new combination Nemanema arenaria (Bussau, 1990) comb. nov. transferred from Oxystomina is also provided.
A Pressure-Invariant Neutral Density Variable for the World's Oceans
Authors: Lang Yandong , Stanley Geoffrey J. , McDougall Trevor J. , Barker Paul M.
Published: October 2020

We present a new method to calculate the neutral density of an arbitrary water parcel. Using this method, the value of neutral density depends only on the parcel’s salinity, temperature, latitude, and longitude and is independent of the pressure (or depth) of the parcel, and is therefore independent of heave in observations or high-resolution models. In this method we move the parcel adiabatically and isentropically like a submesoscale coherent vortex (SCV) to its level of neutral buoyancy on four nearby water columns of a climatological atlas. The parcel’s neutral density γSCV is interpolated from prelabeled neutral density values at these four reference locations in the climatological atlas. This method is similar to the neutral density variable γn of Jackett and McDougall: their discretization of the neutral relationship equated the potential density of two parcels referenced to their average pressure, whereas our discretization equates the parcels’ potential density referenced to the pressure of the climatological parcel. We calculate the numerical differences between γSCV and γn, and we find similar variations of γn and γSCV on the ω surfaces of Klocker, McDougall, and Jackett. We also find that isosurfaces of γn and γSCV deviate from the neutral tangent plane by similar amounts. We compare the material derivative of γSCV with that of γn, finding their total material derivatives are of a similar magnitude.
Accuracy and Long-Term Stability Assessment of Inductive Conductivity Cell Measurements on Argo Floats
Authors: Nezlin Nikolay P. , Dever Mathieu , Halverson Mark , Leconte Jean-Michel , Maze Guillaume , Richards Clark , Shkvorets Igor , Zhang Rui , Johnson Greg
Published: October 2020

This study demonstrates the long-term stability of salinity measurements from Argo floats equipped with inductive conductivity cells, which have extended float lifetimes as compared to electrode-type cells. New Argo float sensor payloads must meet the demands of the Argo governance committees before they are implemented globally. Currently, the use of CTDs with inductive cells designed and manufactured by RBR, Ltd., has been approved as a Global Argo Pilot. One requirement for new sensors is to demonstrate stable measurements over the lifetime of a float. To demonstrate this, data from four Argo floats in the western Pacific Ocean equipped with the RBRargo CTD sensor package are analyzed using the same Owens–Wong–Cabanes (OWC) method and reference datasets as the Argo delayed-mode quality control (DMQC) operators. When run with default settings against the standard DMQC Argo and CTD databases, the OWC analysis reveals no drift in any of the four RBRargo datasets and, in one case, an offset exceeding the Argo target salinity limits. Being a statistical tool, the OWC method cannot strictly determine whether deviations in salinity measurements with respect to a reference hydrographic product (e.g., climatologies) are caused by oceanographic variability or sensor problems. So, this study furthermore investigates anomalous salinity measurements observed when compared with a reference product and demonstrates that anomalous values tend to occur in regions with a high degree of variability and can be better explained by imperfect reference data rather than sensor drift. This study concludes that the RBR inductive cell is a viable option for salinity measurements as part of the Argo program.
Dependence of Superintensity of Tropical Cyclones on SST in Axisymmetric Numerical Simulations
Authors: Li Yuanlong , Wang Yuqing , Lin Yanluan , Fei Rong
Published: October 2020

This study revisits the superintensity of tropical cyclones (TCs), which is defined as the excess maximum surface wind speed normalized by the corresponding theoretical maximum potential intensity (MPI), based on ensemble axisymmetric numerical simulations, with the focus on the dependence of superintensity on the prescribed sea surface temperature (SST) and the initial environmental atmospheric sounding. Results show a robust decrease of superintensity with increasing SST regardless of being in experiments with an SST-independent initial atmospheric sounding or in those with the SST-dependent initial atmospheric soundings as in nature sorted for the western North Pacific and the North Atlantic. It is found that the increase in either convective activity (and thus diabatic heating) in the TC outer region or theoretical MPI or both with increasing SST could reduce the superintensity. For a given SST-independent initial atmospheric sounding, the strength of convective activity in the TC outer region increases rapidly with increasing SST due to the rapidly increasing air–sea thermodynamic disequilibrium (and thus potential convective instability) with increasing SST. As a result, the decrease of superintensity with increasing SST in the SST-independent sounding experiments is dominated by the increasing convective activity in the TC outer region and is much larger than that in the SST-dependent sounding experiments, and the TC intensity becomes sub-MPI at relatively high SSTs in the former. Due to the marginal increasing tendency of convective activity in the TC outer region, the decrease of superintensity in the latter is dominated by the increase in theoretical MPI with increasing SST.
WSR-88D Tornado Intensity Estimates. Part I: Real-Time Probabilities of Peak Tornado Wind Speeds
Authors: Smith Bryan T. , Thompson Richard L. , Speheger Douglas A. , Dean Andrew R. , Karstens Christopher D. , Anderson-Frey Alexandra K.
Published: October 2020

The Storm Prediction Center (SPC) has developed a database of damage-surveyed tornadoes in the contiguous United States (2009–17) that relates environmental and radar-derived storm attributes to damage ratings that change during a tornado life cycle. Damage indicators (DIs), and the associated wind speed estimates from tornado damage surveys compiled in the Damage Assessment Toolkit (DAT) dataset, were linked to the nearest manual calculations of 0.5° tilt angle maximum rotational velocity Vrot from single-site WSR-88D data. For each radar scan, the maximum wind speed from the highest-rated DI, Vrot, and the significant tornado parameter (STP) from the SPC hourly objective mesoscale analysis archive were recorded and analyzed. Results from examining Vrot and STP data indicate an increasing conditional probability for higher-rated DIs (i.e., EF-scale wind speed estimate) as both STP and Vrot increase. This work suggests that tornadic wind speed exceedance probabilities can be estimated in real time, on a scan-by-scan basis, via Vrot and STP for ongoing tornadoes.
The impact of university reputation on employment opportunities: Experimental evidence from Bolivia
Authors: Nogales Ricardo , Córdova Pamela , Urquidi Manuel
Published: October 2020

Higher education enrolment and graduation rates have increased rapidly inter-generationally across much of the world, offering employers the promise of more knowledgeable recruits and promising individuals new means of social advancement. In the case of Bolivia, the labour force is becoming more heterogeneous over time, which could imply positive effects induced by a closer match between labour supply and recruiters’ needs. However, we show that this is not the case. We revisit the transition mechanisms from college to the workplace, positing recruiters’ interpretations of educational credentials as a crucial determining factor for employability in the formal sector. In a two-branch correspondence study, 2848 fictitious CVs were sent to 1424 formal firms in the three main urban Bolivian areas. We find a large university reputation premium. Applicants from well-valued universities are around 40% more likely to receive a positive response – a 2.25 percentage point advantage from a 7.87% baseline likelihood. Thus, the increasingly heterogeneous labour force is generating additional informational frictions in the labour market, rather than promoting a more efficient matching process.
Signaling through the type 2 cannabinoid receptor regulates the severity of acute and chronic graft-versus-host disease
Authors: Yuan Cheng Yin , Zhou Vivian , Sauber Garrett , Stollenwerk Todd , Komorowski Richard , López Alicia , Tolón Rosa María , Romero Julian , Hillard Cecilia J. , Drobyski William R.
Published: October 2020

Graft-versus-host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments. In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R), which is expressed on nearly all immune cells, and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells or administration of a selective CB2R pharmacological antagonist exacerbated acute GVHD lethality. This was accompanied primarily by the expansion of proinflammatory CD8+ T cells, indicating that constitutive CB2R expression on T cells preferentially regulated CD8+ T-cell alloreactivity. Using a novel CB2ReGFP reporter mouse, we observed significant loss of CB2R expression on T cells, but not macrophages, during acute GVHD, indicative of differential alterations in receptor expression under inflammatory conditions. Therapeutic targeting of the CB2R with the agonists Δ9-tetrahydrocannabinol (THC) and JWH-133 revealed that only THC mitigated lethal T cell–mediated acute GVHD. Conversely, only JWH-133 was effective in a sclerodermatous chronic GVHD model where macrophages contributed to disease biology. In vitro, both THC and JWH-133 induced arrestin recruitment and extracellular regulated kinase phosphorylation via CB2R, but THC had no effect on CB2R-mediated inhibition of adenylyl cyclase. This study shows that the CB2R plays a critical role in the regulation of GVHD and suggests that effective therapeutic targeting is dependent upon agonist signaling characteristics and receptor selectivity in conjunction with the composition of pathogenic immune effector cells.
Blastic plasmacytoid dendritic cell neoplasms: results of an international survey on 398 adult patients
Authors: Laribi Kamel , Baugier de Materre Alix , Sobh Mohamad , Cerroni Lorenzo , Valentini Caterina Giovanna , Aoki Tomohiro , Suzuki Ritsuro , Takeuchi Kengo , Frankel Arthur E. , Cota Carlo , Ghez David , Le Calloch Ronan , Pagano Livio , Petrella Tony
Published: October 2020

The purpose of this study is to describe the clinical and prognostic features and to evaluate the outcome of different therapeutic approaches among patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) who have been diagnosed and treated in different institutions. A total of 398 patients from 75 centers were included in the study. Treatment consisted of non-Hodgkin lymphoma (NHL)–like regimens in 129 (32.8%) patients and acute leukemia (AL)–like regimens in 113 (23.5%) patients. In 61 (15.5%) and 16 (4.1%) patients, chemotherapy was followed by allogeneic and autologous hematopoietic stem cell transplantation (HSCT), respectively. Twenty-seven (6.9%) patients received radiotherapy, 6 (1.5%) received new agents, and 62 (15.7%) received palliative care. After a median follow-up of 12 months, median overall survival (OS) was 18 months. Patients who received NHL/AL-like regimens, followed by allogeneic HSCT, had the best outcome; median OS was not reached. OS was 65 months for patients who underwent autologous HSCT; 18 months and 14 months, respectively, for those treated with AL-like and NHL-like regimens without consolidation; and 4 months for those receiving palliative care (P < .001). In BPDCN, chemotherapy with lymphoma- or AL-like regimens, followed by transplantation, represents the therapeutic strategy associated with the best outcome. Consolidation with allogeneic HSCT, when feasible, appears superior to autologous HSCT.
Analysis of transcriptomic differences between NK603 maize and near-isogenic varieties using RNA sequencing and RT-qPCR
Authors: Ben Ali Sina-Elisabeth , Draxler Agnes , Poelzl Diana , Agapito-Tenfen Sarah , Hochegger Rupert , Haslberger Alexander G. , Brandes Christian
Published: October 2020

Background

The insertion of a transgene into a plant organism can, in addition to the intended effects, lead to unintended effects in the plants. To uncover such effects, we compared maize grains of two genetically modified varieties containing NK603 (AG8025RR2, AG9045RR2) to their non-transgenic counterparts (AG8025conv, AG9045conv) using high-throughput RNA sequencing. Moreover, in-depth analysis of these data was performed to reveal the biological meaning of detected differences.

Results

Uniquely mapped reads corresponded to 29,146 and 33,420 counts in the AG8025 and AG9045 varieties, respectively. An analysis using the R-Bioconductor package EdgeR revealed 3534 and 694 DEGs (significant differentially expressed genes) between the varieties AG8025RR2 and AG9045RR2, respectively, and their non-transgenic counterparts. Furthermore, a Deseq2 package revealed 2477 and 440 DEGs between AG8025RR2 and AG9045RR2, respectively, and their counterparts. We were able to confirm the RNA-seq results by the analysis of two randomly selected genes using RT-qPCR (reverse transcription quantitative PCR). PCA and heatmap analysis confirmed a robust data set that differentiates the genotypes even by transgenic event. A detailed analysis of the DEGs was performed by the functional annotation of GO (Gene Ontology), annotation/enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) ontologies and functional classification of resulting key genes using the DAVID Bioinformatics Package. Several biological processes and metabolic pathways were found to be significantly different in both variety pairs.

Conclusion

Overall, our data clearly demonstrate substantial differences between the analyzed transgenic varieties and their non-transgenic counterparts. These differences indicate that several unintended effects have occurred as a result of NK603 integration. Heatmap data imply that most of the transgenic insert effects are variety-dependent. However, identified key genes involved in affected pathways of both variety pairs show that transgenic independent effects cannot be excluded. Further research of different NK603 varieties is necessary to clarify the role of internal and external influences on gene expression. Nevertheless, our study suggests that RNA-seq analysis can be utilized as a tool to characterize unintended genetic effects in transgenic plants and may also be useful in the safety assessment and authorization of genetically modified (GM) plants.
Monitoring priority substances in biota under the Water Framework Directive: how effective is a tiered approach based on caged invertebrates? A proof-of-concept study targeting PFOS in French rivers
Authors: Babut Marc , Ferrari Benoit J. D. , Jame Patrick , Assoumani Azziz , Lestremau François , Hette-Tronquart Nicolas , Miege Cécile , Perceval Olivier
Published: October 2020

Background

This study aims to describe and test a tiered approach for assessing compliance to Environmental Quality standards (EQSs) for priority substances in biota in line with the European Water Framework Directive. This approach is based on caged gammarids and trophic magnification factors (TMFs) at the first tier, with fish analyzed at the second tier at sites predicted to exceed the EQS at the first tier. A dataset was implemented by monitoring perfluorooctane sulfonate (PFOS) in caged gammarids exposed at 15 sites in French rivers, and in fish muscle and rest-of-body from the same sites. Isotopic ratios (δ13C and δ15 N) were also measured in gammarids and fish. Two scenarios were developed to compare measured PFOS concentrations in fish against predicted concentrations based on measures in caged gammarids and TMFs. Scenario (1) compared measured PFOS concentrations in fish fillets with predicted PFOS concentrations based on measured concentrations in caged gammarids and δ15 N. Scenario (2) tested whether or not EQS exceedance was correctly predicted based on measured concentrations in caged gammarids and trophic levels (TLs) from wild fish and gammarid populations.

Results

δ13C and δ15 N variations showed that caged gammarids used local food resources during exposure in the field. PFOS concentrations in gammarids were fairly variable through time at each site. In fish, concentrations ranged from < 1 to 250 ng g−1 (wet weight). After adjustment to the TL at which the EQS is set, 12 sites were above the EQS for PFOS. In scenario (1), predicted concentrations were almost correct at 7 sites out of 15. Most incorrect predictions were overestimations that were slightly improved by applying a lower (neutral) TMF. In scenario (2) we tested several variants for parameters involved in the predictions. The most efficient combination yielded two wrong predictions out of 15. This result was obtained with a higher (more conservative) TMF value, mean concentrations in gammarids from several field exposures during a year, and a TL for gammarids at the median of the distribution in French rivers.

Conclusion

The proposed tiered approach was thus efficient. However, the number of sites was relatively limited, and the dataset was biased towards EQS exceedance. The tiered approach warrants further validation.
Cockle shell-derived aragonite calcium carbonate nanoparticle for targeting cancer and breast cancer stem cells
Authors: Ibiyeye Kehinde Muibat , Idris Sherifat Banke , Zuki Abu Bakar Zakaria
Published: October 2020

Cockle shell-derived aragonite calcium carbonate nanoparticles (CACNP) have demonstrated prospect as nano-sized drug carriers for targeting cancer cells. CACNP is biocompatible, biodegradable and its biomaterial is readily available and is of low cost. In addition, CACNP is highly porous, has a large surface area which confer a high loading capacity. The pH-dependent release properties as well as its potential for surface functionalization with targeting agents make CACNP useful in passive and active targeting of cancer cells and cancer stem cells. In this article, we reviewed the current state of CACNP as nano-sized drug carrier for targeting cancer cells, cancer stem cells and its biocompatibility.
AllCoPol: inferring allele co-ancestry in polyploids
Authors: Lautenschlager Ulrich , Wagner Florian , Oberprieler Christoph
Published: October 2020

Background

Inferring phylogenetic relationships of polyploid species and their diploid ancestors (leading to reticulate phylogenies in the case of an allopolyploid origin) based on multi-locus sequence data is complicated by the unknown assignment of alleles found in polyploids to diploid subgenomes. A parsimony-based approach to this problem has been proposed by Oberprieler et al. (Methods Ecol Evol 8:835–849, 2017), however, its implementation is of limited practical value. In addition to previously identified shortcomings, it has been found that in some cases, the obtained results barely satisfy the applied criterion. To be of better use to other researchers, a reimplementation with methodological refinement appears to be indispensable.

Results

We present the AllCoPol package, which provides a heuristic method for assigning alleles from polyploids to diploid subgenomes based on the Minimizing Deep Coalescences (MDC) criterion in multi-locus sequence datasets. An additional consensus approach further allows to assess the confidence of phylogenetic reconstructions. Simulations of tetra- and hexaploids show that under simplifying assumptions such as completely disomic inheritance, the topological errors of reconstructed phylogenies are similar to those of MDC species trees based on the true allele partition.

Conclusions

AllCoPol is a Python package for phylogenetic reconstructions of polyploids offering enhanced functionality as well as improved usability. The included methods are supplied as command line tools without the need for prior programming knowledge.