bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Morphosyntactic Features of Russian as a Heritage Language in the Speech of Bi/Multilingual Children in Canada
Authors: Makarova Veronika , Terekhova Natalia
Published: October 2021

This article addresses the development of some features of morphology and syntax in the speech of bi/multilingual children in Saskatchewan, Canada, who are heritage speakers of Russian. The article reports on the results of a descriptive study examining some morpho-syntactic characteristics of the Russian speech of 29 children between 5 and 6 years old from immigrant families. These results are compared with a sample of speech data produced by Russian monolingual children (ML). This comparison demonstrates that child RHL speakers produce more morpho-syntactic non-canonical forms than their ML peers, but that the development of noun cases and verbal forms overall is similar to what is observed among ML speakers.
Annotated and updated checklist of marine crabs (Decapoda: Brachyura) of Mozambique supported by morphological and molecular data from shelf and slope species of the “MOZAMBIQUE” surveys
Authors: MUÑOZ ISABEL , GARCÍA-ISARCH EVA , CUESTA JOSE A.
Published: October 2021

An updated checklist of Mozambican marine brachyuran crabs is generated based on an exhaustive revision of the existing literature, together with the additional records provided by the specimens collected throughout the three “MOZAMBIQUE” surveys carried out in Mozambican waters during three consecutive years (2007–2009) by the Instituto Español de Oceanografía, (Spanish Institute of Oceanography, IEO). A total of 269 species, grouped in 15 superfamilies, 26 families and 172 genera are reported in the checklist, and a detailed inventory is produced with the list and remarks about the brachyuran species collected. Thirty-nine crab species belonging to 19 families were identified based on morphological characteristics and/or genetic tools. DNA barcode sequences (16S rRNA and/or COI) were obtained for 37 species, including 16S and COI sequences that are new for 26 and 14 species, respectively. Colour photographs of fresh specimens illustrate the comments about most species, being the first time that the original colour pattern is described for some of them. New records in Mozambican waters are reported for the species Paromolopsis boasi, Mursia aspera, Carcinoplax ischurodous, Tanaoa pustulosus, Euclosiana exquisita, Oxypleurodon difficilis, Naxioides robillardi, Samadinia galathea, Cyrtomaia gaillardi, Paramaja gibba, Pleistacantha ori, Parathranites granosus, Parathranites orientalis, Ovalipes iridescens and Charybdis smithii, and second records for Moloha alcocki, Samadinia pulchra and Charybdis africana. In addition, Raninoides crosnieri, S. galathea and P. ori were collected for the first time after their descriptions. The female of Samadinia galathea is described for the first time, and a potential new species of Mursia is reported. Some records expand the known bathymetric range of certain species and/or their general distribution. New molecular and morphological data suggest the necessity of the revision of P. boasi, R. crosnieri, C. africana and the genera Platymaia and Carcinoplax. The variability and taxonomic validity of some morphological characters in brachyuran systematic is discussed.
Bitara gen. nov. of Tropiduchidae (Hemiptera: Fulgoromorpha) east of Wallace line
Authors: STROIŃSKI ADAM , SZWEDO JACEK
Published: October 2021

A new genus and species of the tropiduchid planthopper of the tribe Tropiduchini is described as Bitara augusta gen. et sp. nov. from Madang Province, Papua New Guinea. It is the 18th species of Tropiduchini and the 9th genus known east of the Wallace line. It is another taxon with characteristic asymmetric genitalia within this tribe.
Best practice in statistics: The use of log transformation
Authors: West Robert M
Published: October 2021

The log transformation is often used to reduce skewness of a measurement variable. If, after transformation, the distribution is symmetric, then the Welch t-test might be used to compare groups. If, also, the distribution becomes close to normal, then a reference interval might be determined.
COVID-19 Bereavement in Ten Latin American Countries: Measurement Invariance of the Pandemic Grief Scale and Its Relation to Suicidal Ideation
Authors: Caycho-Rodríguez Tomás , Valencia Pablo D. , Vilca Lindsey W. , Lee Sherman A. , Carbajal-León Carlos , Vivanco-Vidal Andrea , Saroli-Araníbar Daniela , Reyes-Bossio Mario , White Michel , Rojas-Jara Claudio , Polanco-Carrasco Roberto , Gallegos Miguel , Cervigni Mauricio , Martino Pablo , Palacios Diego Alejandro , Moreta-Herrera Rodrigo , Samaniego-Pinho Antonio , Rivera Marlon Elías Lobos , Figares Andrés Buschiazzo , Puerta-Cortés Diana Ximena , Corrales-Reyes Ibraín Enrique , Calderón Raymundo , Tapia Bismarck Pinto , Ferrari Ilka Franco , Flores-Mendoza Carmen , Gallegos Walter L. Arias
Published: October 2021

The present study aimed to evaluate the cross-cultural measurement invariance of the Pandemic Grief Scale (PGS) in ten Latin American countries. A total of 2,321 people who had lost a family member or other loved one due to COVID-19 participated, with a mean age of 34.22 years old (SD = 11.99). In addition to the PGS, a single item of suicidal ideation was applied. The unidimensional model of the PGS had adequate fit in most countries and good reliability estimates. There was evidence of measurement invariance by country and gender. Also, a one-point increase in the PGS was associated with an almost twofold increase in the odds of suicidal ideation. Scores greater than or equal to 4 on the PGS are proposed as a cut off to identify individuals with suicidal ideation. Strong evidence of the cross-cultural validity of the PGS is provided.
Re-Examining the Effect of Job Sprawl on the Black-White Housing Consumption Gap: Evidence Following the Great Recession
Authors: Ragusett Jared M.
Published: October 2021

This article examines the association between employment decentralization and the Black-White housing consumption gap since the Great Recession. This research investigates the extent to which post-recession spatial patterns of employment facilitate, or impede, the recovery for Black households. The model estimates a statistically significant correlation between job sprawl and the Black-White housing gap, although the direction depends upon the level of sprawl and measure of housing consumption. For example, while job sprawl is associated with a reduction in the Black-White unit size gap, that association only holds in high-sprawl metropolitan areas. In one area of improvement since the recession, job sprawl is correlated with a reduction in the ownership gap in a majority of metropolitan areas. However, job sprawl is also correlated with an intensification of the suburban ownership gap in the vast majority of metropolitan areas in the study. This study counters conventional arguments that unplanned sprawl may reduce intergroup inequality, and that metropolitan land use regulations may therefore exacerbate inequality. The results of this research demonstrate that inequality persists in light of competitive market forces that generate sprawl. Metropolitan land use policies that mitigate sprawl may therefore be legitimate tools for mitigating intergroup inequality in metropolitan housing markets.
Petty in Pink: Clothing Color Moderates Audience Perceptions of a Female Politician’s Verbal Aggression
Authors: Richards Adam S. , Rice Patrick , Covington Loni
Published: October 2021

This research assessed whether the color of a female politician’s clothing affected perceptions of her verbal aggression. In the context of Kamala Harris attacking Donald Trump, a 2 (color: pink vs. gray) × 2 (verbal aggression: low vs. high) experiment was conducted. While wearing pink, participants perceived Harris as more competent and reported more message-consistent perceptions if she used low rather than high verbal aggression. While wearing gray, high rather than low verbal aggression was perceived more favorably.
Deep Ensemble Neural Network Approach for Federal Highway Administration Axle-Based Vehicle Classification Using Advanced Single Inductive Loops
Authors: Li Yiqiao , Tok Andre , Ritchie Stephen G.
Published: October 2021

The Federal Highway Administration (FHWA) vehicle classification scheme is designed to serve various transportation needs such as pavement design, emission estimation, and transportation planning. Many transportation agencies rely on Weigh-In-Motion and Automatic Vehicle Classification sites to collect these essential vehicle classification counts. However, the spatial coverage of these detection sites across the highway network is limited by high installation and maintenance costs. One cost-effective approach has been the use of single inductive loop sensors as an alternative to obtaining FHWA vehicle classification data. However, most data sets used to develop such models are skewed since many classes associated with larger truck configurations are less commonly observed in the roadway network. This makes it more difficult to accurately classify under-represented classes, even though many of these minority classes may have disproportionately adverse effects on pavement infrastructure and the environment. Therefore, previous models have been unable to adequately classify under-represented classes, and the overall performance of the models is often masked by excellent classification accuracy of majority classes, such as passenger vehicles and five-axle tractor-trailers. To resolve the challenge of imbalanced data sets in the FHWA vehicle classification, this paper constructed a bootstrap aggregating deep neural network model on a truck-focused data set using single inductive loop signatures. The proposed method significantly improved the model performance on several truck classes, especially minority classes such as Classes 7 and 11 which were overlooked in previous research. The model was tested on a distinct data set obtained from four spatially independent sites and achieved an accuracy of 0.87 and an average F1 score of 0.72.
Material studies for the recycling of abandoned, lost or otherwise discarded fishing gear (ALDFG)
Authors: Weißbach Gunter , Gerke Gilian , Stolte Andrea , Schneider Falk
Published: October 2021

This study investigates the feasibility of material recycling for retrieved gillnets from the Baltic Sea collected during a campaign of the World Wildlife Fund (WWF) Germany. Fragments from the material were analysed by Fourier transform infrared (FTIR) spectroscopy revealing polyamide 6 (PA6), polypropylene (PP) and polyethylene terephthalate (PET) in net material, swim lines and sink lines, respectively. A visual examination by microscope found large quantities of minerals attached to the surface of the material as well as in knots and loops of the polymer structure. Ash tests showed that a pre-treatment of the material including sorting, shredding, density separation and washing allows to reduce the mineral content from more than 45% of the total to 1.1%. However, for a separation by density, it is important that the entangled fibres can move freely. This is a major challenge for a primary or secondary mechanical recycling because a substantial fibre length reduction is required for the small polymer fibres down to a diameter of 20 µm. Another challenge for all kinds of recycling is the presence of lead lines in gillnets. Automated technology for removing these does not exist until now. A manual removal is indispensable to limit the level of contamination. Due to the complex pre-treatment and the elevated heavy metal concentrations also a tertiary or feedstock recycling seems not to be a possible pathway for retrieved gillnets. Yet, other options such as a primary recycling in concrete or bitumen additives or quaternary recycling via incineration may be conceivable alternatives. But there are also some arguments against these options. Better product design must be the goal to prevent plastic pollution and establish a functioning circular economy. In this context, the heavy metal contamination by abandoned, lost or otherwise discarded fishing gear (ALDFG) must be stopped.
Design of a multi-resiliency exoskeleton and its physiologic cost evaluation in uphill walking and stair climbing locomotion
Authors: Cao Enguo , Ren MengYi , Cui YuTian , Wang Kun , Yang Bin
Published: October 2021

Background

In recent years, as the large own weight of active exoskeleton brings some difficulty to energy-sustainable, studies have shown that passive lower extremity exoskeletons can also reduce the energy consumption of human locomotion, but the energy saving is still relatively small compared with the total consumption.

Methods

A passive lower limb exoskeleton named Multi-Resiliency was described, and design parameters were estimated based on inverse dynamics. Furthermore, a series of experiments was designed for assessing the assisting effect of the exoskeleton in uphill walking and upstairs activities.

Results

In the inverse dynamics analysis, the spring release angle θmax was confirmed to be 45° for increasing assist performance of the exoskeleton. In the exoskeleton wearing experiments, the energy expenditure of subjects were decreased by 14.3% in uphill walking test and 16.0% in stair climbing test respectively.

Conclusion

The results show that the design of Multi-Resiliency exoskeleton is reasonable and it may effectively improve walking efficiency during uphill walking and stair climbing activities.
Erosive arthritis in systemic lupus erythematosus: not only Rhupus
Authors: Ceccarelli Fulvia , Natalucci Francesco , Olivieri Giulio , Perricone Carlo , Pirone Carmelo , Spinelli Francesca Romana , Alessandri Cristiano , Conti Fabrizio
Published: October 2021

Systemic lupus erythematosus (SLE)–related arthritis has been traditionally defined as non-erosive and is therefore considered a minor manifestation requiring a mild treatment. However, the concept of non-erosive arthritis in SLE has been challenged with the advent of sensitive imaging techniques, such as high-resolution ultrasound with power Doppler or magnetic resonance. The application of these new imaging tools has demonstrated that up to 40% of SLE patients with joint involvement can develop erosive damage. Thus, this more aggressive phenotype can be identified not only in patients overlapping with rheumatoid arthritis (RA). This issue has been considered for the first time in the classification criteria proposed by Systemic Lupus International Collaborating Clinics in 2012, in which the old definition of “non-erosive arthritis” was replaced with either synovitis or tenderness in two or more joints with morning stiffness, suggesting the possible presence of an erosive phenotype. Accordingly, the 2019 EULAR/ACR’s SLE recommendations advise treatment with immunosuppressant or biological drugs for patients with RA-like moderate arthritis. As a result, several studies have investigated the presence of biomarkers associated with SLE erosive damage. A relevant role seems to be played by the autoantibodies directed against post-translational modified proteins: above all, a significant association has been observed with antibodies directed against citrullinated and carbamylated proteins. Conversely, the rheumatoid factor was not associated with this more aggressive SLE-related arthritis. Nonetheless, some pro-inflammatory factors have been associated with erosive damage in SLE patients. These results suggest new pathogenic mechanisms underlining erosive arthritis, only partially shared with RA. Hence, in the present narrative review, we summarized available data about erosive arthritis in SLE patients, in the light of its impact on therapeutic decisions.
Clinical update on public and private psychiatric practice shared-care partnerships – Can the twain work together?
Authors: Looi Jeffrey C.L. , Atchison Michelle , Matias May
Published: October 2021

Objective:

We explore the previous research and current context regarding opportunities for shared-care partnerships between public and private psychiatric practice.

Conclusions:

Since the early 2000s, when there was impetus for the development of public-private psychiatric shared-care models as part of a previous National Mental Health Strategy, there has been surprisingly little research and policy development. Given an apparent exodus of psychiatrists to private practice due to current challenges facing the public health sector, it is timely to reconsider models of private and public sector shared-care that may improve the quality of public mental healthcare.
Seeing God's Essence: A Teleological Coordination of the Beatific Vision and Christ's Work of Atonement
Authors: Bankston Will
Published: October 2021

Both Hans Boersma and Michael Allen have recently written important books on the beatific vision. This article engages these works in two main movements. In the first, the efforts of Boersma and Allen will be commended as much needed exhortations for the contemporary church. For the beatific vision combats the modern tendencies of demoting teleology and immanentizing the ultimate criteria of human flourishing. However, the second movement will critique a point that these two theologians share in their respective formulations of this eschatological act. Both posit the incarnate Son as the direct object of the vision. In contrast, this article contends that it is more theologically fitting to give this place to the divine essence. It does so by coordinating the beatific vision with the overarching telos of Christ's atoning work and its implications for theological anthropology.
An optimal method of distribution of the slip zone on thrust bearing surfaces
Authors: Wu Zhenpeng , Nguyen Vanliem , Dong Bowen , Ke Chao , Guo Xiaoyan , Zeng Liangcai
Published: October 2021

Research to achieve a reasonable distribution of the slip zone of the sliding pair for better improvement of the hydrodynamic pressure of the liquid film is an intractable topic. To solve this issue, this paper takes the thrust bearing as the research object, and proposes to use the position number of the grid nodes at the boundary line between the slip and no-slip zone in each radial zone of the inclined pad to be variables. The variables are then defined as chromosomes in an adaptive genetic algorithm (AGA) and used to optimize the bearing capacity of the tilting pad. The results show that the optimal method of the AGA, which has good stability and repeatability, remarkably improves the distribution of the slip zone on the surface of the inclined pad. Therefore, the bearing capacity of the liquid film is significantly improved. Particularly, by using the optimization, the boundary line between the slip/no-slip zone is a composite form of a part of an arc and a part of the whisker. When the liquid flow through the heterogeneous slip/on-slip surfaces is used by this composite splicing method, the liquid pressure is upgraded in two steps. This is more conducive to increasing the pressure on multiple areas on the surface of the tilting pad, thereby achieving higher bearing capacity.
The prevalence of potentially traumatic events in the seventh survey of the population-based Tromsø study (Tromsø 7)
Authors: Thimm Jens C. , Rognmo Kamilla , Rye Marte , Flåm Anna Margrete , Næss Eva Therese , Skre Ingunn , Wang Catharina E. A.
Published: October 2021

Aims: Potentially traumatic events (PTEs) can have detrimental consequences for an individual’s physical and mental health. Exposure to PTEs is therefore increasingly assessed in population-based studies. Consistent with this trend, the most recent wave of the longitudinal population-based Tromsø study (Tromsø 7) in Northern Norway included a list of PTEs. The aim of the present study was to describe the prevalence of PTEs in the sample and examine demographic correlates of reported PTE exposure in this group. Methods: In Tromsø 7, a total of 21,083 participants aged ⩾40 years (52.5% female, mean age 57.3 years) were asked about exposure to nine PTEs that occurred in childhood, in adulthood and in the previous year. Differences between demographic groups in exposure to PTEs were examined using chi-square tests and logistic regression analyses. Results: Overall, 67% of the participants reported at least one PTE across the three time intervals. A life-threatening illness or serious accident of a loved one (36.8%) or of the respondent (24.0%) and bullying (21.5%) were the most frequently reported PTEs. Female sex, younger age, indigenous or immigrant ethnicity and higher education were associated with an increased likelihood of reporting at least one PTE. Group differences with respect to specific PTEs were observed. Conclusions: The experience of PTEs is common among the participants in the Tromsø 7 study. The current study lays the foundation for further research into the associations between PTEs and physical and mental health within the Tromsø study.
Same problems, different concepts and language: What happens when prison climate research goes on a journey?
Authors: Neubacher Frank , Liebling Alison , Kant Deborah
Published: October 2021

Despite the fact that they face the same problems, prison legislation differs between England and Germany. So do concepts and language. Can prison quality research travel under these circumstances? Are research questions and methodologies transferable from one legal culture into another? By using the example of a joint research project designed to transfer prison climate research from England and establish it in Germany and Switzerland we respond to the challenges of transferability and translatability. After examining the divergent legal cultures in England and Germany we present a prison climate research methodology developed by the Cambridge Prisons Research Centre (PRC). We then delineate the preparation, implementation and outcome of a pretest designed to show whether this cross-cultural research project can work. The concept of moral performance, and the methodology, seem to travel well while things are more complicated when it comes to translation.
Geographical Discrimination of Curcuma longa L. in Vietnam Based on LC-HRMS Metabolomics
Authors: Nguyen Thi Kieu-Oanh , Do Hoang-Giang , Duong Ngoc-Tu , Nguyen Tien Dat , Nguyen Quang-Trung
Published: October 2021

Curcuma longa L. has been used as a food, cosmetic, traditional medicine, and natural dye for a long time in tropical and subtropical regions such as India, China, and Vietnam. Curcuminoids are considered the main bioactive compounds in this plant. This study focuses on metabolites profiling of the rhizome methanolic extract of C longa samples collected in 6 different provinces in Vietnam using liquid chromatography coupled with high-resolution mass spectrometry. The partial least-squares discriminant analysis model was then established to discriminate its metabolomes and identify the chemomarkers that help to distinguish C longa from 6 geographical locations. Consequently, collected samples were segregated into 3 main groups: northern (Lang Son, with typical content of 2 terpenoids), center (Nghe An), and southern highland (Lam Dong, with distinctive profile of 3 curcuminoids). The absolute curcuminoids’ amount was also measured based on the calibration curve of reference standards. The differential metabolites including curcumin, demethoxycurcumin, and bisdemethoxycurcumin were found with the highest range in samples from Lang Son, indicating the excellent quality of turmeric cultivated in this area.
Explaining the Gender Gap in News Access Across Thirty Countries: Resources, Gender-Bias Signals, and Societal Development
Authors: Mak Macau K. F.
Published: October 2021

The gender gap in news access affects the opportunities available for a particular gender to advocate politically, as news consumption contributes to citizens’ understanding of politics and their political participation. Given the significance of the issue, this study uses multilevel modelling and investigates how resources (Internet, education, household income), gender-bias signals (female political representation and economic participation), and societal development (press freedom, political freedom, and economic development) influence the size of the gender news gap. The analysis of multinational cross-sectional survey data ( N = 61,677) shows that greater Internet access predicts a larger gender news gap, while female representation in politics interacts with political freedom and press freedom to influence the size of the gap. This study does not only advance the understanding about the individual and societal factors influencing the gender news gap, but also provides insights into solutions to alleviate the gap.
Marx lies within
Authors: Chatterjee Ipsita
Published: October 2021

This paper is a journey towards discovering the Marx that has been part of my intellectual existence. Here, I attempt to trace how and why Marx became manifest in my life and work. I identify four aspects of Marxism that I think, has influenced and enabled me most: Marxism as a way of teaching (pedagogy), Marxism as a way of life (critical humanism), Marxism as a way of combatting alienation (disrupting alienation), and Marxism as a way of comprehending reality (dialectical). I explore Marx’s influence in pedagogy, particularly, a Freire-Marx radical pedagogy as the revolutionary struggle through which the concreteness of dehumanization is communicated dialogically not only among the oppressed, but also to the oppressor, in order to re-constitute reality. I understand Marx’s class consciousness as critical humanism based on compassion because class is not an a priori category, pure container, an empirical formula. Rather, it eventuates in the context of struggle, that is, humans identify with human suffering in the context of oppression to become critically conscious as class beings. I conceptualize how Marx demystifies self-love as alienation, indicating that it was not love at all, but self-estrangement of humans from their true soul-essence, and also, estrangement of humans from nature. Lastly, understanding freedom as emancipation of the species being, a truly social being, a truly natural being means the annihilation of the alienated-self (false-self) and the sensuous manifestation of the communist self (true-self). Accepting that that reality is dialectical and that we must act and think dialectically, and therefore, transform ourselves materially and spiritually is the last contributions of Marx that I discuss here. It is in manifesting these four elements of Marx that lies within me, I reveal the Marx that has influenced and enabled me most
A need for emotional, personal and professional support: Operation room nurses’ experience participating in organ procurement surgical procedures. A qualitative study
Authors: Barisa Branka , Struksnes Solveig Kristin
Published: October 2021

Participating in organ procurement procedures cause emotional stress and risk of long-lasting health problems. These experiences are rarely discussed in plenary, and research specifically aimed at operating room nurses is limited. The aim of this study was to describe how operating room nurses experience participating in organ procurement surgical procedures. A qualitative, descriptive and exploratory design was chosen. The sample consisted of 14 operating room nurses, recruited from The National Transplant Centre, Norway. Data collection was conducted using individual, in-depth interviews. Qualitative inductive manifest content analysis was used. The study is reported according to QUOREC. Four main categories constitute the findings: operating room nurses have experienced emotional and personal impact; they try to handle these emotions using coping strategies; the experiences have promoted professional development; the importance of colleagues, including an open unit culture, is emphasized. Other studies support these findings regarding the impact this surgical procedure has on operating room nurses. This study also emphasizes their need for personal and professional support. Both individual and structural actions are suggested to generate this kind of support. The study may provide a deeper understanding of how participating in the organ procurement process affects those who are involved, and how to facilitate support to them as leader.
Trajectories of Follow-up Compliance in a Fracture Liaison Service and Their Predictors: A Longitudinal Group-Based Trajectory Analysis
Authors: Senay Andréa , Fernandes Julio C , Delisle Josée , Morin Suzanne N , Nagin Daniel , Perreault Sylvie
Published: October 2021

Introduction/Objectives

Identification of groups of patients following similar trajectories of time-varying patient characteristics are often of considerable clinical value. This study provides an example of how the identification of trajectory groups of patients can be useful.

Methods

Using clinical and administrative data of a prospective cohort study aiming to improve the secondary prevention of osteoporosis-related fractures with a Fracture Liaison Service (FLS), trajectory groups for visit compliance over time (2-year follow-up) were predicted using group-based trajectory modeling. Predictors of trajectory groups were identified using multinomial logistic regressions.

Results

Among 532 participants (86% women, mean age 63 years), three trajectories were identified and interpreted as high followers, intermediate followers, and low followers. The predicted probability for group-membership was: 48.4% high followers, 28.1% intermediate followers, 23.5% low followers. A lower femoral bone mineral density and polypharmacy were predictors of being in the high followers compared to the low followers group; predictors for being in the intermediate followers group were polypharmacy and referral to a bone specialist at baseline.

Conclusions

Results provided information on visit compliance patterns and predictors for the patients undergoing the intervention. This information has important implications when implementing such health services and determining their effectiveness.
Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy
Authors: Juluri Krishna R. , Wu Qian Vicky , Voutsinas Jenna , Hou Jue , Hirayama Alexandre V. , Mullane Erin , Miles Nancy , Maloney David G. , Turtle Cameron J. , Bar Merav , Gauthier Jordan
Published: October 2021

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in patients with relapsed/refractory B-cell malignancies; however, it is associated with toxicities including cytokine release syndrome (CRS), neurotoxicity, and impaired hematopoietic recovery. The latter is associated with high-grade cytopenias requiring extended growth factor or transfusional support, potentially leading to additional complications such as infection or hemorrhage. To date, the factors independently associated with hematologic toxicity have not been well characterized. To address this deficit, we retrospectively analyzed 173 patients who received defined-composition CD19 CAR T-cell therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov; NCT01865617), with primary end points of absolute neutrophil count and platelet count at day-28 after CAR T-cell infusion. We observed cumulative incidences of neutrophil and platelet recovery of 81% and 75%, respectively, at 28 days after infusion. Hematologic toxicity was noted in a significant subset of patients, with persistent neutropenia in 9% and thrombocytopenia in 14% at last follow-up. Using debiased least absolute shrinkage selector and operator regression analysis for high-dimensional modeling and considering patient-, disease-, and treatment-related variables, we identified increased CRS severity as an independent predictor for decreased platelet count and lower prelymphodepletion platelet count as an independent predictor of both decreased neutrophil and platelet counts after CD19 CAR T-cell infusion. Furthermore, multivariable models including CRS-related cytokines identified associations between higher peak serum concentrations of interleukin-6 and lower day-28 cell counts; in contrast, higher serum concentrations of transforming growth factor-β1 were associated with higher counts. Our findings suggest that patient selection and improved CRS management may improve hematopoietic recovery after CD19 CAR T-cell therapy.
Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma
Authors: Voorhees Timothy J. , Zhao Beibo , Oldan Jorge , Hucks George , Khandani Amir , Dittus Christopher , Smith Jennifer , Morrison J. Kaitlin , Cheng Catherine J. , Ivanova Anastasia , Park Steven , Shea Thomas C. , Beaven Anne W. , Dotti Gianpietro , Serody Jonathan , Savoldo Barbara , Grover Natalie
Published: October 2021

Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression-free survival (PFS) after CD30.CAR-T cell therapy. We evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow-up of 9.5 months, 17 patients (63%) progressed, with a median PFS of 352 days (95% confidence interval: 116-not reached), and 2 patients died (7%) with a median overall survival of not reached. High metabolic tumor volume (MTV, >60 mL) immediately before lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank, P = .02), which persisted after adjusting for lymphodepletion and CAR-T dose (log rank, P = .01 and P = .006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD3+PD-1+ lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately before lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL. This trial was registered at www.clinicaltrials.gov as #NCT02690545.
An MRD-stratified pediatric protocol is as deliverable in adolescents and young adults as in children with ALL
Authors: Greenwood Matthew , Trahair Toby , Sutton Rosemary , Osborn Michael , Kwan John , Mapp Sally , Howman Rebecca , Anazodo Antoinette , Wylie Brenton , D’Rozario James , Hertzberg Mark , Irving Ian , Yeung David , Coyle Luke , Jager Amanda , Engeler Dan , Venn Nicola , Frampton Chris , Wei Andrew H. , Bradstock Kenneth , Dalla-Pozza Luciano
Published: October 2021

Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study (anzctr.org.au/ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (Australian and New Zealand Children’s Haematology and Oncology Group [ANZCHOG] Study 8) could be administered to patients aged 15 to 39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/consolidation and commencing the next phase of therapy (protocol M or high-risk [HR] treatment) by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, a total of 86 patients were enrolled; 82 were eligible. Median age was 22 years (range, 16-38 years). Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95% confidence interval [CI], 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (P = .77). Median time to protocol M/HR treatment was 96 days (interquartile range, 87.5-103 days) in ALL06 vs 98 days in Study 8 (P = .80). Induction mortality was 3.6%. With a median follow-up of 44 months (1-96 months), estimated 3-year disease-free survival was 72.8% (95% CI, 62.8-82.7), and estimated 3-year overall survival was 74.9% (95% CI, 65.3-84.5). End induction/consolidation MRD negativity rate was 58.6%. Body mass index ≥30 kg/m2 and day 79 MRD positivity were associated with poorer disease-free survival and overall survival. Pediatric therapy was safe and as deliverable in AYA patients as in children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL.
Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial
Authors: Woller Scott C. , Stevens Scott M. , Kaplan David , Wang Tzu-Fei , Branch D. Ware , Groat Danielle , Wilson Emily L. , Armbruster Brent , Aston Valerie T. , Lloyd James F. , Rondina Matthew T. , Elliott C. Greg
Published: October 2021

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.
Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study
Authors: Carney Brian J. , Wang Tzu-Fei , Ren Siyang , George Gemlyn , Al Homssi Amer , Gaddh Manila , Connolly Gregory C. , Shah Vinay I. , Bogue Thomas , Bartosic Abigail , Neuberg Donna , Baumann Kreuziger Lisa , Zwicker Jeffrey I. ,   on behalf of the VENUS Network Investigators
Published: October 2021

Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multicenter, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count <100 000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at 6 hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%) and 33 (27%) with modified-dose anticoagulation; 13 (11%) patients received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33 [94%]) and an acute deep vein thrombosis (28 of 33 [85%]). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% confidence interval [CI], 4.9-20.8) and 6.6% (95% CI, 2.4-15.7) in those who received modified-dose anticoagulation (Fine-Gray hazard ratio, 2.18; 95% CI, 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop deep vein thrombosis in the setting of thrombocytopenia.
Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
Authors: Frauenfeld Leonie , Castrejon-de-Anta Natalia , Ramis-Zaldivar Joan Enric , Streich Sebastian , Salmerón-Villalobos Julia , Otto Franziska , Mayer Annika Katharina , Steinhilber Julia , Pinyol Magda , Mankel Barbara , Ramsower Colleen , Bonzheim Irina , Fend Falko , Rimsza Lisa M. , Salaverria Itziar , Campo Elias , Balagué Olga , Quintanilla-Martinez Leticia
Published: October 2021

Diffuse large B-cell lymphoma (DLBCL) with aberrant coexpression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB) type by the Hans algorithm (HA), was genetically characterized. To capture the complexity of DLBCL-AE, we used an integrated approach that included gene expression profiling (GEP), fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. According to GEP, 32/54 (59%) cases were classified as GCB-DLBCL, 16/54 (30%) as activated B-cell (ABC) DLBCL, and 6/54 (11%) as unclassifiable. The discrepancy between HA and GEP was 41%. Three genetic subgroups were identified. Group 1 included 13/50 (26%) cases without translocations and mainly showing and ABC/MCD molecular profile. Group 2 comprised 11/50 (22%) cases with IRF4 alterations (DLBCL-IRF4), frequent mutations in IRF4 (82%) and NF-κB pathway genes (MYD88, CARD11, and CD79B), and losses of 17p13.2. Five cases each were classified as GCB- or ABC-type. Group 3 included 26/50 (52%) cases with 1 or several translocations in BCL2/BCL6/MYC/IGH, and GCB/EZB molecular profile predominated. Two cases in this latter group showed complex BCL2/BCL6/IRF4 translocations. DLBCL-IRF4 in adults showed a similar copy number profile and shared recurrent CARD11 and CD79B mutations when compared with LBCL-IRF4 in the pediatric population. However, adult cases showed higher genetic complexity, higher mutational load with frequent MYD88 and KMT2D mutations, and more ABC GEP. IRF4 mutations were identified only in IRF4-rearranged cases, indicating its potential use in the diagnostic setting. In conclusion, DLBCL-AE is genetically heterogeneous and enriched in cases with IRF4 alterations. DLBCL-IRF4 in adults has many similarities to the pediatric counterpart.
Lung cancer is also a hereditary disease
Authors: Benusiglio Patrick R. , Fallet Vincent , Sanchis-Borja Mateo , Coulet Florence , Cadranel Jacques
Published: October 2021

Pathogenic genetic variants (formerly called mutations) present in the germline of some individuals are associated with a clinically relevant increased risk of developing lung cancer. These germline pathogenic variants are hereditary and are transmitted in an autosomal dominant fashion. There are two major lung cancer susceptibility syndromes, and both seem to be specifically associated with the adenocarcinoma subtype. Li-Fraumeni syndrome is caused by variants in theTP53tumour-suppressor gene. Carriers are mainly at risk of early-onset breast cancer, sarcoma, glioma, leukaemia, adrenal cortical carcinoma and lung cancer.EGFRvariants, T790M in particular, cause theEGFRsusceptibility syndrome. Risk seems limited to lung cancer. Emerging data suggest that variants inATM, the breast and pancreatic cancer susceptibility gene, also increase lung adenocarcinoma risk. As for inherited lung disease, cancer risk is increased inSFTPA1andSFTPA2variant carriers independently of the underlying fibrosis. In this review, we provide criteria warranting the referral of a lung cancer patient to the cancer genetics clinic. Pathogenic variants are first identified in patients with cancer, and then in a subset of their relatives. Lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.
Improved detection of disease-associated gut microbes using 16S sequence-based biomarkers
Authors: Chrisman Brianna S. , Paskov Kelley M. , Stockham Nate , Jung Jae-Yoon , Varma Maya , Washington Peter Y. , Tataru Christine , Iwai Shoko , DeSantis Todd Z. , David Maude , Wall Dennis P.
Published: October 2021

Background

Sequencing partial 16S rRNA genes is a cost effective method for quantifying the microbial composition of an environment, such as the human gut. However, downstream analysis relies on binning reads into microbial groups by either considering each unique sequence as a different microbe, querying a database to get taxonomic labels from sequences, or clustering similar sequences together. However, these approaches do not fully capture evolutionary relationships between microbes, limiting the ability to identify differentially abundant groups of microbes between a diseased and control cohort. We present sequence-based biomarkers (SBBs), an aggregation method that groups and aggregates microbes using single variants and combinations of variants within their 16S sequences. We compare SBBs against other existing aggregation methods (OTU clustering and Microphenoor DiTaxa features) in several benchmarking tasks: biomarker discovery via permutation test, biomarker discovery via linear discriminant analysis, and phenotype prediction power. We demonstrate the SBBs perform on-par or better than the state-of-the-art methods in biomarker discovery and phenotype prediction.

Results

On two independent datasets, SBBs identify differentially abundant groups of microbes with similar or higher statistical significance than existing methods in both a permutation-test-based analysis and using linear discriminant analysis effect size. . By grouping microbes by SBB, we can identify several differentially abundant microbial groups (FDR <.1) between children with autism and neurotypical controls in a set of 115 discordant siblings. Porphyromonadaceae, Ruminococcaceae, and an unnamed species of Blastocystis were significantly enriched in autism, while Veillonellaceae was significantly depleted. Likewise, aggregating microbes by SBB on a dataset of obese and lean twins, we find several significantly differentially abundant microbial groups (FDR<.1). We observed Megasphaera andSutterellaceae highly enriched in obesity, and Phocaeicola significantly depleted. SBBs also perform on bar with or better than existing aggregation methods as features in a phenotype prediction model, predicting the autism phenotype with an ROC-AUC score of .64 and the obesity phenotype with an ROC-AUC score of .84.

Conclusions

SBBs provide a powerful method for aggregating microbes to perform differential abundance analysis as well as phenotype prediction. Our source code can be freely downloaded from http://github.com/briannachrisman/16s_biomarkers.