bluuebunny/crossref_metadata_2025 huggingface dataset:
South African Evictions Today
Authors: Levenson Zachary
Published: March 2021

In Cape Town, South Africa, some residents risk eviction and even arrest by participating in land occupation. However, occupying land for many residents happened out of necessity. This article follows South African residents and their fight for “adequate housing,” freedom from eviction, and a government that will progressively realize both of these goals.
Cria Pride and Place in the Favela
Authors: de Souza Stefanie Israel
Published: March 2021

This essay gives the reader an inside look at “Cria pride.” Cria is how residents refer to someone who was born-and-raised in certain Brazilian communities. It is a status marker, a sort of favela citizenship, a category of belonging deeply connected to place and the dense web of social relations rooted in place.
Zoning Damned Whores and God’s Police: Maintaining Prostitution through Land Use and Euphemism in Victoria, Australia
Authors: Taylor Elizabeth , Larin Tegan
Published: March 2021

Building a “respectable nation” from a penal colony meant prostitution created regulatory dilemmas in nineteenth-century Australia. This article traces regulations deployed in the state of Victoria since then to define and control women, buildings, and districts associated with prostitution. It argues that approaches of formal condemnation and tacit approval were adopted and increasingly framed around public health and land use zoning. Spatial planning now underpins prostitution control: efforts to legitimize and contain the sex industry have, however, failed to prevent the proliferation of euphemistic “massage parlors.” We argue that despite shifts in rationales, zoning and prostitution regulations maintain stereotypical binaries of “Damned Whores” and “God’s Police.”
Process, Power, and Impact of the Institutional Review Board in Criminology and Criminal Justice Research
Authors: Gunnison Elaine , Helfgott Jacqueline B.
Published: March 2021

While research on Institutional Review Boards (IRBs) has been conducted on issues ranging from quality, process, and effectiveness, gaps remain. Social science researchers have raised issues regarding decisions by IRBs applied to the social sciences based on biomedical research. To date, little is known about the experience of social scientists in criminology and criminal justice with IRBs and this research seeks to fill this gap. An online survey, including open- and closed-ended questions drawn from the validated IRB-Researcher Assessment Tool, was administered to members of the Academy of Criminal Justice Sciences and the American Society of Criminology about their experiences with IRBs. Results revealed that researchers report experiencing challenges with their IRBs including timeline delays of their research, bias against their research, and decisions that protect legal liability rather than human subjects ethics. Recommendations for improving IRB reviews of protocols and challenges unique to criminology and criminal justice are discussed.
Images of relationships and emotions: A theoretically informed grounded theory approach to storybooks with youth characters with intellectual disability
Authors: Reichenberg Monica
Published: March 2021

This study aims to understand how Swedish storybooks targeting youth portray, the relationships (social capital) and emotions of characters with intellectual disability. A collection of 37 storybooks were analysed using grounded theory. The results suggest that romantic relationships dominate in the storybooks. In the portrayal of romantic relationships, sexuality had a prominent role for the characters with intellectual disability. Work relationships were portrayed as fulfilling and joyful, and family relationships as plentiful and secure. The characters with intellectual disability felt secure at home, almost as a safe haven. Romantic relationships were described as exciting and filled with curiosity. At work, the characters with intellectual disability felt joy and a sense of belonging, and the family invoked a sense of security. Negative emotions had a less prominent role in the stories. The study concludes a strong relationship between social capital and emotions in the storybooks.
Planning and analysing ‘Green’ post-COVID-19 orthopaedic perioperative recovery pathway
Authors: Iyengar Karthikeyan P , Jain Vijay K , Kariya Ankur D
Published: March 2021

The effect of the severe acute respiratory syndrome coronavirus 2 pandemic on the National Health Service in the United Kingdom has been profound and unprecedented with suspension of most elective surgeries. As we are emerging from lockdown now, restarting elective surgical procedures in a safe and effective manner is an expected challenge. Many perioperative factors including patient prioritisation, risk assessment, health infrastructure and infection prevention strategies need to be considered for patient safety. The British Orthopaedic Association, along with the National Health Service, have provided recent guidelines for restarting non-urgent and orthopaedic care in the United Kingdom. In this article we review the current guidelines and literature to provide some clarity for clinical practice.
Impact of third generation synthetic turf athletic field age on surface hardness and infill depth spatial variability
Authors: Dickson Kyley H , Straw Chase M , Thoms Adam W , Carson Troy D , Sorochan John C
Published: March 2021

The use of synthetic turf (ST) has become a popular option for many athletic fields. Little is known about how surface hardness and infill depth spatial variability changes over time on third generation (3G) ST athletic fields. A research study was conducted to investigate the impact of field age on surface hardness and infill depth spatial variability from 12 3G ST athletic fields in Tennessee and Georgia (USA) between March 5, 2014 and April 8, 2014. The 3G ST athletic fields tested varied in fiber type including monofilament, slit film, and a combination of monofilament with slit film fibers. All 3G ST athletic fields were directly over gravel with no shockpad present. Surface hardness and infill depth were collected in the same location on all fields. Surface hardness was collected with the Toro Mobile Tester (400–450 samples/field) and infill depth was collected manually with a three-prong infill depth gauge (200–225 samples/field). As field age increased, surface hardness and spatial variability of the surface hardness increased significantly. Surface hardness and infill depth also had a significant negative relationship with one another. The increase in mean surface hardness and variability is partially attributed to infill depth loss and compaction of the remaining infill. Infill depth did not have a significant relationship with age, unless plots were outside the manufacturer’s recommendation for infill depth. Considering the nearly 3000 samples collected in this study, maintaining a minimum infill depth between 30 and 35 mm kept 90% of surface hardness data points below the National Football League limit of 100 Gmax. Results from this study highlight how 3G ST athletic fields can change with age, which may indicate the need for targeted infill applications and decompaction to improve field uniformity over time.
The view from Washington: How the new Biden administration views the EU’s eastern neighbourhood
Authors: Åslund Anders
Published: March 2021

President Joe Biden and his administration are uniquely knowledgeable about Eastern Europe. Therefore, during his term we should expect an activist and well-informed US policy on Eastern Europe and the EU’s eastern neighbourhood. The two main planks of the Biden policy in this region are set to be unconditional support for each country’s national sovereignty against Russia and tough love in the fight against corruption in these countries. Ukraine is the natural focal point. The Biden administration will probably let the US Department of Justice pursue its cases against the Ukrainian oligarchs Dmytro Firtash and Ihor Kolomoiskiy, which is likely to change Ukrainian politics. Eastern Europeans can trust Biden to stand up to Russian aggression as this has been a hallmark of his political career.
Impact of flow pattern, body mass index, and age on intraprocedural fluoroscopic time and radiation dose during sacroiliac joint injections
Authors: Tiegs-Heiden Christin A , Murthy Naveen S , Geske Jennifer R , Diehn Felix E , Lehman Vance T , Liebo Greta B , Verdoorn Jared T , Carr Carrie M , McKenzie Gavin A
Published: March 2021

Purpose

Understanding all factors that may impact radiation dose and procedural time is crucial to safe and efficient image-guided interventions, such as fluoroscopically guided sacroiliac (SI) joint injections. The purpose of this study was to evaluate the effect of flow pattern (intra- vs. periarticular), patient age, and body mass index (BMI) on radiation dose and fluoroscopy time.

Methods

A total of 134 SI joint injections were reviewed. Injectate flow pattern, age, and BMI were analyzed in respect to fluoroscopy time (minutes), radiation dose (kerma area product (KAP); µGy m2), and estimated skin dose (mGy).

Results

BMI did not affect fluoroscopy time, but increased BMI resulted in significantly higher skin and fluoroscopy doses ( p < 0.001). There was no association between fluoroscopy time and flow pattern. Higher skin dose was associated with intraarticular flow ( p = 0.0086), and higher KAP was associated with periarticular flow ( p = 0.0128). However, the odds ratios were close to 1. There was no significant difference between fluoroscopy time or dose based on patient age.

Conclusion

Increased BMI had the largest impact on procedural radiation dose and skin dose. Flow pattern also showed a statistically significant association with radiation dose and skin dose, but the clinical difference was small. Proceduralists should be aware that BMI has the greatest impact on fluoroscopy dose and skin dose during SI joint injections compared to other factors.
GLP-1 receptor agonists: an updated review of head-to-head clinical studies
Authors: Trujillo Jennifer M. , Nuffer Wesley , Smith Brooke A.
Published: March 2021

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. Some also have documented cardiovascular benefit. The GLP-1 RA class has grown in the last decade, with several agents available for use in the United States and Europe. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical trials studying dulaglutide, exenatide twice daily, exenatide once weekly, liraglutide, lixisenatide, semaglutide, and oral semaglutide, 14 head-to-head trials were identified that evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects.
Prophylactic placement of inferior vena cava filters and the risk of death or venous thromboembolism in severe trauma patients: a retrospective study comparing two hospitals with different approaches
Authors: Trung Tran Thien , Bjarnason Haraldur , McDonald Jennifer , Skaga Nils Oddvar , Houghton Damon E , Kim Brian , Stavem Knut , Kløw Nils Einar
Published: March 2021

Background

Prophylactic use of inferior vena cava filters to prevent pulmonary embolism in trauma is controversial. The practice varies between hospitals and countries, in part due to conflicting evidence and guidelines.

Purpose

To compare the effects of pulmonary embolism, deep venous thrombosis and mortality in two hospitals using prophylactic inferior vena cava filter placement or prophylactic anticoagulation alone.

Material and Methods

Patients presenting with severe trauma were recruited from two level-1 trauma centres between January 2008 and December 2013. Recruited patients from an US hospital having prophylactic inferior vena cava filter inserted were compared to a Scandinavian hospital using prophylactic anticoagulation alone. Inclusion criteria were age >15 years, Injury Severity Score >15 and survival >24 h after hospital admission. Patients with venous thromboembolism diagnosed prior to inferior vena cava filter placement were excluded. A Cox proportional hazard regression model was used with adjustment for immortal time bias and predictor variables.

Results

In total, 951 patients were reviewed, 282 from an US hospital having inferior vena cava filters placed and 669 from a Scandinavian hospital without inferior vena cava filters. The mean age was 45.9 vs. 47.4 years and the mean Injury Severity Score was 29.8 vs. 25.9, respectively. Inferior vena cava filter placement was not associated with the hazard of pulmonary embolism (Hazard ratio=0.43; 95% confidence interval (CI) 0.12, 1.45; P=0.17) or mortality (Hazard ratio=1.16; 95% CI 0.70, 1.95; P=0.56). However, an increased rate of deep venous thrombosis was observed with inferior vena cava filters in place (Hazard ratio=3.75; 95% CI 1.68, 8.36; P=0.001).

Conclusion

In severely injured trauma patients, prophylactic inferior vena cava filter placement was not associated with pulmonary embolism or mortality. However, inferior vena cava filters were associated with increased rate of deep venous thrombosis.
Lifestyle Risk Factors, Quality of Life, and Intervention Preferences of Barrett’s Esophagus Patients: A Prospective Cohort Study
Authors: Zhang Xiaotao , Anandasabapathy Sharmila , Abrams Julian , Othman Mohamed , Badr Hoda J
Published: March 2021

Background and Aims

Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett’s Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population.

Methods

Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported on lifestyle risk factors, adherence determinants (e.g., perceived benefits/barriers, risk, intentions), QOL, and intervention preferences.

Results

Most patients (56%) had uncontrolled reflux, were overweight/obese (65.1%), and had low dietary fiber intake (91%). Many (45%) reported poor QOL. Patients’ perceived risk of developing esophageal cancer was high, but their behavior change intentions were low. Despite receiving lifestyle counseling from physicians, there were no significant changes in patients’ QOL or lifestyle risk factors over time. Nonetheless, patients indicated strong interest in internet (62.6%) and multimedia programs (57.9%) addressing acid reflux and weight control.

Conclusion

BE patients reported uncontrolled reflux, poor QOL, and multiple lifestyle risk factors that did not change over time. Despite low levels of intention for making lifestyle changes, patients were interested receiving more information about controlling acid reflux, suggesting a potential teachable moment and opportunity for web-based and multimedia multiple behavior interventions that seek to control acid reflux symptoms through weight loss and a high fiber diet.
Health Economic Evaluations of Hip and Knee Interventions in Orthopaedic Sports Medicine: A Systematic Review and Quality Assessment
Authors: Primeau Codie A. , Zomar Bryn O. , Somerville Lyndsay E. , Joshi Ishita , Giffin J. Robert , Marsh Jacquelyn D.
Published: March 2021

Background:

The economic burden of musculoskeletal diseases is substantial and growing. Economic evaluations compare costs and health benefits of interventions simultaneously to help inform value-based care; thus, it is crucial to ensure that studies are using appropriate methodology to provide valid evidence on the cost-effectiveness of interventions. This is particularly the case in orthopaedic sports medicine, where several interventions of varying costs are available to treat common hip and knee conditions.

Purpose:

To summarize and evaluate the quality of economic evaluations in orthopaedic sports medicine for knee and hip interventions and identify areas for quality improvement.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

The Medline, AMED, OVID Health Star, and EMBASE databases were searched from inception to March 1, 2020, to identify economic evaluations that compared ≥2 interventions for hip and/or knee conditions in orthopaedic sports medicine. We assessed the quality of full economic evaluations using the Quality of Health Economic Studies (QHES) tool, which consists of 16 questions for a total score of 100. We classified studies into quartiles based on QHES score ( extremely poor quality to high quality) and we evaluated the frequency of studies that addressed each of the 16 QHES questions.

Results:

A total of 93 studies were included in the systematic review. There were 41 (44%) cost analyses, of which 21 (51%) inappropriately concluded interventions were cost-effective. Only 52 (56%) of the included studies were full economic evaluations, although 40 of these (77%) fell in the high-quality quartile. The mean QHES score was 83.2 ± 19. Authors consistently addressed 12 of the QHES questions; questions that were missed or unclear were related to statistical uncertainty, appropriateness of costing methodology, and discussion of potential biases. The most frequently missed question was whether the cost perspective of the analysis was stated and justified.

Conclusion:

The number of studies in orthopaedic sports medicine is small, despite their overall good quality. Yet, there are still many highly cited studies based on low-quality or partial economic evaluations that are being used to influence clinical decision-making. Investigators should follow international health economic guidelines for study design and critical appraisal of studies to further improve quality.
Disrupting the Complacency: Disaster Experience and Emergent Environmentalism
Authors: Haney Timothy J.
Published: March 2021

As climate change intensifies, scholars are beginning to ask whether firsthand experience with disaster will cause complacent people to develop greater environmental concern and engage in more proenvironmental behaviors. Will the disruption caused by experiencing a local environmental disaster be enough to motivate residents to change their values and behaviors? The aim of this study is to answer that question by analyzing qualitative interview data collected from 40 residents of Calgary, Alberta, who survived the devastating and costly 2013 southern Alberta flood. Despite normally high levels of climate change denial and complacency, findings indicate that the flood prompted residents to concern themselves more with climate change and the climate crisis and to begin adopting many household-level proenvironmental behaviors. The findings also point to important gender differences in both environmental concern and proenvironmental behaviors. Thus, the article establishes a social-psychological process of attitudinal and behavioral change, allowing us to better understand how jarring environmental events disrupt complacency.
Police Encounters as Stressors: Associations with Depression and Anxiety across Race
Authors: Alang Sirry , McAlpine Donna , McClain Malcolm
Published: March 2021

Stress researchers have emphasized the relationship between social stress and mental health. However, research investigating police brutality as a stressor is scarce. The authors conceptualize police brutality as a stressor, examining racial variation in its effects on mental health. Data came from the Survey of the Health of Urban Residents in the United States ( n = 4,389). Negative encounters with the police were found to be associated with depressed mood and anxiety. The relationship between encounters with the police and depressed mood was stronger among Black respondents and Latinxs compared with Whites. Regardless of personal encounters with the police, the anticipatory stress of police brutality—concern that one might become a victim of police brutality—was associated with depression and anxiety. These findings highlight police brutality as an anticipatory stressor and have implications for whiteness as a resource that protects from the stress of negative police encounters.
The researches concern the influence of the helix angle on the composite machining process
Authors: Jiang Rongsheng , Wang Jinxin , Gao Yu , Zhu Zhaolong , Cao Pingxiang
Published: March 2021

Magnesium oxide-reinforced wood fiber composites (MgO/WF) are a new type of multifunctional material, which can be used in different occasions, such as shopping malls, hotels, and residential buildings. Referring to the relevant literature, there is no research on the milling performance of MgO/WF. In order to better understand the relevant knowledge of the processability of MgO/WF, three cutters with different helix angles were used in this experiment to carry out the cutting of MgO/WF, and the variation trend of its cutting force, tool wear, and surface roughness was measured. The results are as follows: First, under the same cutting parameters, the resultant force decreases with the increase of helix angle. Second, with the increase of helix angle, the tool wear was slightly improved. Third, the surface roughness (Ra) showed an increasing trend with the decrease of helix angle. In the end, when milling MgO/WF, better machined surface quality and less tool wear can be obtained by selecting the tool with larger helix angle.
Cytokine-like protein 1–induced survival of monocytes suggests a combined strategy targeting MCL1 and MAPK in CMML
Authors: Sevin Margaux , Debeurme Franck , Laplane Lucie , Badel Séverine , Morabito Margot , Newman Hanna L. , Torres-Martin Miguel , Yang Qin , Badaoui Bouchra , Wagner-Ballon Orianne , Saada Véronique , Sélimoglu-Buet Dorothée , Kraus-Berthier Laurence , Banquet Sébastien , Derreal Alix , Fenaux Pierre , Itzykson Raphael , Braun Thorsten , Etienne Gabriel , Berthon Celine , Thépot Sylvain , Kepp Oliver , Kroemer Guido , Padron Eric , Figueroa Maria E. , Droin Nathalie , Solary Eric
Published: March 2021

Mouse models of chronic myeloid malignancies suggest that targeting mature cells of the malignant clone disrupts feedback loops that promote disease expansion. Here, we show that in chronic myelomonocytic leukemia (CMML), monocytes that accumulate in the peripheral blood show a decreased propensity to die by apoptosis. BH3 profiling demonstrates their addiction to myeloid cell leukemia-1 (MCL1), which can be targeted with the small molecule inhibitor S63845. RNA sequencing and DNA methylation pattern analysis both point to the implication of the mitogen-activated protein kinase (MAPK) pathway in the resistance of CMML monocytes to death and reveal an autocrine pathway in which the secreted cytokine-like protein 1 (CYTL1) promotes extracellular signal-regulated kinase (ERK) activation through C-C chemokine receptor type 2 (CCR2). Combined MAPK and MCL1 inhibition restores apoptosis of monocytes from patients with CMML and reduces the expansion of patient-derived xenografts in mice. These results show that the combined inhibition of MCL1 and MAPK is a promising approach to slow down CMML progression by inducing leukemic monocyte apoptosis.
A JAK/STAT-mediated inflammatory signaling cascade drives oncogenesis in AF10-rearranged AML
Authors: Chen Bo-Rui , Deshpande Anagha , Barbosa Karina , Kleppe Maria , Lei Xue , Yeddula Narayana , Vela Pablo Sánchez , Campos Alexandre Rosa , Wechsler-Reya Robert J. , Bagchi Anindya , Meshinchi Soheil , Eaves Connie , Jeremias Irmela , Haferlach Torsten , Frank David A. , Ronai Ze’ev , Chanda Sumit , Armstrong Scott A. , Adams Peter D. , Levine Ross L. , Deshpande Aniruddha J.
Published: March 2021

Leukemias bearing fusions of the AF10/MLLT10 gene are associated with poor prognosis, and therapies targeting these fusion proteins (FPs) are lacking. To understand mechanisms underlying AF10 fusion-mediated leukemogenesis, we generated inducible mouse models of acute myeloid leukemia (AML) driven by the most common AF10 FPs, PICALM/CALM-AF10 and KMT2A/MLL-AF10, and performed comprehensive characterization of the disease using transcriptomic, epigenomic, proteomic, and functional genomic approaches. Our studies provide a detailed map of gene networks and protein interactors associated with key AF10 fusions involved in leukemia. Specifically, we report that AF10 fusions activate a cascade of JAK/STAT-mediated inflammatory signaling through direct recruitment of JAK1 kinase. Inhibition of the JAK/STAT signaling by genetic Jak1 deletion or through pharmacological JAK/STAT inhibition elicited potent antioncogenic effects in mouse and human models of AF10 fusion AML. Collectively, our study identifies JAK1 as a tractable therapeutic target in AF10-rearranged leukemias.
Development of luspatercept to treat ineffective erythropoiesis
Authors: Kubasch Anne Sophie , Fenaux Pierre , Platzbecker Uwe
Published: March 2021

Luspatercept (Reblozyl) was recently approved for treating patients with transfusion-dependent lower-risk myelodysplastic syndrome (MDS) with ring sideroblasts (RS) and/or SF3B1 mutation who were not eligible for erythropoiesis-stimulating agents (ESAs) or patients for whom those agents failed. Luspatercept acts as an activin receptor type IIB fusion protein ligand trap that targets the altered transforming growth factor beta pathway in MDS, which is associated with impaired terminal erythroid maturation. Treatment with luspatercept results in decreased SMAD signaling, which enables erythroid maturation by means of late-stage erythroblast differentiation and thus improves anemia. ESAs, the current standard first-line therapeutic option for anemic lower-risk patients with MDS, also improve red cell parameters mainly by expanding proliferation of early erythroid progenitor cells. However, erythropoietin (EPO) and its receptor (EPO-R) are also required for survival of late-stage definitive erythroid cells, and they play an essential role in promoting proliferation, survival, and appropriate timing of terminal maturation of primitive erythroid precursors. Thus, luspatercept joins the mechanism of ESAs in promoting erythroid maturation. Especially in the subgroup of MDS patients with RS, luspatercept showed high clinical activity for the treatment of anemia in the phase 2 (PACE-MDS) trial and subsequently in the phase 3 (MEDALIST) trial, which resulted in approval by both the US Food and Drug Administration and the European Medicines Agency in April 2020. Additional studies are needed to better understand the mechanism of action and pharmacodynamics of this novel agent in MDS.
Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis
Authors: Renosi Florian , Roggy Anne , Giguelay Ambre , Soret Lou , Viailly Pierre-Julien , Cheok Meyling , Biichle Sabeha , Angelot-Delettre Fanny , Asnafi Vahid , Macintyre Elizabeth , Geffroy Sandrine , Callanan Mary , Petrella Tony , Deconinck Eric , Daguindau Etienne , Harrivel Véronique , Bouyer Sabrina , Salaun Véronique , Saussoy Pascale , Feuillard Jean , Fuseau Pascal , Saas Philippe , Adotévi Olivier , Jardin Fabrice , Ferrand Christophe , Preudhomme Claude , Colinge Jacques , Roumier Christophe , Garnache-Ottou Francine
Published: March 2021

Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases. Importantly, 1 T-cell ALL clustered with BPDCN, with compatible morphology, immunophenotype (cCD3+ sCD3− CD123+ cTCL1+ CD304+), and genetics. Many oncogenetic pathways are deregulated in BPDCN compared with normal pDC, such as cell-cycle kinases, and importantly, the transcription factor SOX4, involved in B ontogeny, pDC ontogeny, and cancer cell invasion. High-throughput sequencing (HaloPlex) showed myeloid mutations (TET2, 62%; ASXL1, 46%; ZRSR2, 31%) associated with lymphoid mutations (IKZF1), whereas single-nucleotide polymorphism (SNP) array (Affymetrix SNP array 6.0) revealed frequent losses (mean: 9 per patient) involving key hematological oncogenes (RB1, IKZF1/2/3, ETV6, NR3C1, CDKN2A/B, TP53) and immune response genes (IFNGR, TGFB, CLEC4C, IFNA cluster). Various markers suggest an AS-DC origin, but not in all patients, and some of these abnormalities are related to the leukemogenesis process, such as the 9p deletion, leading to decreased expression of genes encoding type I interferons. In addition, the AS-DC profile is only found in a subgroup of patients. Overall, the cellular ontogenic origin of BPDCN remains to be characterized, and these results highlight the heterogeneity of BPDCN, with a risk of a diagnostic trap.
Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML
Authors: Stahl Maximilian , Menghrajani Kamal , Derkach Andriy , Chan Alexander , Xiao Wenbin , Glass Jacob , King Amber C. , Daniyan Anthony F. , Famulare Christopher , Cuello Bernadette M. , Horvat Troy Z. , Abdel-Wahab Omar , Levine Ross L. , Viny Aaron D. , Stein Eytan M. , Cai Sheng F. , Roshal Mikhail , Tallman Martin S. , Goldberg Aaron D.
Published: March 2021

Azacitidine + venetoclax, decitabine + venetoclax, and low-dose cytarabine + venetoclax are now standard treatments for newly diagnosed older or unfit patients with acute myeloid leukemia (AML). Although these combinations are also commonly used in relapsed or refractory AML (RR-AML), clinical and molecular predictors of response and survival in RR-AML are incompletely understood. We retrospectively analyzed clinical and molecular characteristics and outcomes for 86 patients with RR-AML who were treated with venetoclax combinations. The complete remission (CR) or CR with incomplete hematologic recovery (CRi) rate was 24%, and the overall response rate was 31% with the inclusion of a morphologic leukemia-free state. Azacitidine + venetoclax resulted in higher response rates compared with low-dose cytarabine + venetoclax (49% vs 15%; P = .008). Median overall survival (OS) was 6.1 months, but it was significantly longer with azacitidine + venetoclax compared with low-dose cytarabine + venetoclax (25 vs 3.9 months; P = .003). This survival advantage of azacitidine + venetoclax over low-dose cytarabine + venetoclax persisted when patients were censored for subsequent allogeneic stem cell transplantation (8.1 vs 3.9 months; P = .035). Mutations in NPM1 were associated with higher response rates, whereas adverse cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1 were associated with worse OS. Relapse was driven by diverse mechanisms, including acquisition of novel mutations and an increase in cytogenetic complexity. Venetoclax combination therapy is effective in many patients with RR-AML, and pretreatment molecular characteristics may predict outcomes. Trials that evaluate novel agents in combination with venetoclax therapy in patients with RR-AML that have adverse risk genomic features are warranted.
A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis
Authors: Luo Yunyun , Samuels Jonathan , Krasnokutsky Svetlana , Byrjalsen Inger , Kraus Virginia B. , He Yi , Karsdal Morten A. , Abramson Steven B. , Attur Mukundan , Bay-Jensen Anne C.
Published: March 2021

Background

Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation.

Materials and methods

The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.

Results

In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4–8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011).

Conclusion

Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.

Level of evidence

Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.
Deep active learning for classifying cancer pathology reports
Authors: De Angeli Kevin , Gao Shang , Alawad Mohammed , Yoon Hong-Jun , Schaefferkoetter Noah , Wu Xiao-Cheng , Durbin Eric B. , Doherty Jennifer , Stroup Antoinette , Coyle Linda , Penberthy Lynne , Tourassi Georgia
Published: March 2021

Background

Automated text classification has many important applications in the clinical setting; however, obtaining labelled data for training machine learning and deep learning models is often difficult and expensive. Active learning techniques may mitigate this challenge by reducing the amount of labelled data required to effectively train a model. In this study, we analyze the effectiveness of 11 active learning algorithms on classifying subsite and histology from cancer pathology reports using a Convolutional Neural Network as the text classification model.

Results

We compare the performance of each active learning strategy using two differently sized datasets and two different classification tasks. Our results show that on all tasks and dataset sizes, all active learning strategies except diversity-sampling strategies outperformed random sampling, i.e., no active learning. On our large dataset (15K initial labelled samples, adding 15K additional labelled samples each iteration of active learning), there was no clear winner between the different active learning strategies. On our small dataset (1K initial labelled samples, adding 1K additional labelled samples each iteration of active learning), marginal and ratio uncertainty sampling performed better than all other active learning techniques. We found that compared to random sampling, active learning strongly helps performance on rare classes by focusing on underrepresented classes.

Conclusions

Active learning can save annotation cost by helping human annotators efficiently and intelligently select which samples to label. Our results show that a dataset constructed using effective active learning techniques requires less than half the amount of labelled data to achieve the same performance as a dataset constructed using random sampling.
Dynamic expression of Ralstonia solanacearum virulence factors and metabolism-controlling genes during plant infection
Authors: de Pedro-Jové R. , Puigvert M. , Sebastià P. , Macho A. P. , Monteiro J. S. , Coll N. S. , Setúbal J. C. , Valls M.
Published: March 2021

Background

Ralstonia solanacearum is the causal agent of bacterial wilt, a devastating plant disease responsible for serious economic losses especially on potato, tomato, and other solanaceous plant species in temperate countries. In R. solanacearum, gene expression analysis has been key to unravel many virulence determinants as well as their regulatory networks. However, most of these assays have been performed using either bacteria grown in minimal medium or in planta, after symptom onset, which occurs at late stages of colonization. Thus, little is known about the genetic program that coordinates virulence gene expression and metabolic adaptation along the different stages of plant infection by R. solanacearum.

Results

We performed an RNA-sequencing analysis of the transcriptome of bacteria recovered from potato apoplast and from the xylem of asymptomatic or wilted potato plants, which correspond to three different conditions (Apoplast, Early and Late xylem). Our results show dynamic expression of metabolism-controlling genes and virulence factors during parasitic growth inside the plant. Flagellar motility genes were especially up-regulated in the apoplast and twitching motility genes showed a more sustained expression in planta regardless of the condition. Xylem-induced genes included virulence genes, such as the type III secretion system (T3SS) and most of its related effectors and nitrogen utilisation genes. The upstream regulators of the T3SS were exclusively up-regulated in the apoplast, preceding the induction of their downstream targets. Finally, a large subset of genes involved in central metabolism was exclusively down-regulated in the xylem at late infection stages.

Conclusions

This is the first report describing R. solanacearum dynamic transcriptional changes within the plant during infection. Our data define four main genetic programmes that define gene pathogen physiology during plant colonisation. The described expression of virulence genes, which might reflect bacterial states in different infection stages, provides key information on the R. solanacearum potato infection process.
Identification of 11 candidate structured noncoding RNA motifs in humans by comparative genomics
Authors: Hou Lijuan , Xie Jin , Wu Yaoyao , Wang Jiaojiao , Duan Anqi , Ao Yaqi , Liu Xuejiao , Yu Xinmei , Yan Hui , Perreault Jonathan , Li Sanshu
Published: March 2021

Background

Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge.

Results

Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins.

Conclusions

By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.
Rust expression browser: an open source database for simultaneous analysis of host and pathogen gene expression profiles with expVIP
Authors: Adams Thomas M. , Olsson Tjelvar S. G. , Ramírez-González Ricardo H. , Bryant Ruth , Bryson Rosie , Campos Pablo Eduardo , Fenwick Paul , Feuerhelm David , Hayes Charlotte , Henriksson Tina , Hubbard Amelia , Jevtić Radivoje , Judge Christopher , Kerton Matthew , Lage Jacob , Lewis Clare M. , Lilly Christine , Meidan Udi , Novoselović Dario , Patrick Colin , Wanyera Ruth , Saunders Diane G. O.
Published: March 2021

Background

Transcriptomics is being increasingly applied to generate new insight into the interactions between plants and their pathogens. For the wheat yellow (stripe) rust pathogen (Puccinia striiformis f. sp. tritici, Pst) RNA-based sequencing (RNA-Seq) has proved particularly valuable, overcoming the barriers associated with its obligate biotrophic nature. This includes the application of RNA-Seq approaches to study Pst and wheat gene expression dynamics over time and the Pst population composition through the use of a novel RNA-Seq based surveillance approach called “field pathogenomics”. As a dual RNA-Seq approach, the field pathogenomics technique also provides gene expression data from the host, giving new insight into host responses. However, this has created a wealth of data for interrogation.

Results

Here, we used the field pathogenomics approach to generate 538 new RNA-Seq datasets from Pst-infected field wheat samples, doubling the amount of transcriptomics data available for this important pathosystem. We then analysed these datasets alongside 66 RNA-Seq datasets from four Pst infection time-courses and 420 Pst-infected plant field and laboratory samples that were publicly available. A database of gene expression values for Pst and wheat was generated for each of these 1024 RNA-Seq datasets and incorporated into the development of the rust expression browser (http://www.rust-expression.com). This enables for the first time simultaneous ‘point-and-click’ access to gene expression profiles for Pst and its wheat host and represents the largest database of processed RNA-Seq datasets available for any of the three Puccinia wheat rust pathogens. We also demonstrated the utility of the browser through investigation of expression of putative Pst virulence genes over time and examined the host plants response to Pst infection.

Conclusions

The rust expression browser offers immense value to the wider community, facilitating data sharing and transparency and the underlying database can be continually expanded as more datasets become publicly available.
Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm
Authors: Pan Yuan-Bo , Lu Jianan , Yang Biao , Lenahan Cameron , Zhang Jianmin , Shao Anwen
Published: March 2021

Background

Rupture of intracranial aneurysm (IA) is the main cause of devastating subarachnoid hemorrhage, which urges our understanding of the pathogenesis and regulatory mechanisms of IA. However, the regulatory roles of long non-coding RNAs (lncRNAs) in IA is less known.

Results

We processed the raw SRR files of 12 superficial temporal artery (STA) samples and 6 IA samples to count files. Then the differentially expressed (DE) mRNAs, miRNAs, and lncRNAs between STAs and IAs were identified. The enrichment analyses were performed using DEmRNAs. Next, a lncRNA-miRNA-mRNA regulatory network was constructed using integrated bioinformatics analysis. In summary, 341 DElncRNAs, 234 DEmiRNAs, and 2914 DEmRNAs between the STA and IA. The lncRNA-miRNA-mRNA regulatory network of IA contains 91 nodes and 146 edges. The subnetwork of hub lncRNA PVT1 was extracted. The expression level of PVT1 was positively correlated with a majority of the mRNAs in its subnetwork. Moreover, we found that several mRNAs (CCND1, HIF1A, E2F1, CDKN1A, VEGFA, COL1A1 and COL5A2) in the PVT1 subnetwork served as essential components in the PI3K-Akt signaling pathway, and that some of the non-coding RNAs (ncRNAs) (PVT1, HOTAIR, hsa-miR-17, hsa-miR-142, hsa-miR-383 and hsa-miR-193b) interacted with these mRNAs.

Conclusion

Our annotations noting ncRNA’s role in the pathway may uncover novel regulatory mechanisms of ncRNAs and mRNAs in IA. These findings provide significant insights into the lncRNA regulatory network in IA.
Investigating psychometric properties of the arm activity measure – Thai version (ArmA-TH) sub‐scales using the Rasch model
Authors: Buntragulpoontawee Montana , Khunachiva Jeeranan , Euawongyarti Patreeya , Wongpakaran Nahathai , Wongpakaran Tinakon , Kaewma Atcharee , Ashford Stephen
Published: March 2021

Background

This study investigated the ArmA-TH sub-scale measurement properties based on item response theory using the Rasch model.

Methods

Patients with upper limb hemiplegia resulting from cerebrovascular and other brain disorders were asked to complete the ArmA-TH questionnaire. Rasch analysis was performed to test how well the ArmA-TH passive and active function sub-scales fit the Rasch model by investigating unidimensionality, response category functioning, reliability of person and item, and differential item functioning (DIF) for age, sex, and education.

Results

Participants had stroke or other acquired brain injury (n = 185), and the majority were men (126, 68.1 %), with a mean age of 55 (SD 22). Most patients (91, 49.2 %) had graduated from elementary/primary school. For the ArmA-TH passive function scale, all items had acceptable fit statistics. The scale’s unidimensionality and local independence were supported. The reliability was acceptable. A disordered threshold was found for five items, and none indicated DIF. For the ArmA-TH active function scale, one item was misfit and three were locally dependent. The reliability was good. No items showed DIF. All items had disordered thresholds, and the data fitted the Rasch model better after rescoring.

Conclusions

Both sub-scales of ArmA-TH fitted the Rasch model and were valid and reliable. The disordered thresholds should be further investigated.