bluuebunny/crossref_metadata_2025 huggingface dataset:
X-ray imaging of 30 year old wine grape wood reveals cumulative impacts of rootstocks on scion secondary growth and Ravaz index
Authors: Migicovsky Zoë , Quigley Michelle Y , Mullins Joey , Ali Tahira , Swift Joel F , Agasaveeran Anita Rose , Dougherty Joseph D , Grant Brendan Michael , Korkmaz Ilayda , Malpeddi Maneesh Reddy , McNichol Emily L , Sharp Andrew W , Harris Jackie L , Hopkins Danielle R , Jordan Lindsay M , Kwasniewski Misha T , Striegler R Keith , Dowtin Asia L , Stotts Stephanie , Cousins Peter , Chitwood Daniel H
Published: October 2022

Annual rings from 30 year old vines in a California rootstock trial were measured to determine the effects of 15 different rootstocks on Chardonnay and Cabernet Sauvignon scions. Viticultural traits measuring vegetative growth, yield, berry quality, and nutrient uptake were collected at the beginning (1995 to 1999) and end (2017 to 2020) of the lifetime of a vineyard initially planted in 1991 and removed in 2021. X-ray Computed Tomography (CT) was used to measure ring widths in 103 vines. Ring width was modeled as a function of ring number using a negative exponential model. Early and late wood ring widths, cambium width, and scion trunk radius were correlated with 27 traits. Modeling of annual ring width shows that scions alter the width of the first rings but that rootstocks alter the decay of later rings, consistently shortening ring width throughout the lifetime of the vine. Ravaz index, juice pH, photosynthetic assimilation and transpiration rates, and instantaneous water use efficiency are correlated with scion trunk radius. Ultimately, our research indicates that rootstocks modulate secondary growth over years, altering physiology and agronomic traits. Rootstocks act in similar but distinct ways from climate to modulate ring width, which borrowing techniques from dendrochronology, can be used to monitor both genetic and environmental effects in woody perennial crop species.
Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn’s Disease
Authors: Maddipatla Sushma Chowdary , Kolachala Vasantha L , Venkateswaran Suresh , Dodd Anne F , Pelia Ranjit Singh , Geem Duke , Yin Hong , Sun Yutong , Xu Congmin , Mo Angela , Kosters Astrid , Yang Junkai , Matthews Jason D , Ghosn Eliver , Kugathasan Subra , Qiu Peng
Published: October 2022

Background

Crohn’s disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s.

Methods

Ileal biopsies were obtained from (1) control subjects (n = 6), (2) treatment-naïve patients (n = 7), and (3) established (n = 14) Crohn’s patients along with remission (n = 3) and refractory (n = 11) treatment groups. The biopsies processed using 10x Genomics single cell 5' yielded 139 906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell type proportions, differential expression analysis, and gene ontology enrichment were carried out for each cell type.

Results

We identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between control, treatment-naïve, and established groups, with the significant changes in the epithelial subtypes of the treatment-naïve patients, including microfold, tuft, goblet, enterocyte,s and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed; however, gene expression in the epithelial and immune compartment was different between Crohn’s phenotypes, indicating changes in cellular activity.

Conclusions

Our study identified cellular and transcriptional signatures associated with treatment-naïve Crohn’s disease that collectively point to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity among patients within the same disease phenotype, shining a new light on personalized treatment responses and strategies.
Use of virtual reality for procedural planning of transcatheter aortic valve replacement
Authors: Ruyra Xavier , Permanyer Eduard , Huguet Marina , Maldonado Giuliana
Published: October 2022

This study sought to evaluate the impact of virtual reality (VR) tools in procedural planning of transcatheter aortic valve replacement. A prospective study involving 11 patients referred for transcatheter aortic valve replacement was conducted. A multidetector computed tomography was used to acquire and segment the anatomy of the access route and landing zone. From the information obtained with the multidetector computed tomography in DICOM format, we built a virtual platform (VisuaMed, Techer Team, Valencia, Spain) that contains all the clinical information of the patients and a virtualized model of their anatomy. Wearing VR devices, the professional was able to ‘walk inside’ the anatomy in an interactive and immersive way. Decisions after the evaluation of routine clinical images were compared with those after experience with VR models and intraprocedural findings.
Stressed Hyperplanes and Kazhdan–Lusztig Gamma-Positivity for Matroids
Authors: Ferroni Luis , Nasr George D , Vecchi Lorenzo
Published: October 2022

In this article, we make several contributions of independent interest. First, we introduce the notion of stressed hyperplane of a matroid, essentially a type of cyclic flat that permits to transition from a given matroid into another with more bases. Second, we prove that the framework provided by the stressed hyperplanes allows one to write very concise closed formulas for the Kazhdan–Lusztig, inverse Kazhdan–Lusztig, and $Z$-polynomials of all paving matroids, a class that is conjectured to predominate among matroids. Third, noticing the palindromicity of the $Z$-polynomial, we address its $\gamma $-positivity, a midpoint between unimodality and real-rootedness. To this end, we introduce the $\gamma $-polynomial associated to it, we study some of its basic properties, and we find closed expressions for it in the case of paving matroids. Also, we prove that it has positive coefficients in many interesting cases, particularly in the large family of sparse paving matroids, and other smaller classes such as projective geometries, thagomizer matroids, and other particular graphs. Our last contribution consists of providing explicit combinatorial interpretations for the coefficients of many of the polynomials addressed in this article by enumerating fillings in certain Young tableaux and skew Young tableaux.
Whole Genome Sequencing Reveals the Structure of Environment-Associated Divergence in a Broadly Distributed Montane Bumble Bee, Bombus vancouverensis
Authors: Heraghty Sam D , Rahman Sarthok Rasique , Jackson Jason M , Lozier Jeffrey D
Published: October 2022

Broadly distributed species experience divergent abiotic conditions across their ranges that may drive local adaptation. Montane systems where populations are distributed across both latitudinal and elevational gradients are especially likely to produce local adaptation due to spatial variation in multiple abiotic factors, including temperature, oxygen availability, and air density. We use whole-genome resequencing to evaluate the landscape genomics of Bombus vancouverensis Cresson (Hymenoptera: Apidae), a common montane bumble bee that is distributed throughout the western part of North America. Combined statistical approaches revealed several large windows of outlier SNPs with unusual levels of differentiation across the region and indicated that isothermality and elevation were the environmental features most strongly associated with these variants. Genes found within these regions had diverse biological functions, but included neuromuscular function, ion homeostasis, oxidative stress, and hypoxia that could be associated with tolerance of temperature, desiccation, or high elevation conditions. The whole-genome sequencing approach revealed outliers occurred in genome regions with elevated linkage disequilibrium, elevated mean FST, and low intrapopulation nucleotide diversity. Other kinds of structural variations were not widely associated with environmental predictors but did broadly match geographic separation. Results are consistent with other studies suggesting that regions of low recombination may harbor adaptive variation in bumble bees within as well as between species and refine our understanding of candidate genes that could be further investigated as possible targets of selection across the B. vancouverensis range.
Acquisition of genomic elements were pivotal for the success of Escherichia coli ST410
Authors: Chen Liang , Peirano Gisele , Kreiswirth Barry N , Devinney Rebekah , Pitout Johann D D
Published: October 2022

Background

Escherichia coli ST410 is an emerging MDR clone linked to blaCTX-M-15 and blaOXA-181. Limited comprehensive data about the global distribution of ST410 clades and mobile genetic elements associated with different β-lactamases are available.

Methods

Short- and long-read WGS were performed on a collection of ST410 producing carbapenemases (n = 45) obtained from 11 countries. The evolutionary history of global E. coli ST410 was also investigated.

Results

OXA-181 and NDM-5 were the most frequent carbapenemases and used different underlying strategies to ensure their successful association with ST410 clades. Our phylogenetic analysis of publicly available ST410 genomes amended the previously published ST410 B subclades: ST410-B1 is identical to B1/H24, ST410-B2 includes B2/H24R and B3/H24Rx, while ST410-B3 corresponds to B4/H24RxC. Long-read WGS identified the following genomic events that likely shaped the evolution of ST410-B3: (i) gyrA and parC mutations were acquired via homologous recombination events; (ii) chromosomal integration of blaCMY-2 among ST410-B3; (iii) the emergence of ST410-B3 from ST410-B2 was accompanied by the replacement of IncFII plasmids harbouring blaCTX-M-15 (i.e. F36:31:A4:B1 in ST410-B2 with F1:A1:B49 plasmids in ST410-B3); and (iv) the NDM-5 gene was integrated within F1:A1:B49 plasmids over time.

Conclusions

The global ST410 population producing carbapenemases is dominated by the ST410-B2 and B3 subclades with varied geographical distribution that requires ongoing genomic surveillance. We provided an updated timeline of pivotal genomic events that have shaped the success of the ST410-B3 subclade.
Trading-off privacy and utility: the Washington State experience assessing the performance of a public health digital exposure notification system for coronavirus disease 2019
Authors: Segal Courtney D , Lober William B , Revere Debra , Lorigan Daniel , Karras Bryant T , Baseman Janet G
Published: October 2022

Objective

Digital exposure notifications (DEN) systems were an emergency response to the coronavirus disease 2019 (COVID-19) pandemic, harnessing smartphone-based technology to enhance conventional pandemic response strategies such as contact tracing. We identify and describe performance measurement constructs relevant to the implementation of DEN tools: (1) reach (number of users enrolled in the intervention); (2) engagement (utilization of the intervention); and (3) effectiveness in preventing transmissions of COVID-19 (impact of the intervention). We also describe WA State’s experience utilizing these constructs to design data-driven evaluation approaches.

Methods

We conducted an environmental scan of DEN documentation and relevant publications. Participation in multidisciplinary collaborative environments facilitated shared learning. Compilation of available data sources and their relevance to implementation and operation workflows were synthesized to develop implementation evaluation constructs.

Results

We identified 8 useful performance indicators within reach, engagement, and effectiveness constructs.

Discussion

We use implementation science to frame the evaluation of DEN tools by linking the theoretical constructs with the metrics available in the underlying disparate, deidentified, and aggregate data infrastructure. Our challenges in developing meaningful metrics include limited data science competencies in public health, validation of analytic methodologies in the complex and evolving pandemic environment, and the lack of integration with the public health infrastructure.

Conclusion

Continued collaboration and multidisciplinary consensus activities can improve the utility of DEN tools for future public health emergencies.
Tōjisha Research and Narrative Medicine: Contribution of a Japanese Experiment in the Investigation of Patients’ Personal Experience
Authors: Gaillard Maxence
Published: October 2022

Tōjisha research is a methodology intended to help psychiatric patients through dialogue. It was introduced in the context of community care in Bethel House (Hokkaido, Japan) in the early 2000s and later spread to other parts of Japan as well as abroad because of its originality and apparent therapeutic success. It offers patients a framework to investigate their own problems, symptoms, and delusions and to build a discourse around them. In this paper, I present a short account of tōjisha research and I put it in the context of current debates over the benefits and drawbacks of narrative medicine. I argue that there is an original conception of the self and of empowerment of patients in tōjisha research compared to other models of narrative medicine. Finally, I mobilize these original aspects to address some rebuttals of narrative medicine.
Trimodality Therapy vs Definitive Chemoradiation in Older Adults With Locally Advanced Esophageal Cancer
Authors: Gaber Charles E , Shaheen Nicholas J , Edwards Jessie K , Sandler Robert S , Nichols Hazel B , Sanoff Hanna K , Lund Jennifer L
Published: October 2022

Background

The comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data.

Methods

A cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results–Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer–specific mortality, functional adverse events, and healthy days at home.

Results

A total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively.

Conclusions

Compared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans.
Drug-related problems identified at a Japanese community pharmacy: a cross-sectional study
Authors: Takaki Hiroko , Kaneko Erina , Sonoda Masanobu , Yamano Toru , Ieiri Ichiro
Published: October 2022

Objectives

This study aimed to identify drug-related problems (DRPs) using data regarding the communication of pharmacists with prescribers over the phone at a community pharmacy. Furthermore, we elucidated the frequency of the sources of information for detecting each DRP and evaluated the decisions made by the prescribers for each DRP.

Methods

This cross-sectional study was conducted at a community pharmacy in Fukuoka Prefecture, Japan. We anonymously collected data obtained by pharmacists through contacting prescribers over the phone relating to any problems or doubts found in prescriptions between April 2016 and March 2019. We classified the data and identified DRPs. We elucidated the frequency of sources of information for detecting each DRP using descriptive analyses and evaluated prescribers’ decisions regarding each DRP via multivariate Poisson regression analyses.

Key findings

Of the 95 023 prescriptions, 5073 DRPs were identified (5073/95 023 = 5.34%). The most frequent DRP was inappropriate dosage and administration (1349/5073 = 26.59%), followed by non-adherence (1272/5073 = 25.07%) and incorrect prescription periods (889/5073 = 17.52%). Patient interviews were the most frequent sources of information for detecting following DRPs: non-adherence (1057/1272 = 83.10%), untreated indication (590/631 = 93.50%) and adverse drug reactions (80/107 = 74.77%). Most of the DRPs were resolved by making changes to the prescriptions (4571/5073 = 90.10%).

Conclusions

Inappropriate dosage and administration and non-adherence issues were the most frequent DRPs in a Japanese community pharmacy. Patient interviews were an important source of information for detecting DRPs. Further research is warranted to address the impact of DRPs on patient safety.
Pharmacological and phytochemical potential of Rubus ellipticus: a wild edible with multiple health benefits
Authors: Kewlani Pushpa , Tiwari Deepti , Rawat Sandeep , Bhatt Indra D
Published: October 2022

Objectives

Rubus ellipticus (family Rosaceae) is used for its delicious edible fruits in the Himalayan region and other parts of the globe. However, the full potential of the species is yet to be harnessed. The current review focuses on the phytochemical, traditional uses, morphological, molecular and pharmacological potential of R. ellipticus.

Key findings

The review of the literature reveals that many health-promoting compounds of R. ellipticus have been reported from the species along with the different biological properties, such as nephroprotective, anti-inflammatory, analgesic, anti-pyretic, anti-proliferative, cytotoxicity, anti-cancer, wound healing, anti-fertility, anti-plasmodial, anti-microbial and antioxidant. Traditionally, it is used in many formulations, which are validated through primary pharmacological assays. However, several medicinal properties are still need to be validated through detailed pharmacological and clinical studies.

All the information is available in a scanty form, and the complete information is missing on a single platform. Such type of information will help researchers to better utilize the available data for initiating future research on the species as it has the potential to contribute to the food and pharmaceutical industry. The review highlights the need for further studies on the species to harness its potential in nutraceutical, functional food, energy supplement, and beneficial therapeutic drug development program.
Triterpenoid saponins of Ilex pubescens against TNF-α induced inflammation and apoptosis in human umbilical vein endothelial cells via autophagy pathway
Authors: Yan Xuemei , Shang Xueying , Feng Zhiqiang , Chen Bingying , Wu Yurong , Zhou Yuan , Li Yu , Zhang Lei
Published: October 2022

Objectives

Triterpenoid saponins of Ilex pubescens (IPTS), the main active components of Ilex pubescens, has a therapeutic effect on atherosclerosis (AS). The ingredients in IPTS that could be intracellularly transported by human umbilical vein endothelial cells (HUVECs) may play an essential role in AS. This study attempted to explore its mechanism from the perspectives of HUVECs’ inflammation, apoptosis, and autophagy.

Methods

By using a tumour necrosis factor-α (TNF-α)-induced HUVECs injury model, cell viability and the expression of intercellular adhesion molecule 1 (ICAM1), matrix metalloproteinase 9 (MMP9), cleave-caspase-3 and cleave-caspase-9, in combination with the results of flow cytometry, JC-1 and Hoechst 33258 staining were investigated to evaluate the anti-inflammatory and anti-apoptotic impact effects of IPTS on HUVECs. Afterwards, the expression of microtubule-associated proteins light chain 3II (LC3II) and sequestosome 1 (p62) was determined to test the effect of IPTS on autophagy. Finally, by adding an autophagy inhibitor 3-methyladenine (3-MA), we investigated whether IPTS exerts anti-inflammatory and anti-apoptotic effects through the autophagy pathway.

Key findings

We firstly demonstrated that pretreatment with IPTS could increase the cell viability, maintain the cell morphology and reduce TNF-α-induced inflammation and apoptosis of HUVECs. Moreover, IPTS pretreatment was proved to raise the expression of LC3II /LC3I while decreasing the expression of p62, which indicated that IPTS could activate HUVECs’ autophagy. IPTS has been shown for the first time to exert anti-inflammatory and anti-apoptotic effects through autophagy and thereby resisting TNF-α-induced inflammatory injury of HUVECs.

Conclusions

This study preliminarily confirmed that IPTS ameliorated HUVECs’ inflammation and apoptosis by increasing autophagy.
Effects of artemether on pancreatic islet morphology, islet cell turnover and α-cell transdifferentiation in insulin-deficient Glu
CreERT2;ROSA26-eYFP diabetic mice
Authors: Sarnobat Dipak , Lafferty Ryan A , Charlotte Moffett R , Tarasov Andrei I , Flatt Peter R , Irwin Nigel
Published: October 2022

Objectives

The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested.

Methods

We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on a background of β-cell stress induced by multiple low-dose streptozotocin (STZ) injection in GluCreERT2; ROSA26-eYFP transgenic mice.

Key findings

Artemether intervention did not affect the actions of STZ on body weight, food and fluid intake or blood glucose. Circulating insulin and glucagon were reduced by STZ treatment, with a corresponding decline in pancreatic insulin content, which were not altered by artemether. The detrimental changes to pancreatic islet morphology induced by STZ were also evident in artemether-treated mice. Tracing of α-cell lineage, through co-staining for glucagon and yellow fluorescent protein (YFP), revealed a significant decrease of the proportion of glucagon+YFP− cells in STZ-diabetic mice, which was reversed by artemether. However, artemether had no effect on transdifferentiation of α-cells into β-cells and failed to augment the number of bi-hormonal, insulin+glucagon+, islet cells.

Conclusions

Our observations confirm that artemisinin derivatives do not impart meaningful benefits on islet cell lineage transition events or pancreatic islet morphology.
Increased imported severe Plasmodium falciparum malaria involving hyperparasitaemia (>10%) in a UK hospital following relaxation of COVID-19 restrictions compared to the pre-pandemic period
Authors: Choy Bennett , Bristowe Henrietta , Khozoee Baktash , Lampejo Temi
Published: October 2022

We identified and compared patients diagnosed with Plasmodium falciparum malaria at a large hospital in London, UK, prior to the COVID-19 pandemic vs following relaxation of COVID-19-associated restrictions. We found that parasitaemias, rates of hyperparasitaemia and severe malaria were significantly higher in the period post-relaxation of COVID-19 restrictions.
Research on the psychology of fictional characters based on artificial intelligence—an example study on The Family
Authors: Yuan Ying
Published: October 2022

Using ecological recognition based on artificial intelligence technology and Chinese psychology analysis system, by comparing the characters’ dialogs in The Family, we got the main characters’ big-five personality scores. In order to confirm the validity of this method, we compared the predicted scores with documents related to characters’ psychological analysis and novel descriptions. The prediction results are supported by the literature and plot. This indicates that the analysis of characters’ personalities by literary intelligence is effective. This research method provides data support for literary critics and quantitatively reflects the personality differences of characters in novels.
Blast Injury Patterns Among Israel Defense Forces Fatalities
Authors: Shakargy Josef Daniel , Gendler Sami , Talmy Tomer , Shushan Guy , Radomislensky Irina , Tsur Avishai M , Almog Ofer , Avital Guy , Benov Avi , Gelikas Shaul
Published: October 2022

Introduction

The incidence of blast injuries on the battlefield has risen over the last several decades. In order to improve prevention and treatment, it is essential to understand the severity and bodily distribution of these injuries. This study aims to characterize blast injury patterns among IDF fatalities.

Materials and Methods

This is a descriptive, retrospective study on postmortem reports of military-blast fatalities between the years 1982 and 2021. Body regions injured according to the Abbreviated Injury Scale (AIS) were described. The frequency of body region injury combinations was mapped, and the correlation between injured body regions was calculated using Pearson’s coefficient. Analysis of a subgroup with a postmortem computed tomography (CT-PM) or autopsy was performed, describing severe (AIS ≥ 3) injury patterns.

Results

Overall, 222 fatalities suffered from blast injury, with most injuries affecting the upper and lower extremities (63.7% and 66.5%, respectively), followed by the head (57.1%) and the thorax (56.6%). The median number of injured body regions was 4 (interquartile range, 2-5). The most frequent injury combinations were the upper and lower extremities (51%), the upper extremities and the thorax (45%), and the lower extremities and the thorax (41%). In all, 47/222 (21.2%) fatalities had a documented autopsy or CT-PM report. Among the fatalities with CT-PM or autopsy, the head (63.8%) and the thorax (57.4%) were most frequently severely injured (AIS ≥ 3).

Conclusions

Among blast fatalities in the military setting, the extremities were most commonly injured. However, data suggest that the head and thorax are more likely to sustain severe blast injuries resulting in mortality. Blast injuries in this cohort were characterized by concomitant involvement of several regions. Development of protective gear to minimize the multisystem injuries inflicted by blast injuries is warranted and should be focused on distinct types and anatomical distribution of severe blast injuries as reported in this study.

Level of Evidence

Level III, Retrospective analysis.
Dynamics of binary black holes in young star clusters: the impact of cluster mass and long-term evolution
Authors: Torniamenti Stefano , Rastello Sara , Mapelli Michela , Di Carlo Ugo N , Ballone Alessandro , Pasquato Mario
Published: October 2022

Dynamical interactions in dense star clusters are considered one of the most effective formation channels of binary black holes (BBHs). Here, we present direct N-body simulations of two different star cluster families: low-mass (∼500–800 M⊙) and relatively high-mass star clusters (≥5000 M⊙). We show that the formation channels of BBHs in low- and high-mass star clusters are extremely different and lead to two completely distinct populations of BBH mergers. Low-mass clusters host mainly low-mass BBHs born from binary evolution, while BBHs in high-mass clusters are relatively massive (chirp mass up to ∼100 M⊙) and driven by dynamical exchanges. Tidal disruption dramatically quenches the formation and dynamical evolution of BBHs in low-mass clusters on a very short time-scale (≲100 Myr), while BBHs in high-mass clusters undergo effective dynamical hardening until the end of our simulations (1.5 Gyr). In high-mass clusters, we find that 8 per cent of BBHs have primary mass in the pair-instability mass gap at metallicity Z = 0.002, all of them born via stellar collisions, while only one BBH with primary mass in the mass gap forms in low-mass clusters. These differences are crucial for the interpretation of the formation channels of gravitational-wave sources.
Estimating the depth of gaps opened by planets in eccentric orbit
Authors: Sánchez-Salcedo F J , Chametla R O , Chrenko O
Published: October 2022

Planets can carve gaps in the surface density of protoplanetary discs. The formation of these gaps can reduce the corotation torques acting on the planets. In addition, gaps can halt the accretion of solids on to the planets as dust and pebbles can be trapped at the edge of the gap. This accumulation of dust could explain the origin of the ring-like dust structures observed using high-resolution interferometry. In this work, we provide an empirical scaling relation for the depth of the gap cleared by a planet on an eccentric orbit as a function of the planet-to-star mass ratio q, the disc aspect ratio h, Shakura–Sunyaev viscosity parameter α, and planetary eccentricity e. We construct the scaling relation using a heuristic approach: we calibrate a toy model based on the impulse approximation with 2D hydrodynamical simulations. The scaling reproduces the gap depth for moderate eccentricities (e ≤ 4h) and when the surface density contrast outside and inside the gap is ≤102. Our framework can be used as the basis of more sophisticated models aiming to predict the radial gap profile for eccentric planets.
Assessment of a new sub-grid model for magnetohydrodynamical turbulence. I. Magnetorotational instability
Authors: Miravet-Tenés Miquel , Cerdá-Durán Pablo , Obergaulinger Martin , Font José A
Published: October 2022

Insufficient numerical resolution of grid-based, direct numerical simulations (DNS) hampers the development of instability-driven turbulence at small (unresolved) scales. As an alternative to DNS, sub-grid models can potentially reproduce the effects of turbulence at small scales in terms of the resolved scales, and hence can capture physical effects with less computational resources. We present a new sub-grid model, the MHD-instability-induced-turbulence (MInIT) mean-field model. MInIT is a physically motivated model based on the evolution of the turbulent (Maxwell, Reynolds, and Faraday) stress tensors and their relation with the turbulent energy densities of the magnetorotational (MRI) and parasitic instabilities, modelled with two partial differential evolution equations with stiff source terms. Their solution allows obtaining the turbulent stress tensors through the constant coefficients that link them to the energy densities. The model is assessed using data from MRI in-box DNS and applying a filtering operation to compare the filtered data with that from the model. Using the L2-norm as the metric for the comparison, we find less than one order-of-magnitude difference between the two sets of data. No dependence on filter size or length scale of unresolved scales is found, as opposed to results using the gradient model (which we also use to contrast our model) in which the L2-norm of some of the stresses increases with filter size. We conclude that MInIT can help DNS by properly capturing small-scale turbulent stresses which has potential implications on the dynamics of highly magnetized rotating compact objects, such as those formed during binary neutron star mergers.
Experimental phase function and degree of linear polarization curve of olivine and spinel and the origin of the Barbarian polarization behaviour
Authors: Frattin E , Martikainen J , Muñoz O , Gómez-Martín J C , Jardiel T , Cellino A , Libourel G , Muinonen K , Peiteado M , Tanga P
Published: October 2022

We explore experimentally possible explanations of the polarization curves of the sunlight reflected by the Barbarian asteroids. Their peculiar polarization curves are characterized by a large-inversion angle, around 30°, which could be related to the presence of FeO-bearing spinel embedded in Calcium–Aluminum inclusions. In order to test this hypothesis, we have measured the phase function and degree of linear polarization of six samples of Mg-rich olivine and spinel. For each material, we have analysed the light scattering properties of a millimeter-sized grain and of two powdered samples with size distributions in the micrometer size range. The three spinel samples show a well-defined negative polarization branch with an inversion phase angle located around 24°–30°. In contrast, in the case of the olivine samples, the inversion angle is highly dependent on particle size and tends to decrease for larger sizes. We identify the macroscopic geometries as a possible explanation for the evident differences in the polarization curves between olivine and spinel millimeter samples. Although the polarization behaviour in near backscattering of the Barbara asteroid is similar to that of our spinel mm-sized sample in random orientation, this similarity could result in part from crystal retro-reflection rather than composition. This is part of an ongoing experimental project devoted to test separately several components of CV3-like meteorites, representative of the Barbarians composition, to disentangle their contributions to the polarization behaviour of these objects.
Discovery of double BSS sequences in the old Galactic open cluster Berkeley 17
Authors: Rao Khushboo K , Bhattacharya Souradeep , Vaidya Kaushar , Agarwal Manan
Published: October 2022

Blue straggler stars (BSS) are peculiar objects which normally appear as a single broad sequence along the extension of the main sequence. Only four globular clusters (GCs) have been observed to have two distinct and parallel BSS sequences. For the first time for any open cluster (OC), we report double BSS sequences in Berkeley 17. Using the machine-learning based membership algorithm ML-MOC on Gaia EDR3 data, we identify 627 cluster members, including 21 BSS candidates out to 15 arcmin from the cluster centre. Both the BSS sequences are almost equally populated and parallel to one another in Gaia as well as in Pan-STARRS colour–magnitude diagram (CMD). We statistically confirm their presence and report that both BSS sequences are highly segregated compared to the reference population out to ∼5.5 arcmin and not segregated thereafter. The lower densities of OCs make BSS formation impossible via the collisional channel. Therefore, mass transfer seems to be the only viable channel for forming candidates of both sequences. The gap between the red and blue BSS sequences, on the other hand, is significant and presents a great opportunity to understand the connection between BSS formation and internal as well as external dynamics of the parent clusters.
Loss of Heterozygosity Spectrum Depends on Ploidy Level in Natural Yeast Populations
Authors: Dutta Abhishek , Dutreux Fabien , Schacherer Joseph
Published: October 2022

The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and are poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly show that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 × 10−3, 2.2 × 10−2, and 8.4 × 10−2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias toward the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared with diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates.
TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing
Authors: Demirdizen Engin , Al-Ali Ruslan , Narayanan Ashwin , Sun Xueyuan , Varga Julianna Patricia , Steffl Bianca , Brom Manuela , Krunic Damir , Schmidt Claudia , Schmidt Gabriele , Bestvater Felix , Taranda Julian , Turcan Şevin
Published: October 2022

Background

IDH mutant gliomas are grouped into astrocytomas or oligodendrogliomas depending on the codeletion of chromosome arms 1p and 19q. Although the genomic alterations of IDH mutant gliomas have been well described, transcriptional changes unique to either tumor type have not been fully understood. Here, we identify Tripartite Motif Containing 67 (TRIM67), an E3 ubiquitin ligase with essential roles during neuronal development, as an oncogene distinctly upregulated in oligodendrogliomas.

Methods

We used several cell lines, including patient-derived oligodendroglioma tumorspheres, to knock down or overexpress TRIM67. We coupled high-throughput assays, including RNA sequencing, total lysate-mass spectrometry (MS), and coimmunoprecipitation (co-IP)-MS with functional assays including immunofluorescence (IF) staining, co-IP, and western blotting (WB) to assess the in vitro phenotype associated with TRIM67. Patient-derived oligodendroglioma tumorspheres were orthotopically implanted in mice to determine the effect of TRIM67 on tumor growth and survival.

Results

TRIM67 overexpression alters the abundance of cytoskeletal proteins and induces membrane bleb formation. TRIM67-associated blebbing was reverted with the nonmuscle class II myosin inhibitor blebbistatin and selective ROCK inhibitor fasudil. NOGO-A/Rho GTPase/ROCK2 signaling is altered upon TRIM67 ectopic expression, pointing to the underlying mechanism for TRIM67-induced blebbing. Phenotypically, TRIM67 expression resulted in higher cell motility and reduced cell adherence. In orthotopic implantation models of patient-derived oligodendrogliomas, TRIM67 accelerated tumor growth, reduced overall survival, and led to increased vimentin expression at the tumor margin.

Conclusions

Taken together, our results demonstrate that upregulated TRIM67 induces blebbing-based rounded cell morphology through Rho GTPase/ROCK-mediated signaling thereby contributing to glioma pathogenesis.
Leveraging the CSF proteome toward minimally-invasive diagnostics surveillance of brain malignancies
Authors: Mikolajewicz Nicholas , Khan Shahbaz , Trifoi Mara , Skakdoub Anna , Ignatchenko Vladmir , Mansouri Sheila , Zuccato Jeffrey , Zacharia Brad E , Glantz Michael , Zadeh Gelareh , Moffat Jason , Kislinger Thomas , Mansouri Alireza
Published: October 2022

Background

Diagnosis and prognostication of intra-axial brain tumors hinges on invasive brain sampling, which carries risk of morbidity. Minimally-invasive sampling of proximal fluids, also known as liquid biopsy, can mitigate this risk. Our objective was to identify diagnostic and prognostic cerebrospinal fluid (CSF) proteomic signatures in glioblastoma (GBM), brain metastases (BM), and primary central nervous system lymphoma (CNSL).

Methods

CSF samples were retrospectively retrieved from the Penn State Neuroscience Biorepository and profiled using shotgun proteomics. Proteomic signatures were identified using machine learning classifiers and survival analyses.

Results

Using 30 µL CSF volumes, we recovered 755 unique proteins across 73 samples. Proteomic-based classifiers identified malignancy with area under the receiver operating characteristic (AUROC) of 0.94 and distinguished between tumor entities with AUROC ≥0.95. More clinically relevant triplex classifiers, comprised of just three proteins, distinguished between tumor entities with AUROC of 0.75–0.89. Novel biomarkers were identified, including GAP43, TFF3 and CACNA2D2, and characterized using single cell RNA sequencing. Survival analyses validated previously implicated prognostic signatures, including blood–brain barrier disruption.

Conclusions

Reliable classification of intra-axial malignancies using low CSF volumes is feasible, allowing for longitudinal tumor surveillance.
Molecular marker testing and reporting completeness for adult-type diffuse gliomas in the United States
Authors: Neff Corey , Cioffi Gino , Waite Kristin , Kruchko Carol , Barnholtz-Sloan Jill S , Ostrom Quinn T , Iorgulescu J Bryan
Published: October 2022

Background

A newly developed brain molecular marker (BMM) data item was implemented by US cancer registries for individuals diagnosed with brain tumors in 2018—including IDH and 1p/19q-co-deletion statuses for adult-type diffuse gliomas. We thus investigated the testing/reporting completeness of BMM in the United States.

Methods

Cases of histopathologically confirmed glioblastoma, astrocytoma, and oligodendroglioma diagnosed in 2018 were identified in the National Cancer Database. Adjusted odds ratios (ORadj) and 95% confidence intervals (CI) of BMM testing/reporting were evaluated for association with the selected patient, treatment, and facility-level characteristics using multivariable logistic regression. As a secondary analysis, predictors of MGMT promoter methylation testing/reporting among IDH-wildtype glioblastoma individuals were assessed. Key limitations of the BMM data item were that it did not include any details regarding testing technique or assay type and could not distinguish between a lack of testing and a lack of cancer registry reporting of testing results.

Results

Among 8306 histopathologically diagnosed adult-type diffuse gliomas nationally, overall BMM testing/reporting completeness was 81.1%. Compared to biopsy-only cases, odds of testing/reporting increased for subtotal (ORadj= 1.38 [95% CI: 1.20–1.59], P < .001) and gross total resection (ORadj=1.50 [95% CI: 1.31–1.72], P < .001). Furthermore, the odds were lowest at community centers (hospitals (67.3%; ORadj=0.35 [95% CI: 0.26–0.46], P < .001) and highest at academic/NCI-designated comprehensive cancer centers (85.4%; referent). By geographical location, BMM testing/reporting completeness ranged from a high of 86.8% at New England (referent) to a low of 76.0 % in the West South Central region (ORadj=0.57 [95% CI: 0.42–0.78]; P < .001). Extent of resection, Commission-on-Cancer facility type, and facility location were additionally significant predictors of MGMT testing/reporting among IDH-wildtype glioblastoma cases.

Conclusions

Initial BMM testing/reporting completeness for individuals with adult-type diffuse gliomas in the United States was promising, although patterns varied by hospital attributes and extent of resection.
The relationship between obesity and self-esteem: longitudinal evidence from Australian adults
Authors: Byth Sophie , Frijters Paul , Beatton Tony
Published: October 2022

We examine whether low self-esteem increases the risk of obesity in a panel of Australian adults. To address the problem of endogeneity, we look at weight changes following exogenous shocks to self-esteem, such as the unexpected death of friends and family members. We find that negative shocks adversely affect self-esteem in turn leading to large increases in weight via increased food consumption and reduced exercise. The effects of the negative shocks were found to be larger for the lower educated and females.
AlphaDrug: protein target specific de novo molecular generation
Authors: Qian Hao , Lin Cheng , Zhao Dengwei , Tu Shikui , Xu Lei
Published: October 2022

Traditional drug discovery is very laborious, expensive, and time-consuming, due to the huge combinatorial complexity of the discrete molecular search space. Researchers have turned to machine learning methods for help to tackle this difficult problem. However, most existing methods are either virtual screening on the available database of compounds by protein–ligand affinity prediction, or unconditional molecular generation, which does not take into account the information of the protein target. In this paper, we propose a protein target-oriented de novo drug design method, called AlphaDrug. Our method is able to automatically generate molecular drug candidates in an autoregressive way, and the drug candidates can dock into the given target protein well. To fulfill this goal, we devise a modified transformer network for the joint embedding of protein target and the molecule, and a Monte Carlo tree search (MCTS) algorithm for the conditional molecular generation. In the transformer variant, we impose a hierarchy of skip connections from protein encoder to molecule decoder for efficient feature transfer. The transformer variant computes the probabilities of next atoms based on the protein target and the molecule intermediate. We use the probabilities to guide the look-ahead search by MCTS to enhance or correct the next-atom selection. Moreover, MCTS is also guided by a value function implemented by a docking program, such that the paths with many low docking values are seldom chosen. Experiments on diverse protein targets demonstrate the effectiveness of our methods, indicating that AlphaDrug is a potentially promising solution to target-specific de novo drug design.
38 Spectacular improvement of refractory calcaneal enthesitis with anti TNF alpha
Authors: Sadeg Y , Ferhat A , Hafirassou H , Dahou-makhloufi C
Published: October 2022

Background

Spondyloarthritis is a heterogeneous group of chronic inflammatory rheumatism, of which enthesitis is the most common. Achilles involvement is frequent and can be disabling, resisting various treatments (non-steroidal anti-inflammatory drugs and local treatment). Only anti TNF alpha drugs are effective.

We report the case of a patient with extremely painful achilles enthesitis causing functional disability who responded dramatically to anti TNF alpha.

Observation

Child A.N, 13 years old, followed for juvenile idiopathic arthritis in the form of psoriatic arthritis evolving since the age of 4 years, treated with methotrexate at a rate of 7.5 mg/week, well balanced for 7 years.

Three years later, the patient consulted us for disabling right inflammatory heel pain with the impossibility of putting his shoes on.

The clinical examination revealed a painless position with the inability to put the heel on the ground; difficulty in walking requiring the use of crutches; pain on palpation of the Achilles tendon up to its insertion on the calcaneus, with painful limitation of dorsiflexion. Skin and mucous membrane examination revealed psoriasis lesions on the dorsum of the foot and on the nails.

Laboratory tests: CBC without abnormality, ESR= 25mmH1 CRP =12mg/l

X-ray of the rear feet: no abnormalities.

Ultrasound of the right ankle: enthesitis taking colour doppler at the insertion of the Achilles tendon with erosion within the calcaneus.

Magnetic resonance imaging of the right ankle: medullary oedema in the calcaneus with hyper signal on the DP sequence associated with retro calcaneal bursitis.

The patient was put on NSAIDs without improvement, two ultrasound-guided cortisone injections were performed, followed by total failure. Treatment with an anti TNF alpha (Etanercept 0.8 mg/kg/week 25 mg) was started, the improvement was spectacular after 8 weeks with disappearance of the pain, including when standing, walking and putting shoes on. On the ultrasound (disappearance of the retro calcaneal bursitis and negativation of the doppler signal) no recurrence was noticed.

Conclusion

Enthesitis is an essential lesion in spondyloarthritis. Generally resistant to conventional DMARDs, anti TNF alpha is a treatment of choice.