bluuebunny/crossref_metadata_2025 huggingface dataset:
What sustained multi-disciplinary research can achieve: The space weather modeling framework
Authors: Gombosi Tamas I. , Chen Yuxi , Glocer Alex , Huang Zhenguang , Jia Xianzhe , Liemohn Michael W. , Manchester Ward B. , Pulkkinen Tuija , Sachdeva Nishtha , Al Shidi Qusai , Sokolov Igor V. , Szente Judit , Tenishev Valeriy , Toth Gabor , van der Holst Bart , Welling Daniel T. , Zhao Lulu , Zou Shasha
Published: May 2021

Magnetohydrodynamics (MHD)-based global space weather models have mostly been developed and maintained at academic institutions. While the “free spirit” approach of academia enables the rapid emergence and testing of new ideas and methods, the lack of long-term stability and support makes this arrangement very challenging. This paper describes a successful example of a university-based group, the Center of Space Environment Modeling (CSEM) at the University of Michigan, that developed and maintained the Space Weather Modeling Framework (SWMF) and its core element, the BATS-R-US extended MHD code. It took a quarter of a century to develop this capability and reach its present level of maturity that makes it suitable for research use by the space physics community through the Community Coordinated Modeling Center (CCMC) as well as operational use by the NOAA Space Weather Prediction Center (SWPC).
Histomorphological and Morphometric Evaluation of Microvessel Density in Nodal Non-Hodgkin Lymphoma Using CD34 and CD105
Authors: Kataria Sant Prakash , Malik Shivani , Yadav Roomi , Kapil Raman , Sen Rajeev ,   Sucheta
Published: May 2021

Background Expression of angiogenic markers determined by microvessel density (MVD) could be used as a reliable predictor of prognosis and as a potential target for antiangiogenic therapy in different categories of non-Hodgkin lymphoma (NHL).

Aims The aim of this study was to evaluate MVD using immunohistochemical methods and computer-assisted quantitative image analysis in nodal NHL patients and compare CD34 and CD105 expression in lymph nodes of NHL patients.

Materials and Methods The present study was conducted on 60 lymph node biopsies received in the Department of Pathology at our tertiary care center for histopathological examination. Representative paraffin-embedded tissue sections were stained with hematoxylin and eosin along with immunohistochemical stains for CD34 and CD105. MVDs were analyzed at 400× using automated image analyzer by two investigators independently.

Statistical Analysis Data were calculated, tabulated, and statistically analyzed using SPSS (Statistical Package for Social Studies) statistical program version 18. The values entered were mean of morphometric parameters. In all tests, p-values below 0.05 were regarded as significant.

Results MVD was determined by CD34 and CD105 antibody highly correlated with different categories of NHL. Higher MVD was observed in cases of aggressive NHL as compared with indolent NHL and the difference was statistically significantly. MVD using CD105 was correlated more strongly as compared to CD34 with different categories of NHL.

Conclusion The present study concluded that NHL exhibits potent angiogenic activity that increased significantly with increasing aggressiveness. The study also demonstrated that CD105 is more specific than CD34 as a marker of neoangiogenesis in NHL.
“Radiation Recall Phenomenon” with Novel Cytotoxic Agents: An Emerging Trend in the Last Decade
Authors: Mandal Avik , Singh Pritanjali , Tandon Sarthak , Singh Dharmendra
Published: May 2021

Radiation recall phenomenon (RRP) is an acute inflammatory reaction manifested in the previously irradiated tissues after the administration of various pharmacologic compounds. While skin manifestations are the most common clinical features, patients may also present with visceral recall events including pneumonitis, hematuria, myopathy, and mucositis if any particular organ was exposed to the prior radiation portals. This article has reviewed the published case reports, case series, abstracts, and poster presentations in the past 10 years in any language on RRP caused by various novel cytotoxic drugs including immunotherapies, molecularly targeted agents, and unconventional chemotherapies. We retrieved the data through the literature search of MEDLINE and PubMed using the keywords “radiation,” “recall,” “targeted therapy,” and “immunotherapy,” and references identified in retrieved articles were also used for further search of the literature. With the increasing use of unconventional, novel cytotoxic agents and targeted molecules, concurrent or sequentially with radiation, we expect more incidences of RRP in future that may present with either dermatological or visceral recall reactions.
COVID-19, Cancer, and Congregation: An Observational Study from a Tertiary Care Hospital in New Delhi
Authors: Nair Rajesh , Kaushik M. R. , Kishore Kislay , Singh H. P. , Vardhan Vasu , Suresh P. , Kumar Manish , Rathore Anvesh , Thareja Sandeep , Rana Sandeep , Bhuva Dipen , Malviya Anupam , Patel Amol
Published: May 2021

Objective Indian data on cancer patients with coronavirus disease 2019 (COVID-19) infection and its outcome are limited. Infectivity and outcome among cancer patients staying in large congregations are not known. We conducted this study to address this lacuna in literature.

Methods This was a retrospective–prospective, observational study of hospitalized cancer patients with proven COVID-19 infection, conducted at tertiary care hospital in New Delhi after ethical approval. We analyzed clinical, laboratorial parameters, and outcomes in these patients.

Results All 32 admitted male patients became COVID-19 positive and 10 (31%) patients were symptomatic. Median age was 37.5 years (range: 16–64). Sixteen health-care workers (HCWs) were working in the cancer ward (paramedical staff: 4, nurses: 6, residents: 4, and consultants: 2). Among HCWs, two nursing staff and three paramedical staff contracted asymptomatic COVID-19. Eighteen (56%) and 14 (44%) patients were on curative and palliative treatment, respectively. Leukopenia (total leukocyte count <4,000/μL) was seen in 37.5% of cases. Grades 4, 3, 2, and 1 neutropenia were present in 12.5% of patents. Two (6.25%) patients had features of critical COVID-19. Eight (25%) patients received treatment with hydroxychloroquine + azithromycin. Five patients died. Three patients had features of progressive disease with poor performance status. One critical COVID patient survived and one succumbed to COVID-19. Patients shared a common dining room, sanitation area.

Conclusion Seventy percent of cancer patients were asymptomatic. Cancer patients living in congregation areas are susceptible to COVID-19 with 3% mortality rate. Recent chemotherapy and associated cytopenias may not increase the risk in cancer patients with COVID-19 treated with curative intent. Palliative intended patients are at increased risk of death. N-95, personal protective equipment, and adherence to infection control measures should be encouraged.
Phyllode fall and nutrient content in a mulga (Acacia aneura F.Muell. ex Benth.) community in central Australia in response to rainfall
Authors: Turner J. C. , Friedel M. H. , Neumann M.
Published: May 2021

The fall of phyllodes from Acacia aneura F.Muell. ex Benth. (mulga) in central Australia was studied over 22 months from mid-1958 at four locations within a livestock reserve north of Alice Springs in the Northern Territory, in order to identify rainfall or seasonal triggers. Phyllode fall increased by at least an order of magnitude for short periods following rain of 15–20 mm or more on a ‘mature’ mulga site and similar trends were apparent for ‘young’ and ‘desert form’ mulga on the same site, and on a second, independent, ‘mature’ site. When rates of phyllode fall were high after substantial rain, at both ‘mature’ locations, ~30% of nitrogen and ~50% of phosphorus were withdrawn before abscission, suggesting that mulga was markedly conservative of these nutrients. Conversely, under dry conditions, when phyllode fall was relatively low (<200 mg m−2 day−1), concentrations of nitrogen and phosphorus in fallen phyllodes were higher. Concentrations of potassium, calcium, magnesium and sodium did not vary consistently with increasing rate of phyllode fall, although overall levels of calcium and potassium were considerably higher in the second ‘mature’ location. This legacy study is of renewed interest given the potential of mulga communities to contribute to national carbon stocks, and the consequent need for robust field-based data on growth dynamics and carbon fluxes.
Abutilon hirtum (Indian mallow).
Authors: Vélez-Gavilán Jeanine
Published: May 2021

A. hirtum is a perennial herb or shrub which is a common weed, listed as an invasive in Cuba, French Polynesia and New Caledonia (Oviedo Prieto et al., 2012; PIER, 2015). It is not considered a threat at high elevations (PIER, 2015). It was likely introduced in some countries to cultivate it for traditional medicinal uses, for its fibres or as an ornamental (Kshirsagar and Singh, 2001; Brussell, 2004; Achigan-Dako, 2010; Wesley et al., 2013). No details are given about the level of invasiveness or the impacts of the species where it is reported as invasive. It is reported as a serious weed of agriculture in Ghana, Thailand, Nigeria and Sudan; and as a common weed in India (Achigan-Dako, 2010; PIER, 2015). A risk assessment available on PIER (2015) gives it a score of 5 (reject for introduction).
Nelsonia canescens (blue pussyleaf).
Authors: Rojas-Sandoval Julissa , Acevedo-Rodríguez Pedro
Published: May 2021

N. canescens is a fast-growing species that can grow as a weed in native and secondary wet forests as well as in agricultural land (Daniel, 2001; Ekeleme and Chikoye, 2003; Essandoh et al., 2011; Randall, 2012; Mahbubur, 2013). Consequently, it is outcompeting native and crop plants for common resources such as water, mineral nutrients, space and light (Ekeleme and Chikoye, 2003; Essandoh et al., 2011). In Puerto Rico, N. canescens is listed as invasive in riparian forests, secondary wet forests and disturbed grassy areas (US National Herbarium; Rojas-Sandoval and Acevedo, unpublished data).
Galinsoga parviflora (gallant soldier).
Authors: Rojas-Sandoval Julissa , Acevedo-Rodríguez Pedro
Published: May 2021

G. parviflora is a cosmopolitan fast-growing annual herb with the capacity to invade agricultural and other disturbed areas in most temperate and subtropical regions of the world (Holm et al., 1979). It is highly competitive and can spread quickly, often being the dominant species in a field. G. parviflora generates considerable economic impact on crop systems, greenhouses, gardens and nurseries. It is listed as an invasive and noxious weed in North America, Europe, Asia, Australia, and on islands in the Pacific Ocean (see Distribution Table for details).
Harmonia axyridis (harlequin ladybird).
Authors: Roy Helen , Kenis Marc
Published: May 2021

H. axyridis, a species of Asian origin, has been used as a biological control agent against aphids worldwide. The first releases were made in North America in 1916, but it was not until 1988 that the first individuals were found in the wild. Since then, it has rapidly invaded most of North America and Europe, and it is now spreading in other regions such as South America and South Africa. In most invaded regions, numbers have increased exponentially and H. axyridis has quickly become the most abundant ladybird in a wide range of habitats. The invasion of H. axyridis causes concern for the populations of native ladybirds and other aphidophagous insects, which it may displace through intraguild predation and competition for resources. It is also regarded as a grape [Vitis vinifera] and wine pest, and as a human nuisance because it aggregates in buildings when seeking overwintering sites in the autumn.
Pilosella caespitosa (yellow hawkweed).
Authors: Cortat Ghislaine , Grosskopf Gitta
Published: May 2021

P. caespitosa is a stoloniferous rosette plant which has spread rapidly to exotic locations outside its native range, namely to North America after its introduction as a garden ornamental or contaminant of agricultural seed. It continues to be available as an ornamental and can be easily transported by machinery and as such is likely to spread further. P. caespitosa is an undesirable invader on account of its vigorous growth due to stolon, rhizome and adventitious root bud production and wind-dispersed seeds which are produced in high numbers. P. caespitosa displaces desirable pasture plants leading to loss of forage and biodiversity. Early infestations of P. caespitosa which are still very small may be difficult to spot since this weed occurs on upland pastures and forest meadows in parts of the USA, and it is a declared weed in the states of Idaho and Washington (USDA-NRCS, 2016).
Pilosella officinarum (mouse-ear hawkweed).
Authors: Cortat Ghislaine , Grosskopf Gitta
Published: May 2021

P. officinarum is a prostrate herb which has spread rapidly to exotic locations (e.g. New Zealand, North America and South America) after introduction as a garden ornamental or contaminant of agricultural seed. As it continues to be available as an ornamental and can be easily transported by machinery, P. officinarum is likely to spread further. It is an undesirable invader on account of its vigorous growth due to stolon production and wind-dispersed seeds. P. officinarum displaces the inter-tussock vegetation leading to loss of forage and biodiversity.
Community-Engaged History: A Reflection on the 100th Anniversary of the 1921 Tulsa Race Massacre
Authors: Hill Karlos K.
Published: May 2021

How does scholarship live in the world, connected to real-world issues? Why should historians embrace community-engaged history as a means to effect social change? This essay addresses these questions by chronicling one historian’s efforts to align his scholarly expertise with addressing the polarizing legacies of the 1921 Tulsa Race Massacre, one of the deadliest outbreaks of anti-Black violence in American history.
The Risk and Influencing Factors of Hypertension in Jinchang Cohort
Authors: Miao Qian , Zheng Shan , Luo Yan , Wang Ming-zhen , Zhu Wen-zhi , Shi Qin , Li Hai-yan , Bai Ya-na
Published: May 2021

Background

To investigate the incidence and influencing factors of hypertension in Jinchang cohort.

Methods

A prospective cohort study was conducted to collect the baseline and follow-up information of 22,826 employees from 2011 to 2015 based on the Jinchang cohort platform. The incidence of hypertension in the cohort was calculated and the influencing factors were analyzed by Cox proportional risk model.

Results

The subjects were followed up for an average of 22 years, and the incidence density of hypertension was 56.31/1000 person-years. Multivariate Cox regression results showed that the main risk factors for hypertension in the population included age ≥40 years, alcohol consumption, high-salt diet, history of diabetes, family history of hypertension, overweight and obesity, baseline systolic blood pressure ≥110 mm Hg and diastolic blood pressure ≥75 mm Hg, and higher education levels (middle school, high school, and above) were a protective factor. The incidence of grade 1 hypertension was related to age, drinking, history of diabetes, family history of hypertension and baseline blood pressure levels, and the incidence of grades 2 and 3 hypertension was related to high-salt diet, family history of hypertension, overweight or obesity, and baseline blood pressure levels.

Conclusions

The Jinchang cohort has a higher risk of hypertension. Age, unhealthy lifestyle, history of diabetes, family history of hypertension, obesity, and baseline blood pressure are strongly associated with the onset of hypertension. There are differences in the risk factors for the occurrence of grades 1, 2, and 3 hypertension.
Adherence to Treatment by Initial Antihypertensive Mono and Combination Therapies
Authors: Rea Federico , Savaré Laura , Franchi Matteo , Corrao Giovanni , Mancia Giuseppe
Published: May 2021

Background

Aim of our study was to compare adherence to antihypertensive drug therapy between newly treated patients in whom monotherapy or a 2-drug single-pill combination (SPC) was initially dispensed.

Methods

The 63,448 residents of Lombardy Region (Italy), aged 40–80 years, who were newly treated with antihypertensive drugs during 2016, were identified and followed for 1 year after the first prescription. The outcome of interest was adherence to drug therapy that was measured according to the “proportion of days covered” (PDC) criterion, i.e., the ratio between the number of days in which the drug was available and the days of follow-up. Patients who had a PDC >75% and <25% were defined as highly and poorly adherent to drug therapy, respectively. Log-binomial regression models were fitted to compare the propensity to treatment adherence between the initial therapeutic strategies, after adjusting for baseline demographic and clinical covariates.

Results

About 46% and 17% of patients showed high and poor adherence, respectively. Compared with patients under initial monotherapy (85%), those who were initially treated with a SPC (15%) had higher propensity to be highly adherent and a lower propensity to be poorly adherent to antihypertensive treatment (risk ratio: 1.18, 95% confidence interval 1.16–1.21; 0.42, 0.39–0.45, respectively). This was the case regardless the sex, the age, the patient clinical status, and with almost any type of SPC.

Conclusions

In a real-life setting, patients who were initially prescribed a 2-drug SPC exhibited more frequently a good adherence to antihypertensive treatment than those starting with a single drug.
A Case Report of Capsular Contracture Immediately Following COVID-19 Vaccination
Authors: Restifo Richard J
Published: May 2021

Capsular contracture is fundamentally an immunological/inflammatory response to the implant, treating it as a foreign body in need of exclusion from the immune system. The capsule surrounding the implant is populated by a rich variety of immunologically active cells such as macrophages, T lymphocytes, and myofibroblasts. Vaccination in general and the COVID-19 vaccine in particular result in specific and nonspecific activation of the immune system, including those immune cells in proximity to the implant. This phenomenon has been previously demonstrated in delayed inflammatory reactions to previously implanted hyaluronic acid fillers following COVID-19 vaccination. This report is what is believed to be the first case of the rapid development of severe ipsilateral capsular contracture in the immediate aftermath of the second dose of the BNT162b2 (Pfizer) vaccine.
Circ_0038467 regulates lipopolysaccharide-mediated cell proliferation, apoptosis, and inflammatory response by miR-195-5p/TLR4 axis through NF-κB pathway in MRC-5 cells
Authors: Zheng Yu , Wang Yuanyuan , Zhu Xiuli , Diao Yuqiao , Chen Yuqin , Chen Gang
Published: May 2021

Infantile pneumonia (IP) is an acute lower respiratory infection and brings a heavy burden to children health. Circular RNAs (circRNAs) participate in the regulation of pneumonia process. In this research, the effects of circ_0038467 in regulating lipopolysaccharide (LPS)-induced cell injury and underlying mechanism were revealed. Results showed that circ_0038467 expression and TLR4 protein level were upregulated, while miR-195-5p expression was downregulated in LPS-induced MRC-5 cells. Circ_0038467 silencing restored LPS-mediated inhibition on cell proliferation and promotion on apoptosis and inflammatory response. Additionally, circ_0038467 acted as a sponge of miR-195-5p, which was further revealed to target TLR4. MiR-195-5p inhibitor reversed circ_0038467 silencing-mediated influences under LPS treatment. Furthermore, LPS-activated NF-κB pathway was partly blocked by circ_0038467 silencing, which was restrained by TLR4 overexpression. Circ_0038467 silencing protected MRC-5 cells from LPS-induced injury by miR-195-5p/TLR4 axis through NF-κB pathway, providing a theoretical basis for circRNA-directed IP therapy.
Memory extinction and spontaneous recovery shaping parasitoid foraging behavior
Authors: de Bruijn Jessica A C , Vet Louise E M , Smid Hans M , de Boer Jetske G
Published: May 2021

Animals can alter their foraging behavior through associative learning, where an encounter with an essential resource (e.g., food or a reproductive opportunity) is associated with nearby environmental cues (e.g., volatiles). This can subsequently improve the animal’s foraging efficiency. However, when these associated cues are encountered again, the anticipated resource is not always present. Such an unrewarding experience, also called a memory-extinction experience, can change an animal’s response to the associated cues. Although some studies are available on the mechanisms of this process, they rarely focus on cues and rewards that are relevant in an animal’s natural habitat. In this study, we tested the effect of different types of ecologically relevant memory-extinction experiences on the conditioned plant volatile preferences of the parasitic wasp Cotesia glomerata that uses these cues to locate its caterpillar hosts. These extinction experiences consisted of contact with only host traces (frass and silk), contact with nonhost traces, or oviposition in a nonhost near host traces, on the conditioned plant species. Our results show that the lack of oviposition, after contacting host traces, led to the temporary alteration of the conditioned plant volatile preference in C. glomerata, but this effect was plant species-specific. These results provide novel insights into how ecologically relevant memory-extinction experiences can fine-tune an animal’s foraging behavior. This fine-tuning of learned behavior can be beneficial when the lack of finding a resource accurately predicts current, but not future foraging opportunities. Such continuous reevaluation of obtained information helps animals to prevent maladaptive foraging behavior.
Deep cross-omics cycle attention model for joint analysis of single-cell multi-omics data
Authors: Zuo Chunman , Dai Hao , Chen Luonan
Published: May 2021

Motivation

Joint profiling of single-cell transcriptomics and epigenomics data enables us to characterize cell states and transcriptomics regulatory programs related to cellular heterogeneity. However, the highly different features on sparsity, heterogeneity and dimensionality between multi-omics data have severely hindered its integrative analysis.

Results

We proposed deep cross-omics cycle attention (DCCA) model, a computational tool for joint analysis of single-cell multi-omics data, by combining variational autoencoders (VAEs) and attention-transfer. Specifically, we show that DCCA can leverage one omics data to fine-tune the network trained for another omics data, given a dataset of parallel multi-omics data within the same cell. Studies on both simulated and real datasets from various platforms, DCCA demonstrates its superior capability: (i) dissecting cellular heterogeneity; (ii) denoising and aggregating data and (iii) constructing the link between multi-omics data, which is used to infer new transcriptional regulatory relations. In our applications, DCCA was demonstrated to have a superior power to generate missing stages or omics in a biologically meaningful manner, which provides a new way to analyze and also understand complicated biological processes.

Availability and implementation

DCCA source code is available at https://github.com/cmzuo11/DCCA, and has been deposited in archived format at https://doi.org/10.5281/zenodo.4762065.

Supplementary information

Supplementary data are available at Bioinformatics online.
One step closer towards personalized epilepsy management
Authors: Chen Zhibin , Anderson Alison , Ge Zongyuan , Kwan Patrick
Published: May 2021

This scientific commentary refers to ‘Towards realizing the vision of precision medicine: AI based prediction of clinical drug response’ by De Jong et al. (doi:10.1093/brain/awab108).
The Organization of Frontostriatal Brain Wiring in Healthy Subjects Using a Novel Diffusion Imaging Fiber Cluster Analysis
Authors: Levitt J J , Zhang F , Vangel M , Nestor P G , Rathi Y , Kubicki M , Shenton M E , O’Donnell L J
Published: May 2021

To assess normal organization of frontostriatal brain wiring, we analyzed diffusion magnetic resonance imaging (dMRI) scans in 100 young adult healthy subjects (HSs). We identified fiber clusters intersecting the frontal cortex and caudate, a core component of associative striatum, and quantified their degree of deviation from a strictly topographic pattern. Using whole brain dMRI tractography and an automated tract parcellation clustering method, we extracted 17 white matter fiber clusters per hemisphere connecting the frontal cortex and caudate. In a novel approach to quantify the geometric relationship among clusters, we measured intercluster endpoint distances between corresponding cluster pairs in the frontal cortex and caudate. We show first, the overall frontal cortex wiring pattern of the caudate deviates from a strictly topographic organization due to significantly greater convergence in regionally specific clusters; second, these significantly convergent clusters originate in subregions of ventrolateral, dorsolateral, and orbitofrontal prefrontal cortex (PFC); and, third, a similar organization in both hemispheres. Using a novel tractography method, we find PFC-caudate brain wiring in HSs deviates from a strictly topographic organization due to a regionally specific pattern of cluster convergence. We conjecture cortical subregions projecting to the caudate with greater convergence subserve functions that benefit from greater circuit integration.
Which methods are the most effective in enabling novice users to participate in ontology creation? A usability study
Authors: Zhang Limin , Yang Xingyi , Cota Zuleima , Cui Hong , Ford Bruce , Chen Hsin-liang , Macklin James A , Reznicek Anton , Starr Julian
Published: May 2021

Producing findable, accessible, interoperable and reusable (FAIR) data cannot be accomplished solely by data curators in all disciplines. In biology, we have shown that phenotypic data curation is not only costly, but it is burdened with inter-curator variation. We intend to propose a software platform that would enable all data producers, including authors of scientific publications, to produce ontologized data at the time of publication. Working toward this goal, we need to identify ontology construction methods that are preferred by end users. Here, we employ two usability studies to evaluate effectiveness, efficiency and user satisfaction with a set of four methods that allow an end user to add terms and their relations to an ontology. Thirty-three participants took part in a controlled experiment where they evaluated the four methods (Quick Form, Wizard, WebProtégé and Wikidata) after watching demonstration videos and completing a hands-on task. Another think-aloud study was conducted with three professional botanists. The efficiency effectiveness and user confidence in the methods are clearly revealed through statistical and content analyses of participants’ comments. Quick Form, Wizard and WebProtégé offer distinct strengths that would benefit our author-driven FAIR data generation system. Features preferred by the participants will guide the design of future iterations.
Pulmonary arterial hypertension unveils itself: a cancer-like progression — a case report
Authors: Santos-Ferreira Cátia , Cardoso Daniela , Paiva Benedita , Baptista Rui
Published: May 2021

Background

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis, characterized by progressive remodelling of the small pulmonary arteries that precede the clinical and haemodynamic manifestations of the disease. Thus, a prompt diagnosis and early intervention are crucial.

Case summary

A 39-year-old pregnant women presented with persistent severe hypoxaemia after the diagnosis of influenza B and an elective caesarean delivery at 33 weeks. Ten months after, an extensive and inconclusive investigation that included a lung biopsy, despite of a spontaneous improvement in oxygen saturation, clinical deterioration led to further testing, namely genetic screening. It revealed a fast-progressing case of hereditary PAH caused by BMRP2 mutation.

Discussion

This case highlights the challenges of a timely diagnosis of PAH and the importance of close clinical monitoring of patients at high risk of PAH. In addition, it emphasizes the fast development of severe haemodynamic changes associated with a BMPR2 mutation. The availability of a lung biopsy without signs of pulmonary vascular disease (PVD) and a right heart catheterization with mild pulmonary hypertension at the baseline assessment demonstrates that PVD can progress in a neoplastic-like manner in a matter of months.
In vivo tissue-specific chromatin profiling in Drosophila melanogaster using GFP-tagged nuclei
Authors: Jauregui-Lozano Juan , Bakhle Kimaya , Weake Vikki M
Published: May 2021

The chromatin landscape defines cellular identity in multicellular organisms with unique patterns of DNA accessibility and histone marks decorating the genome of each cell type. Thus, profiling the chromatin state of different cell types in an intact organism under disease or physiological conditions can provide insight into how chromatin regulates cell homeostasis in vivo. To overcome the many challenges associated with characterizing chromatin state in specific cell types, we developed an improved approach to isolate Drosophila melanogaster nuclei tagged with a GFPKASH protein. The perinuclear space-localized KASH domain anchors GFP to the outer nuclear membrane, and expression of UAS-GFPKASH can be controlled by tissue-specific Gal4 drivers. Using this protocol, we profiled chromatin accessibility using an improved version of Assay for Transposable Accessible Chromatin followed by sequencing (ATAC-seq), called Omni-ATAC. In addition, we examined the distribution of histone marks using Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and Cleavage Under Targets and Tagmentation (CUT&Tag) in adult photoreceptor neurons. We show that the chromatin landscape of photoreceptors reflects the transcriptional state of these cells, demonstrating the quality and reproducibility of our approach for profiling the transcriptome and epigenome of specific cell types in Drosophila.
State Responsibility for Protracted Displacement: An International Legal Approach to Durable Solutions
Authors: Mohee Mansha
Published: May 2021

Since the Second World War, displacement has become increasingly protracted and return is in decline. Despite calls for greater international responsibility sharing, many displaced people are subject to a legal limbo, lacking recognition and reparation in international law. This article seeks to establish the legal contours of protracted displacement as an internationally wrongful act that can engage the responsibility of States of origin and result in redress for those displaced. The article argues that there is evidence of a customary international law right of return, which requires States to facilitate voluntary repatriation and provide restitution. Facilitation includes refraining from preventing or obstructing return, suppressing acts of retribution or discrimination, and addressing root causes of displacement. Restitution includes property restitution, compensation for material and moral damages as well as reintegration and reconciliation measures, and offering effective models for return. The article concludes that the progressive development and codification of the law on forced displacement should address temporality, the qualities of return, and the alleviation of extant crises.
Numerical methods for stochastic Volterra integral equations with weakly singular kernels
Authors: Li Min , Huang Chengming , Hu Yaozhong
Published: May 2021

In this paper we first establish the existence, uniqueness and Hölder continuity of the solution to stochastic Volterra integral equations (SVIEs) with weakly singular kernels, with singularities $\alpha \in (0, 1)$ for the drift term and $\beta \in (0, 1/2)$ for the stochastic term. Subsequently, we propose a $\theta $-Euler–Maruyama scheme and a Milstein scheme to solve the equations numerically and obtain strong rates of convergence for both schemes in $L^{p}$ norm for any $p\geqslant 1$. For the $\theta $-Euler–Maruyama scheme the rate is $\min \big\{1-\alpha ,\frac{1}{2}-\beta \big\}~ $ and for the Milstein scheme is $\min \{1-\alpha ,1-2\beta \}$. These results on the rates of convergence are significantly different from those it is similar schemes for the SVIEs with regular kernels. The source of the difficulty is the lack of Itô formula for the equations. To get around this difficulty we use the Taylor formula subsequently carrying out a sophisticated analysis of the equation.
Advancement of antigen-specific immunotherapy: knowledge transfer between allergy and autoimmunity
Authors: Richardson Naomi , Wraith David Cameron
Published: May 2021

Targeted restoration of immunological tolerance to self-antigens or innocuous environmental allergens represents the ultimate aim of treatment options in autoimmune and allergic disease. Antigen-specific immunotherapy (ASI) is the only intervention that has proven disease-modifying efficacy as evidenced by induction of long-term remission in a number of allergic conditions. Mounting evidence is now indicating that specific targeting of pathogenic T cells in autoinflammatory and autoimmune settings enables effective restoration of immune homeostasis between effector and regulatory cells and alters the immunological course of disease. Here, we discuss the key lessons learned during the development of antigen-specific immunotherapies and how these can be applied to inform future interventions. Armed with this knowledge and current high-throughput technology to track immune cell phenotype and function, it may no longer be a matter of ‘if’ but ‘when’ this ultimate aim of targeted tolerance restoration is realised.
Communities and Brokers: How the Transnational Advocacy Network Simultaneously Provides Social Power and Exacerbates Global Inequalities
Authors: Cheng Huimin , Wang Ye , Ma Ping , Murdie Amanda
Published: May 2021

Transnational advocacy networks (TANs) are the most common example of networks in international relations. Despite their familiarity, we know little about how advocacy networks of nongovernmental organizations (NGOs) are structured. Drawing on the cross-disciplinary concepts of emergent communities and distinct brokerage roles, we argue that the network may reinforce power disparities and inequalities at the very same time that it provides social power. TANs are similar to emergent communities of practice, with some organizations acting as various types of brokers within and between communities. Preexisting resources are more likely to lead global North organizations to occupy brokerage roles that provide additional agenda-setting and resource-allocating power. We build a dataset of the 3,903 NGOs connected through 1.3 million ties occurring through meetings and conferences for NGOs put on or coordinated by the United Nations. Using community detection methods, we identify four distinct communities in the overall NGO network, with differences in distributions of brokerage roles across communities. Examining the communities, brokerage role distributions, and preexisting power disparities can help us better understand the divergent findings in previous literature and conceptualize TANs.
LYSINE KETOGLUTARATE REDUCTASE TRANS-SPLICING RELATED 1 is involved in temperature-dependent root growth in rice
Authors: Yu En , Yamaji Naoki , Mochida Keiich , Galis Ivan , Asaka Kanatani , Ma Jian Feng
Published: May 2021

Root length is an important root parameter directly related to the uptake of water and nutrients. However, the molecular mechanisms controlling root length are still not fully understood. Here, we isolated a short-root mutant of rice, dice2 (defective in cell elongation 2). The cell length and meristem size of the roots were decreased in dice2, but the root function in terms of mineral element uptake, root cell width, and root anatomy were hardly altered compared with wild-type (WT) rice. The root growth defect in dice2 could be partially rescued by high temperature. Map-based cloning combined with a complementation test revealed that the short-root phenotype was caused by a nonsense mutation in a gene which was annotated to encode Lysine Ketoglutarate Reductase Trans-Splicing related 1 (OsLKRT1). OsLKRT1, encoding a cytosol-localized protein, was expressed in all cells of the root tip and elongation region as well as the shoot. RNA-seq analysis showed that there was no difference between dice2 and the WT in the expression level of genes involved in root development identified so far. These results indicate that OsLKRT1 is involved in a novel pathway required for root cell elongation in rice, although its exact role remains to be further investigated.
Sugar export from Arabidopsis leaves: actors and regulatory strategies
Authors: Xu Qiyu , Liesche Johannes
Published: May 2021

Plant acclimation and stress responses depend on the dynamic optimization of carbon balance between source and sink organs. This optimization also applies to the leaf export rate of photosynthetically produced sugars. So far, investigations into the molecular mechanisms of how the rate is controlled have focused on sugar transporters responsible for loading sucrose into the phloem sieve element–companion cell complex of leaf veins. Here, we take a broader view of the various proteins with potential direct influence on the leaf sugar export rate in the model plant Arabidopsis thaliana, helped by the cell type-specific transcriptome data that have recently become available. Furthermore, we integrate current information on the regulation of these potential target proteins. Our analysis identifies putative control points and units of transcriptionally and post-transcriptionally co-regulated genes. Most notable is the potential regulatory unit of sucrose transporters (SUC2, SWEET11, SWEET12, and SUC4) and proton pumps (AHA3 and AVP1). Our analysis can guide future research aimed at understanding the regulatory network controlling leaf sugar export by providing starting points for characterizing regulatory strategies and identifying regulatory factors that link sugar export rate to the major signaling pathways.
Stellar intensity interferometry of Vega in photon counting mode
Authors: Zampieri Luca , Naletto Giampiero , Burtovoi Aleksandr , Fiori Michele , Barbieri Cesare
Published: May 2021

Stellar intensity interferometry is a technique based on the measurement of the second-order spatial correlation of the light emitted from a star. The physical information provided by these measurements is the angular size and structure of the emitting source. A worldwide effort is presently underway to implement stellar intensity interferometry on telescopes separated by long baselines and on future arrays of Cherenkov telescopes. We describe an experiment of this type, realized at the Asiago Observatory (Italy), in which we performed for the first time measurements of the correlation counting photon coincidences in post-processing by means of a single photon software correlator and exploiting entirely the quantum properties of the light emitted from a star. We successfully detected the temporal correlation of Vega at zero baseline and performed a measurement of the correlation on a projected baseline of ∼2 km. The average discrete degree of coherence at zero baseline for Vega is $\lt g^{(2)} \gt \, = 1.0034 \pm 0.0008$, providing a detection with a signal-to-noise ratio S/N ≳ 4. No correlation is detected over the km baseline. The measurements are consistent with the expected degree of spatial coherence for a source with the 3.3 mas angular diameter of Vega. The experience gained with the Asiago experiment will serve for future implementations of stellar intensity interferometry on long-baseline arrays of Cherenkov telescopes.
The growth rate of cosmic structures in the local Universe with the ALFALFA survey
Authors: Avila F , Bernui A , de Carvalho E , Novaes C P
Published: May 2021

We investigate the growth rate of structures in the local Universe. For this, we use as a cosmological tracer the HI line extra-galactic sources from the Arecibo Legacy Fast ALFA (ALFALFA) survey to obtain a measurement of the normalized growth rate parameter, fσ8, considered a powerful tool to constrain alternative models of gravity. For these analyses, we calculate the Local Group velocity due to the matter structures distribution in the ALFALFA catalogue and compare it with the Local Group velocity relative to the Cosmic Microwave Background frame to obtain the velocity scale parameter, β. Using Monte Carlo realizations and lognormal simulations, our methodology quantifies the errors introduced by shot-noise and partial sky coverage of the analysed data. The measurement of the velocity scale parameter β and the calculation of the matter fluctuation of the cosmological tracer, $\sigma _{8}^{\text{tr}}$, lead us to fσ8 = 0.46 ± 0.06 at $\bar{z} = 0.013$, in good agreement (at 1σ level) with the value expected in the ΛCDM concordance model. In addition, our analyses of the ALFALFA sample also provide a measurement of the growth rate of structures $f = 0.56 \pm 0.07$, at $\bar{z} = 0.013$.
BRIO: a web server for RNA sequence and structure motif scan
Authors: Guarracino Andrea , Pepe Gerardo , Ballesio Francesco , Adinolfi Marta , Pietrosanto Marco , Sangiovanni Elisa , Vitale Ilio , Ausiello Gabriele , Helmer-Citterich Manuela
Published: May 2021

The interaction between RNA and RNA-binding proteins (RBPs) has a key role in the regulation of gene expression, in RNA stability, and in many other biological processes. RBPs accomplish these functions by binding target RNA molecules through specific sequence and structure motifs. The identification of these binding motifs is therefore fundamental to improve our knowledge of the cellular processes and how they are regulated. Here, we present BRIO (BEAM RNA Interaction mOtifs), a new web server designed for the identification of sequence and structure RNA-binding motifs in one or more RNA molecules of interest. BRIO enables the user to scan over 2508 sequence motifs and 2296 secondary structure motifs identified in Homo sapiens and Mus musculus, in three different types of experiments (PAR-CLIP, eCLIP, HITS). The motifs are associated with the binding of 186 RBPs and 69 protein domains. The web server is freely available at http://brio.bio.uniroma2.it.
Detection of homozygous and hemizygous complete or partial exon deletions by whole-exome sequencing
Authors: Bigio Benedetta , Seeleuthner Yoann , Kerner Gaspard , Migaud Mélanie , Rosain Jérémie , Boisson Bertrand , Nasca Carla , Puel Anne , Bustamante Jacinta , Casanova Jean-Laurent , Abel Laurent , Cobat Aurelie
Published: May 2021

The detection of copy number variations (CNVs) in whole-exome sequencing (WES) data is important, as CNVs may underlie a number of human genetic disorders. The recently developed HMZDelFinder algorithm can detect rare homozygous and hemizygous (HMZ) deletions in WES data more effectively than other widely used tools. Here, we present HMZDelFinder_opt, an approach that outperforms HMZDelFinder for the detection of HMZ deletions, including partial exon deletions in particular, in WES data from laboratory patient collections that were generated over time in different experimental conditions. We show that using an optimized reference control set of WES data, based on a PCA-derived Euclidean distance for coverage, strongly improves the detection of HMZ complete exon deletions both in real patients carrying validated disease-causing deletions and in simulated data. Furthermore, we develop a sliding window approach enabling HMZDelFinder_opt to identify HMZ partial deletions of exons that are undiscovered by HMZDelFinder. HMZDelFinder_opt is a timely and powerful approach for detecting HMZ deletions, particularly partial exon deletions, in WES data from inherently heterogeneous laboratory patient collections.
Hi-C analyses with GENOVA: a case study with cohesin variants
Authors: van der Weide Robin H , van den Brand Teun , Haarhuis Judith H I , Teunissen Hans , Rowland Benjamin D , de Wit Elzo
Published: May 2021

Conformation capture-approaches like Hi-C can elucidate chromosome structure at a genome-wide scale. Hi-C datasets are large and require specialised software. Here, we present GENOVA: a user-friendly software package to analyse and visualise chromosome conformation capture (3C) data. GENOVA is an R-package that includes the most common Hi-C analyses, such as compartment and insulation score analysis. It can create annotated heatmaps to visualise the contact frequency at a specific locus and aggregate Hi-C signal over user-specified genomic regions such as ChIP-seq data. Finally, our package supports output from the major mapping-pipelines. We demonstrate the capabilities of GENOVA by analysing Hi-C data from HAP1 cell lines in which the cohesin-subunits SA1 and SA2 were knocked out. We find that ΔSA1 cells gain intra-TAD interactions and increase compartmentalisation. ΔSA2 cells have longer loops and a less compartmentalised genome. These results suggest that cohesinSA1 forms longer loops, while cohesinSA2 plays a role in forming and maintaining intra-TAD interactions. Our data supports the model that the genome is provided structure in 3D by the counter-balancing of loop formation on one hand, and compartmentalization on the other hand. By differentially controlling loops, cohesinSA1 and cohesinSA2 therefore also affect nuclear compartmentalization. We show that GENOVA is an easy to use R-package, that allows researchers to explore Hi-C data in great detail.
Large-scale identification of protein histidine methylation in human cells
Authors: Kapell Sebastian , Jakobsson Magnus E
Published: May 2021

Methylation can occur on histidine, lysine and arginine residues in proteins and often serves a regulatory function. Histidine methylation has recently attracted attention through the discovery of the human histidine methyltransferase enzymes SETD3 and METTL9. There are currently no methods to enrich histidine methylated peptides for mass spectrometry analysis and large-scale studies of the modification are hitherto absent. Here, we query ultra-comprehensive human proteome datasets to generate a resource of histidine methylation sites. In HeLa cells alone, we report 299 histidine methylation sites as well as 895 lysine methylation events. We use this resource to explore the frequency, localization, targeted domains, protein types and sequence requirements of histidine methylation and benchmark all analyses to methylation events on lysine and arginine. Our results demonstrate that histidine methylation is widespread in human cells and tissues and that the modification is over-represented in regions of mono-spaced histidine repeats. We also report colocalization of the modification with functionally important phosphorylation sites and disease associated mutations to identify regions of likely regulatory and functional importance. Taken together, we here report a system level analysis of human histidine methylation and our results represent a comprehensive resource enabling targeted studies of individual histidine methylation events.
IL-7 Immunotherapy in a Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis
Authors: Turnbull Isaiah R , Mazer Monty B , Hoofnagle Mark H , Kirby John P , Leonard Jennifer M , Mejia-Chew Carlos , Spec Andrej , Blood Jane , Miles Sydney M , Ransom Eric M , Potter Robert F , Gaut Joseph P , Remy Kenneth E , Hotchkiss Richard S
Published: May 2021

A nonimmunocompromised patient developed life-threatening soft tissue infection with Trichosporon asahii, Fusarium, and Saksenaea that progressed despite maximum antifungal therapies and aggressive debridement. Interleukin-7 immunotherapy resulted in clinical improvement, fungal clearance, reversal of lymphopenia, and improved T-cell function. Immunoadjuvant therapies to boost host immunity may be efficacious in life-threatening fungal infections.