bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach
Authors: Gao Guimin , Zhao Fangyuan , Ahearn Thomas U , Lunetta Kathryn L , Troester Melissa A , Du Zhaohui , Ogundiran Temidayo O , Ojengbede Oladosu , Blot William , Nathanson Katherine L , Domchek Susan M , Nemesure Barbara , Hennis Anselm , Ambs Stefan , McClellan Julian , Nie Mark , Bertrand Kimberly , Zirpoli Gary , Yao Song , Olshan Andrew F , Bensen Jeannette T , Bandera Elisa V , Nyante Sarah , Conti David V , Press Michael F , Ingles Sue A , John Esther M , Bernstein Leslie , Hu Jennifer J , Deming-Halverson Sandra L , Chanock Stephen J , Ziegler Regina G , Rodriguez-Gil Jorge L , Sucheston-Campbell Lara E , Sandler Dale P , Taylor Jack A , Kitahara Cari M , O’Brien Katie M , Bolla Manjeet K , Dennis Joe , Dunning Alison M , Easton Douglas F , Michailidou Kyriaki , Pharoah Paul D P , Wang Qin , Figueroa Jonine , Biritwum Richard , Adjei Ernest , Wiafe Seth ,   GBHS Study Team, Ambrosone Christine B , Zheng Wei , Olopade Olufunmilayo I , García-Closas Montserrat , Palmer Julie R , Haiman Christopher A , Huo Dezheng
Published: May 2022

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27–1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th–60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63–2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.
Detecting Mismatch in Functional Narratives of Animal Morphology: A Test Case with Fossils
Authors: Hebdon Nicholas , Polly P David , Peterman David Joseph , Ritterbush Kathleen A
Published: May 2022

Synopsis

A boom in technological advancements over the last two decades has driven a surge in both the diversity and power of analytical tools available to biomechanical and functional morphology research. However, in order to adequately investigate each of these dense datasets, one must often consider only one functional narrative at a time. There is more to each organism than any one of these form–function relationships. Joint performance landscapes determined by maximum likelihood are a valuable tool that can be used to synthesize our understanding of these multiple functional hypotheses to further explore an organism's ecology. We present an example framework for applying these tools to such a problem using the morphological transition of ammonoids from the Middle Triassic to the Early Jurassic. Across this time interval, morphospace occupation shifts from a broad occupation across Westermann Morphospace to a dense occupation of a region emphasizing an exposed umbilicus and modest frontal profile. The hydrodynamic capacities and limitations of the shell have seen intense scrutiny as a likely explanation of this transition. However, conflicting interpretations of hydrodynamic performance remain despite this scrutiny, with scant offerings of alternative explanations. Our analysis finds that hydrodynamic measures of performance do little to explain the shift in morphological occupation, highlighting a need for a more robust investigation of alternative functional hypotheses that are often intellectually set aside. With this we show a framework for consolidating the current understanding of the form–function relationships in an organism, and assess when they are insufficiently characterizing the dynamics those data are being used to explain. We aim to encourage the broader adoption of this framework and these ideas as a foundation to bring the field close to comprehensive synthesis and reconstruction of organisms.
Batch-Mask: Automated Image Segmentation for Organisms with Limbless or Non-Standard Body Forms
Authors: Curlis John David , Renney Timothy , Davis Rabosky Alison R , Moore Talia Y
Published: May 2022

Synopsis

Efficient comparisons of biological color patterns are critical for understanding the mechanisms by which organisms evolve in nature, including sexual selection, predator–prey interactions, and thermoregulation. However, limbless, elongate, or spiral-shaped organisms do not conform to the standard orientation and photographic techniques required for many automated analyses. Currently, large-scale color analysis of elongate animals requires time-consuming manual landmarking, which reduces their representation in coloration research despite their ecological importance. We present Batch-Mask: an automated, customizable workflow to automatically analyze large photographic datasets to isolate non-standard biological organisms from the background. Batch-Mask is completely open-source and does not depend on any proprietary software. We also present a user guide for fine-tuning weights to a custom dataset and incorporating existing manual visual analysis tools (e.g., micaToolbox) into a single automated workflow for comparing color patterns across images. Batch-Mask was 60x faster than manual landmarking and produced masks that correctly identified 96% of all snake pixels. To validate our approach, we used micaToolbox to compare pattern energy in a sample set of snake photographs segmented by Batch-Mask and humans and found no significant difference in the output results. The fine-tuned weights, user guide, and automated workflow substantially decrease the amount of time and attention required to quantitatively analyze non-standard biological subjects. With these tools, biologists can compare color, pattern, and shape differences in large datasets that include significant morphological variation in elongate body forms. This advance is especially valuable for comparative analyses of natural history collections across a broad range of morphologies. Through landmark-free automation, Batch-Mask can greatly expand the scale of space, time, or taxonomic breadth across which color variation can be quantitatively examined.
Guadalupe fur seal pup production predicted from annual variations of sea surface temperature in the southern California Current Ecosystem
Authors: Juárez-Ruiz Ariadna , Pardo Mario A , Hernández-Montoya Julio C , Elorriaga-Verplancken Fernando R , Milanés-Salinas María de los Ángeles , Norris Tenaya , Beier Emilio , Heckel Gisela
Published: May 2022

We evaluated the effects of sea surface temperature anomalies (SSTA) in the southern California Current Ecosystem on the annual Guadalupe fur seal (Arctocephalus townsendi) pup production, a species recovering from near extinction. Pup counts from 1991 to 1993 and from 2006 to 2019 were used to estimate deviations from a long-term trend as a proxy for the population's reproductive success. We estimated interannual SSTA as a subtraction from the linear trend spanning 1991–2019 for a 778,000 km2 area, which represents the primary foraging range of adult females. The long-term increase in pup production followed an exponential curve ( ${\rm{R}}_{\rm{B}}^2 = {\rm{\ }}1$), typical of species in a recovery phase. Pup production deviations from this trend responded to SSTA during the gestation period as a cubic polynomial function ( ${\rm{R}}_{\rm{B}}^2 = {\rm{\ }}0.837$), revealing that SSTA < −0.2°C and between ∼0.6 and 1.38°C increased pup production in the subsequent breeding season, whereas normal to slightly warm (−0.17 to 0.6°C) and extreme SSTA (>1.4°C) decreased pup counts, arguably resulting from low prey availability and quality. This model allowed us to estimate pup production for years without observations, needed to understand the environmental variability influence on the recovery process of this species, and therefore constitutes a practical tool for its conservation and management.
Reproductive seasonality and fecundity of the spiny lobsterPanulirus homarus homarus(Linnaeus, 1758) (Decapoda: Achelata: Palinuridae) in Kenya: implications for sustainable management
Authors: Kulmiye Abdirahman J
Published: May 2022

The scalloped spiny lobster Panulirus homarus homarus (Linnaeus, 1758) is one of the most commercially important lobsters exploited in Kenya. Despite its local importance and wide distribution, detailed knowledge on its reproduction in East Africa is lacking. The study reported herein sought to determine its spawning season based on seasonal variations in female gonadosomatic index (GSI), temporal distribution of ovarian maturity stages, and the proportion of ovigerous females in the monthly samples captured off Mambrui, Kenya. The study also assessed size composition, sex ratio, fecundity, and reproductive potential. A total of 2,454 lobsters were collected during the study period (January 2000-December 2001), covering a size range of 26–115 mm carapace length (CL). Neither the overall sex ratio nor the monthly sex distributions deviated significantly from the expected ratio of 1:1, except for a few months when males and females alternately dominated the samples with no discernible seasonal trends. Analysis of the cyclical changes in reproductive activity shows strong spawning seasonality in synchrony with the Northeast monsoon season in both years. Simultaneous breeding of a wide size range of females (54–90 mm CL) commenced in November and intensified over the following months until April. Outside the Northeast monsoon season, only 10 females, out of the total 517 sexually mature females sampled during the 2000 and 2001 Southeast monsoon seasons, bore eggs, and all were large individuals (>66 mm CL) encountered in the 2001 samples. Fecundity was positively and linearly related to female size (CL) and best described by the equation E = 10,400 CL – 472,040 (R2 = 0.929, N = 59). Estimated fecundity varied between 81,000 and 474,000 eggs per spawn in female lobsters (54 mm–91 mm CL). Female lobsters between 66 mm and 80 mm CL contributed 62% of the estimated total egg production of the population. The widespread retention of egg-bearing females in a fishery where the main fishing season falls during the spawning season, can have detrimental effects on the spawning stock abundance and egg production with increased risk of recruitment failure and stock collapse.
Immigration Pathways of White-Backed Planthopper in the Confluence Area of the Two Monsoon Systems
Authors: Wu Yan , Sun Si-Si , Jiang Zi-Ye , Chen Ai-Dong , Ma Ming-Yong , Zhang Guo , Zhai Bao-Ping , Li Can
Published: May 2022

The white-backed planthopper, WBPH, Sogatella furcifera (Horváth) is a plant pest that migrates long-distances. The migration pathway of WBPH in eastern China coincides with the north-south round trip of the East Asian monsoon. However, in Yunnan China, which is affected by two monsoon systems, the migration pathway is unclear. Light-trap data and analysis of female ovarian development showed that the peak period of immigration of WBPH into western Yunnan was earlier than in eastern Yunnan. Using meteorological reanalysis data and flight parameters of WBPH, trajectory modeling showed that there are two immigration pathways to Yunnan. One is from Myanmar to western Yunnan, and the other is from Vietnam and Laos to eastern Yunnan. The reason for the differences in source areas and immigration pathways between eastern and western Yunnan is that the west wind prevails in western Yunnan and is controlled by South Asian monsoon, while southwesterly winds prevail in eastern Yunnan due to the combined influence of South Asian monsoon and East Asian monsoon. The results indicate that WBPH invades Yunnan via two pathways under a two-monsoon system. These data will allow earlier prediction and population management of WBPH.
‘The illustration of all art expressed in objects of utility’: The formation of the Renaissance collections at the Victoria and Albert Museum
Authors: Evans Mark
Published: May 2022

This article examines the formation of the collections of fifteenth- and sixteenth-century European works of art at the Victoria and Albert Museum. For brevity’s sake, all are characterized here as ‘Renaissance’ objects, rather than by their century of production. During the first quarter-century of the museum’s activity, Renaissance art was a powerful conditioning influence on British culture and society. This encouraged the growth of the Renaissance collections between 1852 and 1875 at a rapid rate that has never since been equalled. The museum’s regularly published inventories of acquisitions include the prices paid for objects; since the purchasing power of the pound sterling altered little between 1854 and 1914, this permits an assessment of the relative value of acquisitions over this formative period. The paper closes with a résumé of the continued development of the collections since the First World War.
A Review ofBartonellaInfections in California—Implications for Public and Veterinary Health
Authors: Billeter Sarah A
Published: May 2022

Bartonella are vector-transmitted, intracellular bacteria that infect a wide variety of blood-feeding arthropods and their vertebrate hosts. In California, more than 13 species of Bartonella have been described from companion animals, livestock, and wildlife, of which four have been associated with human disease. Infections in humans cause a range of symptoms from relatively mild to severe, especially in immunocompromised individuals. Exposure to infected domestic animals and wildlife, and their ectoparasites, may increase the risk of cross-species transmission. The objective of this review was to compile and summarize published materials on human and animal Bartonella infections in California. Medical and veterinary case reports of bartonellosis were highlighted in an effort to increase the awareness of this poorly understood and potentially under-recognized disease among healthcare professionals and veterinarians.
Provisional Measures after Ukraine v Russia (2022)
Authors: Kulick Andreas
Published: May 2022

On 16 March 2022, among others measures, the International Court of Justice (ICJ) ordered the Russian Federation to suspend immediately its military operations in Ukraine. The Order is remarkable for several reasons and, so it is submitted, potentially will entail considerable consequences in international adjudication, before and beyond the ICJ, as well as with respect to international law at large. In international procedural law, it emphasizes the vastness of what parties to international proceedings can ask for and what an international court or tribunal can order in respect of provisional measures. However, possibly the strongest potential of the Order does not lie in what it enables, but what it disables: it may deter states that are not a permanent member of the United Nations Security Council from employing insincere human rights arguments as a pretext for a military intervention in a neighbouring state.
Constraining low redshift [C II] emission by cross-correlating FIRAS and BOSS data
Authors: Anderson C J , Switzer E R , Breysse P C
Published: May 2022

We perform a tomographic cross-correlation analysis of archival FIRAS data and the BOSS galaxy redshift survey to constrain the amplitude of [C II] 2P3/2 → 2P1/2 fine structure emission. Our analysis employs spherical harmonic tomography (SHT), which is based on the angular cross-power spectrum between FIRAS maps and BOSS galaxy over-densities at each pair of redshift bins, over a redshift range of 0.24 < z < 0.69. We develop the SHT approach for intensity mapping, where it has several advantages over existing power spectral estimators. Our analysis constrains the product of the [C II] bias and [C II] specific intensity, $b_{\rm [C \small{\rm II}]}I_{\rm [C \small{\rm II}]}$, to be <0.31 MJy/sr at z ≈ 0.35 and <0.28 MJy/sr at z ≈ 0.57 at $95{{\ \rm per\ cent}}$ confidence. These limits are consistent with most current models of the [C II] signal, as well as with higher-redshift [C II] cross-power spectrum measurements from the Planck satellite and BOSS quasars. We also show that our analysis, if applied to data from a more sensitive instrument such as the proposed PIXIE satellite, can detect pessimistic [C II] models at high significance.
The first seven months of the 2020 X-ray outburst of the magnetar SGR J1935+2154
Authors: Borghese A , Coti Zelati F , Israel G L , Pilia M , Burgay M , Trudu M , Zane S , Turolla R , Rea N , Esposito P , Mereghetti S , Tiengo A , Possenti A
Published: May 2022

The magnetar SGR J1935+2154 underwent a new active episode on 2020 April 27–28, when a forest of hundreds of X-ray bursts and a large enhancement of the persistent flux were detected. For the first time, a radio burst with properties similar to those of fast radio bursts and with a X-ray counterpart was observed from this source, showing that magnetars can power at least a group of fast radio bursts. In this paper, we report on the X-ray spectral and timing properties of SGR J1935+2154 based on a long-term monitoring campaign with Chandra, XMM–Newton, NuSTAR, Swift, and NICER covering a time-span of ∼7 months since the outburst onset. The broad-band spectrum exhibited a non-thermal power-law component (Γ ∼ 1.2) extending up to ∼20–25 keV throughout the campaign and a blackbody component with temperature decreasing from ∼1.5 keV at the outburst peak to ∼0.45 keV in the following months. We found that the luminosity decay is well described by the sum of two exponential functions, reflecting the fast decay (∼1 d) at the early stage of the outburst followed by a slower decrease (∼30 d). The source reached quiescence about ∼80 d after the outburst onset, releasing an energy of ∼6 × 1040 erg during the outburst. We detected X-ray pulsations in the XMM–Newton data sets and derived an average spin-down rate of ∼3.5 × 10−11 s s−1 using the spin period measurements derived in this work and three values reported previously during the same active period. Moreover, we report on simultaneous radio observations performed with the Sardinia Radio Telescope. No evidence for periodic or single-pulse radio emission was found.
Observational properties of puffy discs: radiative GRMHD spectra of mildly sub-Eddington accretion
Authors: Wielgus Maciek , Lančová Debora , Straub Odele , Kluźniak Włodek , Narayan Ramesh , Abarca David , Różańska Agata , Vincent Frederic , Török Gabriel , Abramowicz Marek
Published: May 2022

Numerical general relativistic radiative magnetohydrodynamic simulations of accretion discs around a stellar-mass black hole with a luminosity above 0.5 of the Eddington value reveal their stratified, elevated vertical structure. We refer to these thermally stable numerical solutions as puffy discs. Above a dense and geometrically thin core of dimensionless thickness h/r ∼ 0.1, crudely resembling a classic thin accretion disc, a puffed-up, geometrically thick layer of lower density is formed. This puffy layer corresponds to h/r ∼ 1.0, with a very limited dependence of the dimensionless thickness on the mass accretion rate. We discuss the observational properties of puffy discs, particularly the geometrical obscuration of the inner disc by the elevated puffy region at higher observing inclinations, and collimation of the radiation along the accretion disc spin axis, which may explain the apparent super-Eddington luminosity of some X-ray objects. We also present synthetic spectra of puffy discs, and show that they are qualitatively similar to those of a Comptonized thin disc. We demonstrate that the existing xspec spectral fitting models provide good fits to synthetic observations of puffy discs, but cannot correctly recover the input black hole spin. The puffy region remains optically thick to scattering; in its spectral properties, the puffy disc roughly resembles that of a warm corona sandwiching the disc core. We suggest that puffy discs may correspond to X-ray binary systems of luminosities above 0.3 of the Eddington luminosity in the intermediate spectral states.
Influence of dark matter on gravitational stability of isothermal gas clouds
Authors: Kalashnikov I Yu , Chechetkin V M
Published: May 2022

To date, the presence of dark matter (DM) can be judged only by its gravitational interaction on the visible matter. It is therefore important to find the consequences of this interaction, which can then help to determine both the DM properties and parameters and the dynamics and evolution of visible matter. The gravitational influence of dark matter on the stability of interstellar medium (ISM), the progenitor of stars and star clusters, was considered. An isothermal self-gravity gas was taken as a suitable model describing ISM, particles interacting only gravitationally were considered as DM. The results obtained by analytical methods show that even a small amount of fast DM particles significantly increases the stable radius of the gas cloud and the corresponding mass while a higher relative density of DM destabilizes the gas. It was shown that with typical parameters of ISM and DM, its presence increases the maximum stable mass of isothermal cloud by a factor of 4 and the radius by five.
Maximally informed Bayesian modelling of disc galaxies
Authors: Rigamonti Fabio , Dotti Massimo , Covino Stefano , Haardt Francesco , Landoni Marco , Del Pozzo Walter , Lupi Alessandro , Zibetti Stefano
Published: May 2022

Dissecting the underlying structure of galaxies is of main importance in the framework of galaxy formation and evolution theories. While a classical bulge+disc decomposition of disc galaxies is usually taken as granted, this is only rarely solidly founded upon the full exploitation of the richness of data arising from spectroscopic studies with integral field units. In this work we describe a fully Bayesian estimation method of the global structure of disc galaxies which makes use of the wealth of photometric, kinematic, and mass-to-light ratio data, and that can be seen as a first step towards a machine-learning approach, certainly needed when dealing with larger samples of galaxies. Ours is a novel, hybrid line of action in tackling the problem of galactic parameter estimation, neither purely photometric nor orbit-based. Being rooted on a nested sampler, our code, which is available publicly as an online repository , allows for a statistical assessment of the need for multiple components in the dissecting process. As a first case-study the GPU-optimized code is applied to the S0 galaxy NGC-7683, finding that in this galaxy a pseudo-bulge, possibly the remnant of a bar-like structure, does exist in the center of the system. These results are then tested against the publicly available, orbit-based code DYNAMITE, finding substantial agreement.
Cluster analysis of paediatric Behçet’s disease: Data from The Pediatric Rheumatology Academy-Research Group
Authors: Demir Ferhat , Sönmez Hafize Emine , Bağlan Esra , Akgün Özlem , Coşkuner Taner , Yener Gülçin Otar , Öztürk Kübra , Çakan Mustafa , Karadağ Şerife G , Özdel Semanur , Ayaz Nuray Aktay , Sözeri Betul
Published: May 2022

Objectives

Behçet’s disease (BD) is a systemic vasculitis affecting many organ systems, with the involvement of all-sized arteries and veins. The study aims to determine the main characteristics of paediatric BD patients and also analyse the clustering phenotypes.

Methods

Demographic data, clinical manifestations, laboratory features, treatment schedules, and disease outcomes were achieved from patients’ charts retrospectively. A cluster analysis was performed according to the phenotype.

Results

A total of 225 (109 male/116 female) patients with BD were enrolled in the study. The median ages of disease onset and diagnosis were 131 (36–151) and 156 (36–192) months, respectively. According to cluster analysis, 132 (58.6%) patients belonged to the mucocutaneous-only cluster (C1), while 35 (15.6%) patients fitted to articular type (C2), 25 (11.1%) were in the ocular cluster (C3), 26 (11.6%) were in the vascular cluster (C4), and 7(3.1%) belonged to the gastrointestinal cluster (C5). Ocular and vascular clusters were more common in boys (p < .001), while girls usually presented with the mucocutaneous-only cluster. The disease activity at the diagnosis and the last control was higher in ocular, vascular, and gastrointestinal clusters.

Conclusions

These identified juvenile BD clusters express different phenotypes with different outcomes Our analysis may help clinicians to identify the disease subtypes accurately and to arrange personalized treatment.
Short stature as an initial presenting presentation of unicentric Castleman disease in a child: A case report with long-term follow-up and a literature review
Authors: Sonoda Kaori , Kaneko Utako , Hiura Makoto , Kinoshita Yoshiaki , Umezu Hajime , Ito Shuichi , Saitoh Akihiko , Imai Chihaya
Published: May 2022

Short stature is a common clinical condition in paediatric outpatient clinics and is associated with various clinical conditions, ranging from normal variants to severe diseases. Short stature is known to be caused by chronic inflammatory conditions, in which over-produced inflammatory cytokines are reported to be involved in growth suppression. Castleman disease is a rare lymphoproliferative disorder known as a chronic inflammatory disease with overproduction of interleukin 6, which often causes systemic symptoms such as fever, fatigue, weight loss, and night sweats. Here, we report the case of a 10-year-old female diagnosed with unicentric Castleman disease, who presented with short stature as the sole clinical sign but lacked typical systemic symptoms of Castleman disease. An elevated serum C-reactive protein level led us to suspect a chronic inflammatory condition, and we found an intra-abdominal tumour that was histopathologically confirmed as Castleman disease. The tumour removal resulted in a steady catch-up in her height in the six years following the surgery. We also present a brief review of relevant literature on paediatric cases of Castleman disease associated with growth impairment. Clinicians should be aware that chronic inflammatory conditions can cause growth impairment, which may be a key clinical manifestation of such conditions.
BeStSel: webserver for secondary structure and fold prediction for protein CD spectroscopy
Authors: Micsonai András , Moussong Éva , Wien Frank , Boros Eszter , Vadászi Henrietta , Murvai Nikoletta , Lee Young-Ho , Molnár Tamás , Réfrégiers Matthieu , Goto Yuji , Tantos Ágnes , Kardos József
Published: May 2022

Circular dichroism (CD) spectroscopy is widely used to characterize the secondary structure composition of proteins. To derive accurate and detailed structural information from the CD spectra, we have developed the Beta Structure Selection (BeStSel) method (PNAS, 112, E3095), which can handle the spectral diversity of β-structured proteins. The BeStSel webserver provides this method with useful accessories to the community with the main goal to analyze single or multiple protein CD spectra. Uniquely, BeStSel provides information on eight secondary structure components including parallel β-structure and antiparallel β-sheets with three different groups of twist. It overperforms any available method in accuracy and information content, moreover, it is capable of predicting the protein fold down to the topology/homology level of the CATH classification. A new module of the webserver helps to distinguish intrinsically disordered proteins by their CD spectrum. Secondary structure calculation for uploaded PDB files will help the experimental verification of protein MD and in silico modelling using CD spectroscopy. The server also calculates extinction coefficients from the primary sequence for CD users to determine the accurate protein concentrations which is a prerequisite for reliable secondary structure determination. The BeStSel server can be freely accessed at https://bestsel.elte.hu.
Disentangling single-cell omics representation with a power spectral density-based feature extraction
Authors: Zandavi Seid Miad , Koch Forrest C , Vijayan Abhishek , Zanini Fabio , Mora Fatima Valdes , Ortega David Gallego , Vafaee Fatemeh
Published: May 2022

Emerging single-cell technologies provide high-resolution measurements of distinct cellular modalities opening new avenues for generating detailed cellular atlases of many and diverse tissues. The high dimensionality, sparsity, and inaccuracy of single cell sequencing measurements, however, can obscure discriminatory information, mask cellular subtype variations and complicate downstream analyses which can limit our understanding of cell function and tissue heterogeneity. Here, we present a novel pre-processing method (scPSD) inspired by power spectral density analysis that enhances the accuracy for cell subtype separation from large-scale single-cell omics data. We comprehensively benchmarked our method on a wide range of single-cell RNA-sequencing datasets and showed that scPSD pre-processing, while being fast and scalable, significantly reduces data complexity, enhances cell-type separation, and enables rare cell identification. Additionally, we applied scPSD to transcriptomics and chromatin accessibility cell atlases and demonstrated its capacity to discriminate over 100 cell types across the whole organism and across different modalities of single-cell omics data.
Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire
Authors: Worboys Hannah M , Cooper Nicola J , Burton James O , Young Hannah M L , Waheed Ghazala , Fotheringham James , Gray Laura J
Published: May 2022

Background

Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed.

Methods

A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16.

Results

We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results.

Conclusions

Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group.

PROSPERO Registration

CRD42020223869
Limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: long-term results from the RT1 protocol
Authors: Edmonston Drucilla Y , Wu Shengjie , Li Yimei , Khan Raja B , Boop Frederick A , Merchant Thomas E
Published: May 2022

Background

Our aim was to estimate long-term disease control and complications after conformal radiation therapy (CRT) in children and adolescents with craniopharyngioma.

Materials and Methods

Pediatric patients with craniopharyngioma (n = 101) were enrolled on or treated according to a phase II single institutional protocol from 1998. Surgery was individualized, and CRT (54Gy) was administered using a 1.0 cm or 0.5 cm clinical target volume margin. Patients were followed for 10 years by serial MR imaging and MR angiography and a battery of tests to measure the effects of treatment.

Results

Twenty patients had tumor progression. Twelve patients who had tumor progression died due to tumor (n = 6) or complications related to tumor or treatment (n = 6). With a median follow-up of 14.94 years for survivors, the 10 year estimates (±SE) of progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were 78.84% ± 4.10%, 77.12% ± 4.19%, and 96.02% ± 1.95%, respectively. OS, EFS, and PFS were significantly associated with race, shunt status, and tumor volume. The 10 year cumulative incidence (±SE) of the secondary tumor (1.99% ± 1.40%), secondary malignant tumor (1.0% ± 1.0%), necrosis (1.98% ± 1.39%), vasculopathy (8.47% ± 2.90%), and permanent neurologic deficits (8.28% ± 3.37%) were estimated by competing risk analysis. Three patients required revascularization surgery. Salvage therapy was successful in 13 patients using surgery and radiosurgery.

Conclusions

Limited surgery and CRT using photons results in excellent tumor control. Tumor control and the incidence and severity of complications are associated with host, tumor, and treatment factors.
Evaluation of chlorhexidine sensitization amongst healthcare workers
Authors: Anderson J , Fulton R B , Li J , Cheng I , Fernando S L
Published: May 2022

Background

Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers (HCWs).

Aims

To evaluate the prevalence of sensitization to chlorhexidine amongst HCWs at a large tertiary hospital to assess the potential allergic safety risks associated with chlorhexidine exposure to staff.

Methods

Sensitization to chlorhexidine was evaluated by measurement of serum-specific immunoglobulin E (IgE) in samples collected from staff assessed after a sharps-injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitization was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products because of infection control procedures and the coronavirus disease 2019 pandemic.

Results

A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2%. Prevalence of sensitization in samples collected before and after increased chlorhexidine exposure was 1% and 3%. This did not represent a statistically significant difference.

Conclusions

The prevalence figures for chlorhexidine sensitization in this study are higher than have been estimated previously for similar HCW cohorts. Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitization in this group. Given the risk of severe reactions in sensitized individuals, this study indicates that evaluation of chlorhexidine allergy is important when investigating occupational allergy in HCWs.
The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study
Authors: Ramnarine Sabrina R , Dougherty Patrick M , Rolke Roman , Williams Linda J , Alessi-Fox Christi , Coleman Andrew J , Longo Caterina , Colvin Lesley A , Fallon Marie T
Published: May 2022

Background

There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner’s corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN.

Patients and Methods

Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison.

Results

In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner’s corpuscle density was correlated with mechanical detection (ρ = −0.51), warm detection (ρ = −0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001).

Conclusions

The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.
Transcription Factors Controlling the Rhizobium–Legume Symbiosis: Integrating Infection, Organogenesis and the Abiotic Environment
Authors: Chakraborty Sanhita , Valdés-López Oswaldo , Stonoha-Arther Christina , Ané Jean-Michel
Published: May 2022

Legume roots engage in a symbiotic relationship with rhizobia, leading to the development of nitrogen-fixing nodules. Nodule development is a sophisticated process and is under the tight regulation of the plant. The symbiosis initiates with a signal exchange between the two partners, followed by the development of a new organ colonized by rhizobia. Over two decades of study have shed light on the transcriptional regulation of rhizobium–legume symbiosis. A large number of transcription factors (TFs) have been implicated in one or more stages of this symbiosis. Legumes must monitor nodule development amidst a dynamic physical environment. Some environmental factors are conducive to nodulation, whereas others are stressful. The modulation of rhizobium–legume symbiosis by the abiotic environment adds another layer of complexity and is also transcriptionally regulated. Several symbiotic TFs act as integrators between symbiosis and the response to the abiotic environment. In this review, we trace the role of various TFs involved in rhizobium–legume symbiosis along its developmental route and highlight the ones that also act as communicators between this symbiosis and the response to the abiotic environment. Finally, we discuss contemporary approaches to study TF-target interactions in plants and probe their potential utility in the field of rhizobium–legume symbiosis.
The conjugation of SUMO to the transcription factor MYC2 functions in blue light-mediated seedling development in Arabidopsis
Authors: Srivastava Moumita , Srivastava Anjil Kumar , Roy Dipan , Mansi Mansi , Gough Catherine , Bhagat Prakash Kumar , Zhang Cunjin , Sadanandom Ari
Published: May 2022

A key function of photoreceptor signaling is the coordinated regulation of a large number of genes to optimize plant growth and development. The basic helix loop helix (bHLH) transcription factor MYC2 is crucial for regulating gene expression in Arabidopsis thaliana during development in blue light. Here we demonstrate that blue light induces the SUMOylation of MYC2. Non-SUMOylatable MYC2 is less effective in suppressing blue light-mediated photomorphogenesis than wild-type (WT) MYC2. MYC2 interacts physically with the SUMO proteases SUMO PROTEASE RELATED TO FERTILITY1 (SPF1) and SPF2. Blue light exposure promotes the degradation of SPF1 and SPF2 and enhances the SUMOylation of MYC2. Phenotypic analysis revealed that SPF1/SPF2 function redundantly as positive regulators of blue light-mediated photomorphogenesis. Our data demonstrate that SUMO conjugation does not affect the dimerization of MYC transcription factors but modulates the interaction of MYC2 with its cognate DNA cis-element and with the ubiquitin ligase Plant U-box 10 (PUB10). Finally, we show that non-SUMOylatable MYC2 is less stable and interacts more strongly with PUB10 than the WT. Taken together, we conclude that SUMO functions as a counterpoint to the ubiquitin-mediated degradation of MYC2, thereby enhancing its function in blue light signaling.
Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality
Authors: Cooksey Roxanne , Underwood Jonathan , Brophy Sinead , Atkinson Mark , Kennedy Jonathan , Choy Ernest
Published: May 2022

Objectives

Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.

Methods

Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.

Results

A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).

Conclusions

Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.
Economic Policy Uncertainty and the Yield Curve
Authors: Leippold Markus , Matthys Felix
Published: May 2022

We study the impact of economic policy uncertainty on the term structure of nominal interest rates. In a general equilibrium model populated by an uncertainty averse agent, we show that political uncertainty not only affects the yield curve and the corresponding volatility term structure but also bond risk premia carry a premium for political uncertainty. Our model simultaneously captures both the shape of the yield curve and the hump shape of yield volatilities, a stylized feature that is hard to match with a theoretical model. Our model gives rise to a set of testable predictions for which we find strong support in the data: Higher policy uncertainty leads to a significant decline in yield levels and increases bond yield volatilities. Moreover, policy uncertainty predicts future short rates and has an ambiguous effect on term premia. Finally, short (long) maturity bond risk premia respond negatively (positively) to increases in policy uncertainty.
Cruciferous Weed Isolates of Xanthomonas campestris Yield Insight into Pathovar Genomic Relationships and Genetic Determinants of Host and Tissue Specificity
Authors: Dubrow Zoë E. , Carpenter Sara C. D. , Carter Morgan E. , Grinage Ayress , Gris Carine , Lauber Emmanuelle , Butchachas Jules , Jacobs Jonathan M. , Smart Christine D. , Tancos Matthew A. , Noël Laurent D. , Bogdanove Adam J.
Published: May 2022

Pathovars of Xanthomonas campestris cause distinct diseases on different brassicaceous hosts. The genomic relationships among pathovars as well as the genetic determinants of host range and tissue specificity remain poorly understood despite decades of research. Here, leveraging advances in multiplexed long-read technology, we fully sequenced the genomes of a collection of X. campestris strains isolated from cruciferous crops and weeds in New York and California as well as strains from global collections, to investigate pathovar relationships and candidate genes for host- and tissue-specificity. Pathogenicity assays and genomic comparisons across this collection and publicly available X. campestris genomes revealed a correlation between pathovar and genomic relatedness and provide support for X. campestris pv. barbareae, the validity of which had been questioned. Linking strain host range with type III effector repertoires identified AvrAC (also ‘XopAC’) as a candidate host-range determinant, preventing infection of Matthiola incana, and this was confirmed experimentally. Furthermore, the presence of a copy of the cellobiosidase gene cbsA with coding sequence for a signal peptide was found to correlate with the ability to infect vascular tissues, in agreement with a previous study of diverse Xanthomonas species; however, heterologous expression in strains lacking the gene gave mixed results, indicating that factors in addition to cbsA influence tissue specificity of X. campestris pathovars.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .