bluuebunny/crossref_metadata_2025 huggingface dataset:
Middle age serum sodium levels in the upper part of normal range and risk of heart failure
Authors: Dmitrieva Natalia I , Liu Delong , Wu Colin O , Boehm Manfred
Published: March 2022

Aims

With increasing prevalence of heart failure (HF) owing to the ageing population, identification of modifiable risk factors is important. In a mouse model, chronic hypohydration induced by lifelong water restriction promotes cardiac fibrosis. Hypohydration elevates serum sodium. Here, we evaluate the association of serum sodium at middle age as a measure of hydration habits with risk to develop HF.

Methods and results

We analysed data from Atherosclerosis Risk in Communities study with middle age enrolment (45–66 years) and 25 years of follow-up. Participants without water balance dysregulation were selected: serum sodium within normal range (135–146 mmol/L), not diabetic, not obese and free of HF at baseline (N = 11 814). In time-to-event analysis, HF risk was increased by 39% if middle age serum sodium exceeded 143 mmol/L corresponding to 1% body weight water deficit [hazard ratio 1.39, 95% confidence interval (CI) 1.14–1.70]. In a retrospective case-control analysis performed on 70- to 90-year-old attendees of Visit 5 (N = 4961), serum sodium of 142.5–143 mmol/L was associated with 62% increase in odds of left ventricular hypertrophy (LVH) diagnosis [odds ratio (OR) 1.62, 95% CI 1.03–2.55]. Serum sodium above 143 mmol/L was associated with 107% increase in odds of LVH (OR 2.07, 95% CI 1.30–3.28) and 54% increase in odds of HF (OR 1.54, 95% CI 1.06–2.23). As a result, prevalence of HF and LVH was increased among 70- to 90-year-old participants with higher middle age serum sodium.

Conclusion

Middle age serum sodium above 142 mmol is a risk factor for LVH and HF. Maintaining good hydration throughout life may slow down decline in cardiac function and decrease prevalence of HF.
An exposomic framework to uncover environmental drivers of aging
Authors: Kalia Vrinda , Belsky Daniel W , Baccarelli Andrea A , Miller Gary W
Published: March 2022

The exposome, the environmental complement of the genome, is an omics level characterization of an individual’s exposures. There is growing interest in uncovering the role of the environment in human health using an exposomic framework that provides a systematic and unbiased analysis of the non-genetic drivers of health and disease. Many environmental toxicants are associated with molecular hallmarks of aging. An exposomic framework has potential to advance understanding of these associations and how modifications to the environment can promote healthy aging in the population. However, few studies have used this framework to study biological aging. We provide an overview of approaches and challenges in using an exposomic framework to investigate environmental drivers of aging. While capturing exposures over a life course is a daunting and expensive task, the use of historical data can be a practical way to approach this research.
Secondary infection withStreptococcus pneumoniaedecreases influenza virus replication and is linked to severe disease
Authors: Mueller Brown Karina , Le Sage Valerie , French Andrea J , Jones Jennifer E , Padovani Gabriella H , Avery Annika J , Schultz-Cherry Stacey , Rosch Jason W , Hiller N Luisa , Lakdawala Seema S
Published: March 2022

Secondary bacterial infection is a common complication in severe influenza virus infections. During the H1N1 pandemic of 2009, increased mortality was observed among healthy young adults due to secondary bacterial pneumonia, one of the most frequent bacterial species being Streptococcus pneumoniae (Spn). Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, the ferret model was used to examine whether secondary Spn infection (strains BHN97 and D39) influence replication and airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09). Secondary infection with Spn after H1N1pdm09 infection consistently resulted in a significant decrease in viral titers in the ferret nasal washes. While secondary Spn infection appeared to negatively impact influenza virus replication, animals precolonized with Spn were equally susceptible to H1N1pdm09 airborne transmission. In line with previous work, ferrets with preceding H1N1pdm09 and secondary Spn infection had increased bacterial loads and more severe clinical symptoms as compared to animals infected with H1N1pdm09 or Spn alone. Interestingly, the donor animals that displayed the most severe clinical symptoms had reduced airborne transmission of H1N1pdm09. Based on these data, we propose an asymmetrical relationship between these two pathogens, rather than a synergistic one, since secondary bacterial infection enhances Spn colonization and pathogenesis but decreases viral titers.
Lack of N-glycosylation increases amyloidogenic processing of the amyloid precursor protein
Authors: Lin Tong , van Husen Lea S , Yu Yang , Tjernberg Lars O , Schedin-Weiss Sophia
Published: March 2022

The amyloid precursor protein (APP) is a ubiquitously expressed type 1 transmembrane protein mostly known for serving as a precursor to the amyloid-β peptide (Aβ), a culprit in Alzheimer disease (AD). However, APP also has important physiological functions by being implicated in, for instance, adhesion, signaling, neuronal development, and synaptic function. Human APP contains 2 N-glycosylation sites, at asparagine (N) 467 (N467) and N496. Here, we studied the role of N-glycosylation on APP trafficking and processing by constructing APP-SNAP plasmid vectors for wildtype APP and N-glycosylation site mutants in which N467 or N496 was replaced by glutamine (Q) and expressed these in HEK293T cells. Lack of either of the 2 N-glycans resulted in a reduction in the size of intracellular APP-SNAP-positive vesicles and a reduction of APP-SNAP in the plasma membrane and lysosomes. Importantly, loss of either of the 2 N-glycans resulted in elevated levels of intracellular as well as secreted Aβ42. These data suggest that N-glycans have a major impact on trafficking and processing of APP and could play an important role in the development of AD.
Parametric optimization procedure for efficient window design of educational buildings in the Pearl River Delta of China
Authors: Zhao Yang , Li Yuping , Chen Xingjiang , Xia Dawei , Huang Yu , Lou Siwei
Published: March 2022

Windows are responsible for the largest amount of energy loss related to building envelope. Past studies on the energy consumption of windows have mainly focused on residential and commercial buildings, while few studies have explored the energy consumption of windows in educational buildings. The sizes and locations of classroom windows affect not only the building energy consumption but also the indoor environment quality, which is an issue that needs to be balanced. This paper takes a classroom in Guangzhou as the object. Under the premise of meeting the lighting standards of the classroom, two parameters—window height and sill height —were simulated in different corridors of north–south and east–west classrooms to analyse the impact of their changes on the indoor environment as well as energy consumption based on the parametric platform Grasshopper and its plug-ins Ladybug and Honeybee. The energy consumption of a number of fenestration combinations on both sides of the classroom was optimized automatically by genetic algorithm, and the sizes and positions of windows that benefitted energy savings were obtained. In the best case ~16.6% of energy consumed in a whole year can be saved compared with the worst case. This conclusion can provide a quick decision-making process for the design of window shapes for the purpose of energy savings in the early design stage of educational buildings in the Pearl River Delta such that energy savings can be quickly and clearly guaranteed in the subsequent window configuration.
Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency
Authors: van Kampen Jeroen J A , Dalm Virgil A S H , Fraaij Pieter L A , Oude Munnink Bas B , Schapendonk Claudia M E , Izquierdo-Lara Ray W , Villabruna Nele , Ettayebi Khalil , Estes Mary K , Koopmans Marion P G , de Graaf Miranda
Published: March 2022

Background

Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.

Methods

Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced.

Results

None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus–infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection.

Conclusions

Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments.
EQUAL Trichosporon Score 2022: an ECMM score to measure QUALity of the clinical management of invasive Trichosporon infections
Authors: Sprute Rosanne , Bethe Ullrich , Chen Sharon C.-A. , Cornely Oliver A.
Published: March 2022

Background

Invasive infections due to Trichosporon spp. are life-threatening opportunistic fungal infections that require complex clinical management. Guidelines assist clinicians but can be challenging to comply with.

Objectives

To develop a scoring tool to facilitate and quantify adherence to current guideline recommendations for invasive trichosporonosis.

Methods

We reviewed the current guideline for managing rare yeast infections (ECMM, ISHAM and ASM). The most important recommendations for diagnosis, treatment and follow-up were assembled and weighted according to their strength of recommendation and level of evidence. Additional items considered highly relevant for clinical management were also included.

Results

The resulting EQUAL Trichosporon Score 2022 comprises 18 items, with a maximum score of 39 points. For diagnostics, seven or eight items, depending on whether organ involvement is present or not, apply, resulting in a maximum of 18 or 21 points. Recommendations on diagnostics include imaging, infectious diseases expert consultation, culture, microscopy, molecular techniques, histopathology, and susceptibility testing. For treatment, six recommendations with a maximum of ten points were identified, with two additional points for organ involvement and one point for second-line treatment in uncontrolled disease. Treatment recommendations include immediate initiation, source control, pharmacological treatment, therapeutic drug monitoring, treatment duration and surgical intervention. Follow-up comprises two items with five points maximum, covering follow-up blood cultures and imaging.

Conclusions

The EQUAL Trichosporon Score weighs and aggregates factors recommended for optimal management of Trichosporon infections. It provides a tool for antifungal stewardship as well as for measuring guideline adherence, but remains to be correlated with patient outcomes.
User-centered design of central venous access device documentation
Authors: Kandaswamy Swaminathan , Gill Anne , Wood Shellie , Mckay Leah , Hike Jessica , Popkin Melissa , Ray Edwin , Maude Heather , Johnston Crawford , White Tenia , Orenstein Evan
Published: March 2022

Objective

Safe care of central venous access devices (CVAD) requires clinicians be able to identify key CVAD properties from insertion until safe removal. Our objective was to design and evaluate interfaces to improve CVAD documentation quality and information retrieval.

Materials and Methods

We applied user-centered design (UCD) to CVAD property documentation interfaces. We measured expert agreement and front-line clinician accuracy in retrieving key properties in CVADs documented pre- and postimplementation.

Results

The new approach (1) optimized searches for line types, (2) enabled discrete entry of key properties which propagated to the display name, and (3) facilitated error correction by experts. Expert agreement on key CVAD properties improved from 42% to 83% (P < 0.01). Frontline nurses’ perception of key CVAD properties improved from 31% to 86% (P < 0.01). Ease of use scores improved from 15/100 to 80/100 (P < 0.01).

Conclusions

UCD significantly improved data quality and nurse perception of CVAD properties to guide subsequent care.
BodyMapR: an R package and Shiny application designed to generate anatomical visualizations of cancer lesions
Authors: Miller David M , Shalhout Sophia Z
Published: March 2022

Objectives

Structured real-world data (RWD), such as those found in cancer registries, provide a rich source of information regarding the natural history of cancer. Interactive data visualizations of cancer lesions can provide insights into certain clinical tumor characteristics (CTC). Software that can be integrated into an oncological data collection effort and generate anatomical data visualizations of CTC are limited.

Materials and Methods

We created BodyMapR: an R package and Shiny application that generates anatomical visualizations of cancer lesions from structured data.

Results

BodyMapR is a Shiny application that transposes structured data from REDCap® onto an anatomical map to yield an interactive data visualization.

Conclusions

BodyMapR is freely available under the MIT license and can be obtained from GitHub. BodyMapR is executed in R and deployed as a Shiny application. It can be integrated into an existing cancer research platform and produces an interactive data visualization of CTC.
Inheritance and QTL Mapping for Flower Color inSalvia miltiorrhizaBunge
Authors: Yu Yan , Yang Zaijun , Jiang Yuanyuan , Wang Long , Wu Yichao , Liao Jinqiu , Yang Ruiwu , Zhang Li
Published: March 2022

Salvia miltiorrhiza Bunge is an outcross-pollinated plant with diverse flower colors, ranging from white to purple. To clarify the genetic basis of S. miltiorrhiza flower color, we crossed white-flowered S. miltiorrhiza f. alba with dark violet-flowered S. miltiorrhiza, and selfed F1 to obtain an F2 population. The RGB color system was used to describe the flower color of the parents, F1 progeny, and F2 individuals. Afterward, we used genotyping-by-sequencing technology to construct a high-density linkage map of S. miltiorrhiza based on the F2 population. Finally, the linkage map was used to locate the QTLs of the genes that control flower color in S. miltiorrhiza. Through measurement and cluster analysis of the R, G, and B values of flowers from the parents, F1, and F2 individuals, it was found that the purple flower color of S. miltiorrhiza is a quantitative trait controlled by 2 loci of major genes. The genetic map contained 605 SNPs with a total length of 738.3 cM in 8 linkage groups (LGs), and the average distance between 2 markers was 1.22 cM. Based on the constructed genetic map and the flower R, G, B, and R+G+B values, 2 QTLs were detected for flower color, located on LG4 and LG5. The results of this study lay the foundation for cloning genes that control flower color and studying the molecular mechanism of flower color regulation in S. miltiorrhiza.
First Record of Black Widow Spider Bite Latrodectus cinctus (Araneae: Theridiidae) From Iran
Authors: Nejati Jalil , Bueno-Marí Rubén , Salehi Masoud , Akbari Mohammad Reza , Shahi Mehran
Published: March 2022

The genus Latrodectus contains the most medically important spiders around the world. This study describes the first case of Latrodectus cinctus Blackwall, 1865 bite and clinical treatment from Iran. Also, it is the first collection report from the southeast of the country that can enhance prior knowledge on the geographical distribution of this species. We describe a 42-year-old female patient with neurological pain caused by the spider bite. Also, a summary of the entomological survey and morphological identification of the collected species from the patient’s house is presented.
Genotypic differences in response to different patterns of clonal fragmentation in the aquatic macrophytePistia stratiotes
Authors: Adomako Michael Opoku , Zhang Qian , Yu Fei-Hai
Published: March 2022

Connected individuals (ramets) of clonal plants are frequently fragmented due to disturbance, and such clonal fragmentation may influence their growth. However, it is unclear whether different patterns of clonal fragmentation produce differential effects on plant growth and whether such differences vary with genotypes. We collected one group of connected ramets of the stoloniferous floating invasive macrophyte Pistia stratiotes from each of six provinces (Guangdong, Guangxi, Hubei, Jiangsu, Sichuan and Yunnan Provinces) of China, and assumed that these ramets belonged to different genotypes. After several generations of vegetative propagation to remove potential parental effects, new ramets (hereafter referred to as parent ramets) from each of these assumed genotypes were subjected to four patterns of clonal fragmentation, i.e., all offspring ramets produced during the experiment remained connected to their parent ramet (control), or the primary (1°), secondary (2°) or tertiary (3°) offspring ramets were disconnected from their parent ramet. We found significant growth differences among the assumed genotypes, confirming that the ramets sampled from these six provinces were from different genotypes. Compared with the control, disconnecting the 1°, 2° or 3° ramets did not significantly affect biomass of the whole clone (i.e., the parent ramet plus all offspring ramets) of P. stratiotes. Disconnecting the 1° ramets significantly increased biomass of the parental ramet of all six genotypes compared with the control. However, disconnecting the 2° or 3° ramets had little effect on biomass of the parent ramet for all genotypes except the Guangxi genotype, for which disconnecting the 2° ramets decreased biomass of the parent ramet. Disconnecting the 1°, 2° or 3° ramets had no impact on biomass or number of the 1° or the 3° ramets for any of the genotypes. However, disconnecting the 1° ramets decreased biomass of the 2° ramets for the Guangdong and Yunnan genotypes, but had no effect for the other four genotypes. We conclude that different patterns of clonal fragmentation can have different impacts on parent and offspring ramets of P. stratiotes and such an impact may vary with genotypes.
Adaptive Functioning in Children and Adolescents With Sickle Cell Disease
Authors: Trpchevska Ana , Longoria Jennifer , Okhomina Victoria , Raches Darcy , Potter Brian , Kang Guolian , Heitzer Andrew M , Hankins Jane S
Published: March 2022

Objective

Risk for neurocognitive deficits in sickle cell disease (SCD) is well established, yet minimal research has evaluated the risk for deficits in adaptive functioning. We assessed adaptive functioning in pediatric patients with SCD to test the hypothesis that disease, treatment, and demographic factors were associated with adaptive outcomes.

Methods

Two hundred fifty-six patients (57% HbSS/HbSß0-thalassemia and 43% HbSC/HbSß+-thalassemia), ages 8–18, received routine neuropsychological assessments as part of a larger prospective lifetime cohort study. Adaptive functioning was measured using the Behavior Assessment System for Children, Second or Third Edition. Adaptive scores were compared with normative values using t-test or Wilcoxon signed rank test and linear regression models were used to measure associations between adaptive functioning and age, hydroxyurea (HU) use, sickle genotype, and socioeconomic status. Furthermore, we examined the influence of intellectual and executive functioning on adaptive behavior using hierarchical linear regression analyses.

Results

Parent ratings of adaptive functioning skills did not differ from normative expectations (all false discovery rate [FDR] adjusted p-value [pFDR] > 0.05). Social vulnerability was negatively associated with adaptive scores on most adaptive scales in both genotypes (pFDR < 0.05). HU treatment was not significantly associated with any adaptive scale. Overall IQ was positively associated with Functional Communication and Leadership only for those with HbSS/HbSß0-thalassemia. Higher parent ratings of executive difficulties were correlated with lower adaptive scores (estimate = −0.64, standard error = 0.051, p < .001).

Conclusions

Poorer parent-rated adaptive skills were associated with increased social vulnerability, lower Full-Scale IQ, and parent-rated executive difficulties. Most adaptive scores were in the normal range; however, parent ratings may not fully capture the impact of disease complications and neurocognitive deficits on daily functioning.
University Work: Re-Forming Manuscripts in Elizabeth Jesser Reid’s Correspondence Networks
Authors: McGettigan Katie
Published: March 2022

This essay discusses the process of re-forming the handwritten manuscripts held in Royal Holloway’s Papers of Elizabeth Jesser Reid into a digital archive, Elizabeth Jesser Reid’s Correspondence Networks. The letters and the digital archive map complex networks of reform in which Reid was a lynchpin, and show how the work of founding and running Bedford College, a pioneering women’s education institution, was enmeshed in a wider culture of reform. I employ Sara Ahmed’s idea of ‘queer use’ to examine connections between this nineteenth-century reform work, the digitization process, and forms of labour (administration, housekeeping, community building, and others) that are devalued in the twenty-first-century university, even as they are essential to knowledge production. I argue that digitization as a ‘queer use’ of manuscripts can illuminate the university politics of use, then and now, through analysing a letter in which Bedford’s education mission conflicted with Reid’s antislavery activism.
Molecular basis of priming-induced acquired tolerance to multiple abiotic stresses in plants
Authors: Nair Akshay U , Bhukya Durga Prasad Naik , Sunkar Ramanjulu , Chavali Sreenivas , Allu Annapurna Devi
Published: March 2022

The growth, survival, and productivity of plants are constantly challenged by diverse abiotic stresses. When plants are exposed to stress for the first time, they can capture molecular information and store it as a form of memory, which enables them to competently and rapidly respond to subsequent stress(es). This process is referred to as a priming-induced or acquired stress response. In this review, we discuss how (i) the storage and retrieval of the information from stress memory modulates plant physiological, cellular, and molecular processes in response to subsequent stress(es), (ii) the intensity, recurrence, and duration of priming stimuli influences the outcomes of the stress response, and (iii) the varying responses at different plant developmental stages. We highlight current understanding of the distinct and common molecular processes manifested at the epigenetic, (post-)transcriptional, and post-translational levels mediated by stress-associated molecules and metabolites, including phytohormones. We conclude by emphasizing how unravelling the molecular circuitry underlying diverse priming-stimuli-induced stress responses could propel the use of priming as a management practice for crop plants. This practice, in combination with precision agriculture, could aid in increasing yield quantity and quality to meet the rapidly rising demand for food.
Petal development and elaboration
Authors: Fu Xuehao , Shan Hongyan , Yao Xu , Cheng Jie , Jiang Yongchao , Yin Xiaofeng , Kong Hongzhi
Published: March 2022

Petals can be simple or elaborate, depending on whether they have complex basic structures and/or highly specialized epidermal modifications. It has been proposed that the independent origin and diversification of elaborate petals have promoted plant–animal interactions and, therefore, the evolutionary radiation of corresponding plant groups. Recent advances in floral development and evolution have greatly improved our understanding of the processes, patterns, and mechanisms underlying petal elaboration. In this review, we compare the developmental processes of simple and elaborate petals, concluding that elaborate petals can be achieved through four main paths of modifications (i.e. marginal elaboration, ventral elaboration, dorsal elaboration, and surface elaboration). Although different types of elaborate petals were formed through different types of modifications, they are all results of changes in the expression patterns of genes involved in organ polarity establishment and/or the proliferation, expansion, and differentiation of cells. The deployment of existing genetic materials to perform a new function was also shown to be a key to making elaborate petals during evolution.
Apple vacuolar processing enzyme 4 is regulated by cysteine protease inhibitor and modulates fruit disease resistance
Authors: Dong Chaohua , Li Ronghui , Wang Nan , Liu Yingshuang , Zhang Yugang , Bai Suhua
Published: March 2022

Ring rot is a destructive apple disease caused by Botryosphaeria dothidea. The resistance mechanism of apple plants to B. dothidea remains unclear. Here, we show that APPLE VACUOLAR PROCESSING ENZYME 4 (MdVPE4) is involved in resistance to B. dothidea. MdVPE4 silencing reduced fruit disease resistance, whereas its overexpression improved resistance. Gene expression analysis revealed that MdVPE4 influenced the expression of fruit disease resistance-related genes, such as APPLE POLYGALACTURONASE 1 (MdPG1), APPLE POLYGALACTURONASE INHIBITOR PROTEIN 1 (MdPGIP1), APPLE ENDOCHITINASE 1 (MdCHI1), and APPLE THAUMATIN-LIKE PROTEIN 1 (MdTHA1). The expression of the four genes responding to B. dothidea infection decreased in MdVPE4-silenced fruits. Further analysis demonstrated that B. dothidea infection induced MdVPE4 expression and enzyme activation in apple fruits. Moreover, MdVPE4 activity was modulated by apple cysteine proteinase inhibitor 1 (MdCPI1), which also contributed to resistance towards B. dothidea, as revealed by gene overexpression and silencing analysis. MdCPI1 interacted with MdVPE4 and inhibited its activity. However, MdCPI1 expression was decreased by B. dothidea infection. Taken together, our findings indicate that the interaction between MdVPE4 and MdCPI1 plays an important role in modulating fruit disease resistance to B. dothidea.
The formation of discs in the interior of AGB stars from the tidal disruption of planets and brown dwarfs
Authors: Guidarelli G , Nordhaus J , Carroll-Nellenback J , Chamanady L , Frank A , Blackman E G
Published: March 2022

A significant fraction of isolated white dwarfs host magnetic fields in excess of a MegaGauss. Observations suggest that these fields originate in interacting binary systems where the companion is destroyed thus leaving a singular, highly magnetized white dwarf. In post-main-sequence evolution, radial expansion of the parent star may cause orbiting companions to become engulfed. During the common envelope phase, as the orbital separation rapidly decreases, low-mass companions will tidally disrupt as they approach the giant’s core. We hydrodynamically simulate the tidal disruption of planets and brown dwarfs, and the subsequent accretion disc formation, in the interior of an asymptotic giant branch star. Compared to previous steady-state simulations, the resultant discs form with approximately the same mass fraction as estimated but have not yet reached steady state and are morphologically more extended in height and radius. The long-term evolution of the disc and the magnetic fields generated therein require future study.
Detecting gravitational lenses using machine learning: exploring interpretability and sensitivity to rare lensing configurations
Authors: Wilde Joshua , Serjeant Stephen , Bromley Jane M , Dickinson Hugh , Koopmans Léon V E , Metcalf R Benton
Published: March 2022

Forthcoming large imaging surveys such as Euclid and the Vera Rubin Observatory Legacy Survey of Space and Time are expected to find more than 105 strong gravitational lens systems, including many rare and exotic populations such as compound lenses, but these 105 systems will be interspersed among much larger catalogues of ∼109 galaxies. This volume of data is too much for visual inspection by volunteers alone to be feasible and gravitational lenses will only appear in a small fraction of these data which could cause a large amount of false positives. Machine learning is the obvious alternative but the algorithms’ internal workings are not obviously interpretable, so their selection functions are opaque and it is not clear whether they would select against important rare populations. We design, build, and train several convolutional neural networks (CNNs) to identify strong gravitational lenses using VIS, Y, J, and H bands of simulated data, with F1 scores between 0.83 and 0.91 on 100 000 test set images. We demonstrate for the first time that such CNNs do not select against compound lenses, obtaining recall scores as high as 76 per cent for compound arcs and 52 per cent for double rings. We verify this performance using Hubble Space Telescope and Hyper Suprime-Cam data of all known compound lens systems. Finally, we explore for the first time the interpretability of these CNNs using Deep Dream, Guided Grad-CAM, and by exploring the kernels of the convolutional layers, to illuminate why CNNs succeed in compound lens selection.
An empirical measurement of the halo mass function from the combination of GAMA DR4, SDSS DR12, and REFLEX II data
Authors: Driver Simon P , Robotham Aaron S G , Obreschkow Danail , Peacock John A , Baldry Ivan K , Bellstedt Sabine , Bland-Hawthorn Joss , Brough Sarah , Cluver Michelle , Holwerda Benne W , Hopkins Andrew , Lagos Claudia , Liske Jochen , Loveday Jon , Phillipps Steven , Taylor Edward N
Published: March 2022

We construct the halo mass function (HMF) from the GAMA (Galaxy And Mass Assembly) galaxy group catalogue over the mass range of 1012.7–1015.5 M⊙, and find good agreement with the expectation from Lambda cold dark matter. In comparison to previous studies, this result extends the mass range over which the HMF has now been measured over by an order of magnitude. We combine the GAMA data release (DR) 4 HMF with similar data from the Sloan Digital Sky Survey (SDSS) DR12 and REFLEX II (ROSAT-ESO Flux Limited X-ray Galaxy Cluster Survey) surveys, and fit a four-parameter Murray–Robotham–Power function, valid at $\tilde{z} \approx 0.1$, yielding a density normalization of log10 (ϕ* Mpc$^{3})= -3.96^{+0.55}_{-0.82}$, a high mass turnover of log10 (M* M$_{\odot }^{-1})=14.13^{+0.43}_{-0.40}$, a low-mass power-law slope of $\alpha =-1.68^{+0.21}_{-0.24}$, and a high-mass softening parameter of $\beta =0.63^{+0.25}_{-0.11}$. If we fold in the constraint on ΩM from the Planck 2018 cosmology, we are able to reduce these uncertainties further, but this relies on the assumption that the power-law trend can be extrapolated from 1012.7 M⊙ to zero mass. Throughout, we highlight the effort needed to improve on our HMF measurement: improved halo mass estimates that do not rely on calibration to simulations; reduced halo mass uncertainties needed to mitigate the strong Eddington bias that arises from the steepness of the HMF low-mass slope; and deeper wider area spectroscopic surveys. To our halo mass limit of 1012.7 M⊙, we are directly resolving (‘seeing’) 41 ± 5 per cent of the total mass density, i.e. ΩM,>12.7 = 0.128 ± 0.016, opening the door for the direct construction of three-dimensional dark matter mass maps at Mpc resolution.
Rings and arcs around evolved stars – III. Physical conditions of the ring-like structures in the planetary nebula IC 4406 revealed by MUSE
Authors: Ramos-Larios G , Toalá J A , Rodríguez-González J B , Guerrero M A , Gómez-González V M A
Published: March 2022

We present the analysis of Very Large Telescope Multi Unit Spectroscopic Explorer (MUSE) observations of the planetary nebula (PN) IC 4406. MUSE images in key emission lines are used to unveil the presence of at least five ring-like structures north and south of the main nebula of IC 4406. MUSE spectra are extracted from the rings to unambiguously assess for the first time in a PN their physical conditions, electron density (ne), and temperature (Te). The rings are found to have similar Te as the rim of the main nebula, but smaller ne. Ratios between different ionic species suggest that the rings of IC 4406 have a lower ionization state than the main cavity, in contrast to what was suggested for the rings in NGC 6543, the Cat’s Eye Nebula.
Magnetorotational core collapse of possible gamma-ray burst progenitors – IV. A wider range of progenitors
Authors: Obergaulinger M , Aloy M Á
Published: March 2022

The final collapse of the cores of massive stars can lead to a wide variety of outcomes in terms of electromagnetic and kinetic energies, nucleosynthesis, and remnants. The association of this wide spectrum of explosion and remnant types with the properties of the progenitors remains an open issue. The rotation and magnetic fields in Wolf–Rayet stars of subsolar metallicity may explain extreme events such as superluminous supernovae and gamma-ray bursts powered by proto-magnetars or collapsars. Continuing with numerical studies of magnetorotational core collapse, including detailed neutrino physics, we focus on progenitors with zero-age main-sequence masses in the range between 5 and 39 ${\rm M}_{\odot }$. The pre-collapse stars are 1D models employing prescriptions for the effects of rotation and magnetic fields. Eight of the 10 stars we consider are the results of chemically homogeneous evolution owing to enhanced rotational mixing . All but one of them produce explosions driven by neutrino heating (more likely for low-mass progenitors up to 8 ${\rm M}_{\odot }$) and non-spherical flows or by magnetorotational stresses (more frequent above 26 ${\rm M}_{\odot }$). In most of them and for the one non-exploding model, ongoing accretion leads to black hole formation. Rapid rotation makes subsequent collapsar activity plausible. Models not forming black holes show proto-magnetar-driven jets. Conditions for the formation of nickel are more favourable in magnetorotationally driven models, although our rough estimates fall short of the requirements for extremely bright events if these are powered by radioactive decay. However, the approximate light curves of our models suggest that a proto-magnetar or black hole spin-down may fuel luminous transients (with peak luminosities $\sim 10^{43-44}\, \textrm {erg}$).
Uncommon presentation of brown tumours revealing hyperparathyroidism: Three case reports
Authors: Kaouther Maatallah , Yasmine Makhlouf , Skander Kedous , Kaffel Dhia , Hanene Ferjani , Wafa Triki , Dorra Ben Nessib , Wafa Hamdi
Published: March 2022

Brown tumours (BTs) are focal bone lesions encountered in patients with uncontrolled hyperparathyroidism (HPT). They are due to a proliferation of multinucleated giant cells in osteolytic lesions. Because of early screening of bone metabolism disorders, BTs are rare bone manifestations. More importantly, they scarcely reveal the disease. We demonstrate through these two cases reports unusual locations of BT complicating the course of HPT due to parathyroid hyperplasia.
Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases
Authors: Thompson George R , Boulware David R , Bahr Nathan C , Clancy Cornelius J , Harrison Thomas S , Kauffman Carol A , Le Thuy , Miceli Marisa H , Mylonakis Eleftherios , Nguyen M Hong , Ostrosky-Zeichner Luis , Patterson Thomas F , Perfect John R , Spec Andrej , Kontoyiannis Dimitrios P , Pappas Peter G
Published: March 2022

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.
Co-option of the SHOOT MERISTEMLESS network regulates protocorm-like body development in Phalaenopsis aphrodite
Authors: Fang Su-Chiung , Chen Jhun-Chen , Chang Pou-Yi , Lin Hsiang-Yin
Published: March 2022

The protocorm is a structure that is formed upon germination of an orchid seed. It lacks cotyledons and is ovoid in shape. The protocorm-like body (PLB), on the other hand, is a protocorm-like organ induced from somatic tissues. PLBs have been widely used for orchid micropropagation. Because of its unique structure and its application in the orchid industry, PLB development has drawn considerable interest from orchid and developmental biologists. Our previous genome-wide comparative transcriptome study demonstrated that protocorms and PLBs share similar molecular signatures and suggested that SHOOT MERISTEMLESS (STM)-dependent organogenesis is important for PLB development. Here, we show that overexpression of Phalaenopsis aphrodite STM (PaSTM) greatly enhances PLB regeneration from vegetative tissue-based explants of Phalaenopsis orchids, confirming its regulatory role in PLB development. Expression of PaSTM restored shoot meristem function of the Arabidopsis (Arabidopsis thaliana) stm-2 mutant. Moreover, we identified class S11 MYB transcription factors (TFs) as targets downstream of PaSTM. A cis-acting element, TTGACT, identified in the promoters of S11 MYB TFs was found to be important for PaSTM binding and activation. Overexpression of PaSTM or its downstream targets, PaMYB13, PaMYB14, and PaMYB17, enhanced de novo shoot regeneration in Arabidopsis, indicating the active role of the PaSTM-S11 PaMYB module in organogenesis. In summary, our data demonstrate that PaSTM is important for PLB development. The STM-S11 MYB regulatory module is evolutionarily conserved and may regulate shoot or shoot-related organ development in plants.
Clinical worsening following discontinuation of tocilizumab in diffuse cutaneous systemic sclerosis: a single-centre experience in Japan
Authors: Isomura Yohei , Shirai Yuichiro , Kuwana Masataka
Published: March 2022

Objective

To investigate outcomes following the tapering or discontinuation of tocilizumab in patients with diffuse cutaneous SSc (dcSSc) in a real-world setting.

Methods

Fifteen patients who were treated with tocilizumab for dcSSc were selected from a single-centre cohort database and were evaluated for serial changes in the modified Rodnan total skin thickness score (mRSS) and predicted forced vital capacity (FVC) and the occurrence of clinical worsening events after the introduction of tocilizumab.

Results

Over 12 months of treatment with tocilizumab, the mRSS decreased from 20.4 ± 10.7 to 12.3 ± 8.5 (P = 0.003) and FVC increased from 84.3 ± 13.7% to 88.5 ± 16.4% (P = 0.04). Tocilizumab was tapered or discontinued in seven and three patients, respectively, after improvement in skin thickening without occurrence or progression of organ manifestations. One (14%) of seven patients who underwent tocilizumab tapering experienced a worsening of skin thickening, while all three patients who discontinued tocilizumab experienced a worsening of skin thickening and/or new development of pericarditis, arthritis, interstitial lung disease or pulmonary arterial hypertension. The additional patient who discontinued tocilizumab due to an adverse event experienced subsequent progression of multiple organ manifestations, including skin, lung, lower gastrointestinal and renal involvement, leading to mortality.

Conclusion

Our findings suggest potential benefits of prolonged tocilizumab use in dcSSc patients. The discontinuation of tocilizumab can lead to the progression of skin and visceral manifestations. Tapering rather than the discontinuation of tocilizumab is a viable option in dcSSc patients who experience remarkable clinical improvement.
The role of comorbidities alongside patient and disease characteristics in long-term disease activity in RA using UK inception cohort data
Authors: Busby Amanda D , Wason James , Pratt Arthur G , Young Adam , Isaacs John D , Nikiphorou Elena
Published: March 2022

Objectives

Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and clinical/sociodemographic factors at first presentation.

Methods

Patients from two UK-based RA cohorts were classified into two groups; low (<3.2) and moderate/high (≥3.2) DAS using 28 joint counts (DAS28) at 5/10 years. Clinical variables (e.g. rheumatoid nodules, erosions), sociodemographic factors (e.g. ethnicity, deprivation) and comorbidities were recorded at baseline and yearly thereafter. The Rheumatic Diseases Comorbidity Index quantified patient comorbidity burden. Binary logistic regression models (outcome low vs moderate/high DAS28) were fitted using multiple imputation.

Results

A total of 2701 patients living with RA were recruited (mean age 56.1 years, 66.9% female); 5-year data were available for 1718 (63.4%) patients and 10-year data for 820 (30.4%). Baseline Rheumatic Diseases Comorbidity Index was not associated with DAS28 at 5 [odds ratio (OR) 1.05, 95% CI 0.91, 1.22] or 10 years (OR 0.99, 95% CI 0.75, 1.31) in multivariable analyses. Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ-Disability Index were associated with DAS28 ≥3.2 at both timepoints. Being seropositive was associated with 5-year DAS28 ≥3.2.

Conclusion

This study demonstrates an association between sociodemographic and clinical factors and long-term RA disease activity, in models adjusting for comorbidity burden. The findings call for more holistic and targeted patient management in patients with RA and provide insights for more individualized management plans even on first presentation to rheumatology.
Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)
Authors: Lynggaard Charlotte Duch , Grønhøj Christian , Christensen Robin , Fischer-Nielsen Anne , Melchiors Jacob , Specht Lena , Andersen Elo , Mortensen Jann , Oturai Peter , Barfod Gry Hoffmann , Haastrup Eva Kannik , Møller-Hansen Michael , Haack-Sørensen Mandana , Ekblond Annette , Kastrup Jens , Jensen Siri Beier , von Buchwald Christian
Published: March 2022

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)—xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P = .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P = .017) mL/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 (P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.
Explaining Racial-ethnic Disparities in the Receipt of Medication for Opioid Use Disorder during Pregnancy
Authors: Gao Yitong Alice , Drake Coleman , Krans Elizabeth E. , Chen Qingwen , Jarlenski Marian P.
Published: March 2022

Objective

Factors contributing to racial and ethnic disparities in medication for opioid use disorder (MOUD) receipt during pregnancy are largely unknown. We quantified the contribution of individual, healthcare access and quality, and community factors to racial-ethnic disparities in MOUD during pregnancy and postpartum among Medicaid-enrolled pregnant women with opioid use disorder (OUD).

Methods

This retrospective cohort study used regression and nonlinear decomposition to examine how individual, healthcare access and quality, and community factors explain racial-ethnic disparities in MOUD receipt among Medicaid-enrolled women with OUD who had a live birth from 2011 to 2017. The exposure was self-reported race and ethnicity. The outcomes were any MOUD receipt during pregnancy or postpartum. All factors included were identified from the literature.

Results

Racial-ethnic disparities in individual, healthcare access and quality, and community factors explained 15.8% of the racial-ethnic disparity in MOUD receipt during pregnancy and 68.9% of the disparity in the postpartum period. Despite comparable healthcare utilization, non-White/Hispanic women were diagnosed with OUD 37 days later in pregnancy, on average, than non-Hispanic White women, which was the largest contributor to the racial-ethnic disparity in MOUD receipt during pregnancy (111.0%). The racial-ethnic disparity in MOUD receipt during pregnancy was the largest contributor (112.2%) to the racial-ethnic disparity in MOUD in the postpartum period.

Conclusions

Later diagnosis of OUD in pregnancy among non-White/Hispanic women partially explains the disparities in MOUD receipt in this population. Universal substance use screening earlier in pregnancy, combined with connecting patients to evidence-based and culturally competent care, is one approach that could close the observed racial-ethnic disparity in MOUD receipt.