bluuebunny/crossref_metadata_2025 huggingface dataset:
RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma
Authors: Lambing Silke , Holdenrieder Stefan , Müller Patrick , Tan Yu Pan , Hagen Christian , Garbe Stephan , Schlee Martin , van den Boorn Jasper G. , Bartok Eva , Hartmann Gunther , Renn Marcel
Published: October 2021

Radiation therapy induces cytotoxic DNA damage, which results in cell-cycle arrest and activation of cell-intrinsic death pathways, but its application has been limited by the radioresistance of tumors, such as in malignant melanoma. RIG-I is a cytosolic immune receptor expressed in all somatic cells, including tumor cells, with a key role in sensing viral RNA. RIG-I specific oligonucleotide ligands elicit a robust cell-intrinsic antiviral response and immunogenic cell death in tumor cells and are being tested in clinical trials. Nonetheless, their potential to overcome radioresistance has not yet been explored. Here, we demonstrate that activation of RIG-I enhances the extent and immunogenicity of irradiation-induced tumor cell death in human and murine melanoma cell lines in vitro and improved survival in the murine B16 melanoma model. Pathway analysis of transcriptomic data revealed a central role for p53 downstream of the combination treatment, which was corroborated using p53-/- B16 cells. In vivo, the effect of irradiation on immune-cell activation and inhibition of tumor growth was absent in mice carrying p53-/- B16 tumors, while the response to RIG-I stimulation in those mice was maintained. Our results identify p53 as pivotal for the synergistic antitumoral effect of RIG-I and irradiation, resulting in potent induction of immunogenic tumor-cell death. Thus, the administration of RIG-I ligands in combination with radiotherapy is a promising therapeutic approach to treating radioresistant tumors with a functional p53 pathway, such as malignant melanoma.
scTriangulate, a game-theory based framework for optimal solutions of uni- and multimodal single-cell data
Authors: Li Guangyuan , Song Baobao , Singh Harinder , Prasath V. B. Surya , Grimes H. Leighton , Salomonis Nathan
Published: October 2021

Decisively delineating cell identities from uni- and multimodal single-cell datasets is complicated by diverse modalities, clustering methods, and reference atlases. We describe scTriangulate, a cooperative game-theory framework that mixes-and-matches multiple clustering results, modalities, associated algorithms, and resolutions to achieve an optimal solution. Rather than ensemble approaches which select the “consensus”, scTriangulate picks the most stable solution. When evaluated on diverse multimodal technologies, scTriangulate outperforms alternative approaches to identify consistent high-confidence novel cell populations and modality-specific subtypes. Unlike existing integration strategies that rely on modality-specific joint embedding or geometric graphs, scTriangulate makes no assumption about the distributions of raw underlying values. As a result, this approach can solve unprecedented integration challenges, including the ability to automate reference cell-atlas construction, resolve clonal architecture within molecularly defined cell-populations and subdivide clusters to discover novel splicing-defined disease subtypes. scTriangulate is a flexible strategy for unified integration of single-cell or multimodal clustering solutions, from nearly unlimited sources.
Pharmacological mechanisms on the anti-breast cancer property of Coix lacryma-jobi: A network-based analysis
Authors: Ferrer Angelu Mae , David Janella Rayne , Taquiqui Arvin , Bautista Arci , Deocaris Custer C. , Alinsug Malona V.
Published: October 2021

Breast cancer is considered as one of the three most common cancers around the world and the second leading cause of cancer deaths among women. Coix lachrymal jobi, commonly known as Job’s tears or adlay has been reported to possess anti-cancer properties. Despite evidences provided by clinical data, the usage of Coix lacryma-jobi in treating cancer, particularly breast cancer, has been scarce. Thus, this study was conducted to determine the pharmacological mechanisms underlying its anti-breast cancer property using various network pathway analyses. Bioactive compounds from Coix lacryma-jobi and its potential target genes were obtained from SymMap. Breast cancer-related target genes were collected from CTD. Protein-protein interaction network was analyzed using the STRING database. GO and KEGG pathway enrichment analyses were performed using DAVID to further explore the mechanisms of Coix lacryma-jobi in treating breast cancer. PPI and compound-target-pathway were visualized using Cytoscape. A total of 26 bioactive compounds, 201 corresponding targets, 36625 breast cancer-associated targets were obtained, and 200 common targets were considered potential therapeutic targets. The 9 bioactive compounds identified were berberine, oleic acid, beta-sitosterol, sitosterol, linoleic acid, berberrubine, jatrorrhizine, thalifendine, and stigmasterol. The identified 5 core targets were ESR1, JUN, MAPK14, and RXRA. Coix lacryma-jobi targets enriched in GO terms were mostly involved in regulation of transcription from RNA polymerase II promoter, drug response, steroid hormone receptor activity, and protein binding. This study elucidates on the pharmacological underpinnings on the potency of adlay against breast cancer. Its subsequent drug development will be worth a step forward for a breast cancer-free society.
Formation of multinucleated globoid cells in Krabbe iPSC-derived microglia cultures: a preliminary investigation
Authors: Lieberman Richard , Gao Grace , Hunter Robert B. , Leonard John P. , Cortes Leslie K. , Barker Robert H.
Published: October 2021

Globoid cell leukodystrophy (Krabbe disease) is a severe demyelinating, neurodegenerative lysosomal storage disorder caused by deficiency in glycosphingolipid catabolic enzyme galactosylceramidase (GALC). Histologically, Krabbe disease is characterized by the appearance of large multinucleated globoid cells that express classical macrophage markers (both of brain-resident microglia and peripheral monocyte-derived). Globoid cells reside near areas of degeneration; however, their functional significance in disease progression remains unclear. In the current study, we differentiated microglia-like cells from iPSCs from a donor with infantile Krabbe disease and compared them to microglia generated from two healthy controls and two donors with the lysosomal storage disorder metachromatic leukodystrophy (MLD), which is genetically distinct from Krabbe disease but presents similarly in terms of severity of demyelination and neurodegeneration. We report the novel finding of prominent formation of giant multinucleated globoid cells from the microglia derived from the Krabbe donor, but not from healthy control or MLD donors. The Krabbe microglia displayed reduced IL-6 protein expression upon stimulation with lipopolysaccharide, and the multinucleated globoid cells themselves appeared deficient in phagocytosis of both disease-relevant myelin debris and E. coli, together hinting at an impairment of normal function. The formation of the globoid cells could be attenuated by fully replacing the medium following passaging, suggesting that yet-to-be determined secreted factors are influencing cell fusion in our culture system. While preliminary, our results imply that globoid cells may be detrimental in Krabbe disease by hindering the normal function of brain-residing macrophages.
Cutaneous manifestations and dermoscopic findings are important clues to the diagnosis of Talaromyces marneffei in HIV patients with immune reconstitution inflammatory syndrome: A case report and literature review
Authors: Chaisuwannarak Kornkanok , Chularojanamontri Leena , Junsuwan Natachaya , Eimpunth Sasima
Published: October 2021

Talaromyces (formerly Penicillium) marneffei is a dimorphic fungus that causes talaromycosis (formerly penicilliosis). The condition is predominantly found in patients with HIV. Important diagnostic clues are a history of living or travelling in endemic areas, and central umbilicated skin lesions. Dermoscopy is particularly useful for providing rapid bedside information, with a round, whitish, amorphous structure being the most common finding. Immune reconstitution inflammatory syndrome (IRIS) may occur. Driven by the initiation of antiretroviral therapy, IRIS is an exaggerated response of T cells to pathogens. Although mycobacterial and cryptococcal opportunistic infections are common with IRIS, a linkage between T. marneffei and IRIS has rarely been reported. Here, we report on a literature review of patients with HIV who developed IRIS associated with talaromycosis. Dermatologists should be aware of the cutaneous and dermoscopic findings of talaromycosis as they provide important clues that enable its early diagnosis and treatment.
Additive effects of developmental acclimation and physiological syndromes on lifetime metabolic and water loss rates of a dry‐skinned ectotherm
Authors: Dezetter Mathias , Dupoué Andréaz , Le Galliard Jean‐François , Lourdais Olivier
Published: October 2021

Developmental plasticity and thermal acclimation can contribute to adaptive responses to climate change by altering functional traits related to energy and water balance regulation. How plasticity interacts with physiological syndromes through lifetime in long‐lived species is currently unknown.

Here, we examined the impacts of long‐term thermal acclimation in a long‐lived temperate ectotherm Vipera aspis and its potential flexibility at adulthood for two related functional traits: standard metabolic rate (SMR) and total evaporative water loss (TEWL).

We used climatic chambers to simulate three contrasted daily thermal cycles (warm, medium and cold) differing in mean temperatures (28, 24 and 20℃ respectively) and amplitudes (5, 10 and 13℃ respectively) during immature life (0 to 4 years of age). Individuals were then maintained under common garden conditions (medium cycle) for an additional 3‐year period (4–7 years of age). SMR and TEWL were repeatedly measured in the same individuals throughout life during and after the climate manipulation.

Individuals reduced their SMR (negative compensation) when experiencing the warm cycle but flexibly adjusted their SMR to common garden conditions at adulthood. In addition, thermal conditions during the juvenile life stage led to changes in TEWL persisting until adulthood.

We further found consistent intra‐individual variation for SMR and TEWL and a positive intra‐individual and inter‐individual covariation between them throughout life. Thus, plastic responses were combined with a physiological syndrome linking SMR and TEWL.

Our study demonstrates the capacity of long‐lived organisms to flexibly shift their SMR to reduce daily maintenance costs in warmer and less variable thermal environments, which might be beneficial to low‐energy specialist organisms such as vipers. It further suggests that thermal conditions provide cues for developmental changes in TEWL. Beside plasticity, contrasted individual physiological syndromes could be selected for and contribute to the response to climate change.

A free Plain Language Summary can be found within the Supporting Information of this article.
Environmental effects on the genetic architecture of fitness components in a simultaneous hermaphrodite
Authors: Janicke Tim , Chapuis Elodie , Meconcelli Stefania , Bonel Nicolas , Delahaie Boris , David Patrice
Published: October 2021

Understanding how environmental change affects genetic variances and covariances of reproductive traits is key to formulate firm predictions on evolutionary responses. This is particularly true for sex‐specific variance in reproductive success, which has been argued to affect how populations can adapt to environmental change.

Our current knowledge on the impact of environmental stress on sex‐specific genetic architecture of fitness components is still limited and restricted to separate‐sexed organisms. However, hermaphroditism is widespread across animals and may entail interesting peculiarities with respect to genetic constraints imposed on the evolution of male and female reproduction.

We explored how food restriction affects the genetic variance–covariance (G) matrix of body size and reproductive success of the simultaneously hermaphroditic freshwater snail Physa acuta.

Our results provide strong evidence that the imposed environmental stress elevated the opportunity for selection in both sex functions. However, the G–matrix remained largely stable across the tested food treatments. Importantly, our results provide no support for cross‐sex genetic correlations suggesting no strong evolutionary coupling of male and female reproductive traits.

We discuss potential implications for the adaptation to changing environments and highlight the need for more quantitative genetic studies on male and female fitness components in simultaneous hermaphrodites.
Minimally invasive surgery for suspected early‐stage ovarian cancer; a cost‐effectiveness study
Authors: Dioun S , Chen L , Melamed A , Gockley A , St. Clair CM , Hou JY , Tergas AI , Khoury‐Collado F , Elkin E , Accordino M , Hershman DL , Wright JD
Published: October 2021

Objective

While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses.

Design

Cost‐effectiveness study

Population

Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management.

Methods

The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings.

Main outcome measures

The primary outcome was the cost‐effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost‐effectiveness ratios (ICERs).

Results

MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer‐related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses.

Conclusion

MIS constitutes a cost‐effective management strategy for women with suspicious ovarian masses.

Tweetable abstract

MIS is a cost‐effective management strategy for women with suspicious ovarian masses.
Using machine learning to advance disparities research: Subgroup analyses of access to opioid treatment
Authors: Kong Yinfei , Zhou Jia , Zheng Zemin , Amaro Hortensia , Guerrero Erick G.
Published: October 2021

Objective

To operationalize an intersectionality framework using a novel statistical approach and with these efforts, improve the estimation of disparities in access (i.e., wait time to treatment entry) to opioid use disorder (OUD) treatment beyond race.

Data source

Sample of 941,286 treatment episodes collected in 2015–2017 in the United States from the Treatment Episodes Data Survey (TEDS‐A) and a subset from California (n = 188,637) and Maryland (n = 184,276), states with the largest sample of episodes.

Study design

This retrospective subgroup analysis used a two‐step approach called virtual twins. In Step 1, we trained a classification model that gives the probability of waiting (1 day or more). In Step 2, we identified subgroups with a higher probability of differences due to race. We tested three classification models for Step 1 and identified the model with the best estimation.

Data collection

Client data were collected by states during personal interviews at admission and discharge.

Principal findings

Random forest was the most accurate model for the first step of subgroup analysis. We found large variation across states in racial disparities. Stratified analysis of two states with the largest samples showed critical factors that augmented disparities beyond race. In California, factors such as service setting, referral source, and homelessness defined the subgroup most vulnerable to racial disparities. In Maryland, service setting, prior episodes, receipt of medication‐assisted opioid treatment, and primary drug use frequency augmented disparities beyond race. The identified subgroups had significantly larger racial disparities.

Conclusions

The methodology used in this study enabled a nuanced understanding of the complexities in disparities research. We found state and service factors that intersected with race and augmented disparities in wait time. Findings can help decision makers target modifiable factors that make subgroups vulnerable to waiting longer to enter treatment.
Examining emergency department inequities in Aotearoa New Zealand: Findings from a national retrospective observational study examining Indigenous emergency care outcomes
Authors: Curtis Elana , Paine Sarah‐Jane , Jiang Yannan , Jones Peter , Tomash Inia , Healey Olivia , Reid Papaarangi
Published: October 2021

Objective

There is increasing evidence that EDs may not operate equitably for all patients, with Indigenous and minoritised ethnicity patients experiencing longer wait times for assessment, differential pain management and less evaluation and treatment of acute conditions.

Methods

This retrospective observational study used a Kaupapa Māori framework to investigate ED admissions into 18/20 District Health Boards in Aotearoa New Zealand (2006–2012). Key pre‐admission variable was ethnicity (Māori:non‐Māori), and outcome variables included: ED self‐discharge; ED arrival to assessment time; hospital re‐admission within 72 h; ED re‐presentation within 72 h; ED length of stay; ward length of stay; access block and mortality (in ED or within 10 days of ED departure). Generalised linear regression models controlled for year of presentation, sex, age, deprivation, triage category and comorbidity.

Results

Despite some ED process measures favouring Māori, for example arrival to assessment time (mean difference −2.14 min; 95% confidence interval [CI] −2.42 to −1.86) and access block (odds ratio [OR] 0.89, 95% CI 0.87–0.91), others showed no difference, for example self‐discharge (OR 0.98, 95% CI 0.97–1.00). Despite this, Māori mortality (OR 1.60, 95% CI 1.50–1.71) and ED re‐presentation (OR 1.11, 95% CI 1.09–1.12) were higher than non‐Māori.

Conclusion

To our knowledge, this is the most comprehensive investigation of acute outcomes by ethnicity to date in New Zealand. We found ED mortality inequities that are unlikely to be explained by ED process measures or comorbidities. Our findings reinforce the need to investigate health professional bias and institutional racism within an acute care context.
The chromosome‐scale genome assembly, annotation and evolution of Rhododendron henanense subsp. lingbaoense
Authors: Zhou Xiao‐Jun , Li Jian‐Tao , Wang Hai‐Liang , Han Jun‐Wang , Zhang Kai , Dong Shuai‐Wei , Zhang Yan‐Zhao , Ya Hui‐Yuan , Cheng Yan‐Wei , Sun Shan‐Shan
Published: October 2021

Rhododendron henanense subsp. lingbaoense (hereafter referred to as R. henanense) is an endemic species naturally distributed in the Henan province, China, with high horticultural, ornamental and medicinal value. Herein, we report a de novo genome assembly for R. henanense using a combination of PacBio long read and Illumina short read sequencing technologies. In total, we assembled 634.07 Mb with a contig N50 of 2.5 Mb, representing ~96.93% of the estimated genome size. By applying Hi‐C data, 13 pseudochromosomes of R. henanense genome were assembled, covering ~98.21% of the genome assembly. The genome was composed of ~65.76% repetitive sequences and 31,098 protein‐coding genes, 88.77% of which could be functionally annotated. Rhododendron henanense displayed a high level of synteny with other Rhododendron species from the Hymenanthes subgenus. Our data also suggests that R. henanense genes related to stress responses have undergone expansion, which may underly the unique abiotic and biotic stress resistance of the species. This alpine Rhododendron chromosome‐scale genome assembly provides fundamental molecular resources for germplasm conservation, breeding efforts, evolutionary studies, and elucidating the unique biological characteristics of R. henanense.
Morphometric study of the testis in sheep embryos using unbiased design‐based stereology
Authors: Sadeghinezhad Javad , Ganji Zahra , Sadeghian Chaleshtori Sirous , Bojarzadeh Hadis , Aghabalazadeh Asl Mahdi , Khomejini Ali Bayat , Roominai Ehsan , Hosseini Mohsen , De Silva Margherita
Published: October 2021

Sheep have been used as translational models of human postnatal testicular development. However, the morphometric features of the normal developing testis in sheep embryos have not been previously investigated using stereology. The objective of the present work was to establish normal quantitative parameters for fetal testicular tissue components in sheep, using unbiased design‐based stereological methods. Twenty‐four sheep embryos were divided into four gestational age groups (9–11, 12–14, 15–17 and 18–20 weeks of gestation) on the basis of the embryos’ crown‐rump length. Isotropic, systematic uniform random sections of the left testes were obtained by employing the orientator method. Testicular total volume, the absolute and proportional volumes occupied by the seminiferous tubules and interstitial tissue, as well as the seminiferous tubule length, were estimated using the point‐counting system and the unbiased counting frame principle. All the parameters, with the exception of the interstitial tissue's fractional volume, gradually increased along with gestational age, with the maximum increase especially seen in the late fetal stages. The proportional volume of the interstitial tissue, on the other hand, showed a decreasing trend along with increasing gestational age. The absolute volume of the testes, of the seminiferous tubules and of the interstitial tissue, and the length of the seminiferous tubules showed a significant (p< 0.05) positive linear correlation with gestational age. Several similarities were observed with human testicular embryogenesis. The stereological data emerging from the present study might prove useful as basic contribution to the fields of andrology and embryology and stimulate further research in these areas.
TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs' endothelial corneal dystrophy
Authors: Viberg Andreas , Westin Ida Maria , Golovleva Irina , Byström Berit
Published: October 2021

Purpose

Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine‐thymine‐guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype.

Methods

Blood samples were collected from 85 FECD cases at different stages. Short tandem repeat PCR and triplet repeat‐primed PCR were applied in order to determine TCF4 (CTG)n genotype.

Results

A (CTG)n repeat expansion (n > 50) in TCF4 was identified in 76 of 85 FECD cases (89.4%) and in four of 102 controls (3.9%). The median (CTG)n repeat length was 81 (IQR 39.3) in mild FECD and 87 (IQR 13.0) in severe FECD (p = 0.01). A higher number of (CTG)n repeats in an expanded TCF4 allele increased the probability of severe FECD. Other ocular surgery was overrepresented in FECD cases without a (CTG)n repeat expansion (44.4%, n = 4) compared with 3.9% (n = 3) in FECD cases with an (CTG)n repeat expansion (p < 0.001).

Conclusion

In northern Sweden, the FECD phenotype is associated with (CTG)n expansion in the TCF4 gene, with nearly 90% of patients being hetero‐ or homozygous for (CTG)n expansion over 50 repeats. Furthermore, the severity of FECD was associated with the repeat length in the TCF4 gene. Ocular surgery might act as an environmental factor explaining the clinical disease in FECD without a repeat expansion in TCF4.
Transperineal abdominoperineal resection in the prone jackknife position in male patients with low rectal cancer
Authors: Uematsu Dai , Sugihara Takehiko
Published: October 2021

Introduction

In male patients with low rectal cancer undergoing abdominoperineal resection (APR), successful dissection of the anterior anorectum is key to reducing the risk of circumferential resection margin involvement, intraoperative bowel perforation, and local recurrence, but it is challenging. To overcome difficulties dissecting the anterior anorectum, we present a safe and feasible procedure using a transperineal endoscopic approach during APR (TpAPR).

Materials and Surgical Technique

The male patient is placed in the prone jackknife position. TpAPR precedes the procedure from an abdominal approach. We use some pelvic tissues as clear anatomical landmarks to dissect the anterior anorectum. The key steps of this procedure are shown in the video.

Discussion

The identification of a clear anatomical dissection plane of the anterior anorectum is difficult because of the complex surgical anatomy of the region. Clear anatomical landmarks for dissection of the anterior anorectum are necessary for safe implementation of this procedure. Therefore, TpAPR in the prone jackknife position can be performed to obtain better visualization of each anatomical landmark at a glance.
Evaluation of inbreeding and genetic diversity in Japanese Shorthorn cattle by pedigree analysis
Authors: Uemoto Yoshinobu , Suzuki Keiichi , Yasuda Jumpei , Roh Sanggun , Satoh Masahiro
Published: October 2021

The Japanese Shorthorn is a Japanese Wagyu breed maintained at a small population size. We assessed the degree of inbreeding and genetic diversity among Japanese Shorthorn cattle using pedigree analysis. We analyzed the pedigree records of registered Japanese Shorthorn born between 1980 and 2018, after evaluating the pedigree completeness. The average of the actual inbreeding coefficients increased at the same rates annually from approximately 1.5% in 1980 to 4.2% in 2018 and was higher than the expected inbreeding coefficients over time. The effective population size based on the individual coancestry rate largely decreased from 127.8 in 1980 to 82.6 in 1999, and then remained almost constant at approximately 90. Three effective numbers of ancestors decreased over time until 1995, then remained almost constant. In particular, the effective number of founder genomes (Nge) decreased from 43.8 in 1980 to 11.9 in 2018. The index of genetic diversity based on Nge decreased from 0.99 in 1980 to 0.96 in 2018 due to genetic drift in non‐founder generations. Changes in inbreeding and genetic diversity parameters were similar between Japanese Shorthorn and other Japanese Wagyu breeds, but the magnitude of the changes was lower in the Japanese Shorthorn.
Azacitidine for patients with Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry
Authors: Comont Thibault , Heiblig Mael , Rivière Etienne , Terriou Louis , Rossignol Julien , Bouscary Didier , Rieu Virginie , Le Guenno Guillaume , Mathian Alexis , Aouba Achille , Vinit Julien , Dion Jeremie , Kosmider Olivier , Terrier Benjamin , Georgin‐Lavialle Sophie , Fenaux Pierre , Mekinian Arsène ,   the French VEXAS study group, Groupe Francophone des Myélodysplasies (GFM) and MedecineINterne, HEmato et ONco (MINHEMON) group
Published: October 2021

Azacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin‐like modifier‐activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the efficacy and safety of azacitidine treatment in 11 patients with VEXAS with MDS. Clinical response of VEXAS to azacitidine was achieved in five patients (46%), during 6, 8+, 12, 21, 27+ months respectively, suggesting that azacitidine can be effective in selected patients with VEXAS and associated MDS.
Finding mover–stayer quantile difference due to unobservables using quantile selection corrections
Authors: Lee Myoung‐jae , Choi Jin‐young
Published: October 2021

For movers () from a state and stayers (), it is of interest to know how they differ in their distributions of a response variable given some observed regressors (e.g., wage given education ), which is equivalent to their quantile differences in due to unobservables (e.g., ability) given . In many mover/stayer cases, however, is observed only for the movers, enabling the identification of only quantiles of the movers; for example, moving is migration and is the wage in the host country. For this, we propose a practical parametric way to find quantile differences between movers and stayers despite unobserved for the stayers. Our approach has the advantage comparing the movers to the stayers, whereas the existing semiparametric alternatives compare the movers only to the population to dilute the mover–stayer differences. Also, our approach easily allows heteroskedasticity and heterocorrelation in the and equations. An empirical example demonstrates these points.
Does more market competition lead to higher income and utility in the long run?
Authors: Stauvermann Peter J. , Kumar Ronald R.
Published: October 2021

In this paper, we investigate if more competition leads to higher per capita incomes and/or to a higher level of utility in the long run. To this end, we use a Diamond overlapping‐generations model but relaxing the assumption of perfect competition in the good market. We show that the weaker the competition the more unequal the distribution of income. Surprisingly, we note that in general, tougher competition does not lead either to an increase in per capita incomes or to an increase in nonfirm owners’ utility in the long run.
Modeling the building blocks of country‐level absorptive capacity: Comparing developed and emergent economies
Authors: Silveira Naijela Janaina Costa , Ferraz Diogo , Polloni‐Silva Eduardo , Mello Diego Scarpa de , Falguera Fernanda Pereira Sartori , Moralles Herick Fernando
Published: October 2021

Several studies analyzed the importance of absorptive capacity (AC) to achieve economic development. However, to the best of our knowledge, no study compares the building blocks (BBs) of AC between developed and emergent economies. This paper aims to identify and analyze the impact of the BBs on AC under distinct levels of development (i.e., developed vs. emerging economies) using systematic literature review (SLR) and econometrics. Specifically, both linear and nonlinear analyses were employed. Our findings show that BBs in developed and emergent regions are different. For both groups, R&D, FDI (foreign direct investment), infrastructure, and HDI (human development index) variables are BBs of AC. For developed economies, BBs also contemplate secondary education enrollments, the higher education index, and the percentage of GDP spent on higher education. Moreover, the thresholds of BBs also differ between developed and emergent economies. This identification of BBs and possible AC thresholds is valuable, as it provides information to set goals and strategies before a foreign investment attraction policy. Thus, the results facilitate the development of more suitable strategies to enhance positive productivity spillovers and avoid negative spillovers whenever possible. These results show that policymakers cannot employ the same policies for the development of developed and emerging countries.
Sophistication in a seemingly simple creature: a review of wild holothurian nutrition in marine ecosystems
Authors: Pierrat Joséphine , Bédier Alexandre , Eeckhaut Igor , Magalon Hélène , Frouin Patrick
Published: October 2021

Holothurians are marine invertebrates that are among the most widespread benthic megafauna communities by both biomass and abundance in shallow‐water and deep‐sea ecosystems, their functions supporting important ecological services worldwide. Despite their simple appearance as sea cucumbers, holothurians show a wide range of feeding practices. However, information on what and how these animals eat is scattered and potentially confusing. We provide a comprehensive review of holothurian nutrition in coastal and deep‐sea ecosystems. First, we describe morphological aspects of holothurian feeding and the ultrastructure of tentacles. We discuss the two processes for food capture, concluding that mucus adhesion is likely the main method; two mucous cells, type‐1 and type‐2, possibly allow the adhesion and de‐adhesion, respectively, of food particles. Secondly, this review aims to clarify behavioural aspects of holothurian suspension‐ and deposit‐feeding. We discuss the daily feeding cycle, and selective feeding strategies. We conclude that there is selectivity for fine and organically rich particles, and that feeding through the cloaca is also a route for nutrient absorption. Third, we provide a wide description of the diet of holothurians, which can be split into two categories: living and non‐living material. We suggest that Synallactida, Molpadida, Persiculida, Holothuriida and Elasipodida, ingest the same fractions, and emphasise the importance of bacteria in the diet of holothurians.
Allergic contact dermatitis from dyes used in the temple of spectacles
Authors: Ahrensbøll‐Friis Ulrik , Simonsen Anne Birgitte , Dahlin Jakob , Isaksson Marléne , Zachariae Claus , Johansen Jeanne Duus
Published: October 2021

Background

We observed an increasing number of patients who presented with facial or retro‐auricular dermatitis after skin contact with plastic spectacles or plastic covered temples.

Objectives

To identify the allergens in plastic spectacles that may cause allergic contact dermatitis.

Methods

All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen.

Results

Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14.

Conclusion

Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179.
A Neural Dynamic Model of the Perceptual Grounding of Spatial and Movement Relations
Authors: Richter Mathis , Lins Jonas , Schöner Gregor
Published: October 2021

How does the human brain link relational concepts to perceptual experience? For example, a speaker may say “the cup to the left of the computer” to direct the listener's attention to one of two cups on a desk. We provide a neural dynamic account for both perceptual grounding, in which relational concepts enable the attentional selection of objects in the visual array, and for the generation of descriptions of the visual array using relational concepts. In the model, activation in neural populations evolves dynamically under the influence of both inputs and strong interaction as formalized in dynamic field theory. Relational concepts are modeled as patterns of connectivity to perceptual representations. These generalize across the visual array through active coordinate transforms that center the representation of target objects in potential reference objects. How the model perceptually grounds or generates relational descriptions is probed in 104 simulations that systematically vary the spatial and movement relations employed, the number of feature dimensions used, and the number of matching and nonmatching objects. We explain how sequences of decisions emerge from the time‐ and state‐continuous neural dynamics, how relational hypotheses are generated and either accepted or rejected, followed by the selection of new objects or the generation of new relational hypotheses. Its neural realism distinguishes the model from information processing accounts, its capacity to autonomously generate sequences of processing steps distinguishes it from deep neural network accounts. The model points toward a neural dynamic theory of higher cognition.
Dynamics Versus Development in Numerosity Estimation: A Computational Model Accurately Predicts a Developmental Reversal
Authors: Kim Dan , Opfer John E.
Published: October 2021

Perceptual judgments result from a dynamic process, but little is known about the dynamics of number‐line estimation. A recent study proposed a computational model that combined a model of trial‐to‐trial changes with a model for the internal scaling of discrete numbers. Here, we tested a surprising prediction of the model—a situation in which children's estimates of numerosity would be better than those of adults. Consistent with the model simulations, task contexts led to a clear developmental reversal: children made more adult‐like, linear estimates when to‐be‐estimated numbers were descending over trials (i.e., backward condition), whereas adults became more like children with logarithmic estimates when numbers were ascending (i.e., forward condition). In addition, adults’ estimates were subject to inter‐trial differences regardless of stimulus order. In contrast, children were not able to use the trial‐to‐trial dynamics unless stimuli varied systematically, indicating the limited cognitive capacity for dynamic updates. Together, the model adequately predicts both developmental and trial‐to‐trial changes in number‐line tasks.
Children's Ideas About What Can Really Happen: The Impact of Age and Religious Background
Authors: Payir Ayse , Mcloughlin Niamh , Cui Yixin Kelly , Davoodi Telli , Clegg Jennifer M. , Harris Paul L. , Corriveau Kathleen H.
Published: October 2021

Five‐ to 11‐year‐old U.S. children, from either a religious or secular background, judged whether story events could really happen. There were four different types of stories: magical stories violating ordinary causal regularities; religious stories also violating ordinary causal regularities but via a divine agent; unusual stories not violating ordinary causal regularities but with an improbable event; and realistic stories not violating ordinary causal regularities and with no improbable event. Overall, children were less likely to judge that religious and magical stories could really happen than unusual and realistic stories although religious children were more likely than secular children to judge that religious stories could really happen. Irrespective of background, children frequently invoked causal regularities in justifying their judgments. Thus, in justifying their conclusion that a story could really happen, children often invoked a causal regularity, whereas in justifying their conclusion that a story could not really happen, they often pointed to the violation of causal regularity. Overall, the findings show that children appraise the likelihood of story events actually happening in light of their beliefs about causal regularities. A religious upbringing does not impact the frequency with which children invoke causal regularities in judging what can happen, even if it does impact the type of causal factors that children endorse.
Linguistic Distributional Knowledge and Sensorimotor Grounding both Contribute to Semantic Category Production
Authors: Banks Briony , Wingfield Cai , Connell Louise
Published: October 2021

The human conceptual system comprises simulated information of sensorimotor experience and linguistic distributional information of how words are used in language. Moreover, the linguistic shortcut hypothesis predicts that people will use computationally cheaper linguistic distributional information where it is sufficient to inform a task response. In a pre‐registered category production study, we asked participants to verbally name members of concrete and abstract categories and tested whether performance could be predicted by a novel measure of sensorimotor similarity (based on an 11‐dimensional representation of sensorimotor strength) and linguistic proximity (based on word co‐occurrence derived from a large corpus). As predicted, both measures predicted the order and frequency of category production but, critically, linguistic proximity had an effect above and beyond sensorimotor similarity. A follow‐up study using typicality ratings as an additional predictor found that typicality was often the strongest predictor of category production variables, but it did not subsume sensorimotor and linguistic effects. Finally, we created a novel, fully grounded computational model of conceptual activation during category production, which best approximated typical human performance when conceptual activation was allowed to spread indirectly between concepts, and when candidate category members came from both sensorimotor and linguistic distributional representations. Critically, model performance was indistinguishable from typical human performance. Results support the linguistic shortcut hypothesis in semantic processing and provide strong evidence that both linguistic and grounded representations are inherent to the functioning of the conceptual system. All materials, data, and code are available at https://osf.io/vaq56/.
The value of increased spatial resolution of pesticide usage data for assessing risk to endangered species
Authors: Murphy Erin L. , Eikenberry Steffen , Iacona Gwenllian , Watson Greg , Gerber Leah R.
Published: October 2021

Decision makers often cite data quality as a limitation in environmental management. Value of information approaches evaluate the benefit of new data collection for management outcomes. Pesticide exposure risk assessment for endangered species is one context where data limitations may affect decisions and a value of information type approach could be useful for identifying optimal data quality and resolution. Under the U.S. Federal Insecticide, Fungicide and Rodenticide Act, the U.S. Environmental Protection Agency (EPA) is responsible for registering pesticides before they can be sold and regularly reviewing pesticides. Section 7 of the Endangered Species Act requires that the EPA consider potential impacts of pesticides to listed endangered species and critical habitats in this process, and for the Services—U.S. Fish and Wildlife Service and National Marine Fisheries Service—to complete a formal Section 7 consultation if the EPA deems it necessary. The current process is time‐intensive, lacks transparency and confidence among stakeholders, and leaves hundreds of unreviewed pesticides on the market. Increasing the resolution of pesticide usage data could address these concerns by improving estimated overlaps between species ranges and pesticide usage. Thus, we evaluated the relative importance of different resolutions of pesticide usage data for assessing expected carbaryl exposure to endangered plant species endemic to California. We found that spatially explicit, township resolution usage data (~36 mile2) excluded 33% of terrestrial plants (55/168) and 51% their critical habitats (27/53) from requiring a Section 7 consultation, while coarser resolution data excluded none. In contrast, the EPA's biological evaluation for carbaryl only excludes 4% of terrestrial plants (nationally) from requiring formal Section 7 consultation. This suggests high‐resolution data could increase pesticide review efficiency and decrease the amount of time pesticides remain on the market without a formal evaluation.
Reproductive plasticity as an advantage of snakes during island invasion
Authors: Fisher Samuel , Fisher Robert N. , Alcaraz Sophie E. , Gallo‐Barneto Ramón , Patino‐Martinez Clara , López‐Jurado Luis Felipe , Cabrera‐Pérez Miguel Ángel , Grismer Jesse L.
Published: October 2021

Most invasive species are not studied during their initial colonization of ecosystems to which they were recently introduced. Rather, research is typically performed after invasive species are well established and causing harm to the native biodiversity. Thus, novel adaptations of invasive species during their initial invasions are rarely identified. The California kingsnake (Lampropeltis californiae) is an invasive species in the Canary Islands that originated via escape or release from captive populations. Previous studies have demonstrated several morphological differences between the native California population and the invasive populations on Gran Canaria Island, particularly in regard to color pattern and body mass. In this study, we assessed the reproductive condition of 1,538 museum specimens of L. californiae from the native range, and 668 from Gran Canaria. Our results show that 57.1% of female L. californiae from Gran Canaria were gravid versus 13.4% of those from California. Moreover, average follicle size and clutch size were both greater in the invasive range (20.3 and 65%). In addition, there was a marked phenological shift in the invasive populations, among which follicles appeared 60 days sooner than in the native range. These differences can possibly be attributed to a larger body mass in the invasive populations, a lack of interspecific competition, origination from the pet trade, increased selection for large clutch sizes, and/or increased climate suitability in the invaded habitats. Overall, these reproductive and phenological attributes appear to constitute advantages for L. californiae during the invasion of this newly encountered ecosystem. The phenomenon of reproductive plasticity might generally be advantageous for rapid irruption of snakes on islands.
Clonal cutaneous and neurosyphilis: A pitfall in pseudolymphoma diagnosis
Authors: Yi Lauren G. , Rusu Corina A. , Cropley Thomas G. , Marchi Enrica , Gru Alejandro A. , Greer Kenneth E. , Raghavan Shyam S.
Published: October 2021

Syphilis is a sexually transmitted infectious disease caused by the bacterium Treponema pallidum and can cause a wide variety of cutaneous manifestations, most commonly, a papulosquamous eruption of the trunk and extremities. Treatment with penicillin is curative. We report a case of a 69‐year‐old man who presented with recent onset of blurry vision and a nonpainful, nonpruritic eruption of pink‐to‐violaceous dermal nodules on his upper trunk and upper extremities. Biopsies of two separate locations revealed a dense superficial and deep perivascular atypical lymphocytic infiltrate with admixed plasma cells, histiocytes, and eosinophils. Some scattered cells expressed CD30, PD1, BCL‐6, and ICOS. T‐cell receptor (TCR)‐rearrangement showed an identical TCR‐gamma clone between both biopsy specimens. The patient was subsequently seen by ophthalmology and diagnosed with acute anterior uveitis. Rapid plasma reagin was reactive and cerebrospinal fluid studies showed findings consistent with a diagnosis of neurosyphilis. A T. pallidum immunostain of the skin biopsies was performed upon re‐review, and was diffusely positive for spirochetes at the dermal‐epidermal junction and within injured vessels. The patient was treated with penicillin G with near‐resolution of his skin lesions. This case highlights the unusual ability of syphilis to mimic a T‐cell lymphoma with matching clones across two different biopsy sites.