bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study
Authors: Bohmann Patricia , Stein Michael J , Konzok Julian , Tsoi Lam C , Elder James T , Leitzmann Michael F , Baumeister Sebastian-Edgar , Baurecht Hansjörg
Published: March 2023

Background

Observational research suggests that vitamin D levels affect psoriasis. However, observational studies are prone to potential confounding or reverse causation, which complicates interpreting the data and drawing causal conclusions.

Aim

To apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis.

Methods

Genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) in genome-wide association study (GWAS) data from 417 580 and 79 366 individuals from two independent studies served as instrumental variables (used as the discovery and replication datasets, respectively). As the outcome variable, we used GWAS data of psoriasis (13 229 people in the case group, 21 543 in the control group). We used (i) biologically validated genetic instruments, and (ii) polygenic genetic instruments to assess the relationship between genetically proxied vitamin D and psoriasis. We carried out inverse-variance weighted (IVW) MR analyses for the primary analysis. In sensitivity analyses, we used robust MR approaches.

Results

MR analyses of both the discovery and replication datasets did not show an effect of 25OHD on psoriasis. Neither the IVW MR analysis of the biologically validated instruments [discovery dataset: odds ratio (OR) 0.99; 95% confidence interval (CI) 0.88–1.12, P = 0.873; replication dataset: OR 0.98, 95% CI 0.66–1.46, P = 0.930] nor that of the polygenic genetic instruments (discovery dataset: OR 1.00, 95% CI 0.81–1.22, P = 0.973; replication dataset: OR 0.94, 95% CI 0.64–1.38, P = 0.737) revealed an impact of 25OHD on psoriasis.

Conclusion

The present MR study did not support the hypothesis that vitamin D levels, measured by 25OHD, affect psoriasis. This study was conducted on Europeans, so the conclusions may not be applicable to all ethnicities.
Natural History of Clostridioides difficile Colonization and Infection Following New Acquisition of Carriage in Healthcare Settings: A Prospective Cohort Study
Authors: Curry Scott R , Hecker Michelle T , O’Hagan Justin , Kutty Preeta K , Alhmidi Heba , Ng-Wong Yilen K , Cadnum Jennifer L , Jencson Annette L , Gonzalez-Orta Melany , Saldana Carlos , Wilson Brigid M , Donskey Curtis J
Published: March 2023

Background

Limited information is available on the natural history of Clostridioides difficile colonization and infection in patients with new acquisition of C. difficile in healthcare settings.

Methods

In 3 hospitals and affiliated long-term care facilities, we collected serial perirectal cultures from patients with no diarrhea on enrollment to identify new acquisition of toxigenic C. difficile carriage and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive, with negative cultures before and after, or persistent if 2 or more cultures were positive. Clearance of carriage was defined as 2 consecutive negative perirectal cultures.

Results

Of 1432 patients with negative initial cultures and at least 1 follow-up culture, 39 (2.7%) developed C. difficile infection (CDI) without prior detection of carriage and 142 (9.9%) acquired asymptomatic carriage, with 19 (13.4%) subsequently diagnosed with CDI. Of 82 patients analyzed for persistence of carriage, 50 (61.0%) had transient carriage and 32 (39.0%) had persistent carriage, with an estimated median of 77 days to clearance of colonization (range, 14–133 days). Most persistent carriers had a relatively high burden of carriage and maintained the same ribotype over time, whereas most transient carriers had a low burden of carriage detected only using broth enrichment cultures.

Conclusions

In 3 healthcare facilities, 9.9% of patients acquired asymptomatic carriage of toxigenic C. difficile, and 13.4% were subsequently diagnosed with CDI. Most carriers had transient rather than persistent carriage and most patients developing CDI did not have prior detection of carriage.
A Case of Mpox Reinfection
Authors: Musumeci Stefano , Najjar Iris , Amari Emmanuelle Boffi El , Schibler Manuel , Jacquerioz Frédérique , Yerly Sabine , Renzoni Adriana , Calmy Alexandra , Kaiser Laurent
Published: March 2023

A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive polymerase chain reaction on a rectal swab for Monkeypox virus after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.
Twenty-four-hour proteinuria levels are associated with adverse pregnancy outcomes among women with CKD
Authors: Li Zheng , Chen Shi , Tan Ying , Lv Jicheng , Zhao Minghui , Chen Qian , He Yingdong
Published: March 2023

Background

Proteinuria is commonly measured to assess the renal status of chronic kidney disease (CKD) patients before the 20th week of gestation during pregnancy. High levels of proteiuria have been associated with adverse pregnancy outcomes. However, researchers have not clearly determined what baseline proteinuria levels would be associated with adverse pregnancy outcomes. This study aimed to analyse associations between proteinuria levels and adverse pregnancy outcomes among CKD patients treated with or without steroids/immunosuppressive therapy in early pregnancy.

Methods

This retrospective study included the clinical information of 557 pregnant patients with CKD from 1 January 2009 to 31 December 2021. A multivariable logistic regression analysis was conducted to evaluate the risk of adverse pregnancy outcomes across various proteinuria ranges, which were further stratified by whether the patients were receiving steroids/immunosuppressive therapy.

Results

(i) Proteinuria was assessed on 24-h urine collection. The median (quartile) baseline proteinuria levels were 0.83 g (0.20, 1.92) and 0.25 g (0.06, 0.80) in the steroids/immunosuppressive therapy and therapy-free groups, respectively. (ii) CKD patients with adverse pregnancy outcomes had significantly higher proteinuria levels in the first trimester than patients without adverse pregnancy outcomes. (iii) The risk of adverse pregnancy outcomes increased with increasing baseline proteinuria levels (P < .001). (iv) In the early-pregnancy steroids/immunosuppressive therapy group, the risk of severe preeclampsia was higher in patients with higher baseline proteinuria levels (P < .007) [odds ratio (OR) 30.86 for proteinuria ≥5.00 g/24 h]; in the therapy-free group, the risks of severe preeclampsia, very-low-birth-weight infants, early preterm birth and foetal–neonatal death were higher in patients with higher baseline proteinuria levels (OR 53.16 for proteinuria ≥5.00 g/24 h; OR 37.83 for proteinuria ≥5.00 g/24 h; OR 15.30 for proteinuria ≥5.00 g/24 h; and OR 18.83 for proteinuria ≥5.00 g/24 h, respectively; P < .001, P < .001, P < .001 and P = .006, respectively).

Conclusions

As shown in the present study, a baseline 24-h proteinuria level >1.00 g was associated with adverse maternal outcomes. Furthermore, a 24-h proteinuria level >2.00 g increased the incidence of adverse foetal events among CKD patients.
The Path-Structure Connectivity of Augmented k-ary n-cubes
Authors: Ba Lina , Zhang Yaxian , Zhang Heping
Published: March 2023

For connected graphs $G$ and $H$, the $H$-structure connectivity $\kappa (G; H)$ (resp. $H$-substructure connectivity $\kappa ^{s}(G; H)$) of $G$ is the minimum cardinality of a set of subgraphs $\mathcal{F}$ of $G$ such that each is isomorphic to $H$ (resp. to a connected subgraph of $H$) so that $G-\mathcal{F}$ is disconnected or singleton. In this paper, we consider $P_t$-structure connectivity and $P_t$-substructure connectivity of augmented $k$-ary $n$-cubes $AQ_{n,k}$ for $n\geq 2$, $k\geq 3$ and $1\leq t\leq 4n-2$. We obtain that $\kappa (AQ_{n,k}; P_t)=\kappa ^s(AQ_{n,k}; P_t)=\frac{4n-2}{t}+1$ for $t\mid 4n-2$, $t\nmid 2n-1$, $t>6$, $n\geq 3$ and $k\geq 4$; $\kappa (AQ_{n,k}; P_t)=\kappa ^s(AQ_{n,k}; P_t)=\lceil \frac{4n-2}{t}\rceil $, in other cases.
Ash the Poet and Ash the Tree: Possession by the Past in A. S. Byatt’s Possession: A Romance
Authors: Zhang Xiuchun
Published: March 2023

This article examines five poem extracts written by the fictional Victorian poet Randolph Henry Ash in A. S. Byatt’s Possession: A Romance, which, depicting the Paradise gardens in various mythologies across the world, become rewritten tales of the Paracelsian elemental spirits guarding treasure hoarded in nature.These poems, placed at the heads of different chapters, are read as summaries of the detective stories, indicating to the reader the developments in the forthcoming quest plot. Furthermore, they are interpreted as embodying Roland’s search for coherence in the postmodern world, which culminates in his psychological maturation at the end of his quest. Finally, these poems are deciphered as expressive of Ash’s quest for the prelapsarian Eden which he believes inspires generations of poets’ literary imagination. In conclusion, this article addresses three readings of the philosopher’s stone and two characters' visions of the past.
Weak reproductive isolation and extensive gene flow between Mimulus glaucescens and M. guttatus in northern California
Authors: Ivey Christopher T , Habecker Nicole M , Bergmann Jean Phillippe , Ewald Jacob , Frayer Megan E , Coughlan Jenn M
Published: March 2023

Barriers to reproduction are often how progress in speciation is measured. Nonetheless, an unresolved question concerns the extent to which reproductive barriers diminish gene flow between incipient species. The Sierra Nevada foothill endemic Mimulus glaucescens and the widespread M. guttatus are considered distinct species based on striking differences in vegetative morphology, but barriers to reproduction have not been previously identified, nor has gene flow between species been characterized. Here, we examined 15 potential reproductive barriers within a Northern California area of broad sympatry. Most barriers, with the exception of ecogeographic isolation, were weak or absent, and total isolation for each species was incomplete. Population genomic analyses of range-wide and broadly sympatric accessions revealed extensive gene flow between these taxa, particularly in sympatry. Despite widespread introgression, Mimulus glaucescens, emerged as monophyletic and largely comprised a single ancestry that was found at intermediate frequency within M. guttatus. This result, along with observed ecological and phenotypic differentiation, suggests that natural selection may contribute to the maintenance of distinct phenotypic forms in the earliest stages of speciation. Integrating estimates of barrier strength with direct estimates of gene flow can strengthen a more nuanced interpretation of the process of speciation in natural communities.
Unraveling the small proteome of the plant symbiontSinorhizobium melilotiby ribosome profiling and proteogenomics
Authors: Hadjeras Lydia , Heiniger Benjamin , Maaß Sandra , Scheuer Robina , Gelhausen Rick , Azarderakhsh Saina , Barth-Weber Susanne , Backofen Rolf , Becher Dörte , Ahrens Christian H , Sharma Cynthia M , Evguenieva-Hackenberg Elena
Published: March 2023

The soil-dwelling plant symbiont Sinorhizobium meliloti is a major model organism of Alphaproteobacteria. Despite numerous detailed OMICS studies, information about small open reading frame (sORF)-encoded proteins (SEPs) is largely missing, because sORFs are poorly annotated and SEPs are hard to detect experimentally. However, given that SEPs can fulfill important functions, identification of translated sORFs is critical for analyzing their roles in bacterial physiology. Ribosome profiling (Ribo-seq) can detect translated sORFs with high sensitivity, but is not yet routinely applied to bacteria because it must be adapted for each species. Here, we established a Ribo-seq procedure for S. meliloti 2011 based on RNase I digestion and detected translation for 60% of the annotated coding sequences during growth in minimal medium. Using ORF prediction tools based on Ribo-seq data, subsequent filtering, and manual curation, the translation of 37 non-annotated sORFs with ≤ 70 amino acids was predicted with confidence. The Ribo-seq data were supplemented by mass spectrometry (MS) analyses from three sample preparation approaches and two integrated proteogenomic search database (iPtgxDB) types. Searches against standard and 20-fold smaller Ribo-seq data-informed custom iPtgxDBs confirmed 47 annotated SEPs and identified 11 additional novel SEPs. Epitope tagging and Western blot analysis confirmed the translation of 15 out of 20 SEPs selected from the translatome map. Overall, by combining MS and Ribo-seq approaches, the small proteome of S. meliloti was substantially expanded by 48 novel SEPs. Several of them are part of predicted operons and/or are conserved from Rhizobiaceae to Bacteria, suggesting important physiological functions.
Microbiology education: a significant path to sustainably improve the human and biosphere condition
Authors: Timmis Kenneth
Published: March 2023

In this short piece, I connect the dots between the pervasive influence of microbial activities on our health and that of the planet, including their positive and negative roles in current polycrises, our ability to influence microbes to promote their positive influences and mitigate their negative impacts, the roles of everyone as stewards and stakeholders in personal, family, community, national, and global wellbeing, the need for stewards and stakeholders to possess relevant information in order to fulfil their roles and obligations, and the compelling case for microbiology literacy and introduction of a societally relevant microbiology curriculum in school.
Residential Segregation and Depressive Symptoms in Older Chinese Immigrants: The Mediating Role of Social Processes
Authors: Tang Fengyan , Jiang Yanping , Li Ke , Rosso Andrea L
Published: March 2023

Background and Objectives

Older Chinese immigrants are at risk for depression due to acculturative stress and language barriers. Residential segregation with respect to language use plays an important role in the mental health of historically marginalized populations. Previous research provided mixed evidence about the segregation effect among older Latino and Asian immigrants. Guided by a model of social processes, we examined the direct and indirect effects of residential segregation on depressive symptoms via multiple mechanisms of acculturation, discrimination, social network, social support, social strain, and social engagement.

Research Design and Methods

Four waves of depressive symptoms were assessed in the Population Study of Chinese Elderly (2011–19, N = 1,970), and linked to the 2010–14 American Community Survey estimates of neighborhood context. Residential segregation was measured by the Index of Concentrations at the Extremes which simultaneously assesses Chinese and English language use within a given census tract. Latent growth curve models with adjusted cluster robust standard errors were estimated after controlling for individual-level factors.

Results

Residents of segregated Chinese-speaking neighborhoods had fewer baseline depressive symptoms but a slower rate of symptom reduction than those living in neighborhoods segregated with English-only speakers. Racial discrimination, social strain, and social engagement partially mediated the association between segregation and baseline depressive symptoms; social strain and social engagement partially mediated the association with long-term reduction in depressive symptoms.

Discussion and Implications

This study demonstrates the importance of residential segregation and social processes in shaping mental well-being among older Chinese immigrants and suggests potential mechanisms to alleviate mental health risks.
How to estimate life history ratios to simplify data-poor fisheries assessment
Authors: Prince Jeremy D , Wilcox Chris , Hall Norman
Published: March 2023

Less variable than life history parameters (LHPs), it is life history ratios (LHRs) that define how taxa allocate energy between growth, maintenance and reproduction, and respond to fishing pressure. Limited by small samples, variable data quality, and a focus on LHP estimation, previous meta-analyses have failed to settle debate about the extent to which LHRs are relatively invariant across all taxa or characteristic of specific taxa. We collected de novo 1335 published studies and applying rigorous standardization and quality control procedures developed, and make available, a database of high-quality M/K and Lm/L∞ estimates. We describe two parallel but independent meta-analyses: a cross-validation study of the predictability of M/K by taxonomic category and an evaluation of alternative relationships between the LHRs using Akaike information criteria. These analyses demonstrate that the LHRs are correlated and vary predictably by taxa, with aggregation to the level of family and genera having the most predictive power in our database. We postulate that the LHRs of taxa may relate to their stoichiometric niches, which could open up interesting lines for ecological research and provide new tools for predicting the LHRs of poorly studied taxa.
Behavioural responses of wild, spawning Atlantic cod (Gadus morhua L.) to seismic airgun exposure
Authors: McQueen K , Skjæraasen J E , Nyqvist D , Olsen E M , Karlsen Ø , Meager J J , Kvadsheim P H , Handegard N O , Forland T N , de Jong K , Sivle L D
Published: March 2023

Seismic airgun surveys to map petroleum deposits in the seabed may impact behaviour of marine animals over large distances. Understanding whether fish spawning behaviour is affected by this anthropogenic noise source is important because reproductive success may be impacted. The fine-scale behavioural responses of Atlantic cod to airgun exposure over an extended period were investigated using an acoustic telemetry positioning system on a spawning ground in Norway. During 2019 to 2021, 135 spawning cod were equipped with telemetry sensor tags and were exposed to airgun shooting during the spawning periods of 2020 and 2021, with varying received sound levels comparable to a full-scale survey at distances of 5 to >40 km. Cod demonstrated only weak responses to the disturbance from repeated 3-h treatment periods over 5-d, swimming on average slightly deeper during seismic exposure compared to silent control periods. This response varied between individuals. Longer-term effects of seismic exposure on swimming depth were not detected. No changes in swimming acceleration, displacement, or area use occurred. These results suggest that relatively distant seismic surveys do not substantially alter cod behaviour during the spawning period at received sound exposure levels varying between 115 and 145 dB re 1 µPa2s over a 5-d period.
Practical considerations for specifying a super learner
Authors: Phillips Rachael V , van der Laan Mark J , Lee Hana , Gruber Susan
Published: March 2023

Common tasks encountered in epidemiology, including disease incidence estimation and causal inference, rely on predictive modelling. Constructing a predictive model can be thought of as learning a prediction function (a function that takes as input covariate data and outputs a predicted value). Many strategies for learning prediction functions from data (learners) are available, from parametric regressions to machine learning algorithms. It can be challenging to choose a learner, as it is impossible to know in advance which one is the most suitable for a particular dataset and prediction task. The super learner (SL) is an algorithm that alleviates concerns over selecting the one ‘right’ learner by providing the freedom to consider many, such as those recommended by collaborators, used in related research or specified by subject-matter experts. Also known as stacking, SL is an entirely prespecified and flexible approach for predictive modelling. To ensure the SL is well specified for learning the desired prediction function, the analyst does need to make a few important choices. In this educational article, we provide step-by-step guidelines for making these decisions, walking the reader through each of them and providing intuition along the way. In doing so, we aim to empower the analyst to tailor the SL specification to their prediction task, thereby ensuring their SL performs as well as possible. A flowchart provides a concise, easy-to-follow summary of key suggestions and heuristics, based on our accumulated experience and guided by SL optimality theory.
National Identity and Public Attitudes Toward the World Health Organization
Authors: Ariely Gal
Published: March 2023

This article examines whether assumptions about the contradiction between national identity and support for international organizations are reflected in public support of the World Health Organization (WHO). Study 1 uses a comparative multilevel analysis to examine the link between national identification and confidence in the WHO as well as the influence of globalization on these attitudes. Study 2, which is based on a panel survey in Israel, explores whether attitudes toward the WHO have changed over time and under the influence of the COVID-19 pandemic and whether relations between national identification, national chauvinism, and perceptions of the WHO have also changed. Overall, the findings indicate that there is no clear-cut contradiction between national identity and public support for the WHO.
Narrowing the Gap in the Access to Justice for Child Victims in Postconflict Societies: An Analysis Stemming from the Construction of Child Soldiers in International Law and Policy
Authors: Molima Bameka Christelle
Published: March 2023

ABSTRACT∞

A controversial approach characterizes international law and policy on children affected by armed conflict: it is much more concerned with child soldiers’ victimization than with their victims’ situation. This approach leads to (1) the prioritization of the former over the child victims of their crimes before judicial and non-judicial mechanisms and (2) a significant disparity in how international law and policy respond to the victimization of war-affected children in the presence of those categorized as ‘child soldiers.’ To narrow this gap, this article explores the potential of defining child soldiers as victims who victimize during trials. It does so by discussing the practice observed in local juvenile courts in the North and South Kivu provinces in the Democratic Republic of Congo.
Nonexercise machine learning models for maximal oxygen uptake prediction in national population surveys
Authors: Liu Yuntian , Herrin Jeph , Huang Chenxi , Khera Rohan , Dhingra Lovedeep Singh , Dong Weilai , Mortazavi Bobak J , Krumholz Harlan M , Lu Yuan
Published: March 2023

Objective

Nonexercise algorithms are cost-effective methods to estimate cardiorespiratory fitness (CRF), but the existing models have limitations in generalizability and predictive power. This study aims to improve the nonexercise algorithms using machine learning (ML) methods and data from US national population surveys.

Materials and Methods

We used the 1999–2004 data from the National Health and Nutrition Examination Survey (NHANES). Maximal oxygen uptake (VO2 max), measured through a submaximal exercise test, served as the gold standard measure for CRF in this study. We applied multiple ML algorithms to build 2 models: a parsimonious model using commonly available interview and examination data, and an extended model additionally incorporating variables from Dual-Energy X-ray Absorptiometry (DEXA) and standard laboratory tests in clinical practice. Key predictors were identified using Shapley additive explanation (SHAP).

Results

Among the 5668 NHANES participants in the study population, 49.9% were women and the mean (SD) age was 32.5 years (10.0). The light gradient boosting machine (LightGBM) had the best performance across multiple types of supervised ML algorithms. Compared with the best existing nonexercise algorithms that could be applied to the NHANES, the parsimonious LightGBM model (RMSE: 8.51 ml/kg/min [95% CI: 7.73–9.33]) and the extended LightGBM model (RMSE: 8.26 ml/kg/min [95% CI: 7.44–9.09]) significantly reduced the error by 15% and 12% (P < .001 for both), respectively.

Discussion

The integration of ML and national data source presents a novel approach for estimating cardiovascular fitness. This method provides valuable insights for cardiovascular disease risk classification and clinical decision-making, ultimately leading to improved health outcomes.

Conclusion

Our nonexercise models provide improved accuracy in estimating VO2 max within NHANES data as compared to existing nonexercise algorithms.
Cultural Competence in the Care of LGBTQ+ Patients: A Primer for Breast/Chest Centers
Authors: Mehta Tejas S , Thompson Julie , Applegate Julia M , Wahab Rifat A
Published: March 2023

The number of individuals identifying as lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ+) has doubled over the past 10 years, and this figure continues to rise. The LGBTQ+ community is diverse, encompassing a vast array of differences in gender identity and sexual orientation. Additionally, it is inclusive of people from all races, ethnicities, religions, and socioeconomic backgrounds. This intersectionality of identities and experiences impacts both access to health care and its delivery. Barriers to care for this population are multifactorial and include stigma, discrimination, bias, limited role models, issues with insurance coverage, lack of education and training for health care providers, and lack of research on LGBTQ+ health–related issues. Specific to breast cancer, the screening recommendations for this group are influenced not only by risk but also by gender-affirming hormonal and surgical therapies. This article will provide an overview of the LGBTQ+ population, review breast cancer screening compliance and recommendations, summarize the multitude of health disparities, and offer potential interventions to improve care delivery at the individual, facility, organizational, and health policy levels.
Gene cloning, expression pattern, and response to dietary total lipids and phospholipids of hormone-sensitive lipase (HSL) in the Oriental river prawnMacrobrachium nipponenseDe Haan, 1849 (Decapoda: Caridea: Palaemonidae)
Authors: Wang Qianqian , Cai Chunfang , Zhang Junbiao , Shui Dianzhang , Cui Guangtong , Wang Zhi , Ren Shengjie , Wu Ping , Ye Yuantu
Published: March 2023

Hormone-sensitive lipase (HSL) is an important regulator of cellular lipid homeostasis and catalyzes the hydrolysis of stored triacylglycerol. We identified and cloned for the first time the full-length cDNA sequence of HSL of the prawn Macrobrachium nipponense De Haan, 1849 [De Haan, 1833–1850] from a hepatopancreas cDNA library. The complete HSL sequence is 3,575 bp and encoded a 785 amino acid peptide with the catalytic core (GXSXG) containing a serine residue. The phylogenetic tree revealed that the gene of HSL of M. nipponense is closely related with that of Penaeus vanmameiBoone, 1931. The tissue distribution showed that the mRNA expression level of HSL in the hepatopancreas was significantly higher than that in other tissues (P < 0.05). Furthermore, the HSL expression in hepatopancreas was upregulated with the increase of dietary lipids but partially inhibited when the ratio of phospholipids was increased in the lipid mixture. These results demonstrate that HSL is involved in the lipid metabolism of M. nipponense and highlights the importance of phospholipids in lipid metabolism.
Pipecolic acid synthesis is required for systemic acquired resistance and plant-to-plant-induced immunity in barley
Authors: Brambilla Alessandro , Lenk Miriam , Ghirardo Andrea , Eccleston Laura , Knappe Claudia , Weber Baris , Lange Birgit , Imani Jafargholi , Schäffner Anton R , Schnitzler Jörg-Peter , Vlot A Corina
Published: March 2023

Defense responses in plants are based on complex biochemical processes. Systemic acquired resistance (SAR) helps to fight infections by (hemi-)biotrophic pathogens. One important signaling molecule in SAR is pipecolic acid (Pip), accumulation of which is dependent on the aminotransferase ALD1 in Arabidopsis. While exogenous Pip primes defense responses in the monocotyledonous cereal crop barley (Hordeum vulgare), it is currently unclear if endogenous Pip plays a role in disease resistance in monocots. Here, we generated barley ald1 mutants using CRISPR/Cas9, and assessed their capacity to mount SAR. Endogenous Pip levels were reduced after infection of the ald1 mutant, and this altered systemic defense against the fungus Blumeria graminis f. sp. hordei. Furthermore, Hvald1 plants did not emit nonanal, one of the key volatile compounds that are normally emitted by barley plants after the activation of SAR. This resulted in the inability of neighboring plants to perceive and/or respond to airborne cues and prepare for an upcoming infection, although HvALD1 was not required in the receiver plants to mediate the response. Our results highlight the crucial role of endogenous HvALD1 and Pip for SAR, and associate Pip, in particular together with nonanal, with plant-to-plant defense propagation in the monocot crop barley.
Membrane Protein Detection and Morphological Analysis of Red Blood Cells in Hereditary Spherocytosis by Confocal Laser Scanning Microscopy
Authors: Rey-Barroso Laura , Roldán Mónica , Burgos-Fernández Francisco J , Isola Ignacio , Ruiz Llobet Anna , Gassiot Susanna , Sarrate Edurne , Vilaseca Meritxell
Published: March 2023

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis. Although abnormally shaped RBCs can be identified under conventional light microscopy, HS diagnosis relies on several clinical factors and sometimes on the results of complex molecular testing. It is specially challenging when other causes of anemia coexist or after recent blood transfusions. We propose two different approaches to characterize RBCs in HS: (i) an immunofluorescence assay targeting protein band 3, which is affected in most HS cases and (ii) a three-dimensional morphology assay, with living cells, staining the membrane with fluorescent dyes. Confocal laser scanning microscopy (CLSM) was used to carry out both assays, and in order to complement the latter, a software was developed for the automated detection of spherocytes in blood samples. CLSM allowed the precise and unambiguous assessment of cell shape and protein expression.
NGTS clusters survey – IV. Search for Dipper stars in the Orion Nebular Cluster
Authors: Moulton Tyler , Hodgkin Simon T , Smith Gareth D , Briegal Joshua T , Gillen Edward , Acton Jack S , Battley Matthew P , Burleigh Matthew R , Casewell Sarah L , Gill Samuel , Goad Michael R , Henderson Beth A , Kendall Alicia , Ramsay Gavin , Tilbrook Rosanna H , Wheatley Peter J
Published: March 2023

The dipper is a novel class of young stellar object associated with large drops in flux on the order of 10–50 per cent lasting for hours to days. Too significant to arise from intrinsic stellar variability, these flux drops are currently attributed to disc warps, accretion streams, and/or transiting circumstellar dust. Dippers have been previously studied in young star-forming regions, including the Orion Complex. Using Next Generation Transit Survey (NGTS) data, we identified variable stars from their light curves. We then applied a machine learning random forest classifier for the identification of new dipper stars in Orion using previous variable classifications as a training set. We discover 120 new dippers, of which 83 are known members of the Complex. We also investigated the occurrence rate of discs in our targets, again using a machine learning approach. We find that all dippers have discs, and most of these are full discs. We use dipper periodicity and model-derived stellar masses to identify the orbital distance to the inner disc edge for dipper objects, confirming that dipper stars exhibit strongly extended sublimation radii, adding weight to arguments that the inner disc edge is further out than predicted by simple models. Finally, we determine a dipper fraction (the fraction of stars with discs which are dippers) for known members of 27.8 ± 2.9 per cent. Our findings represent the largest population of dippers identified in a single cluster to date.
Intergenic Regions of Saccharomycotina Yeasts are Enriched in Potential to Encode Transmembrane Domains
Authors: Tassios Emilios , Nikolaou Christoforos , Vakirlis Nikolaos
Published: March 2023

Intergenic genomic regions have essential regulatory and structural roles that impose constraints on their sequences. But regions that do not currently encode proteins also carry the potential to do so in the future. De novo gene emergence, the evolution of novel genes out of previously noncoding sequences has now been established as a potent force for genomic novelty. Recently, it was shown that intergenic regions in the genome of Saccharomyces cerevisiae harbor pervasive cryptic potential to, if theoretically translated, form transmembrane domains (TM domains) more frequently than expected by chance given their nucleotide composition, a property that we refer to as TM-forming enrichment. The source and biological relevance of this property is unknown. Here, we expand the investigation into the TM-forming potential of intergenic regions to the entire Saccharomycotina budding yeast subphylum, in an effort to explain this property and understand its importance. We find pervasive but variable enrichment in TM-forming potential across the subphylum regardless of the composition and average size of intergenic regions. This cryptic property is evenly spread across the genome, cannot be explained by the hydrophobic content of the sequence, and does not appear to localize to regions containing regulatory motifs. This TM-forming enrichment specifically, and not the actual TM-forming potential, is associated, across genomes, with more TM domains in evolutionarily young genes. Our findings shed light on this newly discovered feature of yeast genomes and constitute a first step toward understanding its evolutionary importance.
Non-bacterial vertebral osteitis as the first manifestation of pustulotic arthro-osteitis
Authors: Ueda Yoshitaka , Yokogawa Naoto , Shimada Kota
Published: March 2023

Pustulotic arthro-osteitis (PAO) is an osteoarticular comorbidity of palmoplantar pustulosis, a chronic, recurrent, inflammatory skin disease presenting with erythema, scales, and pustules on the palms and soles. Palmoplantar pustulosis is one of the most common skin diseases in Japan and is accompanied by PAO in 10–30% of patients. PAO often involves anterior chest wall lesions, but vertebral involvement is uncommon. The present report describes a case of PAO in which the initial manifestation was only non-bacterial vertebral osteitis, with palmoplantar pustulosis developing 8 months after its onset. A patient with vertebral osteitis of unknown aetiology should be followed up and examined periodically for skin problems, which may provide a clue to the presence of PAO.
Characterization of proteome profile data of chemicals based on data-independent acquisition MS with SWATH method
Authors: Ishiguro Hiromu , Mizuno Tadahaya , Uchida Yasuo , Sato Risa , Sasaki Hayate , Nemoto Shumpei , Terasaki Tetsuya , Kusuhara Hiroyuki
Published: March 2023

Transcriptomic data of cultured cells treated with a chemical are widely recognized as useful numeric information that describes the effects of the chemical. This property is due to the high coverage and low arbitrariness of the transcriptomic data as profiles of chemicals. Considering the importance of posttranslational regulation, proteomic profiles could provide insights into the unrecognized aspects of the effects of chemicals. Therefore, this study aimed to address the question of how well the proteomic profiles obtained using data-independent acquisition (DIA) with the sequential window acquisition of all theoretical mass spectra, which can achieve comprehensive and arbitrariness-free protein quantification, can describe chemical effects. We demonstrated that the proteomic data obtained using DIA-MS exhibited favorable properties as profile data, such as being able to discriminate chemicals like the transcriptomic profiles. Furthermore, we revealed a new mode of action of a natural compound, harmine, through profile data analysis using the proteomic profile data. To our knowledge, this is the first study to investigate the properties of proteomic data obtained using DIA-MS as the profiles of chemicals. Our 54 (samples) × 2831 (proteins) data matrix would be an important source for further analyses to understand the effects of chemicals in a data-driven manner.
Resistant hypertension in dialysis
Authors: Symonides Bartosz , Lewandowski Jacek , Małyszko Jolanta
Published: March 2023

Hypertension is the most common finding in chronic kidney disease patients, with prevalence ranging from 60% to 90% depending on the stage and etiology of the disease. It is also a significant independent risk factor for cardiovascular disease, progression to end-stage kidney disease and mortality. According to the current guidelines, resistant hypertension is defined in the general population as uncontrolled blood pressure on three or more antihypertensive drugs in adequate doses or when patients are on four or more antihypertensive drug categories irrespective of the blood pressure control, providing that antihypertensive treatment included diuretics. The currently established definitions of resistant hypertension are not directly applicable to the end-stage kidney disease setting. The diagnosis of true resistant hypertension requires confirmation of adherence to therapy and confirmation of uncontrolled blood pressure values by ambulatory blood pressure measurement or home blood pressure measurement. In addition, the term “apparent treatment-resistant hypertension,” defined as an uncontrolled blood pressure on three or more antihypertensive medication classes, or use of four or more medications regardless of blood pressure level was introduced. In this comprehensive review we focused on the definitions of hypertension, and therapeutic targets in patients on renal replacement therapy, including the limitations and biases. We discussed the issue of pathophysiology and assessment of blood pressure in the dialyzed population, management of resistant hypertension as well as available data on prevalence of apparent treatment-resistant hypertension in end-stage kidney disease. To conclude, larger sample-size and even higher quality studies about drug adherence should be conducted in the population of patients with the end-stage kidney disease who are on dialysis. It also should be determined how and when blood pressure should be measured in the group of dialysis patients. Additionally, it should be stated what the target blood pressure values in this group of patients really are. The definition of resistant hypertension in this group should be revisited, and its relationship to both subclinical and clinical endpoints should be established.
Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial
Authors: Trigo-Rodríguez Marta , Cárcel Sheila , Navas Ana , Espíndola-Gómez Reinaldo , Garrido-Gracia José Carlos , Esteban Moreno María Ángeles , León-López Rafael , Pérez-Crespo Pedro María Martínez , Alonso Eduardo Aguilar , Vinuesa David , Romero-Palacios Alberto , Pérez-Camacho Inés , Gutiérrez-Gutiérrez Belén , Martínez-Marcos Francisco Javier , Fernández-Roldán Concepción , León Eva , Caño Alexandra Aceituno , Corzo-Delgado Juan E , Perez-Nadales Elena , Riazzo Cristina , de la Fuente Carmen , Jurado Aurora , Torre-Cisneros Julián , Merchante Nicolás
Published: March 2023

Background

The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention.

Methods

The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020–March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein–1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated.

Results

One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04–0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences.

Conclusions

IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.
Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center
Authors: Farha Natalie , Faisal Muhammad Salman , Allende Daniela S , Sleiman Joseph , Shah Ravi , Farha Nicole , Funchain Pauline , Philpott Jessica R
Published: March 2023

Background

Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy.

Materials and Methods

This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded.

Results

Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non–small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy.

Conclusion

Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.
Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
Authors: Li Lee X , Cappuzzo Federico , Matos Ignacio , Socinski Mark A , Hopkins Ashley M , Sorich Michael J
Published: March 2023

Background

Monotherapy immune checkpoint inhibitor (ICI) used in second- or later-line settings has been reported to induce hyperprogression. This study evaluated hyperprogression risk with ICI (atezolizumab) in the first-, second-, or later-line treatment of advanced non–small cell lung cancer (NSCLC), and provides insights into hyperprogression risk with contemporary first-line ICI treatment.

Methods

Hyperprogression was identified using Response Evaluation Criteria in Solid Tumours (RECIST)-based criteria in a dataset of pooled individual-participant level data from BIRCH, FIR, IMpower130, IMpower131, IMpower150, OAK, and POPLAR trials. Odds ratios were computed to compare hyperprogression risks between groups. Landmark Cox proportional-hazard regression was used to evaluate the association between hyperprogression and progression-free survival/overall survival. Secondarily, putative risk factors for hyperprogression among second- or later-line atezolizumab-treated patients were evaluated using univariate logistic regression models.

Results

Of the included 4644 patients, 119 of the atezolizumab-treated patients (n = 3129) experienced hyperprogression. Hyperprogression risk was markedly lower with first-line atezolizumab—either chemoimmunotherapy or monotherapy—compared to second/later-line atezolizumab monotherapy (0.7% vs. 8.8%, OR = 0.07, 95% CI, 0.04-0.13). Further, there was no statistically significant difference in hyperprogression risk with first-line atezolizumab-chemoimmunotherapy versus chemotherapy alone (0.6% vs. 1.0%, OR = 0.55, 95% CI, 0.22-1.36). Sensitivity analyses using an extended RECIST-based criteria including early death supported these findings. Hyperprogression was associated with worsened overall survival (HR = 3.4, 95% CI, 2.7-4.2, P < .001); elevated neutrophil-to-lymphocyte ratio was the strongest risk factor for hyperprogression (C-statistic = 0.62, P < .001).

Conclusions

This study presents first evidence for a markedly lower hyperprogression risk in advanced NSCLC patients treated with first-line ICI, particularly with chemoimmunotherapy, as compared to second- or later-line ICI treatment.