bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial changes in the trends of direct oral anticoagulant use and incidence of thromboembolisms and major bleeding events in very old patients with non-valvular atrial fibrillation
Authors: Takahashi Masahiko , Morimoto Takeshi , Tsushima Ryu , Sudo Yuya , Sakamoto Ai , Sogo Masahiro , Ozaki Masatomo , Okawa Keisuke
Published: October 2023

Aims

Direct oral anticoagulants (DOACs) have become the first-line antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF). During this period, the incidence of thromboembolisms and major bleeding events has decreased. However, no studies have shown a correlation between them, and even fewer data are available on older patients. Therefore, we evaluated the serial changes in oral anticoagulant (OAC) use and the correlation between DOAC use and the incidence of adverse events among very old patients with NVAF.

Methods and results

We conducted a historical cohort study in 1320 consecutive patients with NVAF aged ≥80 years who received medical treatment for AF from March 2011 to February 2021. We analysed the temporal trends regarding patients using OACs, including the DOAC prescription rate and incidence of adverse events. Over the last decade, the number of patients using OACs has increased from 228 to approximately 600 person-years. The DOAC prescription rate has significantly increased (4–90%, P < 0.001). The age of the patients and proportion of patients with a HASBLED score ≥3 significantly increased (84 ± 4 to 86 ± 4 years, 16–25%, P < 0.001, respectively). The composite incidence of thromboembolisms and major bleeding events significantly decreased (7.02–3.30 events/100 person-years, P < 0.001).

Conclusion

The incidence of thromboembolisms and major bleeding events might be inversely correlated with the increase in the DOAC prescription rate in patients with NVAF aged ≥80 years.
The genomics of adaptation to climate in European great tit (Parus major) populations
Authors: Stonehouse Joanne C , Spurgin Lewis G , Laine Veronika N , Bosse Mirte ,   The Great Tit HapMap Consortium, Groenen Martien A M , van Oers Kees , Sheldon Ben C , Visser Marcel E , Slate Jon
Published: October 2023

The recognition that climate change is occurring at an unprecedented rate means that there is increased urgency in understanding how organisms can adapt to a changing environment. Wild great tit (Parus major) populations represent an attractive ecological model system to understand the genomics of climate adaptation. They are widely distributed across Eurasia and they have been documented to respond to climate change. We performed a Bayesian genome-environment analysis, by combining local climate data with single nucleotide polymorphisms genotype data from 20 European populations (broadly spanning the species’ continental range). We found 36 genes putatively linked to adaptation to climate. Following an enrichment analysis of biological process Gene Ontology (GO) terms, we identified over-represented terms and pathways among the candidate genes. Because many different genes and GO terms are associated with climate variables, it seems likely that climate adaptation is polygenic and genetically complex. Our findings also suggest that geographical climate adaptation has been occurring since great tits left their Southern European refugia at the end of the last ice age. Finally, we show that substantial climate-associated genetic variation remains, which will be essential for adaptation to future changes.
Paper tools for broken hearts: fortune-telling with cards in France, c. 1803–1937
Authors: Pooley William G
Published: October 2023

Fortune-telling using cards became increasingly popular in France in the late eighteenth century. But the history of cards as tools for divination has been overshadowed by myths spun by occultist writers, who claimed Tarot were the only cards truly suited to fortune-telling, because they encoded secret magical truths that dated back to ancient Egypt. This article turns from these myths to alternative sources that show cards in action: criminal prosecutions of fortune-tellers, popular card-reading manuals, and surviving cards from the period. Not only Tarot, but cards of all kinds, from playing cards to decks designed for divination became flexible tools for negotiating relationships among a broad range of the French population. As images, texts and objects to be manipulated, cards unlock common structures of emotion in nineteenth-century France, from the sense of order implied by suits, to the importance of juxtapositions and chance, and of turning things over to uncover their true, hidden meaning.
Failure of Cronobacter sakazakii to acquire direct and cross-protection against lethal stresses after exposure to sublethal ethanol
Authors: Niu Hongmei , Wang Xiang , Wang Yuan , Qin Xiaojie , Liu Yangtai , Li Zhuosi , Wang Xu , Zhang Wantong , Dong Qingli
Published: October 2023

Cronobacter sakazakii may encounter subinhibitory concentrations of ethanol stress over its lifecycle. Bacterial tolerance to homologous or heterologous stress agents may be altered as a result of ethanol adaptive responses. Therefore, the tolerance of ethanol-exposed and control cells to subsequent lethal stresses was evaluated in the current work. It was discovered that sublethal ethanol exposure increased the susceptibility to lethal ethanol stress in C. sakazakii as determined by the Weibull model. Furthermore, sublethal ethanol concentration exposure in C. sakazakii did not lead to any cross-tolerance against other stressors such as benzalkonium chloride (120 mg/L), heat (55 °C), cold (4 °C), simulated gastric fluid (pH 3.0), osmotic stress (sorbitol, 0.75 g/mL), and desiccation stress. Analysis of zeta potential, scanning electron microscope, and surface-enhanced Raman spectroscopy spectra revealed that cellular injury and changes in cellular chemical composition may contribute to the reduced resistance of C. sakazakii after ethanol exposure. Furthermore, sublethal ethanol exposure resulted in an elevated proportion of unsaturated fatty acids (USFA), while reducing the proportion of saturated fatty acids (SFA) and the ratio of SFA to USFA. The developed inactivation models can serve as a valuable source of data to support quantitative microbial risk assessment. Moreover, a better understanding of the response of C. sakazakii to sublethal ethanol exposure may provide valuable insights into the prevention and control of C. sakazakii.
Calculation model and application of ecological water demand of watercourses in low-carbon sponge urban areas based on DPSA algorithm
Authors: Zhang Tianming , Xu Xiaoliang
Published: October 2023

To improve the prediction ability of river ecological water requirement in sponge low-carbon urban areas, a prediction model of it based on big data analysis was proposed. A statistical analysis model of river ecological water requirement in sponge and low-carbon urban areas was established. Differential Particle Swarm Optimization Algorithm (DPSA) was used to calculate the characteristic quantity of river ecological water requirement in sponge and low-carbon urban areas. The detection model of ecosystem hydrothermal balance and lognormal distribution time series of groundwater level were constructed for the prediction of river ecological water requirement in sponge and low-carbon urban areas. Combined with the integrated control method of river ecological environment water demand forecasting and information exchange, a decentralized control model of river ecological water demand in low-carbon sponge urban areas was established. Through applicability analysis and model measurement analysis, combined with comprehensive index measurement, the prediction model of river ecological water requirement in low-carbon sponge urban areas was optimized. The empirical analysis results show that this method has good adaptability and high prediction accuracy for the prediction of river ecological water requirement in sponge low-carbon urban areas and improves the reliability of the prediction of river ecological water requirement and the matching level of urban ecological environment.
Sexual Exposures Associated With Mpox Infection: California, November 2022 to June 2023
Authors: Snyder Robert E , Saadeh Kayla , Tang Eric C , Johnson Kelly A , Holland Samuel N , Quint Joshua , Burghardt Nicole O , Chai Shua J , Fernando Roshani , Barrera Kimberly Gonzalez , Hernandez Cindy , McManus Korie , Lorenz Kieran , Maycott Jarett , McGinley John , Lewnard Joseph A
Published: October 2023

Background

Exposures associated with mpox infection remain imperfectly understood.

Methods

We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox case patients and test-negative controls.

Results

Thirteen of 54 case patients (24.1%) and 5 of 117 controls (4.3%) reported sexual exposure to individuals they identified as potential mpox case patients (“index contacts”; odds ratio [OR], 7.7 [95% confidence interval (CI), 2.5–19.3] relative to individuals who did not report exposure to potential mpox case patients). Among these participants, 10 of 13 case patients (76.9%) and 2 of 5 controls (40.0%) reported that their index contacts were not experiencing symptoms visible to participants during sex (OR, 14.9 [95% CI, 3.6–101.8]). Only 3 of 54 case patients (5.6%) reported exposure to symptomatic index contacts. Case patients reported more anal/vaginal sex partners than did controls (adjusted OR, 2.2 [95% CI, 1.0–4.8] for 2–3 partners and 3.8 [1.7–8.8] for ≥4 partners). Male case patients with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR, 9.3 [95% CI, 1.6–54.8]). Case patients with anorectal lesions more commonly reported receptive anal sex than those without anorectal lesions (adjusted OR, 14.4 [95% CI, 1.0–207.3]).

Conclusions

Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to more sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants’ assessment of symptoms in partners may be imperfect, these findings suggest that individuals without visibly prominent mpox symptoms transmit infection.
Genome-wide DNA Methylation Profiling in Lyme Neuroborreliosis Reveals Altered Methylation Patterns of HLA Genes
Authors: Henningsson Anna J , Hellberg Sandra , Lerm Maria , Sayyab Shumaila
Published: October 2023

Lyme neuroborreliosis (LNB) is a complex neuroinflammatory disorder caused by Borrelia burgdorferi, which is transmitted through tick bites. Epigenetic alterations, specifically DNA methylation (DNAm), could play a role in the host immune response during infection. In this study, we present the first genome-wide analysis of DNAm in peripheral blood mononuclear cells from patients with LNB and those without LNB. Using a network-based approach, we highlighted HLA genes at the core of these DNAm changes, which were found to be enriched in immune-related pathways. These findings shed light on the role of epigenetic modifications in the LNB pathogenesis that should be confirmed and further expanded upon in future studies.
Degradation of glycosylinositol phosphoceramide during plant tissue homogenization
Authors: Takai Yoshimichi , Hasi Rumana Yesmin , Matsumoto Naoko , Fujita Chiho , Ali Hanif , Hayashi Junji , Kawakami Ryushi , Aihara Mutsumi , Ishikawa Toshiki , Imai Hiroyuki , Wakida Mayuko , Ando Kazuya , Tanaka Tamotsu
Published: October 2023

A convenient method for the determination of plant sphingolipids (glycosylinositol phosphoceramide, GIPC; glucosylceramide, GluCer; phytoceramide 1-phosphate, PC1P and phytoceramide, PCer) was developed. This method includes the extraction of lipids using 1-butanol, alkali hydrolysis with methylamine and separation by TLC. The amounts of sphingolipids in the sample were determined based on the relative intensities of standard sphingolipids visualized by primulin/UV on TLC. Using this method, we found that almost all GIPCs were degraded in response to tissue homogenization in cruciferous plants (cabbage, broccoli and Arabidopsis thaliana). The decrease in GIPCs was compensated for by increases in PC1P and PCer, indicating that GIPC was degraded by hydrolysis at the D and C positions of GIPC, respectively. In carrot roots and leaves, most of GIPC degradation was compensated for by an increase in PCer. In rice roots, the decrease in GIPCs was not fully explained by the increases in PC1P and PCer, indicating that enzymes other than phospholipase C and D activities operated. As the visualization of lipids on TLC is useful for detecting the appearance or disappearance of lipids, this method will be available for the characterization of metabolism of sphingolipids in plants.
Is income inequality converging at the regional level? Evidence from LIS data
Authors: Erfurth Philipp
Published: October 2023

Interest in regional convergence in mean incomes has been rekindled by findings that suggest a shift from convergence to divergence. While the majority of existing research has explored convergence in mean incomes, this research focuses specifically on the convergence/divergence of interpersonal income distributions across regions, referred to throughout the study as comparative inter-regional inter-personal income distributions (CIRIPID). The findings suggest that CIRIPID, as measured by the Gini coefficient, converge across countries, but that heterogenous trends are visible within countries. The results highlight that in some countries regions are becoming equally more unequal, while others see regional Gini coefficients trend towards a lower level of inequality. The study also explores the impact of systems of government on CIRIPID. In addition, the study draws on the convergence club methodology to identify heterogeneous CIRIPID convergence paths within countries.
Arabidopsis transcription factor TCP13 promotes shade avoidance syndrome-like responses by directly targeting a subset of shade-responsive gene promoters
Authors: Hur Yoon-Sun , Oh Jeonghwa , Kim Namuk , Kim Sunghan , Son Ora , Kim Jiyoung , Um Ji-Hyun , Ji Zuowei , Kim Min-ha , Ko Jae-Heung , Ohme-Takagi Masaru , Choi Giltsu , Cheon Choong-Ill
Published: October 2023

TCP13 belongs to a subgroup of TCP transcription factors implicated in the shade avoidance syndrome (SAS), but its exact role remains unclear. Here, we show that TCP13 promotes the SAS-like response by enhancing hypocotyl elongation and suppressing flavonoid biosynthesis as a part of the incoherent feed-forward loop in light signaling. Shade is known to promote the SAS by activating PHYTOCHROME-INTERACTING FACTOR (PIF)–auxin signaling in plants, but we found no evidence in a transcriptome analysis that TCP13 activates PIF–auxin signaling. Instead, TCP13 mimics shade by activating the expression of a subset of shade-inducible and cell elongation-promoting SAUR genes including SAUR19, by direct targeting of their promoters. We also found that TCP13 and PIF4, a molecular proxy for shade, repress the expression of flavonoid biosynthetic genes by directly targeting both shared and distinct sets of biosynthetic gene promoters. Together, our results indicate that TCP13 promotes the SAS-like response by directly targeting a subset of shade-responsive genes without activating the PIF–auxin signaling pathway.
Constraints on thermal conductivity in the merging cluster Abell 2146
Authors: Richard-Laferrière A , Russell H R , Fabian A C , Chadayammuri U , Reynolds C S , Canning R E A , Edge A C , Hlavacek-Larrondo J , King L J , McNamara B R , Nulsen P E J , Sanders J S
Published: October 2023

The cluster of galaxies Abell 2146 is undergoing a major merger and is an ideal cluster to study intracluster medium (ICM) physics, as it has a simple geometry with the merger axis in the plane of the sky, its distance allows us to resolve features across the relevant scales and its temperature lies within Chandra’s sensitivity. Gas from the cool core of the subcluster has been partially stripped into a tail of gas, which gives a unique opportunity to look at the survival of such gas and determine the rate of conduction in the ICM. We use deep 2.4-Ms Chandra observations of Abell 2146 to produce a high spatial resolution map of the temperature structure along a plume in the ram-pressure stripped tail, described by a partial cone, which is distinguishable from the hot ambient gas. Previous studies of conduction in the ICM typically rely on estimates of the survival time for key structures, such as cold fronts. Here we use detailed hydrodynamical simulations of Abell 2146 to determine the flow velocities along the stripped plume and measure the time-scale of the temperature increase along its length. We find that conduction must be highly suppressed by multiple orders of magnitude compared to the Spitzer rate, as the energy used is about 1  per cent of the energy available. We discuss magnetic draping around the core as a possible mechanism for suppressing conduction.
Hybrid Epigenomes Reveal Extensive Local Genetic Changes to Chromatin Accessibility Contribute to Divergence in Embryonic Gene Expression Between Species
Authors: Devens Hannah R , Davidson Phillip L , Byrne Maria , Wray Gregory A
Published: October 2023

Chromatin accessibility plays an important role in shaping gene expression, yet little is known about the genetic and molecular mechanisms that influence the evolution of chromatin configuration. Both local (cis) and distant (trans) genetic influences can in principle influence chromatin accessibility and are based on distinct molecular mechanisms. We, therefore, sought to characterize the role that each of these plays in altering chromatin accessibility in 2 closely related sea urchin species. Using hybrids of Heliocidaris erythrogramma and Heliocidaris tuberculata, and adapting a statistical framework previously developed for the analysis of cis and trans influences on the transcriptome, we examined how these mechanisms shape the regulatory landscape at 3 important developmental stages, and compared our results to similar analyses of the transcriptome. We found extensive cis- and trans-based influences on evolutionary changes in chromatin, with cis effects generally larger in effect. Evolutionary changes in accessibility and gene expression are correlated, especially when expression has a local genetic basis. Maternal influences appear to have more of an effect on chromatin accessibility than on gene expression, persisting well past the maternal-to-zygotic transition. Chromatin accessibility near gene regulatory network genes appears to be distinctly regulated, with trans factors appearing to play an outsized role in the configuration of chromatin near these genes. Together, our results represent the first attempt to quantify cis and trans influences on evolutionary divergence in chromatin configuration in an outbred natural study system and suggest that chromatin regulation is more genetically complex than was previously appreciated.
Impact of bound ssRNA length on allostery in the Dengue Virus NS3 helicase
Authors: Amrein Fernando , Sarto Carolina , Cababie Leila A , Gonzalez Flecha F Luis , Kaufman Sergio B , Arrar Mehrnoosh
Published: October 2023

The presence of ATP is known to stimulate helicase activity of the Dengue Virus Non-structural protein 3 helicase (NS3h), and the presence of RNA stimulates NS3h ATPase activity, however this coupling is still mechanistically unclear. Here we use atomistic models and molecular dynamics simulations to evaluate the single-stranded RNA (ssRNA)-length dependence of the NS3h–ssRNA binding affinity and its modulation by bound ATP. Considering complexes with 7, 11, 16 and 26 nucleotides (nts), we observe that both the binding affinity and its modulation by bound ATP are augmented with increased ssRNA lengths. In models with at least 11 nts bound, the binding of ATP results in a shift from a tightly bound to a weakly bound state. We find that the weakly bound state persists during both the ADP-Pi- and ADP-bound stages of the catalytic cycle. We obtain the equilibrium association constants for NS3h binding to an ssRNA 10-mer in vitro, both in the absence and presence of ADP, which further support the alternation between tightly and weakly bound states during the catalytic cycle. The length of bound ssRNA is critical for understanding the NS3h–RNA interaction as well as how it is modulated during the catalytic cycle.
CancerProteome: a resource to functionally decipher the proteome landscape in cancer
Authors: Lv Dezhong , Li Donghao , Cai Yangyang , Guo Jiyu , Chu Sen , Yu Jiaxin , Liu Kefan , Jiang Tiantongfei , Ding Na , Jin Xiyun , Li Yongsheng , Xu Juan
Published: October 2023

Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.hrbmu.edu.cn/CancerProteome), which functionally deciphers and visualizes the proteome landscape in cancer. We manually curated and re-analyzed publicly available MS-based quantification and post-translational modification (PTM) proteomes, including 7406 samples from 21 different cancer types, and also examined protein abundances and PTM levels in 31 120 proteins and 4111 microproteins. Six major analytical modules were developed with a view to describe protein contributions to carcinogenesis using proteome analysis, including conventional analyses of quantitative and the PTM proteome, functional enrichment, protein–protein associations by integrating known interactions with co-expression signatures, drug sensitivity and clinical relevance analyses. Moreover, protein abundances, which correlated with corresponding transcript or PTM levels, were evaluated. CancerProteome is convenient as it allows users to access specific proteins/microproteins of interest using quick searches or query options to generate multiple visualization results. In summary, CancerProteome is an important resource, which functionally deciphers the cancer proteome landscape and provides a novel insight for the identification of tumor protein markers in cancer.
Dynamics of ribosome composition and ribosomal protein phosphorylation in immune signaling in Arabidopsis thaliana
Authors: Siodmak Anna , Martinez-Seidel Federico , Rayapuram Naganand , Bazin Jeremie , Alhoraibi Hanna , Gentry-Torfer Dione , Tabassum Naheed , Sheikh Arsheed H , Kise José Kenyi González , Blilou Ikram , Crespi Martin , Kopka Joachim , Hirt Heribert
Published: October 2023

In plants, the detection of microbe-associated molecular patterns (MAMPs) induces primary innate immunity by the activation of mitogen-activated protein kinases (MAPKs). We show here that the MAMP-activated MAPK MPK6 not only modulates defense through transcriptional regulation but also via the ribosomal protein translation machinery. To understand the effects of MPK6 on ribosomes and their constituent ribosomal proteins (RPs), polysomes, monosomes and the phosphorylation status of the RPs, MAMP-treated WT and mpk6 mutant plants were analysed. MAMP-activation induced rapid changes in RP composition of monosomes, polysomes and in the 60S ribosomal subunit in an MPK6-specific manner. Phosphoproteome analysis showed that MAMP-activation of MPK6 regulates the phosphorylation status of the P-stalk ribosomal proteins by phosphorylation of RPP0 and the concomitant dephosphorylation of RPP1 and RPP2. These events coincide with a significant decrease in the abundance of ribosome-bound RPP0s, RPP1s and RPP3s in polysomes. The P-stalk is essential in regulating protein translation by recruiting elongation factors. Accordingly, we found that RPP0C mutant plants are compromised in basal resistance to Pseudomonas syringae infection. These data suggest that MAMP-induced defense also involves MPK6-induced regulation of P-stalk proteins, highlighting a new role of ribosomal regulation in plant innate immunity.
FL-circAS: an integrative resource and analysis for full-length sequences and alternative splicing of circular RNAs with nanopore sequencing
Authors: Chiang Tai-Wei , Jhong Song-En , Chen Yu-Chen , Chen Chia-Ying , Wu Wei-Sheng , Chuang Trees-Juen
Published: October 2023

Circular RNAs (circRNAs) are RNA molecules with a continuous loop structure characterized by back-splice junctions (BSJs). While analyses of short-read RNA sequencing have identified millions of BSJ events, it is inherently challenging to determine exact full-length sequences and alternatively spliced (AS) isoforms of circRNAs. Recent advances in nanopore long-read sequencing with circRNA enrichment bring an unprecedented opportunity for investigating the issues. Here, we developed FL-circAS (https://cosbi.ee.ncku.edu.tw/FL-circAS/), which collected such long-read sequencing data of 20 cell lines/tissues and thereby identified 884 636 BSJs with 1 853 692 full-length circRNA isoforms in human and 115 173 BSJs with 135 617 full-length circRNA isoforms in mouse. FL-circAS also provides multiple circRNA features. For circRNA expression, FL-circAS calculates expression levels for each circRNA isoform, cell line/tissue specificity at both the BSJ and isoform levels, and AS entropy for each BSJ across samples. For circRNA biogenesis, FL-circAS identifies reverse complementary sequences and RNA binding protein (RBP) binding sites residing in flanking sequences of BSJs. For functional patterns, FL-circAS identifies potential microRNA/RBP binding sites and several types of evidence for circRNA translation on each full-length circRNA isoform. FL-circAS provides user-friendly interfaces for browsing, searching, analyzing, and downloading data, serving as the first resource for discovering full-length circRNAs at the isoform level.
GDPF: a data resource for the distribution of prokaryotic protein families across the global biosphere
Authors: Pan Zhuo , Li Dan-dan , Li Peng , Geng Yu , Jiang Yiru , Liu Ya , Li Yue-zhong , Zhang Zheng
Published: October 2023

Microorganisms encode most of the functions of life on Earth. However, conventional research has primarily focused on specific environments such as humans, soil and oceans, leaving the distribution of functional families throughout the global biosphere poorly comprehended. Here, we present the database of the global distribution of prokaryotic protein families (GDPF, http://bioinfo.qd.sdu.edu.cn/GDPF/), a data resource on the distribution of functional families across the global biosphere. GDPF provides global distribution information for 36 334 protein families, 19 734 superfamilies and 12 089 KEGG (Kyoto Encyclopedia of Genes and Genomes) orthologs from multiple source databases, covering typical environments such as soil, oceans, animals, plants and sediments. Users can browse, search and download the distribution data of each entry in 10 000 global microbial communities, as well as conduct comparative analysis of distribution disparities among multiple entries across various environments. The GDPF data resource contributes to uncovering the geographical distribution patterns, key influencing factors and macroecological principles of microbial functions at a global level, thereby promoting research in Earth ecology and human health.
Crossroads of Antimicrobial and Diagnostic Stewardship: Assessing Risks to Develop Clinical Decision Support to Combat Multidrug-Resistant Pseudomonas
Authors: Zou Iris , Abate Daniel , Newman Michelle , Heil Emily L , Leekha Surbhi , Claeys Kimberly C
Published: October 2023

Background

Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)–integrated tool for prediction of MDRP infection.

Methods

This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP.

Results

The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69–.83] and 0.73 [95% CI, .66–.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57–.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection >3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred.

Conclusions

These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.
A unique cell population expressing the Epithelial-Mesenchymal Transition-transcription factor Snail moderates microglial and astrocyte injury responses
Authors: Clarkson-Paredes Cheryl , Karl Molly T , Popratiloff Anastas , Miller Robert H
Published: October 2023

Insults to the central nervous system (CNS) elicit common glial responses including microglial activation evidenced by functional, morphological, and phenotypic changes, as well as astrocyte reactions including hypertrophy, altered process orientation, and changes in gene expression and function. However, the cellular and molecular mechanisms that initiate and modulate such glial response are less well-defined. Here we show that an adult cortical lesion generates a population of ultrastructurally unique microglial-like cells that express Epithelial-Mesenchymal Transcription factors including Snail. Knockdown of Snail with antisense oligonucleotides results in a postinjury increase in activated microglial cells, elevation in astrocyte reactivity with increased expression of C3 and phagocytosis, disruption of astrocyte junctions and neurovascular structure, increases in neuronal cell death, and reduction in cortical synapses. These changes were associated with alterations in pro-inflammatory cytokine expression. By contrast, overexpression of Snail through microglia-targeted an adeno-associated virus (AAV) improved many of the injury characteristics. Together, our results suggest that the coordination of glial responses to CNS injury is partly mediated by epithelial-mesenchymal transition-factors (EMT-Fsl).
Diagnostic values, association with disease activity and possible risk factors of anti-PAD4 in rheumatoid arthritis: a meta-analysis
Authors: Zhang Guangyue , Xu Jiayi , Du Dongru , Liu Yi , Dai Lunzhi , Zhao Yi
Published: October 2023

Objective

Anti-peptidyl arginine deaminase 4 (anti-PAD4) antibody has been a subject of investigation in RA in the last two decades. This meta-analysis investigated the diagnostic values, association with disease activity and possible risk factors of anti-PAD4 antibody in rheumatoid arthritis.

Method

We searched studies from five databases up to 1 December 2022. Bivariate mixed-effect models were used to pool the diagnostic accuracy indexes, and the summary receiver operating characteristics (SROC) curve was plotted. The quality of diagnostic studies was assessed using QUADAS-2. Non-diagnostic meta-analyses were conducted using the random-effects model. Sensitivity analysis, meta-regression, subgroup analyses and Deeks’ funnel plot asymmetry test were used to address heterogeneity.

Result

Finally, 24 journal articles and one letter were included. Anti-PAD4 antibody had a good diagnostic value between RA and healthy individuals, but it might be lower between RA and other rheumatic diseases. Moreover, anti-PAD4 could slightly enhance RA diagnostic sensitivity with a combination of ACPA or ACPA/RF. Anti-PAD4 antibody was positively correlated with HLA-SE and negatively correlated with ever or current smoking in patients with RA. RA patients with anti-PAD4 antibody had higher DAS28, ESR, swollen joint count (SJC) and the possibility of having interstitial lung disease (ILD) and pulmonary fibrosis compared with those without.

Conclusion

Our study suggests that anti-PAD4 antibody is a potentially useful diagnostic biomarker and clinical indicator for RA. Further mechanistic studies are required to understand the impact of HLA-SE and smoking on the production of anti-PAD4 antibody.
What makes an entrepreneurial university? Institutional moderators of ecosystem impacts in a developing country
Authors: Schaeffer Paola Rücker , Fischer Bruno Brandão , Queiroz Sérgio , Moraes Gustavo Hermínio Salati Marcondes de
Published: October 2023

Entrepreneurial universities have become a key concept in debates concerning regional economic development. Yet, we still fall short of having a clear comprehension of the enablers of such localized impacts arising from academic activity. Such conditions are particularly critical for the context of developing countries, which have mostly mimicked initiatives taking place in the context of developed markets. To address these issues, we analyze the impacts generated by research-intensive universities on local innovation ecosystems. We apply a combination of econometric and case study methods for the state of São Paulo, Brazil. Results suggest that research-intensive universities, mostly public universities, positively impact their respective innovation ecosystems. Moreover, qualified research funds and the existence of a support structure (incubators and science and technology parks) significantly enhance the impacts generated by research-intensive universities. These findings highlight the relationship between the internal constraints of universities and their capacity to generate impacts on local ecosystems.
Pediatric Renal Pseudotumors: A Pictorial Review
Authors: Thomas Aby
Published: October 2023

Many renal lesions in the pediatric age group might mimic a renal neoplasm on imaging but may be proven on biopsy to be a wrong radiologic diagnosis. This describes the pseudotumors that a pediatric radiologist needs to remember and lesions with similar imaging characteristics.
Interstitial lung diseases in inborn errors of immunity
Authors: Sullivan Neal P. , Maniam Nivethietha , Maglione Paul J.
Published: October 2023

Purpose of review

Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts.

Recent findings

Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency.

ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic.
Intraoperative Radiation Exposure in Adolescent Idiopathic and Neuromuscular Scoliosis
Authors: Fares Nicole , Levey Sarah Toner , Ashy Cody , McFadden Ryan , Barfield William , Murphy Robert F. , Dow Matthew A. , Van Nortwick Sara S.
Published: October 2023

Background:

Intraoperative imaging is often used to aid pedicle screw placement during scoliosis operations. Higher rates of cancer and death have been observed in orthopaedic surgeons and radiation technologists, including a fourfold higher rate of breast cancer in female orthopaedic surgeons. The purpose of this study was to evaluate variability in intraoperative radiation during spinal fusions for both adolescent idiopathic scoliosis (AIS) and neuromuscular scoliosis (NMS).

Methods:

A retrospective review of posterior spinal fusion and segmental spinal instrumentation for scoliosis performed by pediatric orthopaedic surgeons from 2017 to 2019 at a single institution was performed. Inclusion criteria included: a diagnosis of AIS or NMS and patients between 8 and 18 years of age. Exclusion criteria included: revision surgery, use of intraoperative navigation, and patients younger than 10 at the time of scoliosis onset within the AIS cohort. Data collected included: preoperative curve, body mass index (BMI), number of levels fused, number of Ponte osteotomies, and fluoroscopy time. One-way analysis of variance tests, Bonferroni post hoc tests, independentttests, and Pearson correlations were utilized with significance determined at the 95% confidence level (a= 0.05).

Results:

A total of 148 patients were included in the study. The average fluoroscopy time was 143 ± 67 seconds. Patients with NMS had higher average fluoroscopy times (193 ± 75 s) compared with patients with AIS (129 ± 58 s,P< 0.001). In patients with AIS, fluoroscopy time correlated to the patient’s preoperative curve (r= 0.182,P= 0.050). Patients with AIS with fewer than 12 levels fused had significantly less radiation exposure than those with 12 or more levels fused (P= 0.01). When controlling for the number of levels fused, patients with AIS with higher BMIs had significantly greater fluoroscopy times (P= 0.001). In patients with NMS, fluoroscopy time negatively correlated with BMI (r= −0.459,P= 0.009) and positively correlated with a preoperative curve (r= 0.475,P= 0.007).

Conclusion:

Fluoroscopy times vary greatly during adolescent spinal fusions for scoliosis. Longer fluoroscopy times are correlated with: NMS diagnosis, larger preoperative curve, BMI, and number of levels fused. Surgeons' knowledge of factors affecting fluoroscopy time will increase awareness and may be the first step in decreasing intraoperative radiation risks.

Level of Evidence:

Level III; Therapeutic—a retrospective study.
Depressive Symptoms in Autistic Youth with Anxiety Disorders
Authors: Greenberg Rebecca L. , Guzick Andrew G. , Schneider Sophie C. , Weinzimmer Saira A. , Kook Minjee , Perozo Garcia Amanda B. , Storch Eric A.
Published: October 2023

Objective:

Anxiety and depression often coexist in youth and share overlapping symptomatology; however, little is known about the comorbidity of anxiety and depression in autistic youth. This study explores (1) the frequency of depressive symptoms among autistic children with clinically significant anxiety, (2) clinical variables that may be associated with elevated depressive symptoms, and (3) whether pretreatment depressive symptoms predict cognitive behavioral therapy (CBT) outcomes for anxiety.

Method:

Children aged 7 to 13 years (N = 87) and their parents participated in a randomized controlled trial comparing 2 versions of a parent-led, telehealth-delivered CBT program. Parents and children completed a variety of clinical assessments and self-report questionnaires before and after treatment.

Results:

Fifty-seven percent of the child sample reported experiencing elevated depressive symptoms while roughly 20% of parents reported elevated depressive symptoms in their child. A strong association between anxiety and depression was found. Heightened feelings of loneliness, per child report, and functional impairment, per parent report, were found to be uniquely associated with elevated depressive symptoms. Finally, depressive symptoms were not a significant predictor of CBT outcomes for anxiety.

Conclusion:

Findings suggest high degrees of comorbidity between anxiety and depression among autistic children and that feelings of loneliness, anxiety, and functional impairment may be early indicators of mood-related concerns. Further research is needed to determine the full extent of the association between anxiety and depression and additional options for treating depression in autistic children.
Changes in diaphragmatic ultrasonography findings and their association with postoperative complications in children undergoing pulmonary resection
Authors: Lee Ji-Hyun , Kang Pyoyoon , Park Jung-Bin , Kim Jin-Tae
Published: October 2023

BACKGROUND

Few studies have investigated the changes in diaphragmatic function and their association with postoperative pulmonary complications (PPCs) in paediatric patients after lung resection.

OBJECTIVE

This study aimed to evaluate diaphragmatic function using ultrasound after lung resection and its influence on PCCs in children.

DESIGN

Prospective observational study.

SETTING

A tertiary children's hospital.

PATIENTS

Children aged 6 years or less who were scheduled for video-assisted thoracoscopic lung resection.

INTERVENTION

Ultrasonographic measurements of diaphragmatic excursion (DE) and thickening fraction (TF) were performed for three epochs: before anaesthesia induction (T0), 1 h postoperatively (T1) and 24 h postoperatively (T2). The thickening fraction is calculated from the thickness of the diaphragm at end expiration and end inspiration at each time point. DET1/DET0, DET2/DET0, TFT1/TFT0 and TFT2/TFT0 (%) were calculated. The incidence of PCCs was also determined.

MAIN OUTCOME MEASURES

The primary outcomes were changes in diaphragmatic excursion and thickening fraction over time, from T0 to T2. The secondary outcomes were the association between ultrasound parameters of diaphragm function and the occurrence of early PPCs within 3 days.

RESULTS

Data from 74 children were analysed. On the operated side, both diaphragmatic excursion and thickening fraction decreased at T1 and recovered slightly at T2, and were significantly lower than the T0 values. Children with PPCs had significantly lower DET2/DET0 and TFT2/TFT0 scores on the operated side than those without PPCs. According to the receiver operating characteristic analysis, the DET2/DET0 (< 61.1%) on the operated side was associated with PPCs with an area under the curve of 0.764.

CONCLUSIONS

Peri-operative diaphragmatic function assessed by ultrasonography changed after lung resection in children. The diaphragmatic excursion and thickening fraction decreased postoperatively, and a prolonged decrease in diaphragmatic excursion was associated with pulmonary complications after lung surgery in children.

CLINICAL TRIAL REGISTRY

ClinicalTrials.gov, NCT04400370
CSF3R T618I Collaborates With RUNX1-RUNX1T1 to Expand Hematopoietic Progenitors and Sensitizes to GLI Inhibition
Authors: Swoboda Anja S. , Arfelli Vanessa C. , Danese Anna , Windisch Roland , Kerbs Paul , Redondo Monte Enric , Bagnoli Johannes W. , Chen-Wichmann Linping , Caroleo Alessandra , Cusan Monica , Krebs Stefan , Blum Helmut , Sterr Michael , Enard Wolfgang , Herold Tobias , Colomé-Tatché Maria , Wichmann Christian , Greif Philipp A.
Published: October 2023

Activating colony-stimulating factor-3 receptor gene (CSF3R) mutations are recurrent in acute myeloid leukemia (AML) with t(8;21) translocation. However, the nature of oncogenic collaboration between alterations of CSF3R and the t(8;21) associated RUNX1-RUNX1T1 fusion remains unclear. In CD34+ hematopoietic stem and progenitor cells from healthy donors, double oncogene expression led to a clonal advantage, increased self-renewal potential, and blast-like morphology and distinct immunophenotype. Gene expression profiling revealed hedgehog signaling as a potential mechanism, with upregulation of GLI2 constituting a putative pharmacological target. Both primary hematopoietic cells and the t(8;21) positive AML cell line SKNO-1 showed increased sensitivity to the GLI inhibitor GANT61 when expressing CSF3R T618I. Our findings suggest that during leukemogenesis, the RUNX1-RUNXT1 fusion and CSF3R mutation act in a synergistic manner to alter hedgehog signaling, which can be exploited therapeutically.
Association between retinal pigment epithelium tear and anti-vascular endothelial growth factor therapy: A systematic review and meta-analysis
Authors: Shi Hekai , Guo Nuojin , Zhao Zeming , Duan Jialiang
Published: October 2023

Purpose:

To identify the prevalence of retinal pigment epithelium tear (RPET) after anti-vascular endothelial growth factor (VEGF) therapy and determine the efficacy of continued anti-VEGF therapy in patients with RPET.

Methods:

We screened all relevant clinical trials and observational studies in several online databases. The main outcomes were the incidence of RPET after anti-VEGF therapy and changes in visual acuity for patients with RPET treated with continued anti-VEGF. The time point for outcome assessment was the last follow-up time.

Results:

The pooled incidence of RPET after anti-VEGF therapy from twenty-four studies with 17,354 patients was 1.9% (95% CI: 1.3–2.7%). Most new RPET cases were concentrated in the first month at baseline or after the first injection during anti-VEGF therapy and gradually decreased by the subsequent month or injection. Thirteen studies with 157 patients reported that for patients who received anti-VEGF therapy after RPET, their pooled best-corrected visual acuity improved but did not reach a significant level (SMD 0.34; 95% CI: -0.03, 0.71).

Conclusion:

The incidence of RPET after anti-VEGF therapy is low. The intravitreal anti-VEGF injection might accelerate this process . For patients with RPET, maintenance of anti-VEGF therapy ensure visual acuity stability.
Fibrinogen Aα gene genotyping in patients with inherited afibrinogenemia deficiency; a novel mutation in Iranian afibrinogenemia patients
Authors: Moazzeni Ali , Naderi Majid , Dorgalaleh Akbar , Alizadeh Shaban
Published: October 2023

Background

Congenital fibrinogen deficiencies (CFD) are a group of rare bleeding disorders (RBD). Afibrinogenemia as a subclass of these disorders would occurs as a result of mutations in fibrinogen gene. Here in, the sequences of Aα chain of fibrinogen (FGA) in patients with inherited afibrinogenemia disorder in south-eastern of Iran were analysed.

Methods

The FGA gene exons were amplified using PCR method and the DNA sequences were analysed to study the mutations in Aα chain of Fibrinogen.

Results

Results showed that there was no large deletion in FGA gene. Although a frame shift mutation: c.196_197insT p.Ser66PhefsX10 in a patient and a novel mutation of IVS2-1G>A in two other patients were detected which were different from those detected in European population.

Conclusion

Different mutations are responsible of afibrinogenemia deficiency which requires more relevant studies for confirmation. The type and distribution of mutations in fibrinogen gene in Iranian patients is significantly different with reported mutations in European patients.