bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of chemotherapies for unresectable extramammary Paget disease: a single-centre retrospective study
Authors: Wada Shogo , Ogata Dai , Nakano Eiji , Namikawa Kenjiro , Yamazaki Naoya 
Published: May 2023

Abstract

Background
Extramammary Paget disease (EMPD) is a cutaneous neoplasm that can metastasize to the lymph nodes and distant organs, resulting in a poor prognosis. For unresectable distant metastases of EMPD, no consensus has been reached regarding optimal chemotherapy owing to a lack of data.

Objectives
To evaluate the efficacy of three regimens: docetaxel (DTX) monotherapy; combination therapy with 5-ﬂuorouracil, epirubicin, carboplatin, vincristine and mitomycin C (FECOM); and tegafur (S-1) monotherapy.

Methods
This single-centre retrospective study included 32 patients diagnosed with unresectable EMPD and treated with chemotherapy between 2002 and 2022 at the National Cancer Center Hospital in Japan. Patient characteristics, responses to treatment and survival data were evaluated for each of the first-line therapies.

Results
Among the 17 patients who received DTX monotherapy, the response rate (RR) and disease control rate (DCR) were 47% and 77%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 12.3 months [95% confidence interval (CI) 6.1–26.6] and 19.2 months (95% CI 8.5–not reached), respectively. Among the 11 patients who received combination FECOM chemotherapy, the RR and DCR were 55% and 64%, respectively. The median PFS and OS were 6.8 months (95% CI 3.5–not reached) and 13.4 months (95% CI 8.6–21.3), respectively. Among the four patients who received S-1 monotherapy, the RR and DCR were 0% and 25%, respectively. The median PFS and OS were 5.4 months (95% CI 2.3–not reached) and 12.5 (95% CI 2.3–not reached) months, respectively.

Conclusions
Further investigations with prospective analysis are required to confirm these findings.
Activation of the aryl hydrocarbon receptor inhibits the development of experimental autoimmune pancreatitis through IL-22-mediated signaling pathways
Authors: Kamata Ken , Hara Akane , Minaga Kosuke , Yoshikawa Tomoe , Kurimoto Masayuki , Sekai Ikue , Okai Natsuki , Omaru Naoya , Masuta Yasuhiro , Otsuka Yasuo , Takada Ryutaro , Takamura Shiki , Kudo Masatoshi , Strober Warren , Watanabe Tomohiro 
Published: May 2023

Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in hematopoietic and non-hematopoietic cells. Activation of the AhR by xenobiotics, microbial metabolites, and natural substances induces immunoregulatory responses. Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disorder of the pancreas driven by autoimmunity. Although AhR activation generally suppresses pathogenic autoimmune responses, the roles played by the AhR in AIP have been poorly defined. In this study, we examined how AhR activation affected the development of experimental AIP caused by the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Experimental AIP was induced in MRL/MpJ mice by repeated injections of polyinosinic-polycytidylic acid. Activation of the AhR by indole-3-pyruvic acid and indigo naturalis, which were supplemented in the diet, inhibited the development of experimental AIP, and these effects were independent of the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Interaction of indole-3-pyruvic acid and indigo naturalis with AhRs robustly augmented the production of IL-22 by pancreatic islet α cells. The blockade of IL-22 signaling pathways completely canceled the beneficial effects of AhR ligands on experimental AIP. Serum IL-22 concentrations were elevated in patients with type 1 AIP after the induction of remission with prednisolone. These data suggest that AhR activation suppresses chronic fibroinflammatory reactions that characterize AIP via IL-22 produced by pancreatic islet α cells.
In Search of Lost Haim: Homer and Heimat in the Dialectic of Enlightenment
Authors: Youd David 
Published: May 2023

Abstract
In this essay, I return to Horkheimer and Adorno’s reading of the Odyssey in the Dialectic of Enlightenment to suggest that Odysseus’s crew comes to figure ‘the Jew’ as a representative of nature in the antisemitic Imaginary—the nature that enlightenment continues to repress. Escape from enlightenment’s deadlock will depend on the ‘remembrance’ of that nature, an operation itself considered ‘Jewish’ and enacted in the epic’s dialectical form.
Monocyte heterogeneity in cardiovascular disease
Authors: Ruder Adele V , Wetzels Suzan M W , Temmerman Lieve , Biessen Erik A L , Goossens Pieter 
Published: May 2023

AbstractMonocytes circulate the vasculature at steady state and are recruited to sites of inflammation where they differentiate into macrophages (MФ) to replenish tissue-resident MФ populations and engage in the development of cardiovascular disease (CVD). Monocytes display considerable heterogeneity, currently reflected by a nomenclature based on their expression of cluster of differentiation (CD) 14 and CD16, distinguishing CD14++CD16− classical (cMo), CD14++CD16+ intermediate (intMo) and CD14+CD16++ non-classical (ncMo) monocytes. Several reports point to shifted subset distributions in the context of CVD, with significant association of intMo numbers with atherosclerosis, myocardial infarction, and heart failure. However, clear indications of their causal involvement as well as their predictive value for CVD are lacking.As recent high-parameter cytometry and single-cell RNA sequencing (scRNA-Seq) studies suggest an even higher degree of heterogeneity, better understanding of the functionalities of these subsets is pivotal. Considering their high heterogeneity, surprisingly little is known about functional differences between MФ originating from monocytes belonging to different subsets, and implications thereof for CVD pathogenesis. This paper provides an overview of recent findings on monocyte heterogeneity in the context of homeostasis and disease as well as functional differences between the subsets and their potential to differentiate into MФ, focusing on their role in vessels and the heart. The emerging paradigm of monocyte heterogeneity transcending the current tripartite subset division argues for an updated nomenclature and functional studies to substantiate marker-based subdivision and to clarify subset-specific implications for CVD.
Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension
Authors: Mohammed Mazher , Ogunlade Blessing , Elgazzaz Mona , Berdasco Clara , Lakkappa Navya , Ghita Ioana , Guidry Jessie J , Sriramula Srinivas , Xu Jiaxi , Restivo Luke , Mendiola Plá Michelle A , Bowles Dawn E , Beyer Andreas M , Yue Xinping , Lazartigues Eric , Filipeanu Catalin M 
Published: May 2023

Abstract

Aims
Angiotensin-converting enzyme 2 (ACE2) is a critical component of the compensatory renin–angiotensin system that is down-regulated during the development of hypertension, possibly via ubiquitination. However, little is known about the mechanisms involved in ACE2 ubiquitination in neurogenic hypertension. This study aimed at identifying ACE2 ubiquitination partners, establishing causal relationships and clinical relevance, and testing a gene therapy strategy to mitigate ACE2 ubiquitination in neurogenic hypertension.

Methods and results
Bioinformatics and proteomics were combined to identify E3 ubiquitin ligases associated with ACE2 ubiquitination in chronically hypertensive mice. In vitro gain/loss of function experiments assessed ACE2 expression and activity to validate the interaction between ACE2 and the identified E3 ligase. Mutation experiments were further used to generate a ubiquitination-resistant ACE2 mutant (ACE2-5R). Optogenetics, blood pressure telemetry, pharmacological blockade of GABAA receptors in mice expressing ACE2-5R in the bed nucleus of the stria terminalis (BNST), and capillary western analysis were used to assess the role of ACE2 ubiquitination in neurogenic hypertension. Ubiquitination was first validated as leading to ACE2 down-regulation, and Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) was identified as a E3 ligase up-regulated in hypertension and promoting ACE2 ubiquitination. Mutation of lysine residues in the C-terminal of ACE2 was associated with increased activity and resistance to angiotensin (Ang)-II-mediated degradation. Mice transfected with ACE2-5R in the BNST exhibited enhanced GABAergic input to the paraventricular nucleus (PVN) and a reduction in hypertension. ACE2-5R expression was associated with reduced Nedd4-2 levels in the BNST.

Conclusion
Our data identify Nedd4-2 as the first E3 ubiquitin ligase involved in ACE2 ubiquitination in Ang-II-mediated hypertension. We demonstrate the pivotal role of ACE2 on GABAergic neurons in the maintenance of an inhibitory tone to the PVN and the regulation of pre-sympathetic activity. These findings provide a new working model where Nedd4-2 could contribute to ACE2 ubiquitination, leading to the development of neurogenic hypertension and highlighting potential novel therapeutic strategies.
Positive fungal interactions are key drivers in Antarctic endolithic microcosms at the boundaries for life sustainability
Authors: Biagioli Federico , Coleine Claudia , Buzzini Pietro , Turchetti Benedetta , Sannino Ciro , Selbmann Laura 
Published: May 2023

Abstract
In the ice-free areas of Victoria Land in continental Antarctica, where the conditions reach the limits for life sustainability, highly adapted and extreme-tolerant microbial communities exploit the last habitable niches inside porous rocks (i.e. cryptoendolithic communities). These guilds host the main standing biomass and principal, if not sole, contributors to environmental/biogeochemical cycles, driving ecosystem processes and functionality in these otherwise dead lands. Although knowledge advances on their composition, ecology, genomic and metabolic features, a large-scale perspective of occurring interactions and interconnections within and between endolithic fungal assemblages is still lacking to date. Unravelling the tight relational network among functional guilds in the Antarctic cryptoendolithic communities may represent a main task. Aiming to fill this knowledge gap, we performed a correlation-network analysis based on amplicon-sequencing data of 74 endolithic microbiomes collected throughout Victoria Land. Endolithic communities' compositional pattern was largely dominated by Lichenized fungi group (83.5%), mainly represented by Lecanorales and Lecideales, followed by Saprotrophs (14.2%) and RIF+BY (2.4%) guilds led by Tremellales and Capnodiales respectively. Our findings highlighted that fungal functional guilds' relational spectrum was dominated by cooperative interactions led by lichenised and black fungi, deeply engaged in community trophic sustain and protection, respectively. On the other hand, a few negative correlations found may help in preserving niche boundaries between microbes living in such strict spatial association.
Detecting and excluding disturbed forest areas improves site index determination using bitemporal airborne laser scanner data
Authors: Moan Maria Å , Noordermeer Lennart , White Joanne C , Coops Nicholas C , Bollandsås Ole M 
Published: May 2023

Abstract
Bitemporal airborne laser scanning (ALS) data are increasingly being used in forest management inventories for the determination of site index (SI). SI determination using bitemporal ALS data requires undisturbed height growth of dominant trees. Therefore, areas with disturbed top height development are unsuitable for SI determination, and should be identified and omitted before modelling, predicting and estimating SI using bitemporal ALS data. The aim of this study was to explore methods for classifying the suitability of forest areas for SI determination based on bitemporal ALS data. The modelling approaches k-nearest neighbour, logistic regression and random forest were compared for classifying disturbed (at least one dominant tree has disappeared) and undisturbed plots. A forest inventory with plot re-measurements and corresponding bitemporal ALS data from the Petawawa Research Forest in Ontario, Canada, was used as a case study. Based on the field data, two definitions of a disturbed plot were developed: (1) at least one dominant tree had died, was harvested or had fallen during the observation period, or (2) at least one dominant tree was harvested or had fallen during the observation period. The first definition included standing dead trees, which we hypothesized would be more difficult to accurately classify from bitemporal ALS data. Models of disturbance definition 1 and 2 yielded Matthews correlation coefficients of 0.46–0.59 and 0.62–0.80, respectively. Fit statistics of SI prediction models fitted to undisturbed plots were significantly better (P &lt; 0.05) than fit statistics of SI prediction models fitted to all plots. Our results show that bitemporal ALS data can be used to separate disturbed from undisturbed forest areas with moderate to high accuracy in complex temperate mixedwood forests and that excluding disturbed forest areas significantly improves fit statistics of SI prediction models.
A Simple Nomogram for Predicting Hospital Mortality of Patients Over 80 Years in ICU: An International Multicenter Retrospective Study
Authors: Liu Chao , Liu Xiaoli , Hu Mei , Mao Zhi , Zhou Yibo , Peng Jinyu , Geng Xiaodong , Chi Kun , Hong Quan , Cao Desen , Sun Xuefeng , Zhang Zhengbo , Zhou Feihu 
Published: May 2023

AbstractObjectivesThis study aimed to develop and validate an easy-to-use intensive care unit (ICU) illness scoring system to evaluate the in-hospital mortality for very old patients (VOPs, over 80 years old).MethodsWe performed a multicenter retrospective study based on the electronic ICU (eICU) Collaborative Research Database (eICU-CRD), Medical Information Mart for Intensive Care Database (MIMIC-III CareVue and MIMIC-IV), and the Amsterdam University Medical Centers Database (AmsterdamUMCdb). Least Absolute Shrinkage and Selection Operator regression was applied to variables selection. The logistic regression algorithm was used to develop the risk score and a nomogram was further generated to explain the score.ResultsWe analyzed 23 704 VOPs, including 3 726 deaths (10 183 [13.5% mortality] from eICU-CRD [development set], 12 703 [17.2%] from the MIMIC, and 818 [20.8%] from the AmsterdamUMC [external validation sets]). Thirty-four variables were extracted on the first day of ICU admission, and 10 variables were finally chosen including Glasgow Coma Scale, shock index, respiratory rate, partial pressure of carbon dioxide, lactate, mechanical ventilation (yes vs no), oxygen saturation, Charlson Comorbidity Index, blood urea nitrogen, and urine output. The nomogram was developed based on the 10 variables (area under the receiver operating characteristic curve: training of 0.792, testing of 0.788, MIMIC of 0.764, and AmsterdamUMC of 0.808 [external validating]), which consistently outperformed the Sequential Organ Failure Assessment, acute physiology score III, and simplified acute physiology score II.ConclusionsWe developed and externally validated a nomogram for predicting mortality in VOPs based on 10 commonly measured variables on the first day of ICU admission. It could be a useful tool for clinicians to identify potentially high risks of VOPs.
Model order reduction for seismic waveform modelling: inspiration from normal modes
Authors: Hawkins R , Khalid M H , Smetana K , Trampert J 
Published: May 2023

SUMMARY
The computational cost of full waveform simulation in seismological contexts is known to be expensive and generally requires large clusters of computers working in parallel. Although there have been many methods proposed over recent years to reduce this burden, in this work, we focus on a particular method called model order reduction (MOR) whereby a full waveform system of equations is projected onto a lower dimensional space to reduce computational and memory requirements at the cost of introducing approximation errors. In this paper, inspired by normal mode (NM) theory, we use the eigenmodes of the seismic wave equation to span this lower dimensional space. From this we argue that NM theory can be seen as an early form of MOR. Using this as inspiration, we demonstrate how free body oscillations and a form of Petrov–Galerkin projection can be applied in regional scale problems utilizing recent advanced eigensolvers to create a MOR scheme. We also demonstrate how this can be applied to inverse problems. We further conjecture that MOR will have an important role to play in future full waveform applications, particularly those of a time-critical nature such as seismic hazard monitoring.
P- and S-wave energy current density vectors dot product imaging condition of source time-reversal imaging
Authors: Hu Nan , Zhang Wei , Xu Jincheng , Yang Hui , Li Yanpeng 
Published: May 2023

SUMMARY
Source time-reversal imaging (TRI) based on decoupled elastic wave equation can utilize vector P- and S-wave time differences and achieve high-precision source location in complex geological models. The imaging condition is critical for TRI. However, because of the orthogonally polarized properties of P and S waves, traditional vector dot product imaging condition directly applied to TRI will decrease the effective imaging values. In contrast, the energy current density vectors of P and S waves represent the propagation directions of the wavefields and are almost parallel. Their dot product can result in the maximum imaging energy. Based on this principle, we propose a P- and S-wave energy current density vectors dot product imaging condition (PSEDPIC), which uses the propagation direction information of P and S waves at the source point to suppress imaging artefacts generated by waves with inconsistent propagation directions. Numerical tests reveal that PSEDPIC can (1) reduce the image artefacts, (2) improve the imaging spatial resolution and (3) allow a shallower imaging region. In addition, if the numerical simulation algorithm used in TRI can reconstruct the seismic wavefield accurately in the presence of surface topography, the impact of an observation system with elevation differences on imaging can be eliminated automatically. For this reason, we use the curvilinear grid finite-difference method to directly reconstruct the wavefield in TRI to solve the problem of data elevation correction. The test results of 3-D synthetic and field data for microseismic monitoring demonstrate the effectiveness of the proposed method.
Influence of trailing edge curve on the performance of radial turbine in turbocharger
Authors: Yun Jeong-Eui , Atac Omer Faruk , Kim Jung-Bae , Kim Gi-Yong 
Published: May 2023

Abstract
To combat climate change and promote sustainable engine development, the optimization of the turbocharger development process is necessary to decrease emissions and increase fuel economy. This article presents the influence of trailing edge curves on the performance of the significantly small radial turbine impeller of an automotive turbocharger used in a 0.8-l two-cylinder gasoline engine by comparing numerical analysis results under two boundary conditions: a constant pressure ratio and constant mass flow rate. The curve of a trailing edge depends on several parameters; however, in this study, the exponent ($n$) was selected to modify the turbine impeller trailing edge profile, as it exhibits a more significant influence on the curve than other parameters. Hence, computational fluid dynamics analyses were conducted on the radial turbine for various trailing edge curves under a constant pressure ratio and constant mass flow rate, and the results were compared. The results indicated that the efficiency improvement was negligible under the pressure ratio and mass flow rate conditions due to inadequate alterations. Nevertheless, a significant shaft power improvement was observed based on changes in the trailing edge curve under a constant pressure ratio. In contrast, the same changes caused a considerable decrease in the shaft power under a constant mass flow rate.
On the Algebraicity of Polyquadratic Plectic Points
Authors: Fornea Michele , Gehrmann Lennart 
Published: May 2023

Abstract
We establish direct evidence of the arithmetic significance of plectic Stark–Heegner points for elliptic curves of arbitrarily large rank. The main contribution is a proof of the algebraicity of plectic points associated to polyquadratic CM extensions of totally real number fields. Moreover, we relate the non-vanishing of plectic points to analytic and algebraic ranks of elliptic curves.
Reduced Exercise Capacity, Chronotropic Incompetence, and Early Systemic Inflammation in Cardiopulmonary Phenotype Long Coronavirus Disease 2019
Authors: Durstenfeld Matthew S , Peluso Michael J , Kaveti Punita , Hill Christopher , Li Danny , Sander Erica , Swaminathan Shreya , Arechiga Victor M , Lu Scott , Goldberg Sarah A , Hoh Rebecca , Chenna Ahmed , Yee Brandon C , Winslow John W , Petropoulos Christos J , Kelly J Daniel , Glidden David V , Henrich Timothy J , Martin Jeffrey N , Lee Yoo Jin , Aras Mandar A , Long Carlin S , Grandis Donald J , Deeks Steven G , Hsue Priscilla Y 
Published: May 2023

Abstract

Background
Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or “long COVID”) remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

Methods
We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults &gt;1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers.

Results
Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (&lt;85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1–8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent.

Conclusions
Cardiopulmonary symptoms &gt;1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with “long COVID.”
CRISPR Correction of the GBA Mutation in Human-Induced Pluripotent Stem Cells Restores Normal Function to Gaucher Macrophages and Increases Their Susceptibility to Mycobacterium tuberculosis
Authors: Ramalingam Sivaprakash , Kumar Amit , Krug Stefanie , Mohan Harikrishnan , Rao Desirazu N , Bishai William R , Chandrasegaran Srinivasan 
Published: May 2023

Abstract
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA−/−) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/−) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA−/−, GBA+/− and GBA+/+ hiPSCs showed that GBA mutation correction restores normal macrophage functions: GCase activity, motility, and phagocytosis. Furthermore, infection of GBA−/−, GBA+/− and GBA+/+ macrophages with the Mycobacterium tuberculosis H37Rv strain showed that impaired mobility and phagocytic activity were correlated with reduced levels of bacterial engulfment and replication suggesting that GD may be protective against tuberculosis.