bluuebunny/crossref_metadata_2025 huggingface dataset:
Geography of Artificial Intelligence Technologies in Russia
Authors: Zemtsov S. P.
Published: January 2025

The geography of innovation makes it possible to identify spatial patterns of creation, implementation, and diffusion of new technologies, but with the development of communications, an illusion appeared that space is insignificant. In accordance with the aim of the study, the article shows that creation and implementation of artificial intelligence (AI) as one of the radical innovations cannot be widespread. It will be concentrated in centers with high innovation potential and specialized tacit knowledge, where the intensity of knowledge spillovers is higher. In Russia, an education in AI can be obtained in 21 regions, research is conducted in 35, and technology is being developed in 40. The article proposes a rating of regional potential for AI creating, assessing scientific and technological development and density of the main elements of regional innovation ecosystems. The rating shows a high concentration of potential in the largest urban agglomeration, Moscow, and several creative cores: Moscow oblast, St. Petersburg, the Republic of Tatarstan, and Novosibirsk oblast. Sixteen centers have been identified capable of both creating and implementing certain AI technologies: Sverdlovsk, Nizhny Novgorod, Chelyabinsk, Samara, Tomsk, and Rostov oblasts, Krasnodar krai, etc.; 23 regions that are predominantly acceptor centers using AI advanced production technologies and 41 regions with minimal potential. Leading regions may receive priority attention and funding by investors. In acceptor regions, public policy priority may be given to supporting production automation, and in lagging regions, preference may be given to increasing the population’s receptivity to digital technologies.
Surveillance in inflammatory bowel disease: white light endoscopy with segmental re-inspection versus dye-based chromoendoscopy – a multi-arm randomised controlled trial (HELIOS)
Authors: te Groen Maarten , Wijnands Anouk M , den Broeder Nathan , de Jong Dirk J , van Dop Willemijn A , Duijvestein Marjolijn , Fidder Herma H , van Schaik Fiona , Hirdes Meike M C , van der Meulen-de Jong Andrea E , Maljaars P W Jeroen , Voorneveld Philip W , de Boer K H Nanne , Peters Charlotte P , Oldenburg Bas , Hoentjen Frank
Published: January 2025

Background

It remains unclear if the increased colorectal neoplasia detection rate in inflammatory bowel disease (IBD) by high-definition (HD) dye-based chromoendoscopy compared with HD white-light endoscopy is due to enhanced contrast or increased inspection times. Longer withdrawal times may yield similar neoplasia detection rates as found by HD chromoendoscopy.

Objective

To compare colorectal neoplasia detection rates for HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy, using single-pass HD white-light endoscopy as an additional control group.

Design

In a multicentre, randomised controlled trial, IBD patients aged ≥18 years without active disease and scheduled for endoscopic surveillance were included. Patients were 2:2:1 randomised to HD white-light endoscopy with segmental re-inspection of each colonic segment (double pass), HD chromoendoscopy or single-pass HD white-light endoscopy. The primary outcome was colorectal neoplasia detection rate. Assuming equal colorectal neoplasia rates (non-inferiority margin of 10%) between segmental re-inspection and chromoendoscopy and superiority of segmental re-inspection vs single-pass HD white-light endoscopy, a sample size of 566 patients was required.

Results

In total, 563 patients were analysed per-protocol. Colorectal neoplasia detection rates were 10.3% (n=24/234) for HD white-light endoscopy with segmental re-inspection and 13.1% (n=28/214) for HD chromoendoscopy. This confirmed non-inferiority to HD chromoendoscopy (Δ−2.8%, lower limit 95% CI −7.8, p<0.01). In addition, the number of detected colorectal neoplasia per 10 min of withdrawal time was similar between HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy (0.062 vs 0.058, p=0.83). Single-pass HD white-light endoscopy yielded a lower colorectal neoplasia rate (6.1%; n=7/115) than segmental re-inspection but this was not statistically significant (Δ4.1%, 95% CI −2.2:9.6%, p=0.19).

Conclusions

HD white-light endoscopy with segmental re-inspection was non-inferior to HD chromoendoscopy for colorectal neoplasia detection in IBD patients. It can therefore be assumed that the benefit of HD chromoendoscopy may be explained by the longer withdrawal time and not necessarily the enhanced contrast. However, re-inspection per se did not lead to a significantly higher colorectal neoplasia rate than single-pass HD white-light endoscopy alone.
Dynamical systems of modified Gauss–Bonnet gravity: cosmological implications
Authors: Singh Ashutosh
Published: January 2025

In this paper, we derive the field equations of modified Gauss–Bonnet gravity termed as f(R, G) gravity for the non-flat Friedmann–Robertson–Walker (FRW) spacetime. We utilize the dynamical system approach to study the cosmic dynamics of two different class of f(R, G) models composed of radiation and matter (cold dark matter and baryonic matter). The linear perturbations around the fixed points are studied to explore the corresponding stability of points. The cosmological implications are studied in

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models to identify the qualitative evolution of universe with the flat-FRW spacetime. The qualitative differences between the considered class of models are discussed in detail. The fixed points corresponding to the late-time accelerated and radiation phase of the universe will exist in the model but, the existence of fixed point corresponding to the matter dominated phase will depend on the functional form of f(R, G). Furthermore, the autonomous systems are utilized to study the cosmographic parameters along with the statefinder diagnostic.
Data from Activation of NKT Cells in an Anti-PD-1–Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells
Authors: Bae Eun-Ah , Seo Hyungseok , Kim Byung-Seok , Choi Jeongwon , Jeon Insu , Shin Kwang-Soo , Koh Choong-Hyun , Song Boyeong , Kim Il-Kyu , Min Byung Soh , Han Yoon Dae , Shin Sang Joon , Kang Chang-Yuil
Published: January 2025

Abstract
PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1–resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T-cell exhaustion. We also found that invariant natural killer T cell stimulation by the synthetic ligand α-galactosylceramide (αGC) can enhance the antitumor effect in anti-PD-1–resistant tumors by restoring the effector function of tumor antigen–specific exhausted CD8 T cells. IL2 and IL12 were among the cytokines produced by αGC stimulation critical for reinvigorating exhausted CD8 T cells in tumor-bearing mice and patients with cancer. Furthermore, we observed a synergistic increase in the antitumor effect between αGC-loaded antigen-presenting cells and PD-1 blockade in a therapeutic murine tumor model. Our study suggests NKT cell stimulation as a promising therapeutic strategy for the treatment of patients with anti-PD-1–resistant cancer.

Significance: These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer. Cancer Res; 78(18); 5315–26. ©2018 AACR.
PRDM1 is a key regulator of the natural killer T–cell central memory program and effector function
Authors: Tian Gengwen , Barragán Gabriel A. , Yu Hangjin , Martinez-Amador Claudia , Adaikkalavan Akshaya , Rios Xavier , Guo Linjie , Drabek Janice M. , Pardias Osmay , Xu Xin , Montalbano Antonino , Zhang Chunchao , Li Yanchuan , Courtney Amy N. , Di Pierro Erica J. , Metelitsa Leonid S.
Published: January 2025

Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.CAR) were transduced with the gRNA library and exposed to CD1d+ leukemia or CD1d–GD2+ neuroblastoma cells, respectively, over six challenge cycles in vitro. Quantification of gRNA abundance revealed enrichment of PRDM1-specific gRNAs in both NKTs and GD2.CAR NKTs, a result that was validated through targeted PRDM1 knockout. Transcriptional, phenotypic, and functional analyses demonstrated that CAR NKTs with PRDM1 knockout underwent central memory–like differentiation and resisted exhaustion. However, these cells downregulated the cytotoxic mediator granzyme B and showed reduced in vitro cytotoxicity and only moderate in vivo antitumor activity in a xenogeneic neuroblastoma model. In contrast, shRNA-mediated PRDM1 knockdown preserved effector function while promoting central memory differentiation, resulting in GD2.CAR NKTs with potent in vivo antitumor activity. Thus, we have identified PRDM1 as a regulator of NKT memory differentiation and effector function that can be exploited to improve the efficacy of NKT-based cancer immunotherapies.
Supplementary Table 4 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Top 15 Genes increased in relapse vs diagnosis LCE-MM.
Supplemental Figure 9 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Infer Copy Number Variant Analysis for Subclonal Tracking.
Supplemental Figure 8 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Patients Identified from the CoMMpass Dataset with Light Chain Escape.
Supplemental Figure 6 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Characterization of LAMP5 Effects on MM cell Prognosis, Prognosis and Viability.
Supplemental Figure 1 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Normal Bone Marrow Cell Populations Across Timepoints.
Figure 5 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Patients from the CoMMpass database with LCE have a poor prognosis. A, Fifteen patients identified from CoMMpass with LCE showed significantly shorter PFS from diagnosis than those without LCE. B, Patients identified from CoMMpass with LCE showed significantly shorter OS from diagnosis than those without LCE. C, Patients from CoMMpass with LCE with high LAMP5 expression had a trend toward significantly shorter PFS compared with those with LCE and low LAMP5. D, Patients from CoMMpass with LCE with high LAMP5 expression had nonsignificantly shorter OS compared with those with LCE and low LAMP5. E, Patients from CoMMpass with LCE had nonsignificantly shorter time to diffuse lytic lesions compared with those without LCE. F, In particular, all patients identified with both LCE and high LAMP5 expression had diffuse lytic lesions at diagnosis, or soon after. G, The GEP70 score was nonsignificantly higher in patients with LCE and high LAMP5 compared with those with low LAMP5. H, The GEP5 score was significantly higher in patients with LCE and high LAMP5 compared with those with low LAMP5. *, P < 0.05
Figure 4 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Multiple myeloma (MM) subpopulation gene-set exhibits osteolytic features and is detrimental to OS. A, Through the disease course for patient #1093, spikes in serum calcium occurred during periods of disease activity with high levels of LCE-MM. B, The GEP70 score for high-risk MM was significantly higher in the LCE-MM subpopulation compared with the IGH-MM subpopulation. C, Five key genes in the GEP70 score were even more upregulated in LCE-MM compared with IGH-MM. D, In the MMRF cohort, 325 patients had RNA-seq and osteolytic data at diagnosis, with 83 showing high LCE-MM gene-set scores and 79 showing low LCE-MM gene-set scores by gene-set enrichment analysis. E, In the GSE24080 cohort, 254 microarray samples were available from patients at diagnosis, with gene-set enrichment identifying 57 new diagnosis samples with high and 62 samples with low LCE-MM gene-set scores. F, Most of the samples in the MMRF dataset that were enriched for the LCE-MM signature had ≥3 osteolytic lesions (*, P < 0.05; **, P < 0.01; ***, P < 0.001 by the Fisher exact test). G, LCE-MM enriched samples in the MMRF developed diffuse osteolytic lesions at a more rapid rate than those with a low LCE-MM signature (P = 4.9 × 10−3 by Cox-p test). H, Samples in the GSE24080 dataset that were enriched for the LCE-MM gene-set had increased lytic bone lesions relative to samples with a low LCE-MM gene-set score (P < 0.05 by t test). I, In the MMRF dataset patients with high LCE-MM gene enrichment score had worse OS than those with low LCE-MM gene enrichment. J, In the GSE24080 dataset patients with high LCE-MM gene enrichment score also had worse OS than those with low LCE-MM gene enrichment (log-rank test). Dotted lines indicated 50% survival.
Figure 2 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Differential gene expression between multiple myeloma (MM) subpopulations at diagnosis. A, Volcano plot showing genes expressed at higher levels at timepoint 1 in LCE-MM and those higher expressed in IGH-MM with log2 fold-change (l2FC) cutoff above 0.25 (vertical dashed lines) and statistical significance defined as multiple comparison adjusted P value < 0.05 (horizontal dashed line) by linear regression (LCE-MM n = 4,370 cells, IGH-MM n = 281 cells). B,LAMP5 had the highest fold change in LCE-MM compared with IGH-MM (l2FC: 1.68, P = 6.68 × 10−131, left), with an expression pattern mostly restricted to this subpopulation and low in normal cell types (right). C, Another notable transcript overexpressed in LCE-MM compared with IGH-MM was the oncogene MYC (l2FC: 1.06, P: 1.63 × 10−33). Of note, both MM subpopulation overexpressed MYC compared with normal cells. D, Gene-set enrichment analysis using the KEGG identified the oxidative phosphorylation pathway to be upregulated in LCE-MM. E, In IGH-MM, the HIF-1 signaling pathway was the most overrepresented gene-set. CA, cancer; ER, endoplasmic reticulum; OR, odds ratio (***, P < 0.001).
Medical and early developmental outcomes for patients with congenital ventriculomegaly
Authors: Coronel Anna , Bierbrauer Karin S. , He Hua , Tolusso Leandra Kay , Peiro Jose L.
Published: January 2025

Introduction: This study evaluated whether comorbidities such as genetic conditions, other congenital anomalies, infection, and other exposures impact the mortality rate and/or neurologic outcomes of patients with congenital ventriculomegaly.

Methods: This was a retrospective cohort study that assessed the mortality rate and developmental delay of 91 patients diagnosed with congenital ventriculomegaly followed at Cincinnati Children’s Hospital Medical Center between Jan 1, 2010-Dec 31, 2020.

Results: Of the 91 patients included in the study, 20 (22.0%) had a genetic diagnosis. The mortality rate was higher for patients with a genetic diagnosis compared to those without a genetic diagnosis (p=0.022), as was the rate of developmental delay (p=0.026). The presence of comorbidities (confirmed genetic condition, confirmed maternal exposures or infections, and/or additional anomalies) were not associated with an increased risk of mortality nor developmental delay.

Conclusions: Patients diagnosed with congenital ventriculomegaly and a genetic condition have a significantly higher risk of early mortality and developmental delay compared to those without a genetic diagnosis. Therefore, diagnostic genetic testing should be considered after identification of congenital ventriculomegaly to facilitate counseling about prognosis and care management.
Das Update der EULAR-Empfehlungen für die systemische Sklerose zeigt Fortschritt zumindest bei der Lungenbeteiligung
Authors: Aringer Martin
Published: January 2025

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies. Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review. The evidence derived was discussed and overarching principles, recommendations and future research agenda were iteratively developed with voting rounds. Results: The task force agreed on 22 recommendations covering 8 clinical/organ domains including Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease (ILD), gastrointestinal manifestations and arthritis. Most new recommendations are related to skin fibrosis and ILD. These included novel recommendations for the use of mycophenolate mofetil, nintedanib, rituximab and tocilizumab for the treatment of these crucial disease manifestations. The recommendations also included first-line and second-line interventions, providing increased utility for rheumatology practitioners. Important additions to the future research agenda included consideration of novel interventions for the management of vascular, musculoskeletal and gastrointestinal manifestations and calcinosis, as well as for the local management of digital ulcers. Conclusion: These updated recommendations include the first set of synthetic and biological targeted therapies recommended for key fibrotic manifestations of SSc as well as first-line combination treatment for newly diagnosed pulmonary artery hypertension and prioritise a new research agenda for the coming years.
Das Muster der gewöhnlichen interstitiellen Pneumonie bei rheumatischen Autoimmunerkrankungen
Authors: Luppi Fabrizio , Manfredi Andreina , Faverio Paola , Andersen Michael Brun , Bono Francesca , Pagni Fabio , Salvarani Carlo , Bendstrup Elisabeth , Sebastiani Marco
Published: January 2025

Die gewöhnliche interstitielle Pneumonie (UIP) ist durch die fortschreitende Lungenparenchymveränderung gekennzeichnet, die bei verschiedenen rheumatischen Autoimmunerkrankungen (ARD), einschließlich rheumatoider Arthritis und Bindegewebserkrankungen, beobachtet werden kann. Aus diagnostischer Sicht kann ein UIP-Muster im Zusammenhang mit ARD bildgebende und pathologische Merkmale aufweisen, mit denen es von dem Muster im Zusammenhang mit der idiopathischen Lungenfibrose (IPF) unterschieden werden kann, etwa das «Straight-Edge»-Zeichen in der HRCT und lymphoplasmazytäre Infiltrate bei histologischen Proben. Ein multidisziplinärer Ansatz (MDD), an dem zumindest Pneumologen, Rheumatologen und Radiologen beteiligt sind, ist für den Differenzialdiagnoseprozess von grundlegender Bedeutung. Der MDD ist jedoch auch für die Bewertung des Schweregrads, des Fortschreitens und des Ansprechens auf die Behandlung erforderlich, die auf der Kombination von Veränderungen der Symptome, Entwicklungen der Lungenfunktion und bei ausgewählten Patienten auf einer seriellen CT-Evaluierung basiert. Im Gegensatz zur IPF können bei Patienten mit ARD sowohl die funktionelle Bewertung als auch die von den Patienten berichteten Ergebnisse durch systemische Beteiligung und Komorbiditäten, einschließlich muskuloskelettaler Manifestationen der Erkrankung, beeinflusst werden. Im Hinblick auf die pharmakologische Behandlung wurden Immunsuppressiva trotz des Mangels an solider Evidenz in den meisten Fällen als Eckpfeiler der Therapie angesehen; in letzter Zeit wurden auch antifibrotische Medikamente für die Behandlung von progressiven fibrosierenden interstitiellen Lungenerkrankungen (ILD) außer IPF vorgeschlagen. Bei der ARD-ILD soll die therapeutische Wahl die Notwendigkeit der Kontrolle von systemischen und Lungenbeteiligungen mit dem Risiko unerwünschter Ereignisse durch Multimorbiditäten und -therapien in Einklang bringen. Ziel dieser Übersichtsarbeit ist es, die Definition, die radiologischen und die morphologischen Merkmale des UIP-Musters bei ARD zusammen mit den Risikofaktoren, diagnostischen Kriterien, einer prognostischen Bewertung und Überwachungs- und Behandlungsansätzen der UIP-ARD zusammenzufassen.
Erfolgreiche Behandlung eines Patienten mit therapierefraktärer rheumatoider Arthritis-assoziierter interstitieller Lungenerkrankung mit Upadacitinib: ein Fallbericht
Authors: Nishii Yuuya , Okamoto Masaki , Zaizen Yoshiaki , Kojima Takashi , Nouno Takashi , Naitou-Nishida Yoshiko , Matsuo Norikazu , Takeoka Hiroaki , Ishida Motoko , Nakamura Masataka , Masuda Toru , Tanaka Takafumi , Miyamura Tomoya , Hoshino Tomoaki
Published: January 2025

Es gibt keine ausreichende Evidenz für die Wirksamkeit von Januskinase-Inhibitoren (JAKi), einer Klasse gezielter synthetischer krankheitsmodifizierender Antirheumatika (tsDMARD), bei der Behandlung der interstitiellen Lungenerkrankung (ILD), die mit rheumatoider Arthritis (RA) assoziiert ist. Hier stellen wir einen Fall von RA-ILD vor, der gegenüber früheren Behandlungen refraktär war und ein günstiges Ansprechen auf Upadacitinib zeigte. Ein 69-jähriger Mann, ehemaliger Raucher, wurde mit RA-ILD diagnostiziert, basierend auf einer persistierenden symmetrischen Polyarthritis, erhöhten CRP-Spiegeln (C-reaktives Protein) und Erythrozyten-Sedimentationsraten, einer verminderten Diffusionskapazität für Kohlenmonoxid/vermindertes Alveolarvolumen (DLCO 69,9%) und einer bilateralen Milchglastrübung mit Traktionsbronchiektasie, vorwiegend im unteren Lungenlappen. Es wurde eine initiale Behandlung mit oralem Prednisolon und Methotrexat begonnen; der Patient zeigte jedoch eine Verschlechterung der Dyspnoe, Anomalien in der hochauflösenden Computertomografie des Brustraums und eine verminderte Lungenfunktion. Die Prednisolon-Dosis wurde erhöht und Methotrexat zugunsten von Tacrolimus ersetzt; Tacrolimus wurde jedoch schließlich aufgrund einer Nierenfunktionsstörung abgesetzt. Nachfolgende Behandlungsänderungen beinhalteten Abatacept gefolgt von intravenösem Cyclophosphamid, doch die ILD-Aktivität verschlechterte sich weiter und erfüllte die Kriterien einer progressiven Lungenfibrose. Etwa 4,5 Jahre nach der RA-Diagnose verbesserten sich die Dyspnoe, die radiologischen Anomalien und die DLCO nach Umstellung der Behandlung auf Upadacitinib, einer der JAKi. Die JAKi-Therapie kann als Behandlungsoption für refraktäre RA-ILD infrage kommen.
Zusammenhang zwischen Muskelqualitätsindex und Lungenfunktion bei Post-COVID-19-Patienten
Authors: González-Islas Dulce , Robles-Hernández Robinson , Flores-Cisneros Laura , Orea-Tejeda Arturo , Galicia-Amor Susana , Hernández-López Nadia , Sánchez-Santillán Rocío , Sánchez-Santillán Rocío , García-Hernández Juan Carlos , Castorena-Maldonado Armando
Published: January 2025

Hintergrund: Die SARS-CoV-2-Pandemie hatte Auswirkungen auf viele kritisch kranke Patienten, verursachte Folgeerscheinungen, beeinträchtigte die Lungenfunktion und betraf zudem den Bewegungsapparat. Wir haben den Zusammenhang zwischen Lungenfunktion und Muskelqualitätsindex bei schwer erkrankten Patienten nach COVID-19 bewertet. Methoden: Es wurde eine Querschnittsstudie an einer Post-COVID-19-Kohorte in einem Maximalversorgungszentrum durchgeführt. Die Studie umfasste Patienten, bei denen eine schwere bis kritische COVID-19-Erkrankung aufgetreten war. Anthropometrische Messungen wie Body-Mass-Index (BMI) und Handgriffstärke wurden zur Berechnung des Muskelqualitätsindex (MQI) erhalten. Darüber hinaus wurden eine Spirometrie, Messungen des exspiratorischen und inspiratorischen Drucks und eine Bewertung der Kohlenmonoxid-Diffusionskapazität (DLCO) in der Lunge durchgeführt. Anhand des MQI erfolgte eine Unterteilung in 2 Gruppen: niedriger MQI (unter dem 50. Perzentil) und hoher MQI (über dem 50. Perzentil), basierend auf dem Geschlecht. Die Gruppenunterschiede wurden analysiert, und es wurde eine multivariate lineare Regressionsanalyse durchgeführt, um den Zusammenhang zwischen der Atemfunktion und dem MQI zu bewerten. Ergebnisse: Von den 748 analysierten Patienten mussten 61,96% mechanisch beatmet werden und der mittlere Krankenhausaufenthalt betrug 17 Tage. Bei Patienten mit einem niedrigen MQI wurde beobachtet, dass sowohl die mechanische Atemfunktion als auch die DLCO niedriger waren. Die multivariate Analyse ergab bei Patienten mit einem niedrigen MQI signifikant niedrigere Befunde bei der mechanischen Atemfunktion. Schlussfolgerung: Der niedrige MQI ist ein unabhängiger Prädiktor für Lungenfunktionsparameter bei Patienten mit Post-COVID-19-Syndrom.
Rundherddiagnostik: Fortschritt durch integrierte Tool-in-Lesion-Tomosynthese in der Roboter-Navigationsbronchoskopie
Authors: Hagmeyer Lars
Published: January 2025

Background and Objective: As the presentation of pulmonary nodules increases, the importance of a safe and accurate method of sampling peripheral pulmonary nodules is highlighted. First-generation robotic bronchoscopy has successfully assisted navigation and improved peripheral reach during bronchoscopy. Integrating tool-in-lesion tomosynthesis (TiLT) may further improve yield. Methods: We performed a first-in-human clinical trial of a new robotic electromagnetic navigation bronchoscopy system with integrated digital tomosynthesis technology (Galaxy System, Noah Medical). Patients with moderate-risk peripheral pulmonary nodules were enrolled in the study. Robotic bronchoscopy was performed using electromagnetic navigation with TiLT-assisted lesion guidance. Non-specific results were followed up until either a clear diagnosis was achieved or repeat radiology at 6 months demonstrated stability. Results: Eighteen patients (19 nodules) were enrolled. The average lesion size was 20 mm, and the average distance from the pleura was 11.6 mm. The target was successfully reached in 100% of nodules, and the biopsy tool was visualized inside the target lesion in all cases. A confirmed specific diagnosis was achieved in 17 nodules, 13 of which were malignant. In one patient, radiological monitoring confirmed a true non-malignant result. This translates to a yield of 89.5% (strict) to 94.7% (intermediate). Complications included one pneumothorax requiring observation only and another requiring an overnight chest drain. There was one case of severe pneumonia following the procedure.
The central control of energy metabolism; hypothalamic obesity is not one disease.
Authors: van Santen Hanneke M.
Published: January 2025

Background
The hypothalamus, a neuro-endocrine gland located centrally in the brain, weighs only on average 4 grams but is the captain on the ship of our energy balance. In the hypothalamus, signals of the satiety and hunger hormones are integrated and individuals with a dysfunctional hypothalamus develop obesity. The hypothalamus, however, integrates much more than the satiety and hunger hormones and hypothalamic obesity may be the result of a combination of factors.
Summary
The consequences of hypothalamic dysfunction can be categorized in six different domains. By systematically evaluating each domain, the underlying cause for obesity may be better understood and doors for successful management can be opened. The different domains are; pituitary gland dysfunction, behavioral problems, disturbance of the circadian rhythm, hyperphagia, low resting energy expenditure and temperature dysregulation. All of these domains may contribute to the development of obesity and may be more or less present in the individual patient.
Key Messages
Hypothalamic obesity is not one disease, but different underlying contributing factors may be present. Consequently, hypothalamic obesity management is not one-size-fits-all but needs to be personalized. In this paper, the current state of the art for both the diagnostics and approach of acquired hypothalamic obesity is reviewed.
Examining Healthy Lifestyles as a Mediator of the Association Between Socially Determined Vulnerabilities and Incident Heart Failure
Authors: Singh Nickpreet , Jonas Chanel , Pinheiro Laura C. , Lau Jennifer D. , Cui Jinhong , Long Leann , Banerjee Samprit , Durant Raegan W. , Sterling Madeline R. , Shikany James M. , Safford Monika M. , Levitan Emily B. , Goyal Parag
Published: January 2025

BACKGROUND:

Increased burden of socially determined vulnerabilities (SDV), which include nonmedical conditions that contribute to patient health, is associated with incident heart failure (HF). Mediators of this association have not been examined. We aimed to determine if a healthy lifestyle mediates the association between SDV and HF.

METHODS:

We included adults aged 45 to 64 years old across the United States from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke) without evidence of HF at baseline. The primary exposure was a count of SDV based on the Healthy People 2030 framework. The primary outcome was incident HF. We assessed the role of a healthy behavior score (HBS range, 0–8) and its components (adherence to a Mediterranean diet, physical activity, lack of sedentary lifestyle, and smoking abstinence) as potential mediators of the association between SDV and incident HF.

RESULTS:

We included 13 on 525 participants. The median HBS was 4, with 16% with low HBS (0–2), 55% with moderate HBS (3–5), and 29% with high HBS (6–8). Increasing burden of SDV was associated with a stepwise increase in incident HF (adjusted hazard ratio, 1.84 [95% CI, 1.32–2.52] for 1 SDV, 2.59 [95% CI, 1.87–3.60] for 2 SDV, and 4.20 [95% CI, 3.08–5.73] for ≥3 SDV). There was no statistically significant mediation of HBS for the association of SDV count of 1 and incident HF. HBS score mediated 10.6% of the association between SDV count of 2 and incident HF and 11.1% of the association for those with ≥3 SDV. This increased to 10.8% and 18.3%, respectively, in the complete case analysis. Regarding individual components of HBS as mediators, only avoidance of a sedentary lifestyle was statistically significant (8.6% mediation) for the association of SDV count of 2 and incident HF.

CONCLUSIONS:

A healthy lifestyle plays a small role in mediating the association between high SDV count and incident HF.
Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension
Authors: Mutchler Ashley L. , Haynes Alexandria Porcia , Saleem Mohammad , Jamison Sydney , Khan Mohd Mabood , Ertuglu Lale , Kirabo Annet
Published: January 2025

Access to excess dietary sodium has heightened the risk of cardiovascular diseases, particularly affecting individuals with salt sensitivity of blood pressure. Our research indicates that innate antigen-presenting immune cells contribute to rapid blood pressure increases in response to excess sodium intake. Emerging evidence suggests that epigenetic reprogramming, with subsequent transcriptional and metabolic changes, of innate immune cells allows these cells to have a sustained response to repetitive stimuli. Epigenetic mechanisms also steer T-cell differentiation in response to innate immune signaling. Immune cells respond to environmental and nutritional cues, such as salt, promoting epigenetic regulation changes. This article aims to identify and discuss the role of epigenetic mechanisms in the immune system contributing to salt-sensitive hypertension.
Prognostic Impact of 1‐Year Changes in Creatinine‐ and Cystatin C‐Based Estimated Glomerular Filtration Rate After Stroke on 5‐Year Outcomes: Insights From the Third China National Stroke Registry
Authors: Zhang Yin , Pan Yuesong , Yan Hongyi , Meng Xia , Lin Jinxi , Wang Mengxing , Li Hao , Xu Qin , Chen Pan , Wang Anxin , Zhou Yilun , Wang Yongjun
Published: January 2025

Background

The impact of long‐term renal function change on stroke outcomes remains unclear. This study used the CNSR‐III (Third China National Stroke Registry) cohort to determine whether changes in estimated glomerular filtration rate based on creatinine and cystatin C (eGFR
Cr+CysC
) during the first year post stroke were associated with 5‐year stroke outcomes.

Methods and Results

We included 4270 patients with centrally tested serum creatinine and cystatin C at admission and 1 year post admission and evaluated 5‐year follow‐up data. Patients were stratified into quintiles based on the 1‐year changes in eGFR. The primary outcomes included all‐cause mortality, stroke disability, and stroke recurrence. In patients with acute ischemic stroke, the mean baseline eGFR
Cr+CysC
was 88.6±22.6 mL/min per 1.73 m
2
, which decreased by 5.6% to 83.6±20.7 mL/min per 1.73 m
2
at 1 year. Compared with patients with relatively stable eGFR
Cr+CysC
(Q3), those with decreased eGFR
Cr+CysC
(Q1) exhibited significantly increased adjusted risk of death (hazard ratio [HR], 1.96 [95% CI, 1.27–3.04],
P
=0.003) and those with increased eGFR
Cr+CysC
(Q5) exhibited borderline significance (HR, 1.51 [95% CI, 0.94–2.42],
P
=0.09), after adjusting for confounders, including baseline eGFR
Cr+CysC
and albumin‐to‐creatinine ratio. Patients with a significant decrease (odds ratio [OR], 1.74 [95% CI, 1.25–2.42],
P
=0.001) or increase (OR, 1.51 [95% CI, 1.06–2.15],
P
=0.02) in eGFR
Cr+CysC
also experienced a higher risk of disability.

Conclusions

Both the decline and increase in eGFR
Cr+CysC
levels in the first year post stroke were independently associated with all‐cause mortality and stroke disability. These findings indicate that monitoring eGFR
Cr+CysC
changes could be important for predicting long‐term outcomes and informing poststroke care strategies.
Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
Authors: Cheng Yijun , Chen Bin , Zhang Miao , Chen Zhenghong , Liu Mingjian , Zhang Ziqian , Tang Hao , Wang Dapeng , Lv Wenwen , Li Biao , Dai Yuting , Shang Hanbing
Published: January 2025

Background

Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and the underlying mechanism remain poorly understood.

Methods and Results

Thirteen patients diagnosed with unilateral severe CAS underwent pre‐ and post‐CEA assessments, including
18
fluoro‐2‐deoxy‐
d
‐glucose positron emission tomography/magnetic resonance imaging, cognitive assessments, and routine blood tests before and after CEA. Unilateral carotid common artery occlusion and ligation release (reperfusion) surgeries were performed in mice to mimic CAS and CEA. Cognitive function, cerebral blood flow, and white matter damage were evaluated in mice using the Morris water maze test, Doppler flowmetry, laser‐speckle imaging, diffusion tensor imaging, Luxol fast blue staining, transmission electron microscopy, and western blot assays post unilateral carotid common artery occlusion and reperfusion. Genomic sequencing of the white matter was performed to explore the potential underlying mechanism. CEA significantly enhanced the Montreal Cognitive Assessment scores in patients with CAS and preoperative cognitive impairment. Moreover, CEA led to notable improvements in cerebral blood flow, energy metabolism, and white matter integrity, while concurrently reducing blood inflammation. In the mouse model, reperfusion surgery alleviated cognitive deficits, increased cerebral blood flow, and alleviated white matter damage following unilateral carotid common artery occlusion. Furthermore, transcriptional surveys have revealed substantial alterations in the upregulation of Nrf2 signaling and metabolic pathways, coupled with the inhibition of neuroinflammation, cellular communication, and immune cell population signaling following reperfusion.

Conclusions

CEA ameliorated CAS‐induced cognitive dysfunction by improving the cerebral functional structure. These beneficial effects may be attributed to their antioxidant and anti‐inflammatory properties.
Multi-AGV multitask collaborative scheduling based on an improved ant colony algorithm
Authors: Zhu Yazhen , Song Qing , Li Meng
Published: January 2025

Research on multitask scheduling systems in factory environments is a popular topic in the field of intelligent manufacturing. Existing research mainly focuses on the optimization of automated guided vehicle (AGV) path planning and scheduling, emphasizing on the minimization of conflicts and deadlocks, multi-objective task scheduling, and metaheuristic algorithm optimization, while ignoring path stability and real-time path planning in dynamic environments. Therefore, this paper aims to address these issues to better handle dynamic changes in actual operating environments. This paper establishes a mathematical model with the optimization objective of minimizing the overall running time of material distribution tasks and proposes an improved ant colony algorithm to optimize the model. First, the concept of prior time is introduced to improve the traditional ant colony algorithm. The path of the ongoing task is introduced with a time calculation, and the occupancy time window of each grid point on the path is calculated. Based on this, the initial pheromone distribution on subsequent paths is altered dynamically, which accelerates the convergence of the ants to a collision-free path. Second, in the pheromone update stage, the method of calculating the pheromone increment in the traditional ant colony algorithm is modified. The original distance influence factor is changed to a time influence factor, which ensures that all tasks still have the minimum running time when calculating a collision-free path. Finally, through 30 sets of simulation experiments on material distribution tasks, it is shown that the proposed algorithm shortens the total running time by 15.14%, 12.87%, and 10.59% compared to two ant colony algorithms and one strategic multi-AGV scheduling algorithm, respectively, thus verifying the effectiveness of the proposed method.
Relationship between additional mutations at diagnosis and treatment response in patients with essential thrombocythemia
Authors: Mosnier Carole , Bellal Sarah , Cottin Laurane , Boyer-Perrard Francoise , Lemoine Sandrine , Bachelot Amélie , Argentin Joris , Pawlicki Bertille , Copin Marie-Christine , Jouanneau-Courville Rébecca , Malinge Anaïs , Riou Jérémie , Hunault Mathilde , Ugo Valérie , Orvain Corentin , Luque Paz Damien
Published: January 2025

Patients with essential thrombocythemia (ET) have a chronic evolution with a risk of hematological transformation associated with a dismal outcome. Since patients with resistance or intolerance have an adverse prognosis, it is important to identify which patient will respond to first-line treatment. We therefore aim to describe the association between additional mutations and response to first-line treatment in patients with ET. In this retrospective study, we analyzed the molecular landscape of 121 ET patients first-line treated with hydroxyurea (n=86) or pegylated interferon (n=35). Patients undergoing peg-IFN therapy were younger and had higher proportion of low and very low risk of thrombosis recurrence. Sixty-two patients (51%) had ≥1 additional mutations at diagnosis. The most frequent additional mutations involved TET2 (15.7%) DNMT3A (10.7%), non-W515-MPL (6.6%), ASXL1 (4.13%), and splicing factors SRSF2 and SF3B1 (6.6%) genes. At 12-months of treatment, 75 (62%) patients achieved complete response (CR), 37 (31%) partial response, and 7 (6%) no response. The presence of at least one additional mutation at diagnosis was associated with not achieving CR (HR: 0.66;p=0.045), whereas treatment with interferon was associated with higher CR (HR: 2.01;p=0.002). The number of additional mutations at diagnosis was associated with hematologic progressions (p<0.0001). None of the patients receiving peg-IFN therapy progressed to myelofibrosis, while 16/86 patients (19%) treated with HU developed secondary myelofibrosis. In conclusion, our results suggest that the presence of at least one additional mutation at diagnosis is associated with failure to achieve CR and is also associated with an increased risk of hematologic evolution.
A novel tool for assessing pediatric emergency care in low- and middle-income countries: a pilot study
Authors: Jarrett Sonia Y. , Redfern Andrew , Li Joyce , Gutierrez Camilo E. , Patel Priyanka , Akinola Olurotimi , Niescierenko Michelle L.
Published: January 2025

Background

Globally, most children seek emergency care at general rather than specialized pediatric emergency departments. There remains significant variation in the provision of pediatric emergency care, particularly in resource-constrained settings. The objective of this study is to pilot a self-assessment tool to evaluate pediatric emergency care capabilities in low- and middle-income country (LMIC) hospitals on the African Continent.

Methods

This was a prospective cross-sectional descriptive study using a convenience sample of sub-Saharan African hospitals. The assessment tool was developed by operationalizing the technical contents of existing standards and guidelines from international bodies including the World Health Organization and International Federation of Emergency Medicine. The pilot was conducted at emergency departments located across different regions on the African continent. Descriptive statistics were used to evaluate different domains of pediatric emergency care capabilities including pediatric triage, protocols, staffing, training, equipment, consumables, and medicines.

Results

Sixteen hospitals with emergency departments completed the assessment tool (participation rate of 76%). The hospitals were in nine different countries across four regions of sub-Saharan Africa. National/academic hospitals comprised 56.3% of the participating hospitals. The majority, 44%, of these hospitals saw pediatric patient volumes of 2,000–4,999 patients per year. Dedicated pediatric triage spaces and resuscitation spaces were available at 37.5% and 56.3%, respectively. Formal pediatric resuscitation guidelines were used at 62.5%. Doctors on the self-assessment teams came from primarily pediatrics and general practitioner training backgrounds (both 68.8%). Basic respiratory and airway support equipment (e.g. oxygen, bag-valve mask devices) were available in all participating hospitals, whereas advanced airway equipment (e.g. pediatric intubation equipment) was available in 37.5% of hospitals. Most medicines from the World Health Organization Essential Medicines list were available at participating hospitals.

Conclusions

To date, this is the first assessment tool dedicated to the comprehensive evaluation of pediatric emergency care in LMICs. This pilot provides a first approach to evaluate pediatric emergency healthcare capabilities in the hospital setting with future directions to improve the tool based on qualitative feedback.
Racial/ethnic differences in the associations between social support and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Naqvi Jeanean B. , Formagini Taynara , Allison Matthew A. , Kandula Namratha R. , Park Jee Won , Larsen Britta A.
Published: January 2025

Background

Despite the established link between social support and cardiovascular disease (CVD) outcomes, few studies have examined racial/ethnic variation in these associations. This study utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) to investigate racial/ethnic differences in perceived social support and in the link between support and incident hard CVD events and mortality.

Method

Participants (N = 6,814) were 45–84 years of age who identified as White, Black, Hispanic/Latino, or Chinese without known clinical CVD at baseline (2000–2002). Racial/ethnic differences in perceived support (overall, emotional, informational, and instrumental) were tested using multiple regression with adjustments for demographic, socioeconomic, lifestyle/psychosocial, and clinical risk factors, and immigration history. Racial/ethnic differences in the association between perceived support and incident CVD events or mortality were tested using Cox proportional hazards models with progressive adjustments for the same covariates.

Results

At baseline, the mean age was 62.15 years (SD = 10.23); 38.5% identified as White, 27.8% as Black, 22.0% as Hispanic/Latino, and 11.8% as Chinese. Black and Hispanic/Latino participants reported higher levels of overall support, emotional support, and informational support than White participants (p’s < 0.05). Chinese participants reported less informational support (p = .010) than White participants. Higher informational support was associated with decreased risk for hard CVD events. This association did not differ by race/ethnic group.

Conclusion

Despite racial/ethnic differences in perceptions of support, perceived informational support was protective against CVD for participants of all racial/ethnic backgrounds.