bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated reference values for static lung volumes from a healthy population in Austria
Authors: Mraz Tobias , Asgari Shervin , Karimi Ahmad , Breyer Marie-Kathrin , Hartl Sylvia , Sunanta Owat , Ofenheimer Alina , Burghuber Otto C. , Zacharasiewicz Angela , Lamprecht Bernd , Schiffers Caspar , Wouters Emiel F. M. , Breyer-Kohansal Robab 
Published: April 2024

Abstract
Background
Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed.

Methods
We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6–80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models.

Results
Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results.

Conclusion
GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6–80 years of age).
Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression
Authors: Wang Hui , Tang Cui , Xiang Yuxia , Zou Chan , Hu Jianming , Yang Guoping , Zhou Wenhu 
Published: April 2024

AbstractThrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine’s potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.
Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy
Authors: He Long , Zhong Zhuotai , Wen Shuting , Li Peiwu , Jiang Qilong , Liu Fengbin 
Published: April 2024

AbstractMore than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.
The protein phosphatase-2A subunit PR130 is involved in the formation of cytotoxic protein aggregates in pancreatic ductal adenocarcinoma cells
Authors: Nguyen Alexandra , Mustafa Al-Hassan M. , Leydecker Alessa K. , Halilovic Melisa , Murr Janine , Butter Falk , Krämer Oliver H. 
Published: April 2024

AbstractAs a major source of cellular serine and threonine phosphatase activity, protein phosphatase-2A (PP2A) modulates signaling pathways in health and disease. PP2A complexes consist of catalytic, scaffolding, and B-type subunits. Seventeen PP2A B-type subunits direct PP2A complexes to selected substrates. It is ill-defined how PP2A B-type subunits determine the growth and drug responsiveness of tumor cells. Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis. We analyzed the responses of murine and human mesenchymal and epithelial PDAC cells to the specific PP2A inhibitor phendione. We assessed protein levels by immunoblot and proteomics and cell fate by flow cytometry, confocal microscopy, and genetic manipulation. We show that murine mesenchymal PDAC cells express significantly higher levels of the PP2A B-type subunit PR130 than epithelial PDAC cells. This overexpression of PR130 is associated with a dependency of such metastasis-prone cells on the catalytic activity of PP2A. Phendione induces apoptosis and an accumulation of cytotoxic protein aggregates in murine mesenchymal and human PDAC cells. These processes occur independently of the frequently mutated tumor suppressor p53. Proteomic analyses reveal that phendione upregulates the chaperone HSP70 in mesenchymal PDAC cells. Inhibition of HSP70 promotes phendione-induced apoptosis and phendione promotes a proteasomal degradation of PR130. Genetic elimination of PR130 sensitizes murine and human PDAC cells to phendione-induced apoptosis and protein aggregate formation. These data suggest that the PP2A-PR130 complex dephosphorylates and thereby prevents the aggregation of proteins in tumor cells.
Graphical Abstract
Addition of inflammation-related biomarkers to the CAIDE model for risk prediction of all-cause dementia, Alzheimer’s disease and vascular dementia in a prospective study
Authors: Trares Kira , Wiesenfarth Manuel , Stocker Hannah , Perna Laura , Petrera Agnese , Hauck Stefanie M. , Beyreuther Konrad , Brenner Hermann , Schöttker Ben 
Published: April 2024

AbstractBackgroundIt is of interest whether inflammatory biomarkers can improve dementia prediction models, such as the widely used Cardiovascular Risk Factors, Aging and Dementia (CAIDE) model.MethodsThe Olink Target 96 Inflammation panel was assessed in a nested case-cohort design within a large, population-based German cohort study (n = 9940; age-range: 50–75 years). All study participants who developed dementia over 20 years of follow-up and had complete CAIDE variable data (n = 562, including 173 Alzheimer’s disease (AD) and 199 vascular dementia (VD) cases) as well asn = 1,356 controls were selected for measurements. 69 inflammation-related biomarkers were eligible for use. LASSO logistic regression and bootstrapping were utilized to select relevant biomarkers and determine areas under the curve (AUCs).ResultsThe CAIDE model 2 (including Apolipoprotein E (APOE) ε4 carrier status) predicted all-cause dementia, AD, and VD better than CAIDE model 1 (withoutAPOEε4) with AUCs of 0.725, 0.752 and 0.707, respectively. Although 20, 7, and 4 inflammation-related biomarkers were selected by LASSO regression to improve CAIDE model 2, the AUCs did not increase markedly. CAIDE models 1 and 2 generally performed better in mid-life (50–64 years) than in late-life (65–75 years) sub-samples of our cohort, but again, inflammation-related biomarkers did not improve their predictive abilities.ConclusionsDespite a lack of improvement in dementia risk prediction, the selected inflammation-related biomarkers were significantly associated with dementia outcomes and may serve as a starting point to further elucidate the pathogenesis of dementia.
NSF DARE—Transforming modeling in neurorehabilitation: Four threads for catalyzing progress
Authors: Valero-Cuevas Francisco J. , Finley James , Orsborn Amy , Fung Natalie , Hicks Jennifer L. , Huang He , Reinkensmeyer David , Schweighofer Nicolas , Weber Douglas , Steele Katherine M. 
Published: April 2024

AbstractWe present an overview of the Conference on Transformative Opportunities for Modeling in Neurorehabilitation held in March 2023. It was supported by the Disability and Rehabilitation Engineering (DARE) program from the National Science Foundation’s Engineering Biology and Health Cluster. The conference brought together experts and trainees from around the world to discuss critical questions, challenges, and opportunities at the intersection of computational modeling and neurorehabilitation to understand, optimize, and improve clinical translation of neurorehabilitation. We organized the conference around four key, relevant, and promising Focus Areas for modeling: Adaptation & Plasticity, Personalization, Human-Device Interactions, and Modeling ‘In-the-Wild’. We identified four common threads across the Focus Areas that, if addressed, can catalyze progress in the short, medium, and long terms. These were: (i) the need to capture and curate appropriate and useful data necessary to develop, validate, and deploy useful computational models (ii) the need to create multi-scale models that span the personalization spectrum from individuals to populations, and from cellular to behavioral levels (iii) the need for algorithms that extract as much information from available data, while requiring as little data as possible from each client (iv) the insistence on leveraging readily available sensors and data systems to push model-driven treatments from the lab, and into the clinic, home, workplace, and community. The conference archive can be found at (dare2023.usc.edu). These topics are also extended by three perspective papers prepared by trainees and junior faculty, clinician researchers, and federal funding agency representatives who attended the conference.
Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy
Authors: Fang Hsin-Wei , Tseng Po-Lin , Hu Tsung-Hui , Wang Jing-Houng , Hung Chao-Hung , Lu Sheng-Nan , Chen Chien-Hung 
Published: April 2024

Abstract
Background
No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF).

Methods
A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled.

Results
The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment.

Conclusions
In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.
Association between increased systemic immune-inflammation index and postoperative delirium in older intertrochanteric fracture patients
Authors: Yan Xiaoxiao , Huang Jin , Chen Xiachan , Lin Mian 
Published: April 2024

Abstract
Background and purpose
The systemic immune-inflammation index (SII), a novel inflammation index derived from the counts of circulating platelets, neutrophils and lymphocytes, has been studied in the treatment of acute cancer and ischemic stroke (AIS). However, the clinical value of the SII in postoperative delirium patients has not been further investigated. The purpose of our research was to study the incidence and preoperative risk factors for postoperative delirium (POD) and verify whether the SII could serve as a potential marker for POD in older intertrochanteric fracture patients. Finally, we created a novel nomogram for predicting POD in older patients with intertrochanteric fractures.

Methods
We enrolled elderly patients with intertrochanteric fractures who underwent proximal femoral nail antirotation (PFNA) between February 2021 and April 2023. Univariate and multivariate logistic analyses were subsequently performed to confirm the risk factors and construct a nomogram model.Calibration curve and clinical decision curve analysis (DCA) were used to assess the model’s fitting performance. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility.

Results
A total of 293 patients were eligible for inclusion in the study, 25.6% (75/293) of whom had POD. The POD patients had higher SII values than the non-POD patients. The SII was strongly correlated with POD in older intertrochanteric fracture patients, and the optimal cutoff value was 752.6 × 109. Multivariate analysis revealed that age, diabetes, total albumin, SII > 752.6 × 109 and a CRP > 20.25 mg/L were independent risk factors for POD patients. By incorporating these 5 factors, the model achieved a concordance index of 0.745 (95% CI, 0.683–0.808) and had a well-fitted calibration curve and good clinical application value.

Conclusion
The SII is a simple and valuable biomarker for POD, and the new nomogram model can be used to accurately predict the occurrence of POD. They can be utilized in clinical practice to identify those at high risk of POD in older intertrochanteric fracture patients.
Airway and anesthesia management in tracheoesophageal fistula closure implantation: a single-centre retrospective study
Authors: Dechong Zhu , He Huang , Jigang Zhang , Cunming Liu 
Published: April 2024

Abstract
Objective
To review and analyze the airway and anesthesia management methods for patients who underwent endoscopic closure of tracheoesophageal fistula (TEF) and to summarize the experience of intraoperative airway management.

Method
We searched the anesthesia information system of the First Affiliated Hospital of Nanjing Medical University for anesthesia cases of TEF from July 2020 to July 2023 and obtained a total of 34 anesthesia records for endoscopic TEF occlusion. The intraoperative airway management methods and vital signs were recorded, and the patients’ disease course and follow-up records were analyzed and summarized.

Results
The airway management strategies used for TEF occlusion patients included nasal catheter oxygen (NCO, n = 5), high-flow nasal cannula oxygen therapy (HFNC, n = 4) and tracheal intubation (TI, n = 25). The patients who underwent tracheal intubation with an inner diameter of 5.5 mm had stable hemodynamics and oxygenation status during surgery, while intravenous anesthesia without intubation could not effectively inhibit the stress response caused by occluder implantation, which could easily cause hemodynamic fluctuations, hypoxemia, and carbon dioxide accumulation. Compared with those in the TI group, the NCO group and the HFNC group had significantly longer surgical times, and the satisfaction score of the endoscopists was significantly lower. In addition, two patients in the NCO group experienced postoperative hypoxemia.

Conclusion
During the anesthesia process for TEF occlusions, a tracheal catheter with an inner diameter of 5.5 mm can provide a safe and effective airway management method.
Efficacy of supervised immersive virtual reality-based training for the treatment of chronic fatigue in post-COVID syndrome: study protocol for a double-blind randomized controlled trial (IFATICO Trial)
Authors: Tesarz Jonas , Lange Hannah , Kirchner Marietta , Görlach Axel , Eich Wolfgang , Friederich Hans-Christoph 
Published: April 2024

Abstract
Background
The treatment of persistent fatigue after COVID-19 infection is complex. On the one hand, it involves maintaining a sufficient level of physical and mental activity to counteract possible degenerative processes of the body and nervous system. On the other hand, physical and mental activities can also lead to worsening of symptoms. Therefore, the challenge in treating Post-COVID fatigue is to stimulate the body and central nervous system in a way that stimulates growth and improvement, but does not overtax individual physical and mental limits. Special training programs try to take these characteristics into account, but often reach their limits. A promising approach is offered by new fitness technologies based on immersive virtual realities that stimulate both body and brain while minimizing physical and psychological stress. The aim of this study is to investigate the efficacy of supervised immersive Virtual Reality (VR)-based activity training compared to conventional activity training for patients with Post-COVID-associated fatigue.

Methods
In a single centre, individually randomised, prospective, double-blind two-arm exploratory superiority trial with parallel group design, N = 100 patients with persistent fatigue after COVID-19 infection will be recruited. The intervention includes a supervised immersive neuromuscular training (12 sessions of 30 min over 6 weeks) based on a novel VR-exercise device. We will systematically compare the effects of this intervention on Post-COVID-associated fatigue with a supervised conventional activation program of comparable scope without an immersive environment. The primary outcome is the difference between groups in absolute change in the mean fatigue symptom severity measured on the Fatigue Severity Scale (FSS) from baseline to posttreatment assessment. Posttreatment assessment in both groups will be conducted by blinded outcome assessors. At three and six months afterwards, patients are sent self-report questionnaires for follow up. The main analysis will be based on the intention-to-treat principle.

Discussion
To the best of our knowledge, this is the first exploratory study on a supervised immersive neuromuscular training for the treatment of persistent fatigue after COVID-19 infection.

Trial registration
German register for clinical studies (ID: DRKS00032059)
Prospectively registered on June 16th 2023.
URL of trial registration:
Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies
Authors: Campochiaro Corrado , Farina Nicola , De Luca Giacomo , Batani Veronica , Trignani Giorgia , Vignale Davide , Palmisano Anna , Matucci-Cerinic Marco , Dagna Lorenzo 
Published: April 2024

Abstract
Introduction
Idiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM.

Methods
Patients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period.

Results
Among the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed.

Conclusion
Our data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.