bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypnosis support in anaesthesia is rarely used in German anaesthesia departments - a nationwide survey among leading physicians of anaesthesia departments
Authors: Bügers Lisa , Wähner Anna , Schubert Ann-Kristin , Dinges Hanns-Christian , Torossian Alexander , Volberg Christian 
Published: September 2024

Abstract
Background
The aim of this study was to investigate whether and to what extent perioperative hypnosis and relaxation techniques are used in German anaesthesia departments, what they are, where any difficulties in their application lie and how great the interest in this type of therapy is. Another research question was to find out whether there are specialist areas in which these methods are used more frequently than in other specialist areas.

Methods
A descriptive survey was conducted by means of a questionnaire in all hospitals with anaesthesia departments in Germany. 1124 questionnaires were sent out by post. The survey period was five months from 27/02/2023 to 31/07/2023. The clinic directors of all anaesthesiology departments in German hospitals were surveyed.

Results
476 departments (42%) responded by pre-paid envelope. Of these, only 39 (8%) use hypnosis and relaxation techniques perioperatively. These are mostly progressive muscle relaxation, hypnotic trance according to Erickson, calming words and suggestions or the use of virtual reality (e.g. using VR-glasses).

Conclusions
Hypnosis techniques have been shown in many studies to be effective in increasing patient comfort (less anxiety and stress) and reducing both the need for medication and perioperative pain. The therapy is rarely used in Germany, although once established it can be easily integrated into perioperative procedures. Many departments have shown great interest in the topic. In the interests of patients, a structural change should be considered to promote the use of hypnotic procedures.
HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma
Authors: Cigliano Antonio , Gigante Isabella , Serra Marina , Vidili Gianpaolo , Simile Maria M. , Steinmann Sara , Urigo Francesco , Cossu Eleonora , Pes Giovanni M. , Dore Maria P. , Ribback Silvia , Milia Egle P. , Pizzuto Elena , Mancarella Serena , Che Li , Pascale Rosa M. , Giannelli Gianluigi , Evert Matthias , Chen Xin , Calvisi Diego F. 
Published: September 2024

Abstract
Background
Intrahepatic cholangiocarcinoma (iCCA) is a lethal primary liver tumor characterized by clinical aggressiveness, poor prognosis, and scarce therapeutic possibilities. Therefore, new treatments are urgently needed to render this disease curable. Since cumulating evidence supports the oncogenic properties of the Heat Shock Factor 1 (HSF1) transcription factor in various cancer types, we investigated its pathogenetic and therapeutic relevance in iCCA.

Methods
Levels of HSF1 were evaluated in a vast collection of iCCA specimens. The effects of HSF1 inactivation on iCCA development in vivo were investigated using three established oncogene-driven iCCA mouse models. In addition, the impact of HSF1 suppression on tumor cells and tumor stroma was assessed in iCCA cell lines, human iCCA cancer-associated fibroblasts (hCAFs), and patient-derived organoids.

Results
Human preinvasive, invasive, and metastatic iCCAs displayed widespread HSF1 upregulation, which was associated with a dismal prognosis of the patients. In addition, hydrodynamic injection of a dominant-negative form of HSF1 (HSF1dn), which suppresses HSF1 activity, significantly delayed cholangiocarcinogenesis in AKT/NICD, AKT/YAP, and AKT/TAZ mice. In iCCA cell lines, iCCA hCAFs, and patient-derived organoids, administration of the HSF1 inhibitor KRIBB-11 significantly reduced proliferation and induced apoptosis. Cell death was profoundly augmented by concomitant administration of the Bcl-xL/Bcl2/Bcl-w inhibitor ABT-263. Furthermore, KRIBB-11 reduced mitochondrial bioenergetics and glycolysis of iCCA cells.

Conclusions
The present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.
Effect of a soft exosuit on daily life gait performance in people with incomplete spinal cord injury: study protocol for a randomized controlled trial
Authors: Visch L. , Groen B. E. , Geurts A. C. H. , van Nes I. J. W. , Keijsers N. L. W. 
Published: September 2024

Abstract
Background
People with incomplete spinal cord injury (iSCI) often have gait impairments that negatively affect daily life gait performance (i.e., ambulation in the home and community setting) and quality of life. They may benefit from light-weight lower extremity exosuits that assist in walking, such as the Myosuit (MyoSwiss AG, Zurich, Switzerland). A previous pilot study showed that participants with various gait disorders increased their gait speed with the Myosuit in a standardized environment. However, the effect of a soft exosuit on daily life gait performance in people with iSCI has not yet been evaluated.

Objective
The primary study objective is to test the effect of a soft exosuit (Myosuit) on daily life gait performance in people with iSCI. Second, the effect of Myosuit use on gait capacity and the usability of the Myosuit in the home and community setting will be investigated. Finally, short-term impact on both costs and effects will be evaluated.

Methods
This is a two-armed, open label, randomized controlled trial (RCT). Participants will be randomized (1:1) to the intervention group (receiving the Myosuit program) or control group (initially receiving the conventional program). Thirty-four people with chronic iSCI will be included. The Myosuit program consists of five gait training sessions with the Myosuit at the Sint Maartenskliniek. Thereafter, participants will have access to the Myosuit for home use during 6 weeks. The conventional program consists of four gait training sessions, followed by a 6-week home period. After completing the conventional program, participants in the control group will subsequently receive the Myosuit program. The primary outcome is walking time per day as assessed with an activity monitor at baseline and during the first, third, and sixth week of the home periods. Secondary outcomes are gait capacity (10MWT, 6MWT, and SCI-FAP), usability (D-SUS and D-QUEST questionnaires), and costs and effects (EQ-5D-5L).

Discussion
This is the first RCT to investigate the effect of the Myosuit on daily life gait performance in people with iSCI.

Trial registration
Clinicaltrials.gov NCT05605912. Registered on November 2, 2022.
High fidelity adaptive mirror simulations with reduced order models
Authors: Stadler Bernadett , Biasi Roberto , Manetti Mauro , Obereder Andreas , Ramlau Ronny , Tintori Matteo 
Published: September 2024

AbstractIn the design process of large adaptive mirrors numerical simulations represent the first step to evaluate the system design compliance in terms of performance, stability and robustness. For the next generation of Extremely Large Telescopes increased system dimensions and bandwidths lead to the need of modeling not only the deformable mirror alone, but also all the system supporting structure or even the full telescope. The capability to perform the simulations with an acceptable amount of time and computational resources is highly dependent on finding appropriate methods to reduce the size of the resulting dynamic models. In this paper we present a framework developed together with the company Microgate to create a reduced order structural model of a large adaptive mirror as a preprocessing step to the control system simulations. The reduced dynamic model is then combined with the remaining system components allowing to simulate the full adaptive mirror in a computationally efficient way. We analyze the feasibility of our reduced models for Microgate’s prototype of the adaptive mirror of the Giant Magellan Telescope.
Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19
Authors: Ha Dat P. , Shin Woo-Jin , Liu Ze , Doche Michael E. , Lau Roy , Leli Nektaria Maria , Conn Crystal S. , Russo Mariangela , Lorenzato Annalisa , Koumenis Constantinos , Yu Min , Mumenthaler Shannon M. , Lee Amy S. 
Published: September 2024

Abstract
Background
Despite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19.

Results
Here we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na+/K+-ATPase α3 isoform is critical for OLN suppression of GRP78 stress induction. OLN, in nanomolar range, enhances apoptosis, sensitizes colorectal cancer cells to chemotherapeutic agents, and reduces the viability of patient-derived colon cancer organoids. Likewise, OLN, suppresses GRP78 expression and impedes tumor growth in an orthotopic breast cancer xenograft model. Furthermore, OLN blocks infection by SARS-CoV-2 and its variants and enhances existing anti-viral therapies. Notably, GRP78 overexpression mitigates OLN-mediated cancer cell apoptotic onset and suppression of virus release.

Conclusion
Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.
Is artificial intelligence for medical professionals serving the patients?
Authors: Wilhelm Christoph , Steckelberg Anke , Rebitschek Felix G. 
Published: September 2024

Abstract
Background
Algorithmic decision-making (ADM) utilises algorithms to collect and process data and develop models to make or support decisions. Advances in artificial intelligence (AI) have led to the development of support systems that can be superior to medical professionals without AI support in certain tasks. However, whether patients can benefit from this remains unclear. The aim of this systematic review is to assess the current evidence on patient-relevant benefits and harms, such as improved survival rates and reduced treatment-related complications, when healthcare professionals use ADM systems (developed using or working with AI) compared to healthcare professionals without AI-related ADM (standard care)—regardless of the clinical issues.

Methods
Following the PRISMA statement, MEDLINE and PubMed (via PubMed), Embase (via Elsevier) and IEEE Xplore will be searched using English free text terms in title/abstract, Medical Subject Headings (MeSH) terms and Embase Subject Headings (Emtree fields). Additional studies will be identified by contacting authors of included studies and through reference lists of included studies. Grey literature searches will be conducted in Google Scholar. Risk of bias will be assessed by using Cochrane’s RoB 2 for randomised trials and ROBINS-I for non-randomised trials. Transparent reporting of the included studies will be assessed using the CONSORT-AI extension statement. Two researchers will screen, assess and extract from the studies independently, with a third in case of conflicts that cannot be resolved by discussion.

Discussion
It is expected that there will be a substantial shortage of suitable studies that compare healthcare professionals with and without ADM systems concerning patient-relevant endpoints. This can be attributed to the prioritisation of technical quality criteria and, in some cases, clinical parameters over patient-relevant endpoints in the development of study designs. Furthermore, it is anticipated that a significant portion of the identified studies will exhibit relatively poor methodological quality and provide only limited generalisable results.

Systematic review registration
This study is registered within PROSPERO (CRD42023412156).
Neurodegenerative disorders, metabolic icebergs, and mitohormesis
Authors: Phillips Matthew C. L. , Picard Martin 
Published: September 2024

AbstractNeurodegenerative disorders are typically “split” based on their hallmark clinical, anatomical, and pathological features, but they can also be “lumped” by a shared feature of impaired mitochondrial biology. This leads us to present a scientific framework that conceptualizes Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) as “metabolic icebergs” comprised of a tip, a bulk, and a base. The visible tip conveys the hallmark neurological symptoms, neurodegenerative regions, and neuronal protein aggregates for each disorder. The hidden bulk depicts impaired mitochondrial biology throughout the body, which is multifaceted and may be subdivided into impaired cellular metabolism, cell-specific mitotypes, and mitochondrial behaviours, functions, activities, and features. The underlying base encompasses environmental factors, especially modern industrial toxins, dietary lifestyles, and cognitive, physical, and psychosocial behaviours, but also accommodates genetic factors specific to familial forms of AD, PD, and ALS, as well as HD. Over years or decades, chronic exposure to a particular suite of environmental and genetic factors at the base elicits a trajectory of impaired mitochondrial biology that maximally impacts particular subsets of mitotypes in the bulk, which eventually surfaces as the hallmark features of a particular neurodegenerative disorder at the tip. We propose that impaired mitochondrial biology can be repaired and recalibrated by activating “mitohormesis”, which is optimally achieved using strategies that facilitate a balanced oscillation between mitochondrial stressor and recovery phases. Sustainably harnessing mitohormesis may constitute a potent preventative and therapeutic measure for people at risk of, or suffering with, neurodegenerative disorders.
Hepatoprotective effects of magnolol in fatty liver hemorrhagic syndrome hens through shaping gut microbiota and tryptophan metabolic profile
Authors: Lv Yujie , Ge Chaoyue , Wu Lianchi , Hu Zhaoying , Luo Xinyu , Huang Weichen , Zhan Shenao , Shen Xinyu , Yu Dongyou , Liu Bing 
Published: September 2024

Abstract
Background
Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut–liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks.

Results
Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites.

Conclusions
Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.
Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia
Authors: Mei Yihan , Liu Yu , Liu Wenbing , Chen Manling , Liu Xiaoyu , Wang Shangshang , Mou Junli , Xing Haiyan , Tang Kejing , Tian Zheng , Rao Qing , Wang Min , Gu Runxia , Qiu Shaowei , Wang Jianxiang 
Published: September 2024

AbstractBesides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing. Based on the STARTRAC-like algorithm, we defined bystander T cells and tumor-reactive T cells. Compared with bystander T cells, tumor-reactive T cells presented as senescent-like cytotoxic terminally differentiated T cells (Temra) with upregulated NK-related markers. Additionally, we found ADGRG1 could serve as the specific marker of CD8+ T tumor-reactive T cell and validated it through the Runx1Runx1t1/+; Mx1-Cre mouse model. In chimeric antigen receptor (CAR)-T and target cell system, ADGRG1 was selectively upregulated upon antigen-TCR encounter. Moreover, ADGRG1+CD8+ T cells released a higher level of IFN-γ and showed higher cell-killing ability when exposed to matched AML blasts. Together, our findings depict the single-cell profile of tumor-reactive T cells in AML BM and propose that ADGRG1 can act as an indicator of T cell tumor reactivity in AML, which may be further harnessed for adoptive cell therapy and tumor-reactive TCR enrichment.
An L-type calcium channel blocker nimodipine exerts anti-fibrotic effects by attenuating TGF-β1 induced calcium response in an in vitro model of thyroid eye disease
Authors: Chen Qian , Pan Yuan , Hu Yunwei , Chen Guanyu , Chen Xiaoqing , Xie Yanyan , Wang Minzhen , Li Zhuang , Huang Jun , Shi Yuxun , Huang Haixiang , Zhang Te , Wang Mei , Zeng Peng , Wang Sha , Chen Rongxin , Zheng Yongxin , Zhong Liuxueying , Yang Huasheng , Liang Dan 
Published: September 2024

Abstract
Background
Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca2+ signaling participates in tissue fibrosis. However, whether an alteration of Ca2+ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca2+ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-β1 induced in vitro TED model.

Methods
Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2′-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca2+ response on TGF-β1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-β1 induced in vitro TED model. The roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways.

Results
LTCC inhibitor nimodipine blocked the TGF-β1 induced intracellular Ca2+ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway.

Conclusions
TGF-β1 induces an LTCC-mediated Ca2+ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.
Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation
Authors: Xie Lin , Liu Hanze , Zhang Ke , Pan Yijun , Chen Mengyao , Xue Xiangyue , Wan Guoxing 
Published: September 2024

Abstract
Background
Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations.

Results
Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation.

Conclusions
This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.