bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury
Authors: Wang Yi , Fu Xiaolong , Zeng Li , Hu Yan , Gao Rongyang , Xian Siting , Liao Songjie , Huang Jianxiang , Yang Yonggang , Liu Jilong , Jin Hai , Klaunig James , Lu Yuanfu , Zhou Shaoyu 
Published: May 2024

AbstractNuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.
CaV1.3 channel clusters characterized by live-cell and isolated plasma membrane nanoscopy
Authors: Schwenzer Niko , Teiwes Nikolas K. , Kohl Tobias , Pohl Celine , Giller Michelle J. , Lehnart Stephan E. , Steinem Claudia 
Published: May 2024

AbstractA key player of excitable cells in the heart and brain is the L-type calcium channel CaV1.3. In the heart, it is required for voltage-dependent Ca2+-signaling, i.e., for controlling and modulating atrial cardiomyocyte excitation-contraction coupling. The clustering of CaV1.3 in functionally relevant channel multimers has not been addressed due to a lack of stoichiometric labeling combined with high-resolution imaging. Here, we developed a HaloTag-labeling strategy to visualize and quantify CaV1.3 clusters using STED nanoscopy to address the questions of cluster size and intra-cluster channel density. Channel clusters were identified in the plasma membrane of transfected live HEK293 cells as well as in giant plasma membrane vesicles derived from these cells that were spread on modified glass support to obtain supported plasma membrane bilayers (SPMBs). A small fraction of the channel clusters was colocalized with early and recycling endosomes at the membranes. STED nanoscopy in conjunction with live-cell and SPMB imaging enabled us to quantify CaV1.3 cluster sizes and their molecular density revealing significantly lower channel densities than expected for dense channel packing. CaV1.3 channel cluster size and molecular density were increased in SPMBs after treatment of the cells with the sympathomimetic compound isoprenaline, suggesting a regulated channel cluster condensation mechanism.
Pan-cancer discovery of somatic mutations from RNA sequencing data
Authors: Tang Gongyu , Liu Xinyi , Cho Minsu , Li Yuanxiang , Tran Dan-Ho , Wang Xiaowei 
Published: May 2024

AbstractIdentification of somatic mutations (SMs) is essential for characterizing cancer genomes. While DNA-seq is the prevalent method for identifying SMs, RNA-seq provides an alternative strategy to discover tumor mutations in the transcribed genome. Here, we have developed a machine learning based pipeline to discover SMs based on RNA-seq data (designated as RNA-SMs). Subsequently, we have conducted a pan-cancer analysis to systematically identify RNA-SMs from over 8,000 tumors in The Cancer Genome Atlas (TCGA). In this way, we have identified over 105,000 novel SMs that had not been reported in previous TCGA studies. These novel SMs have significant clinical implications in designing targeted therapy for improved patient outcomes. Further, we have combined the SMs identified by both RNA-seq and DNA-seq analyses to depict an updated mutational landscape across 32 cancer types. This new online SM atlas, OncoDB (https://oncodb.org), offers a more complete view of gene mutations that underline the development and progression of various cancers.
The role of elasticity on adhesion and clustering of neurons on soft surfaces
Authors: Marinaro Giovanni , Bruno Luigi , Pirillo Noemi , Coluccio Maria Laura , Nanni Marina , Malara Natalia , Battista Edmondo , Bruno Giulia , De Angelis Francesco , Cancedda Laura , Di Mascolo Daniele , Gentile Francesco 
Published: May 2024

AbstractThe question of whether material stiffness enhances cell adhesion and clustering is still open to debate. Results from the literature are seemingly contradictory, with some reports illustrating that adhesion increases with surface stiffness and others suggesting that the performance of a system of cells is curbed by high values of elasticity. To address the role of elasticity as a regulator in neuronal cell adhesion and clustering, we investigated the topological characteristics of networks of neurons on polydimethylsiloxane (PDMS) surfaces - with values of elasticity (E) varying in the 0.55–2.65 MPa range. Results illustrate that, as elasticity increases, the number of neurons adhering on the surface decreases. Notably, the small-world coefficient – a topological measure of networks – also decreases. Numerical simulations and functional multi-calcium imaging experiments further indicated that the activity of neuronal cells on soft surfaces improves for decreasing E. Experimental findings are supported by a mathematical model, that explains adhesion and clustering of cells on soft materials as a function of few parameters - including the Young’s modulus and roughness of the material. Overall, results indicate that – in the considered elasticity interval – increasing the compliance of a material improves adhesion, improves clustering, and enhances communication of neurons.
Anxiety, depression and distress outcomes from the Health4Life intervention for adolescent mental health: a cluster-randomized controlled trial
Authors: Smout S. , Champion K. E. , O’Dean S. , Teesson M. , Gardner L. A. , Newton N. C. 
Published: May 2024

AbstractMental disorders are a leading cause of disease burden worldwide. As onset typically occurs in adolescence, prevention during this period is critical. The Health4Life-school-based multiple health behavior change (MHBC) intervention targets six lifestyle risk factors: diet, sleep, physical activity, screentime, alcohol use and smoking. Health4Life has been evaluated in a cluster-randomized controlled trial in 71 Australian schools (6,639 grade seven students). This study presents intervention effects on secondary outcomes of depressive, anxiety and psychological distress symptoms. Generalized linear mixed-effect analyses of data from baseline, post-intervention (7 weeks), 12 months and 24 months showed that the Health4Life intervention was no more effective than an active control in reducing depressive, anxiety or psychological distress symptoms at a 24 or 12 month follow-up; however, there were short-term benefits for psychological distress and depressive symptoms immediately post-intervention. This study offers new evidence that multiple health behavior change interventions may improve adolescent mental health, but future research should explore methods to address anxiety and sustain effects over the longer term. A priori ANZCTR trial registration: ACTRN12619000431123.
Experiment of electrothermal stress for different types of end turn grading in the inverter‐fed form‐wound windings
Authors: Zhao Wenhuan , Wang Peng , Zhu Yingwei , Zhang Yue , Yang Shuai , Liu Yan , Shi Yang , Yu Chaofan 
Published: May 2024

AbstractEnd turn grading with resistive–capacitive coupling experiences severe electrothermal stress when subjected to pulse width modulation (PWM) voltage. In this paper, several experiments and simulations were carried conducted for four types of end turn grading. First of all, the temperature rise in the end turn grading increased with a decrease in rise time. When the rise time was less than 500 ns, the temperature rise at the terminal was higher owing to the increased capacitive current coupled from the main wall insulation. Further, the current in the linear region exhibited minimal variation at different fundamental frequencies resulting in synchronized the temperature rise at the terminal and overlap. Furthermore, the jump voltage was the key factor influencing temperature rise in end turn grading, confirmed by comparing different voltage magnitudes. Finally, the transient behaviour of the maximum field in the stress grading material was determined at rise time. The experimental and simulation results indicate that balancing and interdependently addressing the electrical and thermal stress protection in end turn grading is crucial. The study aims to provide an experimental and theoretical foundation for an insulation system of inverter‐fed rotating machinery operating under PWM voltage.
Signature of systemic rotation in 21 galactic globular clusters from APOGEE-2
Authors: Petralia Ilaria , Minniti Dante , Fernández-Trincado José G. , Lane Richard R. , Schiavon Ricardo P. 
Published: May 2024

Context. Traditionally, globular clusters (GCs) have been assumed to be quasi-relaxed non-rotating systems, characterized by spherical symmetry and orbital isotropy. However, in recent years, a growing set of observational evidence has been unveiling an unexpected dynamical complexity in Galactic GCs. Indeed, kinematic studies have demonstrated that a measurable amount of internal rotation is present in many present-day GCs.
Aims. The objective of this work is to analyse the APOGEE-2 value-added catalog (VAC) DR17 data of a sample of 21 GCs to extend the sample exhibiting signatures of systemic rotation and better understand the kinematic properties of GCs overall. Also, we aim to identify the fastest rotating GC from the sample of objects with suitable measurements.
Methods. From the sample of 23 GCs included in this work, the presence of systemic rotation was detected in 21 of the GCs, using three different methods. All these methods use the radial velocity referred to the cluster systemic velocity (Ṽr). Using the first method, it was possible to visually verify the clear-cut signature of systemic rotation; whereas using the second and third methods, it was possible to determine the amplitude of the rotation curve (Arot) and the position angle (PA) of the rotation axis.
Results. This study shows that 21 GCs have a signature of systemic rotation. For these clusters, the rotation amplitude and the position angle of the rotation axis (PA0) have been calculated. The clusters cover a remarkable range of rotational amplitudes, from 0.77 km s−1 to 13.85 km s−1.
Comparing bulge RR Lyrae stars with bulge giants
Authors: Olivares Carvajal J. , Zoccali M. , De Leo M. , Contreras Ramos R. , Quezada C. , Rojas-Arriagada Á. , Valenti E. , Albarracín R. , Valenzuela Navarro Á. 
Published: May 2024

Context. The structure and kinematics of the old component of the Galactic bulge are still a matter of debate. It is clear that the bulk of the bulge as traced by red clump stars includes two main components, which are usually identified as the metal-rich and metal-poor components. They have different shapes, kinematics, mean metallicities, and alpha-element abundances. It is our current understanding that they are associated with a bar and a spheroid, respectively. On the other hand, RR Lyrae variables trace the oldest population of the bulge. While it would be natural to think that they follow the structure and kinematics of the metal-poor component, the data analysed in the literature show conflicting results.
Aims. We aim to derive a rotation curve for bulge RR Lyrae stars in order to determine that the old component traced by these stars is distinct from the two main components observed in the Galactic bulge.
Methods. This paper combines APOGEE-2S spectra with OGLE-IV light curves, near-infrared photometry, and proper motions from the VISTA Variables in the Vía Láctea survey for 4193 RR Lyrae stars. Six-dimensional phase-space coordinates were used to calculate orbits within an updated Galactic potential and to isolate the stars.
Results. The stars that stay confined within the bulge represent 57% of our sample. Our results show that bulge RR Lyrae variables rotate more slowly than metal-rich red clump stars and have a lower velocity dispersion. Their kinematics is compatible with them being the low-metallicity tail of the metal-poor component. We confirm that a rather large fraction of halo and thick disc RR Lyrae stars pass by the bulge within their orbits, increasing the velocity dispersion. A proper orbital analysis is therefore critical to isolate bona fide bulge variables. Finally, bulge RR Lyrae seem to trace a spheroidal component, although the current data do now allow us to reach a firm conclusion about the spatial distribution.
Update zur ESC-Leitlinie Kardioonkologie
Authors: Romann Sebastian Welf , Frey Norbert , Lehmann Lorenz 
Published: May 2024

Was ist neu?
Die kardioonkologische Leitlinie, veröffentlicht in Zusammenarbeit mit der EHA (Europäische Gesellschaft für Hämatologie), der ESTRO (Europäische Gesellschaft für therapeutische Radiologie und Onkologie) und der ESC (Europäische Gesellschaft für Kardiologie), bietet 272 Empfehlungen zur Risikostratifizierung vor Therapiebeginn, zum Monitoring während der Therapie und zur Behandlung therapieassoziierter kardiovaskulärer Nebenwirkungen.
Risikostratifizierung Bei allen onkologischen Patienten soll vor Beginn einer neuen Systemtherapie eine Risiko-Einordnung durchgeführt werden. Anhand dieser staffelt sich die Empfehlung zur weiteren kardiologischen Betreuung während der Chemotherapie.
Individualisierte Strategien In einzelnen Bereichen, bspw. bei Immun-Checkpoint-Inhibitoren oder zur möglichen protektiven Wirkung von Statinen bei Anthrazyklin-Therapie, gibt es neuere Daten, die noch nicht in der Guideline berücksichtigt werden konnten.
Protektion und Behandlung toxischer Nebenwirkungen Generell sollte bei moderater oder schwerer Kardiotoxizität eine Unterbrechung oder ein Abbruch der Therapie erwogen werden. Gegebenenfalls kann die Hinzunahme eines ACE-Blockers, Angiotensin-Rezeptor-Blockers oder eines Betablockers erwogen werden.
Echokardiografische Parameter Die Leitlinie empfiehlt die Parameter LVEF und GLS, doch muss eine Therapieentscheidung, basierend auf dem GLS allein, nach aktueller Datenlage abgelehnt werden.
Praktische Umsetzung Die Leitlinie betont die Bedeutung interdisziplinärer Betreuung zwischen Onkologen und Kardiologen.
Wie geht es weiter in der Kardioonkologie? Eine weitere Individualisierung der kardioonkologischen Therapie ist wünschenswert und sollte das Ziel sein. KI-gestützte Systeme sollten weiterentwickelt und etabliert werden.
Vom Mut, neue Ansätze auszuprobieren
Authors: Heeser Alexandra 
Published: May 2024

ZusammenfassungImmer weniger Fachkräfte versorgen immer mehr, meist multimorbide Patienten. Um dem Fachkräftemangel entgegenzuwirken, bedarf es neben verbesserten politischen Rahmenbedingungen auch innovativer Lösungsansätze der Arbeitgeber.
Optimizing Surgical Outcomes and the Role of Preventive Surgery: A Scoping Review
Authors: Cauley Ryan P. , Rahmani Benjamin , Adebagbo Oluwaseun D. , Park John , Garvey Shannon R. , Chen Amy , Nickman Sasha , Tobin Micaela , Valentine Lauren , Weidman Allan A. , Singhal Dhruv , Dowlatshahi Arriyan , Lin Samuel J. , Lee Bernard T. 
Published: May 2024

Abstract
Background Plastic and reconstructive surgeons are often presented with reconstructive challenges as a sequela of complications in high-risk surgical patients, ranging from exposure of hardware, lymphedema, and chronic pain after amputation. These complications can result in significant morbidity, recovery time, resource utilization, and cost. Given the prevalence of surgical complications managed by plastic and reconstructive surgeons, developing novel preventative techniques to mitigate surgical risk is paramount.
Methods Herein we aim to understand efforts supporting the nascent field of preventive surgery, including (1) enhanced risk stratification, (2) medical optimization and prehabilitation, (3) surgical mitigation techniques, and (4) advancements in postoperative care. Through an emphasis on four surgical cohorts who may benefit from preventive surgery, two of which are at high risk of morbidity from wound-related complications (patients undergoing sternotomy and spine procedures) and two at high risk of other morbidities, including lymphedema and neuropathic pain, we aim to provide a comprehensive and improved understanding of preventive surgery. Additionally, the role of risk analysis for these procedures and the relationship between microsurgery and prophylaxis is emphasized.
Results Although multiple risk mitigation methods have demonstrated clear benefits, including prophylactic surgical procedures and earlier involvement of plastic surgery, their use is widely variable across institutions. Many current risk assessment tools are suboptimal for supporting more algorithmic approaches to reduce surgical risk.
Conclusion Reconstructive surgeons are ideally placed to lead efforts in the creation and validation of accurate risk assessment tools and to support algorithmic approaches to surgical risk mitigation. Through a paradigm shift, including universal promotion of the concept of “Preventive Surgery,” major improvements in surgical outcomes may be achieved.
Blunt Trauma Induced Closed Femoral Bone Fracture in a Rat Model: Are Vessels Safe to Use for Microsurgery? Further Insight into the Zone of Injury Concept
Authors: Basaran Karaca , Datli Asli , Sagir Mehmet , Sar Mehmet , Bilgi Esra 
Published: May 2024

Abstract
Background The study aims to investigate the zone of injury for major vessels after high-velocity traumas, as it is unclear whether avoiding vascular structures is necessary during microvascular anastomosis or how long it takes for them to be used again.
Methods This study uses Doppler ultrasonography and a rat model to evaluate the histopathological changes and flow velocity of major vessels in the zone of injury after high-velocity trauma with closed femoral bone fracture. Osteosynthesis was performed using an intramedullary wire. Samples were collected from day 3 and week 3. The unaffected contralateral side is used as control.
Results Results from arterial and venous flow assessments showed no evidence of ischemia in the extremities. Both arteries and veins were patent in both intervals and on the control side. The evaluation of the vessels showed arterial injury with a slightly reduced arterial flow on day 3 and week 3. The venous flow was slightly reduced on day 3 but not on week 3. Statistically, arterial endothelial injury was higher on day 3 than on week 3 (p = 0.006). Media inflammation was also higher on day 3 (p = 0.06). Arterial endothelization distribution was higher in week 3 (p = 0.006). No significant differences were found in arterial media irregularity, necrosis, platelet aggregation, bleeding, and wall rupture. Venous samples showed no significant differences in any parameter (p < 0.05).
Conclusion High-velocity trauma increases the risk of thrombosis in vessels. Intravascular repair can start on day 2 and continue till week 3 with significant endothelization. Although physiologic findings do not alter arterial or venous flow, histologic findings support vessel injuries leading to potential complications. Microsurgery should be considered out of the injury zone until adequate vessel healing is achieved.
Effects of Elective Revision after Breast Reconstruction on Patient-Reported Outcomes
Authors: Zong Amanda M. , Leibl Kayla E. , Weichman Katie E. 
Published: May 2024

Abstract
Background There has been increasing emphasis on patient-reported satisfaction as a measure of surgical outcomes. While previous research has investigated factors influencing patient satisfaction following breast reconstruction, there are few studies on how patient satisfaction is impacted by revision procedures. The purpose of this study was to investigate whether elective revisions following breast reconstruction are significantly associated with changes in patient-reported outcomes and quality of life.
Methods A retrospective review was conducted of patients who underwent immediate autologous or alloplastic breast reconstruction at a single institution from 2015 to 2021. Patients were included if they had completed BREAST-Q preoperatively, post–initial reconstruction, and post-revision procedures. Patients were excluded if they received adjuvant radiation or if they had previously undergone breast reconstruction procedures. The primary outcome measures were BREAST-Q domains. Demographic, clinical, and surgical variables were also analyzed.
Results Of the 123 patients included for analysis, 61 underwent autologous breast reconstruction and 62 underwent alloplastic reconstruction. Mean age was 49.31 ± 11.58 years and body mass index (BMI) was 29.55 ± 5.63 kg/m2. Forty-eight patients underwent no revision procedures and 75 patients underwent at least one revision. Between these two groups, there were no differences in age, BMI, complication rates, socioeconomic status, or preoperative BREAST-Q scores. Patients reported significantly higher satisfaction with outcome after their first revision compared with after initial reconstruction alone (p = 0.04). Autologous reconstruction patients who had at least one revision had significantly higher satisfaction with outcome (p = 0.02) and satisfaction with surgeon (p = 0.05) in the 2-year follow-up period compared with patients who had no revisions.
Conclusion Revision procedures following autologous breast reconstruction are associated with higher patient satisfaction with outcome. Further research should explore specific factors influencing patient decision-making regarding whether to undergo revisions.