bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aktuelle Diagnostik und Behandlung der Sprunggelenks-Distorsion in Deutschland
Authors: Lichte Philipp , Weber Christian , Otto Michael , Bläsius Felix , Gutteck Natalia , Hildebrand Frank , Arbab Dariusch 
Published: April 2024

Zusammenfassung
Hintergrund
Die Distorsion des oberen Sprunggelenks (OSG) ist eine der häufigsten Verletzungen des Bewegungsapparates. Das Verletzungsmuster bestimmt die zu wählende Therapie und ist entscheidend für das Outcome. Die isolierte Ruptur des Außenbandapparates ist die häufigste strukturelle Verletzung. Hierfür wird leitliniengerecht eine konservative Therapie empfohlen, für Kombinationsverletzungen besteht hingegen hinsichtlich des diagnostischen und therapeutischen Vorgehens keine einheitliche Vorgehensweise. Ziel der bundesweiten Umfrage war es, einen Überblick über die aktuelle diagnostische Strategie und die gängigen therapeutischen Konzepte in Deutschland zu gewinnen.

Material und Methoden
Mitglieder der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) wurden eingeladen, an einer online Umfrage zum diagnostischen und zum therapeutischen Vorgehen bei OSG-Distorsion mit einem Fragebogen, bestehend aus 20 Fragen, teilzunehmen. Neben Fragen zur Fachrichtung und zum Tätigkeitsfeld wurden die Teilnehmer gebeten, ihr diagnostisches und therapeutisches Vorgehen darzustellen.

Ergebnisse
Insgesamt nahmen 806 Teilnehmer an der Umfrage teil. Die Mehrzahl der Befragten waren Orthopäden und Unfallchirurgen und in der Klinik tätig. Bei der Erstvorstellung werden der Schubladen Test (89,5 %) und der Inversions‑/Eversionstest (81,6 %) am häufigsten durchgeführt. Eine Röntgenuntersuchung führen 88,1 % regelhaft bei Erstvorstellung durch, 26,5 % auch eine sonographische Untersuchung. Die isolierte Verletzung des Lig. fibulotalare anterius (LFTA) behandeln 99,7 % konservativ, in 78,8 % der Fälle mit Vollbelastung in der Orthese. Die vollständige Außenbandruptur würden 79,9 % konservativ behandeln. Eine kombinierte Außenbandruptur mit Syndesmosenverletzung würden 30,1 % der Befragten konservativ behandeln.

Diskussion
Aufgrund der Heterogenität der Verletzungsmuster nach einer OSG-Distorsion bestehen keine einheitlichen diagnostischen und therapeutischen Behandlungsempfehlungen. Die Ottawa Ankle Rules und die Sonographie werden trotz der guten Studienlage nur wenig eingesetzt. Die isolierte LFTA-Ruptur wird von einem Großteil der Befragten leitliniengerecht diagnostiziert und behandelt. Bei kombinierten Verletzungen des Innen- und Außenbandapparates entscheidet sich die Mehrheit für ein konservatives Vorgehen, was durch die Literatur bei geringer Evidenz als gerechtfertigt erscheint. Kombinierte Verletzungen der Syndesmose und des Außenbandapparates würde die Mehrzahl der Befragten operativ behandeln, was ebenfalls mit den Empfehlungen der Literatur korreliert. Der Versorgungsstandard in Deutschland entspricht somit weitgehend den Literaturempfehlungen.

Graphic abstract
Determination of aluminium concentrations in black, green, and white tea samples: effects of different infusion times and teapot species on aluminium release
Authors: Öztürk Elif , Yıldırım Sercan , Akyol Asli 
Published: April 2024

AbstractTea is the most consumed beverage in the world after water and contains heavy metals and trace elements that may cause potential negative effects on health. Aluminium (Al) concentrations in black, green, and white tea with different infusion times and teapot materials were evaluated in this study. Commercially available tea samples were brewed in 5 different teapots, consisting of aluminium, copper, glass, steel, and porcelain materials for 5, 10, and 15 min. Al concentrations in tea samples were determined by high-performance liquid chromatography with a fluorescence detector. Al concentrations in tea samples were in the range of 38.46 ± 5.08–844.75 ± 10.86 µg/L. Both teapot type (p < 0.001) and infusion time (p < 0.001) significantly influenced Al concentrations in tea samples. The interaction between tea type, teapot material, and infusion time was statistically significant (p < 0.001). The hazard ratio was less than 1 for black and white tea infusions except for one sample whereas it was greater than 1 for green tea. These data suggest that green tea consumption might be a potential risk factor for Al exposure.
Disrupting FKF1 homodimerization increases FT transcript levels in the evening by enhancing CO stabilization
Authors: Cho Sung Won , Lokhandwala Jameela , Park Jun Sang , Kang Hye Won , Choi Mingi , Yang Hong-Quan , Imaizumi Takato , Zoltowski Brian D. , Song Young Hun 
Published: April 2024

Abstract
Key message
FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days.

Abstract
In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1.
Radiomics and machine learning for renal tumor subtype assessment using multiphase computed tomography in a multicenter setting
Authors: Uhlig Annemarie , Uhlig Johannes , Leha Andreas , Biggemann Lorenz , Bachanek Sophie , Stöckle Michael , Reichert Mathias , Lotz Joachim , Zeuschner Philip , Maßmann Alexander 
Published: April 2024

Abstract
Objectives
To distinguish histological subtypes of renal tumors using radiomic features and machine learning (ML) based on multiphase computed tomography (CT).

Material and methods
Patients who underwent surgical treatment for renal tumors at two tertiary centers from 2012 to 2022 were included retrospectively. Preoperative arterial (corticomedullary) and venous (nephrogenic) phase CT scans from these centers, as well as from external imaging facilities, were manually segmented, and standardized radiomic features were extracted. Following preprocessing and addressing the class imbalance, a ML algorithm based on extreme gradient boosting trees (XGB) was employed to predict renal tumor subtypes using 10-fold cross-validation. The evaluation was conducted using the multiclass area under the receiver operating characteristic curve (AUC). Algorithms were trained on data from one center and independently tested on data from the other center.

Results
The training cohort comprised n = 297 patients (64.3% clear cell renal cell cancer [RCC], 13.5% papillary renal cell carcinoma (pRCC), 7.4% chromophobe RCC, 9.4% oncocytomas, and 5.4% angiomyolipomas (AML)), and the testing cohort n = 121 patients (56.2%/16.5%/3.3%/21.5%/2.5%).
The XGB algorithm demonstrated a diagnostic performance of AUC = 0.81/0.64/0.8 for venous/arterial/combined contrast phase CT in the training cohort, and AUC = 0.75/0.67/0.75 in the independent testing cohort. In pairwise comparisons, the lowest diagnostic accuracy was evident for the identification of oncocytomas (AUC = 0.57–0.69), and the highest for the identification of AMLs (AUC = 0.9–0.94)

Conclusion
Radiomic feature analyses can distinguish renal tumor subtypes on routinely acquired CTs, with oncocytomas being the hardest subtype to identify.

Clinical relevance statement
Radiomic feature analyses yield robust results for renal tumor assessment on routine CTs. Although radiologists routinely rely on arterial phase CT for renal tumor assessment and operative planning, radiomic features derived from arterial phase did not improve the accuracy of renal tumor subtype identification in our cohort.
Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy
Authors: Rodler Severin , Danninger Dina , Eismann Lennert , Kazmierczak Philipp Maximilian , Jokisch Friedrich , Li Minglun , Becker Armin , Kretschmer Alexander , Stief Christian , Westhofen Thilo 
Published: April 2024

Abstract
Background
Salvage radical prostatectomy (sRP) is an important treatment option for patients with recurrent prostate cancer (PCa) after radiotherapy (RT) or focal therapy (FT). However, health-related quality of life (HRQOL) after sRP depending on the primary treatment is understudied.

Methods
Patients who underwent Salvage RP for recurrent PCa were analyzed. The primary outcome of this study was HRQOL assessed by the quality-of-life questionnaire (QLQ)-C30 and its prostate specific QLQ-PR25 add-on. Secondary outcomes were functional outcome parameters (erectile function, continence) and biochemical recurrence-free survival (BRFS). Statistical analyses employed the chi-square test, Mann–Whitney U test, and Kaplan–Meier method, with a p value < 0.05 denoting significance.

Results
37 patients with RT as primary treatment (RT-sRP) and 22 patients with focal therapy prior sRP (FT-sRP) were analyzed. Mean global health score was not significantly different preoperatively (71.9 vs. 67.3, p = 0.89) as well as after a median of 32 months follow-up (54.9 vs. 50.6, p = 0.63) with impaired HRQOL after sRP in both groups. Baseline erectile dysfunction was more prevalent in the RT-sRP group (mean IIEF-5: 5.0) than in the FT-sRP group (mean IIEF-5: 8.5, p = 0.037). No differences were observed at follow-up for erectile function (IIEF-5-Score: 0.5 vs 2.5, p = 0.199) and continence (continence rate: 48.4% vs 52.9% (p = 0.763) between the RT-sRP and FT-sRP group. 5-year-BRFS was 60% (RT-sRP) and 68% (FT-sRP, p = 0.849).

Conclusions
sRP impacts HRQOL in patients with PCa after RT and FT with no significant differences. Comparison with HRQOL and BRFS of treatment alternatives is paramount to counsel patients for appropriate treatments.
Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects
Authors: Karimi Esmat , Gohlke Jochen , van der Borgh Mila , Lindqvist Johan , Hourani Zaynab , Kolb Justin , Cossette Stacy , Lawlor Michael W. , Ottenheijm Coen , Granzier Henk 
Published: April 2024

AbstractNebulin, a critical protein of the skeletal muscle thin filament, plays important roles in physiological processes such as regulating thin filament length (TFL), cross-bridge cycling, and myofibril alignment. Pathogenic variants in the nebulin gene (NEB) cause NEB-based nemaline myopathy (NEM2), a genetically heterogeneous disorder characterized by hypotonia and muscle weakness, currently lacking curative therapies. In this study, we examined a cohort of ten NEM2 patients, each with unique pathogenic variants, aiming to understand their impact on mRNA, protein, and functional levels. Results show that pathogenic truncation variants affect NEB mRNA stability and lead to nonsense-mediated decay of the mutated transcript. Moreover, a high incidence of cryptic splice site activation was found in patients with pathogenic splicing variants that are expected to disrupt the actin-binding sites of nebulin. Determination of protein levels revealed patients with either relatively normal or markedly reduced nebulin. We observed a positive relation between the reduction in nebulin and a reduction in TFL, or reduction in tension (both maximal and submaximal tension). Interestingly, our study revealed a pathogenic duplication variant in nebulin that resulted in a four-copy gain in the triplicate region of NEB and a much larger nebulin protein and longer TFL. Additionally, we investigated the effect of Omecamtiv mecarbil (OM), a small-molecule activator of cardiac myosin, on force production of type 1 muscle fibers of NEM2 patients. OM treatment substantially increased submaximal tension across all NEM2 patients ranging from 87 to 318%, with the largest effects in patients with the lowest level of nebulin. In summary, this study indicates that post-transcriptional or post-translational mechanisms regulate nebulin expression. Moreover, we propose that the pathomechanism of NEM2 involves not only shortened but also elongated thin filaments, along with the disruption of actin-binding sites resulting from pathogenic splicing variants. Significantly, our findings highlight the potential of OM treatment to improve skeletal muscle function in NEM2 patients, especially those with large reductions in nebulin levels.
Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe
Authors: Kelkar Sneha S. , Prabhu Vimalanand S. , Zhang Jingchuan , Ogando Yoscar M. , Roney Kyle , Verma Rishi P. , Miles Nicola , Marth Christian 
Published: April 2024

Abstract
Purpose
To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe.

Methods
Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics.

Results
ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively).

Conclusion
Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.
Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring
Authors: Guiducci Silvia , Res Giulia , Bonadies Luca , Savio Federica , Brigadoi Sabrina , Priante Elena , Trevisanuto Daniele , Baraldi Eugenio , Galderisi Alfonso 
Published: April 2024

Abstract Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007). Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants.

What is Known:• Parenteral nutrition may affect glucose profile during the first days of life of preterm infants.

What is New:• Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.
Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas
Authors: Long Qiuzhong , Li Zhengtian , Yang Wenkang , Huang Ke , Du Gang 
Published: April 2024

Abstract
Background
Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further.

Methods
Clinical and genomic data were obtained from the UCSC Xena database. All STS patients’ subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS.

Results
A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients’ treatment.

Conclusions
Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.
Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender
Authors: Dalli Jeffrey , Epperlein Jonathan P. , Hardy Niall P. , Khan Mohammad Faraz , Mac Aonghusa Pol , Cahill Ronan A. 
Published: April 2024

Abstract
Introduction
Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation.

Methods
Patients undergoing elective colorectal resection had colonic ICGFA both immediately after operative commencement prior to any dissection and again, as usual, just before anastomotic construction. Video recordings of both ICGFA acquisitions were blindly quantified post hoc across selected colonic regions of interest (ROIs) using tracking-quantification software and computationally compared with satisfactory perfusion assumed in second time-point ROIs, demonstrating 85% agreement with baseline ICGFA. ROI quantification outputs detailing projected perfusion sufficiency-insufficiency zones were compared to the actual surgeon-selected transection/anastomotic construction site for left/right-sided resections, respectively. Anastomotic outcomes were recorded, and tissue lactate was also measured in the devascularised colonic segment in a subgroup of patients. The novel perfusion zone projections were developed as full-screen recommendations via overlay heatmaps.

Results
No patient suffered intra- or early postoperative anastomotic complications. Following computational development (n = 14) the software recommended zone (ROI) contained the expert surgical site of transection in almost all cases (Jaccard similarity index 0.91) of the nine patient validation series. Previously published ICGFA time-series milestone descriptors correlated moderately well, but lactate measurements did not. High resolution augmented reality heatmaps presenting recommendations from all pixels of the bowel ICGFA were generated for all cases.

Conclusions
By benchmarking to the patient’s own baseline perfusion, this novel QICGFA method could allow the deployment of algorithmic personalised NIR bowel transection point recommendation in a way fitting existing clinical workflow.
Is mild dehydration a risk for progression of childhood chronic kidney disease?
Authors: Le Page Amelia K. , Johnson Evan C. , Greenberg Jason H. 
Published: April 2024

AbstractChildren with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.
Graphical Abstract