bluuebunny/crossref_metadata_2025 huggingface dataset:
Update Mammakarzinom 2023 Teil 2 – Brustkrebs in fortgeschrittenen Krankheitsstadien
Authors: Lux Michael P. , Hartkopf Andreas D. , Fehm Tanja N. , Welslau Manfred , Müller Volkmar , Schütz Florian , Fasching Peter A. , Janni Wolfgang , Witzel Isabell , Thomssen Christoph , Beierlein Milena , Belleville Erik , Untch Michael , Thill Marc , Tesch Hans , Ditsch Nina , Aktas Bahriye , Banys-Paluchowski Maggie , Kolberg-Liedtke Cornelia , Wöckel Achim , Kolberg Hans-Christian , Harbeck Nadia , Bartsch Rupert , Schneeweiss Andreas , Ettl Johannes , Würstlein Rachel , Krug David , Taran Florin-Andrei , Lüftner Diana , Stickeler Elmar
Published: December 2023

Eine Reihe von neuen Therapien hat in den letzten Jahren die Fortschritte in der Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom bestimmt. Diese Substanzen sind hauptsächlich die CDK4/6-Inhibitoren und weitere Substanzen, welche die endokrine Resistenz überwinden können, die oralen selektiven Östrogenrezeptor-Degradierer, die Antikörper-Medikament Konjugate (ADCs) und die PARP-Inhibitoren. In dieser Übersichtsarbeit werden die neuesten Studienergebnisse zusammengefasst und bewertet, die in den letzten Monaten veröffentlicht worden sind. Dies beinhaltet die Gesamtüberlebensdaten der Destiny-Breast03-Studie, die erste Analyse der CAPItello-291-Studie, den Vergleich einer CDK4/6-Inhibitor-Therapie mit Chemotherapie in der ersten Therapielinie (RIGHT Choice-Studie), die erste Analyse der Destiny-Breast02-Studie im Therapie-Setting nach T-DM1-Therapie und die erste Analyse der Serena-2-Studie.

Die meisten dieser Studien haben das Potenzial, die Therapielandschaft für Patientinnen mit fortgeschrittenem Mammakarzinom deutlich zu verändern, und zeigen, dass die Entwicklung neuer Therapien mit einer nach wie vor hohen Geschwindigkeit immer neue Ergebnisse produziert.
Besonderheiten der Seilrettung mittels Hubschrauber bei Highline-Unfällen
Authors: Bludau Jakob , Benkert Aaron , Halbwirth Gernot , Seidler Mario , Falkner Gabriel , Amrain Martin , Irmler Lukas , Buck Boris , Knaus Roy , Schniepp Roman
Published: December 2023

Die Trendsportart „Highlinen” gewinnt zunehmend an Popularität. Die Installation von teils kilometerlangen Highlines in schwer zugänglichen Gebieten erfordert die Etablierung von standardisierten und sicheren Prozeduren zur organisierten Rettung. Auf Basis einer Risiko- und Verfahrensanalyse wurden spezielle Handlungsabläufe und Risiken bei einer Kaperbergung eines Highline-Verunfallten identifiziert und bewertet sowie eine Verfahrensbeschreibung mit zeitlicher und funktionaler Gliederung erstellt. Anhand von realen Trainingsflügen wird die Verfahrensbeschreibung diskutiert und 4 häufige Risikosituationen nochmals diskutiert. Als Sonderform einer Kaperbergung bestehen zeit- und handlungsdefinierte Risikosituationen, welche mittels Prozedurentraining potenziell trainiert werden können. Ein Aufbau mit Sicherheitsmaßnahmen (mehrfache Redundanz, Materialschutz Highline) entschärft bei realen Trainingsflügen das Szenario.
Best Practice Guideline – Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie
Authors: Vogel-Minea Claudia Maria , Bader Werner , Blohmer Jens-Uwe , Duda Volker , Eichler Christian , Fallenberg Eva Maria , Farrokh André , Golatta Michael , Gruber Ines , Hackelöer Bernhard-Joachim , Heil Jörg , Madjar Helmut , Marzotko Ellen , Merz Eberhard , Müller-Schimpfle Markus , Mundinger Alexander , Ohlinger Ralf , Peisker Uwe , Schäfer Fritz KW , Schulz-Wendtland Ruediger , Solbach Christine , Warm Mathias , Watermann Dirk , Wojcinski Sebastian , Dudwiesus Heiko , Hahn Markus
Published: December 2023

Die Mammasonografie hat sich seit vielen Jahren neben der Mammografie als wichtige Methode zur Abklärung von Brustbefunden etabliert.

Der Arbeitskreis Mammasonografie der DEGUM beabsichtigt mit der „Best Practice Guideline“ den senologisch tätigen Kolleginnen und Kollegen neben dem in Teil I publizierten aktuellen Dignitätskriterien- und Befundungskatalog in dem vorliegenden Teil II die additiven und fakultativen Anwendungsmodalitäten zur Abklärung von Brustbefunden zu beschreiben und dazu DEGUM-Empfehlungen zu äußern, um die Differenzialdiagnose von unklaren Läsionen zu erleichtern.

Die vorliegende „Best Practice Guideline“ hat sich zum Ziel gesetzt, den Anforderungen zur Qualitätssicherung und der Gewährleistung einer qualitätskontrollierten Durchführung der Mammasonografie nachzukommen. Die wichtigsten Aspekte der Qualitätssicherung werden in diesem Teil II der Best Practice Guideline erläutert.
Transient Auditory Neuropathy with Resurgence of Electrophysiological Waveforms Observed between the Neonatal Period and Age 3 Years
Authors: Evans Adele K. , Baudoin Morgan E. , Knight Haley E. , Giles Amanda
Published: December 2023

Abstract Auditory neuropathy spectrum disorder (ANSD) is a spectrum of conditions marked by diminished auditory function and believed to be caused by the impaired neural transmission of auditory stimulation in the setting of functional outer hair cells. There are reports
of “spontaneously resolving” or “transient” ANSD (transient auditory neuropathy [TAN]) in the literature. In this case report of TAN, we demonstrate the resurgence of the auditory brainstem response waveform morphology over a 3-year period to reveal electrophysiological
testing consistent with the patient's functional hearing level by age 3 years.
Cluster Preface: Functional Dyes
Authors: Yang Youjun , Fan Jiangli
Published: December 2023

Youjun Yang (left) received his BS (2002) from the University of Science and Technology of China, and his PhD (2007) with Prof. Robert M. Strongin at Louisiana State University. Then, he joined the Anslyn group at UT Austin as a postdoc. In 2010, he joined the faculty of the school of pharmacy, East China University of Science and Technology (ECUST). His research interests include NIR fluorescent dyes, photo-responsive dyes, and fluorescent molecular probes.

Jiangli Fan (right) obtained her PhD at Dalian University of Technology (2005). Now she is a Professor at the School of Chemical Engineering at Dalian University of Technology, and she received the Distinguished Young Scholars of NSFC (2019). Her research interests mainly focus on the development of functional dyes for biomedical analysis and disease treatment.
Clinicopathological Evaluation of Patients with Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer Progressing on Endocrine Treatment: A Real-World Retrospective Study from a Regional Cancer Center
Authors: Shanthala S. , Amirtham Usha , Lokesh K. N. , Jacob Linu , Babu Govinda
Published: December 2023

Metastatic breast cancer (MBC) is an incurable disease with the primary aim of treatment being the improvement of the patient's quality of life and the delay of disease progression. A substantial proportion of patients with hormone receptor (HR)-positive MBC eventually experience progression despite endocrine treatment. As endocrine resistance remains a significant challenge, we aim to comprehend the intricate relationship between clinicopathological characteristics and the utility of various parameters as predictive markers for hormonal treatment response. This study, conducted at a single center, is ambispective in nature and includes hormone receptor (HR)-positive, human epidermal growth factor 2–negative MBC patients who progressed while on endocrine treatment, selected through purposeful sampling. Nominal data were analyzed in terms of frequency distribution, and continuous variables were represented as median/mean ± standard deviation. Spearman's correlation test and chi-square test were employed to examine variable dependencies. Data comparisons were performed using the independent t-test, one-way analysis of variance, or Mann–Whitney's test. The majority of our study participants (n = 44, 64.70%) presented with de novo metastasis, while the remainder (n = 24, 35.29%) were patients who progressed from early-stage breast cancer to metastasis. The overall mean age of our study population at presentation was 47 ± 11 years. Patients with upfront stage 4 tumors presented at an older age, exhibited grade 2 tumors, had a higher frequency of bone-only metastasis, and experienced longer progression-free survival (PFS) compared to patients who progressed from the early stage to metastasis. Multiple visceral involvements had a significant negative impact on PFS in contrast to cases with single visceral or bone-only involvement. No significant associations with PFS were observed for the Ki-67 index, first-line chemotherapy, or endocrine therapy. The extent of metastasis to various organs emerged as the most influential factor in determining PFS. Consequently, we propose the necessity for larger prospective studies aimed at identifying superior or additional biomarkers.
Uterine Microbiome: Does the Sampling Technique Matter?
Authors: Lüll Kreete , Org Elin
Published: December 2023

Studies have proven the significance of microbial communities in various parts of the human body for health. In recent years it has been discovered that the uterine cavity is not sterile, and endometrium has its own microbiome which appears to have an impact on female fertility and gynecological pathologies. Lactobacillus has shown to dominate the microbial profile in the uterus and is considered an indicator of a healthy uterine environment. Yet, many argue that the Lactobacillus dominance is due to vaginal contamination during the sampling process. To date there is no clearly defined healthy endometrial microbial profile, which is largely due to the fact that determining the microbial community from the endometrium is complicated, and there is currently no consensus on sampling methods for the endometrial microbiome. As a result, this restricts ability to replicate discoveries made in other cohorts. Here we aim to give an overview of the sampling methods used and discuss what impedes the endometrial microbiome studies as well as how to reach a consensus on the study design. This knowledge could be incorporated into the future research and the knowledge on endometrial microbiome could be included into the diagnostics and treatment of female reproductive health.
A Review of the Applications of Artificial Intelligence in the Process Analysis and Optimization of Chemical Products
Authors: Shen Runqiu , Su Weike
Published: December 2023

Continuous flow chemistry is an enabling technology for automated synthesis. Artificial intelligence (AI) is a powerful tool in various areas of automated synthesis in flow chemistry, including process analysis technology and synthesis reaction optimization. The merger of continuous flow chemistry and AI drives chemical production in a more intelligent, automated, and flexible direction. This review discusses the recent application of AI in analyzing and optimizing chemical products produced by continuous flow chemistry with the most innovative equipment and techniques.
Anorectal Abscess
Authors: Kata Anna , Abelson Jonathan S.
Published: December 2023

Anorectal abscesses are a common colorectal emergency. The hallmark of treatment is obtaining source control while avoiding injury to the underlying sphincter complex. Understanding the anatomy of an anorectal abscess is critical to planning the appropriate drainage strategy and decreasing the risk of complex fistula formation. Use of antibiotics should be reserved for those with extensive cellulitis, signs of systemic infection, or patients who are immunocompromised. Whether antibiotics prevent future fistula formation is an area of active research. Primary fistulotomy at time of the index drainage is controversial; however, there may be situations where it is appropriate. It is important to counsel patients that after effective drainage of an anorectal abscess, they have a 30 to 50% chance of developing an anal fistula that will then require further treatment.
Research on metaphor processing during the past five decades: a bibliometric analysis
Authors: Peng Zhibin , Khatin-Zadeh Omid
Published: December 2023

Metaphor processing has been the subject of extensive research over the past five decades. A systematic review of metaphor processing publications through bibliometric tools can provide a clear overview of research on metaphor processing. In this study, we used the CiteSpace bibliometric tool to conduct a systematic review of publications related to metaphor processing. A total of 3271 works published and indexed in the Web of Science (WoS) were gathered. These works had been published between 1970 and 2022. We analyzed the co-citations of these works by CiteSpace to identify the most influential publications in metaphor processing research. A co-occurrence term analysis was done to identify dominant topics in this area of research. The results of this analysis showed that Language, comprehension, metaphor, figurative language, and context were the most frequent keywords. The most prominent clusters were students, figurative language, right hemisphere, embodied cognition, comprehension, N400, and anger. Based on the results of this analysis, we suggest that task properties such as response format and linguistic features should be carefully taken into account in future studies on metaphor processing.
Evaluation of the impact of a pharmacy transitions of care program
Authors: Dalton Heather , Hinely Molly T , Kostelic Emily M
Published: December 2023

Purpose

Pharmacist-driven transitions of care interventions have been shown to improve patient clinical outcomes. However, the evidence in the literature on the impact of pharmacy transitions of care services on hospitalization and emergency department visit rates is inconclusive. The purpose of this study is to determine the impact of a pharmacist-driven transitions of care program on hospitalization and emergency department visit rates at an academic medical center.

Methods

This retrospective observational cohort study was conducted via pre- and postintervention analyses. The data collection period included 30 days before the date of pharmacist intervention and 30 days after the date of intervention. The study evaluated patients who were enrolled in the Transitional Inpatient Rounding Experience (TIRE) program at Wake Forest Baptist Health between August 2017 and September 2020. Patients excluded were less than 18 years old, in hospice care, discharged to long-term care, or did not have a hospitalization within 90 days of intervention. The Wilcoxon signed rank test was utilized to analyze continuous data. Standard descriptive statistics were used for categorical data.

Results

One hundred patients met the inclusion criteria for this study. For the primary outcome, the TIRE intervention resulted in a reduction of 31 hospitalizations, or 50% (62 prior hospitalizations in the 30 days before the intervention vs 31 admissions in the 30 days after the intervention; P < 0.001). There were significant reductions in the secondary outcomes of 90-day hospitalizations (24% fewer with intervention; P = 0.028) and 30-day emergency department visits (65% fewer with intervention; P =0.006). For the outcome of 90-day emergency department visits, there was a 36% reduction (P = 0.240).

Conclusion

The results of the study demonstrate that a pharmacy transitions of care program may lead to a reduction in hospitalization and emergency department visit rates. The study also found potential cost savings associated with a pharmacy transitions of care program.
PredictONCO: a web tool supporting decision-making in precision oncology by extending the bioinformatics predictions with advanced computing and machine learning
Authors: Stourac Jan , Borko Simeon , Khan Rayyan T , Pokorna Petra , Dobias Adam , Planas-Iglesias Joan , Mazurenko Stanislav , Pinto Gaspar , Szotkowska Veronika , Sterba Jaroslav , Slaby Ondrej , Damborsky Jiri , Bednar David
Published: December 2023

PredictONCO 1.0 is a unique web server that analyzes effects of mutations on proteins frequently altered in various cancer types. The server can assess the impact of mutations on the protein sequential and structural properties and apply a virtual screening to identify potential inhibitors that could be used as a highly individualized therapeutic approach, possibly based on the drug repurposing. PredictONCO integrates predictive algorithms and state-of-the-art computational tools combined with information from established databases. The user interface was carefully designed for the target specialists in precision oncology, molecular pathology, clinical genetics and clinical sciences. The tool summarizes the effect of the mutation on protein stability and function and currently covers 44 common oncological targets. The binding affinities of Food and Drug Administration/ European Medicines Agency -approved drugs with the wild-type and mutant proteins are calculated to facilitate treatment decisions. The reliability of predictions was confirmed against 108 clinically validated mutations. The server provides a fast and compact output, ideal for the often time-sensitive decision-making process in oncology. Three use cases of missense mutations, (i) K22A in cyclin-dependent kinase 4 identified in melanoma, (ii) E1197K mutation in anaplastic lymphoma kinase 4 identified in lung carcinoma and (iii) V765A mutation in epidermal growth factor receptor in a patient with congenital mismatch repair deficiency highlight how the tool can increase levels of confidence regarding the pathogenicity of the variants and identify the most effective inhibitors. The server is available at https://loschmidt.chemi.muni.cz/predictonco.
RMTLysPTM: recognizing multiple types of lysine PTM sites by deep analysis on sequences
Authors: Chen Lei , Chen Yuwei
Published: December 2023

Post-translational modification (PTM) occurs after a protein is translated from ribonucleic acid. It is an important living creature life phenomenon because it is implicated in almost all cellular processes. Identification of PTM sites from a given protein sequence is a hot topic in bioinformatics. Lots of computational methods have been proposed, and they provide good performance. However, most previous methods can only tackle one PTM type. Few methods consider multiple PTM types. In this study, a multi-label classification model, named RMTLysPTM, was developed to recognize four types of lysine (K) PTM sites, including acetylation, crotonylation, methylation and succinylation. The surrounding sites of a lysine site were selected to constitute a peptide segment, representing the lysine at the center. Deep analysis was conducted to count the distribution of 2-residues with fixed location across the four types of lysine PTM sites. By aggregating the distribution information of 2-residues in one peptide segment, the peptide segment was encoded by informative features. Furthermore, a prediction engine that can precisely capture the traits of the above representations was designed to recognize the types of lysine PTM sites. The cross-validation results on two datasets (Qiu and CPLM training datasets) suggested that the model had extremely high performance and RMTLysPTM had strong generalization ability by testing it on protein Q16778 and CPLM testing datasets. The model was found to be generally superior to all previous models and those using popular methods and features. A web server was set up for RMTLysPTM, and it can be accessed at http://119.3.127.138/.
MaxCLK: discovery of cancer driver genes via maximal clique and information entropy of modules
Authors: Liu Jian , Ma Fubin , Zhu Yongdi , Zhang Naiqian , Kong Lingming , Mi Jia , Cong Haiyan , Gao Rui , Wang Mingyi , Zhang Yusen
Published: December 2023

Motivation

Cancer is caused by the accumulation of somatic mutations in multiple pathways, in which driver mutations are typically of the properties of high coverage and high exclusivity in patients. Identifying cancer driver genes has a pivotal role in understanding the mechanisms of oncogenesis and treatment.

Results

Here, we introduced MaxCLK, an algorithm for identifying cancer driver genes, which was developed by an integrated analysis of somatic mutation data and protein–protein interaction (PPI) networks and further improved by an information entropy index. Tested on pancancer and single cancers, MaxCLK outperformed other existing methods with higher accuracy. About pancancer, we predicted 154 driver genes and 787 driver modules. The analysis of co-occurrence and exclusivity between modules and pathways reveals the correlation of their combinations. Overall, our study has deepened the understanding of driver mechanism in PPI topology and found novel driver genes.

Availability and implementation

The source codes for MaxCLK are freely available at https://github.com/ShandongUniversityMasterMa/MaxCLK-main.
The function of red and banded patterns in snakes: the ophiophagy hypothesis
Authors: Mouy Henri
Published: December 2023

The functions of bright bands in coral and other snakes have long been a puzzle. The most common opinion is that coral snakes display aposematic marks and that other red and black banded snakes in the Americas are mimics of coral snakes. I previously found that this prevailing opinion is weakly supported and unlikely, that red and bands had probably evolved independently or conjointly many times, and that a present selection for bands and red seems to exist in a significant fraction of the world. Here, I review the potential selective forces for red and bands in snakes. I find that snakes as predators are a priori plausible selective agents. I find that ophiophagy appears to be an exceptionally high risk in snakes that are themselves ophiophagous. Testing the working hypothesis that bands and red are protective against snake predators via their association with ophiophagy, as ophiophagous snakes are at higher risk, I find that the consumption of elongate vertebrates predicts band and red coloration with a very high level of confidence: red and bands are probably defensive against snake predators. Noting an apparent correlation of coloration with specific defensive behaviours and ontogenetic colour changes, I review both and find that ophiophagous snakes are remarkable for using stereotypical defences and not being aggressive, while ontogenetic colour changes seem to affect red and bands in snakes disproportionately. Defence against ophidian predators may be an unexpected natural selection shaping the appearance and behaviours of many snakes.
Extra-cranial cholinergic lesions in dementia with Lewy bodies
Authors: Goldstein David S
Published: December 2023

This scientific commentary refers to ‘Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies’ by Okkels et al. (https://doi.org/10.1093/brain/awad391).
Measurement matters for assessing the role of chronically altered perfusion in post-stroke aphasia
Authors: Thompson Cynthia K , Walenski Matthew
Published: December 2023

This scientific commentary refers to ‘Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities’, by Ivanova et al. (https://doi.org/10.1093/braincomms/fcad252).
Vestibular damage affects the precision and accuracy of navigation in a virtual visual environment
Authors: Chari Divya A , Ahmad Maimuna , King Susan , Boutabla Anissa , Fattahi Cameron , Panic Alexander S , Karmali Faisal , Lewis Richard F
Published: December 2023

Vestibular information is available to the brain during navigation, as are the other self-generated (idiothetic) and external (allothetic) sensorimotor cues that contribute to central estimates of position and motion. Rodent studies provide strong evidence that vestibular information contributes to navigation but human studies have been less conclusive. Furthermore, sex-based differences have been described in human navigation studies performed with the head stationary, a situation where dynamic vestibular (and other idiothetic) information is absent, but sex differences in the utilization of vestibular information have not been described. Here, we studied men and women with severe bilateral vestibular damage as they navigated through a visually barren virtual reality environment and compared their performance to normal men and women. Two navigation protocols were employed, which either activated dynamic idiothetic cues (‘dynamic task’, navigate by turning, walking in place) or eliminated them (‘static task’, navigate with key presses, head stationary). For both protocols, we employed a standard ‘triangle completion task’ in which subjects moved to two visual targets in series and then were required to return to their perceived starting position without localizing visual information. The angular and linear ‘accuracy’ (derived from response error) and ‘precision’ (derived from response variability) were calculated. Comparing performance ‘within tasks’, navigation on the dynamic paradigm was worse in male vestibular-deficient patients than in normal men but vestibular-deficient and normal women were equivalent; on the static paradigm, vestibular-deficient men (but not women) performed better than normal subjects. Comparing performance ‘between tasks’, normal men performed better on the dynamic than the static paradigm while vestibular-deficient men and both normal and vestibular-deficient women were equivalent on both tasks. Statistical analysis demonstrated that for the angular precision metric, sex had a significant effect on the interaction between vestibular status and the test paradigm. These results provide evidence that humans use vestibular information when they navigate in a virtual visual environment and that men and women may utilize vestibular (and visual) information differently. On our navigation paradigm, men used vestibular information to improve navigation performance, and in the presence of severe vestibular damage, they utilized visual information more effectively. In contrast, we did not find evidence that women used vestibular information while navigating on our virtual task, nor did we find evidence that they improved their utilization of visual information in the presence of severe vestibular damage.
Identification of biomarkers for the early detection of non-small cell lung cancer: a systematic review and meta-analysis
Authors: Mohamed Eithar , García Martínez Daniel J , Hosseini Mohammad-Salar , Yoong Si Qi , Fletcher Daniel , Hart Simon , Guinn Barbara-ann
Published: December 2023

Lung cancer (LC) causes few symptoms in the earliest stages, leading to one of the highest mortality rates among cancers. Low-dose computerised tomography (LDCT) is used to screen high-risk individuals, reducing the mortality rate by 20%. However, LDCT results in a high number of false positives and is associated with unnecessary follow-up and cost. Biomarkers with high sensitivities and specificities could assist in the early detection of LC, especially in patients with high-risk features. Carcinoembryonic antigen (CEA), cytokeratin 19 fragments and cancer antigen 125 have been found to be highly expressed during the later stages of LC but have low sensitivity in the earliest stages. We determined the best biomarkers for the early diagnosis of LC, using a systematic review of eight databases. We identified 98 articles that focussed on the identification and assessment of diagnostic biomarkers and achieved a pooled area under curve of 0.85 (95% CI 0.82–0.088), indicating that the diagnostic performance of these biomarkers when combined was excellent. Of the studies, 30 focussed on single/antigen panels, 22 on autoantibodies, 31 on miRNA and RNA panels, and 15 suggested the use of circulating DNA combined with CEA or neuron-specific enolase (NSE) for early LC detection. Verification of blood biomarkers with high sensitivities (Ciz1, exoGCC2, ITGA2B), high specificities (CYFR21-1, antiHE4, OPNV) or both (HSP90α, CEA) along with miR-15b and miR-27b/miR-21 from sputum may improve early LC detection. Further assessment is needed using appropriate sample sizes, control groups that include patients with non-malignant conditions, and standardised cut-off levels for each biomarker.
Multiple Cardiac Biomarkers to Improve Prediction of Cardiovascular Events: Findings from the Generation Scotland Scottish Family Health Study
Authors: Welsh Paul , Kimenai Dorien M , Shah Anoop S V , Gadd Danni A , Marioni Riccardo E , Woodward Mark , Sudlow Cathie L M , Campbell Archie , Cleland John G F , Pellicori Pierpaolo , Hayward Caroline , Mills Nicholas L , Sattar Naveed
Published: December 2023

Background

Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific, combined cardiac biomarker approach for cardiovascular risk prediction.

Methods

In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 risk factors.

Results

The study population comprised 18 383 individuals (58.9% women, median age of 48 years [25th–75th percentile, 35–58 years]). During the median follow up of 11.6 (25th–75th percentile, 10.8–13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to the base model was for women GDF-15 and for men NT-proBNP (change in c-index: + 0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination.

Conclusions

A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.
Privacy-Preserving Image Retrieval with Multi-Modal Query
Authors: Zhou Fucai , Zhang Zongye , Hou Ruiwei
Published: December 2023

The ever-growing multi-modal images pose great challenges to local image storage and retrieval systems. Cloud computing provides a solution to large-scale image data storage but suffers from privacy issues and lacks the support for multi-modal image retrieval. To address these, a searchable encryption-empowered privacy-preserving multi-modal image retrieval method is proposed. First, we design a hybrid image retrieval framework that fuses visual features and textual features at a decision level and further supports similar image retrieval and multi-keyword image retrieval. Second, we construct a new hybrid inverted index structure to distinguish high-frequency terms from low-frequency terms and index them through hierarchical index trees and data blocks, respectively, which greatly improves query efficiency. Third, we design a prime encoding-based multi-keyword query method that converts mapping operations in bloom filters into inner product calculations, and further implements secure multi-keyword image query. Experiments against the Baseline schemes are conducted to verify the performance of the scheme in terms of high efficiency.
Effect of total dissolved gas supersaturation and flow velocity on survival and swimming ability of juvenile Schizothorax prenanti
Authors: Yuan Quan , Du Jun , Li Kefeng , Wang Yuanming , Liang Ruifeng
Published: December 2023

Although developing large-scale hydropower cascades in the upper Yangtze River effectively improves the hydropower resource utilization, it produces total dissolved gas (TDG) supersaturation. In the flood season, the high level of TDG supersaturation (TDGS) frequently occurs in the downstream of dams, causing migratory fish to suffer from gas bubble trauma (GBT) and reducing their survival and swimming ability. Currently, there is a deficiency in particular approaches to evaluate the ecological hazard posed by TDGS on migratory fish as they traverse different flow velocities within their migratory routes. This study assessed the vulnerability of juvenile Schizothorax prenanti (S. prenanti) to GBT from the static setting to 9.0 BL/s during exposure to nominal levels of 100%, 110%, 120% and 130% TDG. The mortality occurs when the flow velocity surpasses 6.0 and 7.5 BL/s in 100% and 110% TDG levels, respectively. For fish exposed to 120% and 130% TDG levels, the relationship between survival time and flow velocity is an approximately inverse bell-shaped curve with increasing velocity. The optimal velocity of maximal survival time of juvenile S. prenanti is 3.0 and 4.5 BL/s in 120% and 130% TDG-supersaturated water. Both TDG level and flow velocity significantly affect burst swimming speed (Uburst) and critical swimming speed (Ucrit). The cases involving GBT showed substantial declines in Uburst and Ucrit, exceeding 6.0 BL/s and TDG levels greater than 120%. The results may contribute to formulating a specific management strategy for hydropower operation during the migratory period and conserving vulnerable species in the Yangtze River.
Differential heat shock protein responses in two species of Pacific salmon and their utility in identifying heat stress
Authors: von Biela Vanessa R , Regish Amy M , Bowen Lizabeth , Stanek Ashley E , Waters Shannon , Carey Michael P , Zimmerman Christian E , Gerken Jonathon , Rinella Daniel , McCormick Stephen D
Published: December 2023

Rapid and accelerating warming of salmon habitat has the potential to lower productivity of Pacific salmon (Oncorhynchus species) populations. Heat stress biomarkers can indicate where warming is most likely affecting fish populations; however, we often lack clear classifications that separate individuals with and without heat stress needed to make these tools operational. We conducted a heat exposure experiment with trials lasting 12 or 36 h using juvenile Chinook salmon (Oncorhynchus tshawytscha) and coho salmon (Oncorhynchus kisutch) to validate heat stress biomarkers in white muscle. Following habituation to 13°C, individuals were exposed to water temperatures that increased to 15°C, 17°C, 19°C, 21°C or 23°C. Heat shock protein 70 abundance (HSP70 measured by ELISA) and transcription of 13 genes (mRNA measured by qPCR) including three heat shock protein genes (hsp70, hsp90, hsp27) were measured. A distinct heat stress response was apparent by 21°C in juvenile Chinook salmon and 23°C in juvenile coho salmon using HSP70. A threshold for heat stress classification in Chinook salmon of > 2 ng HSP70 mg.1 total protein identified heat stress in 100% of 21 and 23°C treated individuals compared to 4% in cooler treatments. For coho salmon, > 3 ng HSP70 mg.1 total protein identified heat stress in 100% of 23°C treated individuals compared to 4% in cooler treatments. Transcription from a panel of genes separated individuals between cooler and stressful temperature experiences (≥21°C for Chinook salmon and ≥23°C for coho salmon) with ~ 85% correct classification. Our findings indicate that juvenile Chinook salmon were more temperature-sensitive than juvenile coho salmon and support the use of a HSP70 threshold sampled from muscle for assessing heat stress in individual wild Pacific salmon with an option for non-lethal biopsies for spawning adults.
Soil moisture and temperature drive emergence delays associated with fire seasonality in eucalypt forests
Authors: Ryan Casey , Callow John Nikolaus , Lewandrowski Wolfgang , Tangney Ryan
Published: December 2023

Many ecosystems are well adapted to fire, although the impacts of fire seasonality and its effect on post-fire recruitment are less well understood. Late summer or autumn fires within eucalypt forests with a Mediterranean-type climate allow for seedling emergence during the cooler and wetter seasons. The emergence and survival after spring fires may be impacted by higher soil temperatures and water stress, delaying recruitment until the subsequent winter period. During this delay, seeds may be exposed to predation and decay, which reduce the viable seed bank. This study examines post-fire recruitment dynamics in a eucalypt forest ecosystem (Northern Jarrah Forest (NJF) of southwestern Western Australia) and whether it may be vulnerable to human-induced changes to fire season. Here, we compare in situ post-fire seedling emergence patterns between autumn and spring burns and account for a potential ecological mechanism driving seasonal differences in emergence by determining the thermal germination requirements of seeds for 15 common species from the NJF. Our results demonstrate that 93% of species had thermal optima between 10°C and 20°C, analogous with soil temperatures measured during the germination window (late April to October). Concurrent in situ post-fire emergence was highest 144 days after an autumn (seasonal) fire, followed by a 10–72% decline. In contrast, there was no emergence within the first 200 days following a spring (aseasonal) fire. We conclude that aseasonal fire in the NJF can lead to a complete delay in recruitment in the first season post-fire, resulting in a lower inter-fire growth period and increasing the potential for further reductions in recruitment through seed predation and decay. The study suggests that aseasonal fire has an immediate and significant impact on initial recruitment in the NJF, but further research is required to determine any longer-term effects of this delay and its implications for fire management in southwestern Western Australia.
Female agents of Hell, Stoic luxury, and failing leaders: Erictho, Tisiphone, and the female gaze in Lucan, Statius, Dante, and Boccaccio
Authors: Anagnostou-Laoutides Eva
Published: December 2023

The Underworld imagery developed by Lucan (BC 6.507–830), Statius (Th. 4.345–645), Valerius Flaccus (Arg. 1.827–50), and Silius Italicus (Pun. 2 and 13) to reprove Rome’s power-hungry leaders, accused of the death of thousands in civil war battles, excited the imagination of Christian writers such as Lactantius, Ausonius, Jerome, and the Spanish Presbyter Iuvencus. The article explores the investment of this imagery with the Stoic notion of excess (luxury) and its impact on defining the Christian concept of sin as received and further developed by Dante and Boccaccio. So far, scholarly discussion has tended to focus on the Homeric overcoat of pietas and its opposite furor, which under the influence of Posidonius (135–51 BCE), came to be associated with traditional Roman virtues. Instead, I here focus on Erictho (Lucan) and Tisiphone (Statius) as symbols of sinful temptation and effeminizing excess (luxury), typically gripping its victims through the eyes. In response to these infernal female figures, Dante and Boccaccio attributed epic proportions to ethical life, turning it into a canvas on which they debated the Christian moral code of their times. The gendered principles underpinning sinful excess in both pagan and Christian authors are discussed, alongside the role of poetry in counter-proposing the figures of Piety and Clemency.
Free to Be! Youth Participatory Action Research as a Promotive Context for Black Youth Development
Authors: Rowan Jazlyn N , Palmer Ja’Toria S , Johnson Casey Ellis , Riley Tennisha N
Published: December 2023

The U.S. education system often functions as an adverse developmental context for Black students. Discriminatory policies and racist ideologies contribute to a series of cascading inequities in students' learning experiences. For example, years of data indicate an overrepresentation of Black students suspended and/or expelled from school. Moreover, Black Americans’ experiences and contributions to U.S. society are often left out of curricula, compounding the physical exclusion of Black students from classrooms with the exclusion of their experiences. While such contexts inhibit learning and growth at critical developmental stages, the out-of-school time (OST) context can amplify the voices of Black students and support their learning and development in ways that address these exclusionary practices. Specifically, youth participatory action research (YPAR) during OST is an important critical pedagogical approach that provides a safe context for Black students to engage in challenging oppressive policies and practices within schools. The current study engages four Black/African American youth (aged 15–18 years old) in YPAR and positions youth as active learners and experts in their learning and developmental growth. Findings suggest an equitable OST context can contribute to our understanding of Black students' experiences in school and the co-creation of solutions for a more just learning environment.
Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn’s Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets
Authors: Lewis Amy , Humphreys David T , Pan-Castillo Belen , Berti Giulio , Felice Carla , Gordon Hannah , Gadhok Radha , Nijhuis Anke , Mehta S Shameer , Eleid Liliane , Iqbal Sidra , Armuzzi Alessandro , Minicozzi Annamaria , Giannoulatou Eleni , ChinAleong Joanne , Feakins Roger , Sagi-Kiss Virag , Barisic Dora , Koufaki Margarita-Ioanna , Bundy Jacob G , Lindsay James O , Silver Andrew
Published: December 2023

Background and Aims

No effective therapeutic intervention exists for intestinal fibrosis in Crohn’s disease [CD]. We characterized fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies.

Methods

We undertook immunohistochemistry, metabolic, signalling pathway and epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/NSCD fibroblasts were cultured with TGFβ and valproic acid [VPA].

Results

Stricturing CD was characterized by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFβ stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appeared ‘metabolically primed’ and responded more strongly to both TGFβ and VPA. Treatment with VPA revealed TGFβ-dependent and TGFβ-independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters.

Conclusions

Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype and metabolic priming characterize SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFβ-mediated CD fibrosis. HDAC inhibitor therapy may ‘reset’ the epigenetic changes associated with fibrosis.
Prevalence and prognostic impact of dynamic atrial functional mitral regurgitation assessed by isometric handgrip exercise
Authors: Spieker Maximilian , Sidabras Jonas , Lagarden Hannah , Christian Lucas , Angendohr Stephan , Zweck Elric , Bejinariu Alexandru , Veulemanns Verena , Schulze Christian , Polzin Amin , Rana Obaida , Westenfeld Ralf , Kelm Malte , Horn Patrick
Published: December 2023

Aims

In atrial functional mitral regurgitation (aFMR), a considerable proportion of patients displays a discrepancy between symptoms and echocardiographic findings at rest. Exercise testing plays a substantial role in assessing the haemodynamic relevance of mitral regurgitation (MR) and is recommended by current guidelines. Here, we aimed to assess the prevalence, extent, and prognostic impact of exercise-induced changes in patients with aFMR.

Methods and results

Patients with at least mild MR who underwent handgrip exercise echocardiography at the University Hospital Duesseldorf between January 2019 and September 2021 were enrolled. Patients were followed up for 1 year to assess clinical outcomes. Eighty patients with aFMR were included [median age: 80 (77–83) years; 53.8% female]. The median N-terminal pro-brain natriuretic peptide level was 1756 (1034–3340) ng/L. At rest, half of the patients (53.8%) had mild MR, 20 patients (25.0%) had moderate MR, and 17 patients (21.2%) had severe MR. In approximately every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Handgrip exercise led to a reclassification of MR severity in 28 patients (35.0%). At 1-year follow-up, adverse events occurred more often in patients with severe MR at rest (76.5%) and exercise-induced dynamic severe MR (66.7%) than in those with non-severe MR (28.6%; P < 0.001).

Conclusion

Handgrip exercise during echocardiography revealed exercise-induced changes in aFMR in every third patient. These data may have implications for therapeutic decision-making in symptomatic patients with non-severe aFMR at rest.
Thrombus entrapment with left atrial appendage closure to facilitate early cardioversion in tachycardiomyopathy: a case report
Authors: Bruno Jolie , Räber Lorenz , Schnegg Bruno , Primiceri Livia
Published: December 2023

Background

The aetiological spectrum of heart failure with reduced ejection fraction is various. Tachycardiomyopathy is recognized as one of the cause, usually made retrospectively. In this clinical context, rhythm control with restoration of sinus rhythm is considered crucial to minimize ventricular function damage and allow contractility recovery. However, the presence of a thrombus in the left atrial appendage is a limiting factor, typically requiring anticoagulation until the thrombus resolves, at least 3 weeks, thus delaying the therapy.

Case summary

We present a case of 65-year-old man with diagnosis of new-onset acute symptomatic heart failure with severe reduced ejection fraction (left ventricular ejection fraction 15%), in the context of a typical tachycardic atrial flutter and concomitant thrombus in the left atrial appendage confirmed by transoesophageal echocardiography. We successfully performed a thrombus entrapment procedure by means of percutaneous left atrial appendage closure, which allowed immediate restoration of sinus rhythm through cavotricuspid isthmus ablation. After the institution of the heart failure therapy, titrated up to the maximum tolerated dose, we observed a complete restoration of left ventricular function after 6 months.

Discussion

Thrombus entrapment by means of left atrial appendage closure is a valid strategy that enables early cardioversion with arrhythmia ablation and rapid restoration of normal cardiac rhythm in severe heart failure with reduced ejection fraction, even in acute situations and typical atrial flutter.