bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for the Activation of the Cobalt‐Carbon Bond and Control of the Adenosyl Radical in Coenzyme B12 Catalysis
Authors: Shibata Naoki , Toraya Tetsuo 
Published: March 2023

AbstractAdenosylcobalamin (AdoCbl), or coenzyme B12, is a naturally occurring organometallic compound that serves as a cofactor for enzymes that catalyze intramolecular group‐transfer reactions and ribonucleotide reduction in a wide variety of organisms from bacteria to animals. AdoCbl‐dependent enzymes are radical enzymes that generate an adenosyl radical by homolysis of the coenzyme's cobalt‐carbon (Co−C) bond for catalysis. How do the enzymes activate and cleave the Co−C bond to form the adenosyl radical? How do the enzymes utilize the high reactivity of the adenosyl radical for catalysis by suppressing undesirable side reactions? Our recent structural studies, which aimed to solve these problems with diol dehydratase and ethanolamine ammonia‐lyase, established the crucial importance of the steric strain of the Co−C bond and conformational stabilization of the adenosyl radical for coenzyme B12 catalysis. We outline here our results obtained with these eliminating isomerases and compare them with those obtained with other radical B12 enzymes.
Der Rote Keulenkopf
Authors: Petersen Frank 
Published: March 2023

ZusammenfassungWährend die Ursache der Ergotoxikose noch immer im Dunkeln lag, wurde das Mutterkorn erstmals in der zweiten Hälfte des 15. Jahrhunderts in einer Nürnberger Sammlung medizinischer Rezepturen für die Behandlung von Gebärmutterbeschwerden genannt. 1582 veröffentlichte der Frankfurter Stadtarzt Adam Lonicer in seinem „Kreuterbuch“ das Mutterkorn als Medikation bei Regelschmerzen. Erst im 17. Jahrhundert erkannten der französische Mediziner und Botaniker Denis Dodart sowie der Schweizer Arzt Johann Conrad Brunner im Mutterkorn den Auslöser des gangränösen und konvulsiven Ergotismus. Das Auslesen der Sklerotien aus der Roggenernte und die wachsende Akzeptanz der Kartoffel als Nahrungsmittel drängten den Ergotismus deutlich zurück. Die dadurch bedingte Unterbelegung in den Antoniterhöspitälern brachte den Orden zunehmend in finanzielle Schwierigkeiten. Die tiefgreifenden kulturellen und politischen Umwälzungen seit dem 16. Jahrhundert und die ökonomische Situation der Antoniter führten 1776 zu ihrer Integration in den Malterserorden. Anfang des 18. Jahrhunderts veröffentlichten zwei Mediziner der Universität Tübingen ihre Abhandlungen zum Mutterkorn, in denen erstmals von Hebammen berichtet wurde, die das Sklerotium als Wehenmittel einsetzten. Beide Schulmediziner warnten darin eindringlich vor seinen Gefahren in der Geburtsheilkunde. Trotz der Risiken hielten Hebammen und Geburtshelfer an der Mutterkornarznei fest. Erst mit der Veröffentlichung des Vortrags des US‐amerikanischen Arztes Oliver Prescott Jr. im Jahr 1813, in dem er – bei richtiger Anwendung – die Bedeutung des Mutterkorns in der Obstetrik und der Gynäkologie hervorhob, fand die Mutterkornarznei auch Eingang in die europäische Schulmedizin.
ScY@C3v(8)‐C82:Metal‐Metalσ2Bond in MixedRare‐EarthDi‐metallofullerenes†
Authors: Zheng Lihao , Roselló Yannick , Yan Yingjing , Yao Yang‐Rong , Fan Xiaolin , Poblet Josep M. , Rodríguez‐Fortea Antonio , Chen Ning 
Published: March 2023

Comprehensive SummaryThe experimental investigation of rare‐earth metal‐metal bonds remains a challenge in the study of chemical bonds. Herein, we report the synthesis and characterization of a novel heteronuclear di‐metallofullerene, ScY@C3v(8)‐C82, which contains a mixed rare‐earth metal‐metal bond. ScY@C3v(8)‐C82was successfully synthesized by arc‐discharging method and characterized by mass spectrometry, UV‐vis‐NIR spectroscopy and single‐crystal X‐ray diffraction crystallography, which unambiguously determined its molecular structure. Theoretical calculations were also performed to study the optimized positions of Sc‐Y metallic dimer and the electronic configuration. The combined experimental and theoretical results confirmed that both Sc and Y atoms transfer two electrons to theC3v(8)‐C82cage,i.e., (ScY)4+@(C3v(8)‐C82)4–. In particular, a covalent Sc‐Y σ2bond, which has never been reported before, is proven to be formed insideC3v(8)‐C82fullerene cage. This work presents a novel di‐metallofullerene containing mixed rare‐earth metal‐metal bond and expands the understanding of metal‐metal bonding of rare earth elements.
Impact of mitral regurgitation in patients with acute heart failure: insights from the RELAX‐AHF‐2 trial
Authors: Pagnesi Matteo , Adamo Marianna , ter Maaten Jozine M. , Beldhuis Iris E. , Cotter Gad , Davison Beth A. , Felker G. Michael , Filippatos Gerasimos , Greenberg Barry H. , Pang Peter S. , Ponikowski Piotr , Sama Iziah E. , Severin Thomas , Gimpelewicz Claudio , Voors Adriaan A. , Teerlink John R. , Metra Marco 
Published: March 2023

AbstractAimsThe impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX‐AHF‐2) trial.Methods and resultsPatients enrolled in RELAX‐AHF‐2 with available data regarding MR status were included in this analysis. Baseline characteristics, in‐hospital data, and clinical outcomes through 180‐day follow‐up were evaluated. The impact of moderate/severe MR was assessed. Among 6420 AHF patients with known MR status, 1810 patients (28.2%) had moderate/severe MR. Compared to patients with no/mild MR, those with moderate/severe MR were more likely to have history of heart failure (HF), prior HF hospitalization, more comorbidities, symptoms/signs of HF, lower left ventricular ejection fraction and higher N‐terminal pro‐B‐type natriuretic peptide levels. Moderate/severe MR was associated with longer length of hospital stay, higher rates of residual dyspnoea, increased jugular venous pressure through the index hospitalization and a higher unadjusted risk of the composite of cardiovascular (CV) death or rehospitalization for HF/renal failure (RF) through 180 days (crude hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.03–1.27, p = 0.01). The association between moderate/severe MR and poorer outcomes was not maintained in a multivariable model including several covariates of interest (adjusted HR 1.03, 95% CI 0.91–1.17, p = 0.65). Similar findings were observed for HF/RF rehospitalization alone.ConclusionsIn patients with AHF, moderate/severe MR was associated with a worse clinical profile but did not have an independent prognostic impact on clinical outcomes.
Disproportionate exercise‐induced pulmonary hypertension in relation to cardiac output in heart failure with preserved ejection fraction: a non‐invasive echocardiographic study
Authors: Saito Yuki , Obokata Masaru , Harada Tomonari , Kagami Kazuki , Sorimachi Hidemi , Yuasa Naoki , Kato Toshimitsu , Wada Naoki , Okumura Yasuo , Ishii Hideki 
Published: March 2023

AimsPulmonary hypertension (PH) and pulmonary vascular remodelling are common in patients with heart failure with preserved ejection fraction (HFpEF). Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non‐invasively by the mean pulmonary artery pressure–cardiac output relationship (mPAP/CO slope). We sought to characterize the pathophysiology of disproportionate exercise‐induced PH in relation to CO (DEi‐PH) and its prognostic impact in patients with HFpEF.Methods and resultsA total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi‐PH was defined as the mPAP/CO slope >5.2 mmHg/L/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi‐PH. Compared with controls (n = 179) and HFpEF without DEi‐PH (n = 83), HFpEF with DEi‐PH (n = 83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV–pulmonary artery coupling, limitation in CO augmentation, more right‐sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan–Meier analyses showed that HFpEF patients with DEi‐PH had higher rates of composite outcomes of all‐cause mortality or heart failure events than those without (log‐rank p = 0.0002).ConclusionPatients with HFpEF and DEi‐PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi‐PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF.
Synthesis and Reactivity of Dithienopyrazines**
Authors: Kreuzer Franziska , Aubele Anna , Mena‐Osteritz Elena , Bäuerle Peter 
Published: March 2023

AbstractHeteroacenes developed to widely used building blocks in organic semiconductors for application in organic electronics due to their tunable structures and properties concomitant with inherent stability. Here, we report efficient preparation and investigation of so far unknown heterotriacenes, basic anti‐ and syn‐dithienopyrazine 5 and 6. The comparison of the two isomers with respect to electronic properties and follow‐up reactions gives insights into structure‐property and ‐reactivity relationships. Examples of transition metal‐catalyzed C−C cross‐coupling reactions of corresponding halogenated derivatives show the practical impact for extended π‐conjugated systems applied in optoelectronic devices.
The automated collapse data constructor technique and the data‐driven methodology for seismic collapse risk assessment
Authors: Bijelić Nenad , Lignos Dimitrios G. , Alahi Alexandre 
Published: March 2023

AbstractMajority of the past research on application of machine learning (ML) in earthquake engineering focused on contrasting the predictive performance of different ML algorithms. In contrast, the emphasis of this paper is on the use of data to boost the predictive performance of surrogates. To that end, a novel data engineering methodology for seismic collapse risk assessment is proposed. This method, termed the automated collapse data constructor (ACDC), stems from combined understanding of the ground motion characteristics and the collapse process. In addition, the data‐driven collapse classifier (D2C2) methodology is proposed which enables conversion of the collapse data from a regression format to a classification format. The D2C2 methodology can be used with any classification tool, and it allows estimation of seismic collapse capacities in a way analogous to the incremental dynamic analysis. The proposed methodologies are tested in a case study using decision trees (XGBoost) and neural network classifiers with an extensive dataset of collapse responses of a 4‐story and an 8‐story steel moment resisting frames. The results suggest that the ACDC methodology allows for dramatic improvement of the predictive performance of data‐driven tools while at the same time significantly reducing data requirements. Specifically, the proposed method can reduce the number of ground motions required for collapse risk assessment from at least forty, as traditionally used, to less than twenty motions. Moreover, interpretation of feature importance conforms with the engineering understanding while revealing a novel, period‐dependent measure of ground motion duration. All data and code developed in this research are made openly available.
Vanished MDM2 amplification in multiple recurrences of an irradiated poorly differentiated sarcoma with amplified TRIO::TERT fusion gene
Authors: Goffinet Samantha , Di Mauro Ilaria , Doyen Jérôme , Boyer Julien , Birtwisle‐Peyrottes Isabelle , Keslair Frédérique , Pedeutour Florence , Dadone‐Montaudie Bérengère 
Published: March 2023

AbstractAmong sarcomas, MDM2 amplification is usually a molecular hallmark of well‐differentiated liposarcoma and dedifferentiated liposarcoma (DDLPS) and occasionally a secondary genetic anomaly in other sarcomas. Histological evaluation and FISH analysis showing MDM2 amplification led to the diagnosis of DDLPS for a tumor located on the left arm of a 71‐year‐old patient. The patient was treated by adjuvant radiotherapy (RT) but the tumor recurred soon after. Array‐comparative genomic hybridization and targeted RNA/DNA sequencing of the primary tumor and of four recurrences were done. Strikingly, the MDM2 amplification observed in the primary tumor had vanished in the recurrences. In contrast, other rearrangements, such as amplification of the genes TRIO and TERT as well as TRIO::TERT fusion were detected retrospectively in the primary tumor and in all the recurrences. The transitory nature of the MDM2 amplification raised the hypothesis that RT was active on cells that contained MDM2 amplification but not on other tumor cells with only the TERT and TRIO alterations. In contrast to MDM2 amplification, the TRIO::TERT amplified fusion was stable over time. The detection of this fusion was crucial in the analysis of the diagnostically challenging last tumor; it allowed to determine that it was a fourth recurrence, instead of a new independent tumor. It also suggested the diagnosis undifferentiated pleomorphic sarcoma rather than DDLPS. The TRIO::TERT fusion is not well explored. The current study shows that its role in sarcomas, with or without MDM2 amplification, should be more extensively researched.
Ensemble the recent architectures of deep convolutional networks for skin diseases diagnosis
Authors: Duman Erkan , Tolan Zafer 
Published: March 2023

AbstractIf you decided to utilize deep learning in any image processing application, you would be faced with the issue, “Which architecture should I use?” due to the proliferation of existing CNN models and their advancements. Unfortunately, your answer will only be partially correct because each alternative has its advantage. The underlying idea of this research is to combine recent CNN models instead of selecting just one for optimal accuracy. Our study applied this idea to color lesion images to diagnose skin diseases. By ensembling, the recent CNNs, over 99% classification accuracy and over 97% sensitivity were achieved for the ISIC‐2017 dataset, which contains 2000 lesion images. Our mean sensitivity and AUC values for classifying 10000 color lesion images into seven different skin diseases (ISIC‐2018) were 0.825% and 0.922%, respectively. In categorizing over 25000 images from the ISIC 2019 dataset, our suggested technique achieved a mean sensitivity of over 90%.
Disrupted maternal communication and disorganized attachment in the Arab society in Israel
Authors: Ariav‐Paraira Inbar , Oppenheim David , Sagi‐Schwartz Abraham , Zreik Ghadir 
Published: March 2023

AbstractDisrupted maternal communication during mother‐infant interaction has been found to be associated with infants’ disorganized attachment, but has been studied primarily in North American and European samples and not in Arab samples. To address this gap the study examined the association between disrupted maternal communication and infant attachment in a sample of 50 Arab mothers and their one‐year‐old infants in Israel. Attachment was assessed with the Strange Situation Procedure (SSP), and disrupted communication with the AMBIANCE. Disrupted communication was higher in mothers of infants with disorganized and ambivalent attachment than in mothers of securely attached infants. The findings support the link between disrupted communication and disorganized attachment in the Arab society in Israel and add to our understanding of maternal behavior associated with ambivalent attachment.
JNK/c‐Jun pathway activation is essential for HBx‐induced IL‐35 elevation to promote persistent HBV infection
Authors: Li Xuefen , Zhu Qiaoyun , Ye Bo , Zhu Chunxia , Dong Yuejiao , Ni Qin 
Published: March 2023

AbstractBackgroundImmunoregulation plays pivotal roles during chronic hepatitis B virus (HBV) infection. Studies have shown that Interleukin (IL)‐35 is an important molecule associated with inadequate immune response against HBV. However, the mechanisms involved in the up‐regulation of IL‐35 expression during persistent HBV infection remain unknown.MethodsIn this study, we constructed a plasmid expressing the HBV X protein (pCMV‐HBx) to evaluate the relationship between HBx and IL‐35. Activation of the JNK/c‐Jun pathway was analyzed and chromatin immunoprecipitation followed by sequencing and luciferase reporter assays were performed to determine whether c‐Jun could regulate IL‐35 transcription.ResultsHBx can significantly activate IL‐35 promoter in both LO2 and HepG2 cells compared to the control plasmid (pCMV‐Tag2) using the dual‐luciferase assay. Whereas other viral proteins, such as S, preS1, the core protein, had no significant effect on IL‐35 expression. Similarly, WB and qRT‐PCR also showed that HBx can significantly promote IL‐35 expression at protein and mRNA levels in the aforementioned cells. The relevant pathway mechanism showed that the expression of JNK and c‐Jun genes was significantly higher in transfected cells carrying pCMV‐HBx than in the pCMV‐Tag2‐transfected and ‐untransfected cells. WB analysis revealed that phosphorylated JNK and c‐Jun were overexpressed after HBx action. Conversely, the addition of the JNK/c‐Jun signaling pathway inhibitor could significantly suppress HBx‐induced IL‐35 expression in a dose‐dependent manner.ConclusionsA novel molecular mechanism of HBV‐induced IL‐35 expression was revealed, which involves JNK/c‐Jun signaling in up‐regulating IL‐35 expression via HBx, resulting in transactivation of the IL‐35 subunit EBI3 and p35 promoter.
The Mental Illness‐Health Matrix and the Mental State Space Matrix: Complementary meta‐conceptual frameworks for evaluating psychological states
Authors: Lomas Tim , VanderWeele Tyler J. 
Published: March 2023

AbstractObjectiveIt is increasingly appreciated that mental health may not just involve a relative absence of mental illness, but the active presence of positive psychological desiderata. However, research attention on mental illness and health has tended to remain siloed and disconnected—proceeding along parallel tracks—with their potential relationship underexplored and undertheorized. As such, we sought to develop theoretical models to help us better understand the interaction of these two domains of experience.MethodsThrough extensive engagement with relevant literature, we created two complementary meta‐conceptual frameworks to represent and evaluate states of mental illness and health.ResultsThe Mental Illness‐Health Matrix allows different forms of mental illness and health to be situated and assessed within a common framework. The Mental State Space Matrix further enables these various forms to be conceptualized and appraised in terms of numerous common parameters (e.g., valence and arousal).ConclusionIt is hoped that these frameworks will stimulate and support further research on the inter‐relational dynamics of illness and health. Indeed, the matrices themselves are provisional works‐in‐progress, with their articulation here intended as a foundation for their further development as understanding of these topics evolves and improves.
Interactive effects of nitrogen and phosphorus on growth and stoichiometry of lake phytoplankton
Authors: Frost Paul C. , Pearce Nolan J. T. , Berger Stella A. , Gessner Mark O. , Makower A. Katharina , Marzetz Vanessa , Nejstgaard Jens C. , Pralle Aljona , Schälicke Svenja , Wacker Alexander , Wagner Nicole D. , Xenopoulos Marguerite A. 
Published: March 2023

AbstractPhytoplankton responses to nutrient enrichment are often assumed to be universal, but in practice they can significantly vary because the effect size to an increased supply of one nutrient may depend on the availability of the other. Here, we used two complementary two‐way factorial experiments to determine how responses of lake phytoplankton to increased N and P supply vary with increasing concentrations of the other nutrient. We manipulated dissolved N and P concentrations in a 4‐d bioassay conducted with lake phytoplankton and measured/determined chlorophyllaand carbon (C)‐specific growth rates, phytoplankton size‐classes, chlorophyll‐specific N and P removal, and seston C : N : P ratios. These data were used to assess the presence and type of interactive effects between N and P on phytoplankton. For most response variables, the effects of increased N supply depended on the background concentration of P and vice versa. The specific nature of effects differed among response variables and depended on the N and P concentrations present in the bioassay. Generally, increases of N or P alone elicited few and weaker effects than increasing the supply of one element in combination with the other. Overall, our results show that phytoplankton responses to increased N or P supplies are context dependent and likely reflect multiple processes involved in nutrient uptake and use. These results also show that phytoplankton responses to N and P supply ratios can depend on the supply rate of the other nutrient, which complicates understanding how single nutrient enrichment affects lake phytoplankton producers.
An hp‐adaptive multi‐element stochastic collocation method for surrogate modeling with information re‐use
Authors: Galetzka Armin , Loukrezis Dimitrios , Georg Niklas , De Gersem Herbert , Römer Ulrich 
Published: March 2023

AbstractThis article introduces an ‐adaptive multi‐element stochastic collocation method, which additionally allows to re‐use existing model evaluations during either ‐ or ‐refinement. The collocation method is based on weighted Leja nodes. After ‐refinement, local interpolations are stabilized by adding and sorting Leja nodes on each newly created sub‐element in a hierarchical manner. For ‐refinement, the local polynomial approximations are based on total‐degree or dimension‐adaptive bases. The method is applied in the context of forward and inverse uncertainty quantification to handle non‐smooth or strongly localized response surfaces. The performance of the proposed method is assessed in several test cases, also in comparison to competing methods.
The lived experience of Chinese medical tourists receiving cancer care: A qualitative study
Authors: Xu Tuzhen , Liu Fuqin , Cesario Sandra K. , Moore Brenda 
Published: March 2023

AbstractAimThe purpose of this study was to describe and explore the lived experience of Chinese medical tourists receiving cancer care in clinical settings in the United States.DesignA qualitative phenomenological design.MethodsIn this study, Hermeneutic phenomenology was used to interview 11 participants on WeChat, a popular social media platform of China. Hermeneutic phenomenology methods and hermeneutic circles were used to analyse data.ResultsFive themes identified were: the application process involves various challenges; overcoming transportation and language barriers; feeling content with healthcare received in the United States; nearly perfect experience, except for long waiting times; and high cost of being a medical tourist.ConclusionDespite the cost and complexity of cancer treatment, Chinese medical tourists valued their experience in US clinical settings. Although, they experienced real challenges, they overcame obstacles with self‐determination and varied resources. Therefore, culturally appropriate healthcare is highly recommended.Relevance to clinical practiceThe findings of this study are relevant for clinical practice, particularly cancer care to medical tourists in the United States. To better support the Chinese medical tourists with cancer, various strategies and techniques, as reported in this study, could be helpful. It is highly recommended to provide healthcare providers to enable them to understand and respect the diversity norms of other cultures.