bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective noncovalent proteasome inhibiting activity of trifluoromethyl‐containinggem‐quaternary aziridines
Authors: Ielo Laura , Patamia Vincenzo , Citarella Andrea , Schirmeister Tanja , Stagno Claudio , Rescifina Antonio , Micale Nicola , Pace Vittorio 
Published: April 2023

AbstractThe ubiquitin‐proteasome pathway (UPP) represents the principal proteolytic apparatus in the cytosol and nucleus of all eukaryotic cells. Nowadays, proteasome inhibitors (PIs) are well‐known as anticancer agents. However, although three of them have been approved by the US Food and Drug Administration (FDA) for treating multiple myeloma and mantel cell lymphoma, they present several side effects and develop resistance. For these reasons, the development of new PIs with better pharmacological characteristics is needed. Recently, noncovalent inhibitors have gained much attention since they are less toxic as compared with covalent ones, providing an alternative mechanism for solid tumors. Herein, we describe a new class of bis‐homologated chloromethyl(trifluoromethyl)aziridines as selective noncovalent PIs. In silico and in vitro studies were conducted to elucidate the mechanism of action of such compounds. Human gastrointestinal absorption (HIA) and blood–brain barrier (BBB) penetration were also considered together with absorption, distribution, metabolism, and excretion (ADMET) predictions.
Data‐driven dissection of the fever effect in autism spectrum disorder
Authors: Muller Efrat , Shalev Ido , Bachmat Eitan , Eran Alal 
Published: April 2023

AbstractSome individuals with autism spectrum disorder (ASD) demonstrate marked behavioral improvements during febrile episodes, in what is perhaps the only present‐day means of modulating the core ASD phenotype. Understanding the nature of this so‐calledfever effectis therefore essential for leveraging this natural temporary relief of symptoms to a sustained efficacious intervention. Toward this goal, we used machine learning to analyze the rich clinical data of the Simons Simplex Collection, in which one out of every six children with ASD was reported to improve during febrile episodes, across multiple ASD domains. Reported behavioral improvements during febrile episodes were associated with maternal infection in pregnancy (OR = 1.7, 95% CI = [1.42, 2.03], P = 4.24 × 10−4) and gastrointestinal (GI) dysfunction (OR = 1.46, 95% CI = [1.15, 1.81], P = 1.94 × 10−3). Family members of children reported to improve when febrile have an increased prevalence of autoimmune disorders (OR = 1.43, 95% CI = [1.23, 1.67],P = 3.0 × 10−6), language disorders (OR = 1.63, 95% CI = [1.29, 2.04],P = 2.5 × 10−5), and neuropsychiatric disorders (OR = 1.59, 95% CI = [1.34, 1.89],P < 1 × 10−6). Since both GI abnormalities and maternal immune activation have been linked to ASD via proinflammatory cytokines, these results might suggest a possible involvement of immune dysregulation in the fever effect, consistent with findings in mouse models. This work advances our understanding of the fever‐responsive ASD subtype and motivates the future studies to directly test the link between proinflammatory cytokines and behavioral modifications in individuals with ASD.
Machine Learning in Lithium‐Ion Battery Cell Production: A Comprehensive Mapping Study
Authors: Haghi Sajedeh , Hidalgo Marc Francis V. , Niri Mona Faraji , Daub Rüdiger , Marco James 
Published: April 2023

AbstractWith the global quest for improved sustainability, partially realized through the electrification of the transport and energy sectors, battery cell production has gained ever‐increasing attention. An in‐depth understanding of battery production processes and their interdependence is crucial for accelerating the commercialization of material developments, for example, at the volume predicted to underpin future electric vehicle production. Over the last five years, machine learning approaches have shown significant promise in understanding and optimizing the battery production processes. Based on a systematic mapping study, this comprehensive review details the state‐of‐the‐art applications of machine learning within the domain of lithium‐ion battery cell production and highlights the fundamental aspects, such as product and process parameters and adopted algorithms. The compiled findings derived from multi‐perspective comparisons demonstrate the current capabilities and reveal future research opportunities in this field to further accelerate sustainable battery production.
SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway
Authors: Zhou Jie , Peng Shengmeng , Fan Huiyang , Li Jin , Li Zean , Wang Ganping , Zeng Lexiang , Guo Zhenghui , Lai Yiming , Huang Hai 
Published: April 2023

AbstractBackgroundThe mechanism involved in prostate cancer (PCa) metastasis is still poorly understood, and several oncogenes are known to regulate this process. However, the role of spalt‐like transcription factor 4 (SALL4) in PCa metastasis remains unclear.MethodsWe performed RNA‐sequencing to compare the mRNA expression profiles of seven localized PCa tissues and six metastatic PCa tissues. SALL4 was then identified and compared in the localized PCa and metastatic PCa. Immunohistochemical studies, qRT‐PCR, and Western blot were performed to analyze the expression of SALL4 in PCa patients and cell lines. SALL4 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database and in our 68 clinical samples. Subsequently, we knocked down SALL4 in DU145 and PC3 cells and performed a series of functional assays to explore the effect of SALL4 on PCa progression. Finally, protein levels of SALL4 and core components of the MAPK pathway were measured by Western blot, and cells were treated with PD0325901 to observe proliferation and metastasis.ResultsSignificantly higher expression of SALL4 was found in metastatic PCa than in localized PCa. In addition, high SALL4 expression was significantly associated with high pathological T stage, N stage, Gleason score, and poor disease‐free survival in TCGA database and in our clinical samples. Functional studies indicated that knockdown of SALL4 in DU145 and PC3 inhibited proliferation, migration, and angiogenesis. Furthermore, the ERK and P38 protein phosphorylation significantly reduced after knockdown of SALL4 in DU145 and PC3, indicating the inactivation of the MAPK signaling pathway. Finally, the proliferation and migration ability of DU145 and PC3 cells were significantly decreased after PD0325901 treatment.ConclusionsSALL4 predicts unfavorable outcome and is closely associated with PCa progression, suggesting that SALL4 may be a promising prognostic marker and potential therapeutic target for PCa.
A systematic review with evidence mapping of supportive care interventions for melanoma patients and caregivers
Authors: Thompson Jake R. , Salam Rehana A. , Hanna Sarah , Dieng Mbathio , Saw Robyn P. M. , Bartula Iris 
Published: April 2023

AbstractAimWe conducted a systematic review and evidence gap mapping to explore the existing supportive care interventions and their impact on well‐being outcomes for melanoma patients and caregivers.MethodsWe searched MEDLINE, Embase, Web of Science Index Medicus, CINAHL, Lilacs, CENTRAL (Cochrane Library) and PsycINFO in December 2022, including interventional studies assessing the effectiveness of any supportive care intervention among melanoma patients and/or their caregivers.FindingsTwenty studies were included in this review. These studies consisted of randomised controlled trials (n = 11, 55%), pre‐post studies (n = 7, 35%) and quasi‐experimental trials (n = 2, 10%). All studies originated from high‐income countries and focused primarily on melanoma patients, with no studies identified that focused solely on caregivers. Educational interventions were the most common (n = 7, 35%), followed by psychoeducational interventions (n = 6, 30%) and psychotherapeutic interventions (n = 4, 20%). Nearly all included studies (n = 18, 90%) reported a positive effect of the intervention on the primary outcome of interest; however, most studies (n = 17, 85%) were judged to be at moderate or high risk of bias. Due to heterogeneity of study designs, intervention characteristics and outcome measures, meta‐analysis was not conducted.ImplicationsSupportive care interventions have positive impacts on melanoma patient well‐being outcomes, while being acceptable and feasible to conduct. More research is needed regarding supportive care interventions for melanoma caregivers. Future research should focus on eliminating sources of bias through rigorous methodology, with the development of standardised outcome measures for psychosocial outcomes to facilitate future meta‐analyses.
Controlled E. coli Aggregation Mediated by DNA and XNA Hybridization
Authors: Gasse Cécile , Srivastava Puneet , Schepers Guy , Jose Joachim , Hollenstein Marcel , Marlière Philippe , Herdewijn Piet 
Published: April 2023

AbstractChemical cell surface modification is a fast‐growing field of research, due to its enormous potential in tissue engineering, cell‐based immunotherapy, and regenerative medicine. However, engineering of bacterial tissues by chemical cell surface modification has been vastly underexplored and the identification of suitable molecular handles is in dire need. We present here, an orthogonal nucleic acid‐protein conjugation strategy to promote artificial bacterial aggregation. This system gathers the high selectivity and stability of linkage to a protein Tag expressed at the cell surface and the modularity and reversibility of aggregation due to oligonucleotide hybridization. For the first time, XNA (xeno nucleic acids in the form of 1,5‐anhydrohexitol nucleic acids) were immobilized via covalent, SNAP‐tag‐mediated interactions on cell surfaces to induce bacterial aggregation.
A highly stable and low‐cost 12T radiation hardened SRAM cell design for aerospace application
Authors: Liu Zhongyang , Xie Yuqiao , Xu Tao , Liu Qing , Bi Dawei , Hu Zhiyuan , Zou Shichang , Zhang Zhengxuan 
Published: April 2023

SummaryIn this paper, a highly stable and low‐cost 12T (HSLC12T) radiation hardened static‐random‐access‐memories (SRAM) cell is proposed in 55 nm CMOS technology. Based on polarity reversal design and read/write separation structure, the proposed HSLC12T cell can recover from any single event upsets (SEUs) induced at all its sensitive nodes and even single event double‐node‐upsets (SEDNUs) induced at its internal storage node pair Q‐QN, while also having the maximum read static noise margin (RSNM) and lower static hold power, as well as excellent write speed and write‐ability. Though the HSLC12T cell exhibits a larger read delay, it has the best overall performance of all other cells. This is proven by having the highest electrical quality metric (EQM) value, thus making the proposed HSLC12T cell a better choice for aerospace applications.
Immediate major dynamic changes in the T‐ and NK‐cell subset composition after cardiac transplantation
Authors: Iske Jasper , Wiegmann Bettina , Ius Fabio , Chichelnitskiy Evgeny , Ludwig Kristina , Kühne Jenny F. , Hitz Anna Maria , Beushausen Kerstin , Keil Jana , Iordanidis Susanne , Rojas Sebastián V. , Sommer Wiebke , Salman Jawad , Haverich Axel , Warnecke Gregor , Falk Christine S 
Published: April 2023

AbstractEarly kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart‐transplanted patients were collected before (pre‐), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dimCD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56brightCD16− NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+CD25− and diminished CD69−CD25−CD4+ or CD8+ T‐cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo‐specific immune responses.
MHC class II‐deficient mice allow functional human CD4+ T‐cell development
Authors: Läderach Fabienne , Zdimerova Hana , Rieble Lisa , Schuhmachers Patrick , Engelmann Christine , Valencia‐Camargo Alma Delia , Kirchmeier Daniel , Böni Michelle , Münz Christian 
Published: April 2023

AbstractHumanized mouse models have been developed to study cell‐mediated immune responses to human pathogens in vivo. How immunocompetent human T cells are selected in a murine thymus in such humanized mice remains poorly explored. To gain insights into this mechanism, we investigated the differentiation of human immune compartments in mouse MHC class II‐deficient immune‐compromised mice (humanized Ab0 mice). We observed a strong reduction in human CD4+ T‐cell development but despite this reduction Ab0 mice had no disadvantage during Epstein–Barr virus (EBV) infection. Viral loads were equally well controlled in humanized Ab0 mice compared to humanized NSG mice, and improved T‐cell recognition of autologous EBV‐transformed B cells was observed, especially with respect to cytotoxicity. MHC class II blocking experiments with CD4+ T cells from humanized Ab0 mice demonstrated MHC class II restriction of lymphoblastoid cell line recognition. These findings suggest that a small number of CD4+ T cells in humanized mice can be solely selected on human MHC class II molecules, presumably expressed by reconstituted human immune cells, leading to improved effector functions.
Experimental study on the dynamic responses of the end‐anchored floating bridge subjected to joint actions of earthquakes and water waves
Authors: Yan Jialei , Liu Jiabin , Liu Zhichao , Li Hui , Guo Anxin 
Published: April 2023

AbstractThis study experimentally investigates a dynamic behavior of an end‐anchored floating bridge under the joint actions of earthquakes and water waves. A truncated model with a geometrical scale of 1:100 was utilized for the hydrodynamic test, and an actuator was used to generate the earthquake input. A series of trials were conducted for the floating bridge model under the combined action of two different sea states and three earthquake inputs with increasing intensity based on the concept of the incremental dynamic analysis method. For comparison, the dynamic responses of the floating bridge model under earthquake action in still water and pure wave action were also conducted. Based on the test data, the dynamic responses, particularly focused on the sway, heave, roll, and pitch motions of the pontoons, of the test model were experimentally analyzed. The experimental results showed that earthquake excitation along the longitudinal axis of the bridge girder would induce noticeable oscillation of the bridge pontoons in still water. The magnitude of the coupled effects of earthquakes and water waves is dependent on the intensity of the earthquake inputs and the sea state.
Procalcitonin levels in pregnancy: A systematic review and meta‐analysis of observational studies
Authors: Prabhu Malavika , Wilkie Gianna , MacEachern Mark , LaBuda Dana , Purtell Jasmine , Rao Krishna , Riley Laura E. , Fuller Matthew , Rosser Morgan , Habib Ashraf S. , Bauer Melissa E. 
Published: April 2023

AbstractBackgroundThe utility of procalcitonin to identify obstetric sepsis is unknown.ObjectiveTo calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3).Search StrategyNLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022.Selection CriteriaTen or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities.Data Collection and AnalysisEach abstract and full‐text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle‐Ottawa Scale. A meta‐analysis was performed using a random effects model.Main ResultsThe systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta‐analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036–0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049–0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005–1.292 ng/mL).ConclusionsAmong healthy pregnant women not in labor, procalcitonin levels are comparable to those in non‐pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non‐pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities.ProsperoCRD42020157376, registered 4/28/2020.
The relation of classroom climate to adolescents' countering hate speech via social skills: A positive youth development perspective
Authors: Wachs Sebastian , Valido Alberto , Espelage Dorothy L. , Castellanos Melisa , Wettstein Alexander , Bilz Ludwig 
Published: April 2023

AbstractIntroductionHate speech is a current challenge for schools around the globe. At the same time, students worldwide stand up to hate speech by countering it. Guided by a positive youth development perspective, the present study investigated the direct and indirect associations between classroom climate (environmental assets), social skills (personal assets), and countering hate speech (as a proxy of thriving) among adolescents.MethodsThe sample included 3225 students in grades 7–9 (51.7% self‐identified as female) from 40 schools in Germany (n = 1841) and Switzerland (n = 1384). Students completed self‐report questionnaires that assessed classroom climate, three facets of social skills (i.e., perspective‐taking, prosocial behavior, assertiveness), and counterspeech.ResultsThe results of the 2‐(1‐1‐1)‐1 multilevel mediation analysis revealed that classroom climate (L2) and the three facets of social skills (L1) had a direct positive effect on counterspeech (L1). Furthermore, classroom climate (L2) also had a direct positive effect on the three facets of social skills (L1). Finally, classroom climate (L2) had an indirect positive effect on counterspeech (L1) via all three aspects of social skills (L1).ConclusionThe findings highlight that successful anti‐hate speech programs may entail a combination of environmental and personal factors for increasing adolescents' active contribution to an inclusive and discrimination‐free classroom environment where hate speech is not tolerated.
Toward developing a valid and reliable assessment of adults' nature of engineering views
Authors: Kaya Erdogan , Deniz Hasan , Yesilyurt Ezgi 
Published: April 2023

AbstractBackgroundPre‐college engineering education reform documents aim to help students develop engineering literacy. Helping students develop sophisticated epistemological views about engineering makes a significant contribution toward developing engineering‐literate citizenry. Despite these widely recognized benefits, research on students' and teachers' epistemological views about engineering, commonly termed nature of engineering (NOE) views, has remained stagnant due to the absence of an open‐ended questionnaire whose collected evidence of validity indicates its appropriateness for assessing students' and teachers' NOE understanding.PurposeThe purpose of this study is threefold: (a) describing the development of a new open‐ended instrument, the Views of Nature of Engineering Questionnaire version B (VNOE‐B), (b) providing evidence in support of the VNOE‐B validity and reliability, and (c) discussing the implications of the newly developed instrument for future research.Design/MethodWe aimed to provide evidence for the content and face validity of the VNOE‐B by seeking input from a panel of science/engineering educators. Evidence for the construct validity was determined by analyzing the open‐ended questionnaire and semistructured interview responses provided by pre‐service and in‐service teachers (considered novices in this field) and experts (engineers and engineering educators).ResultsOur findings indicate that the VNOE‐B is consistently successful in differentiating between experts' and novices' NOE views. All engineering experts held sophisticated NOE views across all NOE views under study, whereas most novices held partially informed or uninformed NOE views.ConclusionEvidence of validity supports the appropriateness of the VNOE‐B as an open‐ended instrument for assessing adults' NOE views. Its application may guide teacher educators in determining the efficacy of teacher professional development in meeting the aim of improving in‐service teachers' NOE understanding. Additionally, VNOE‐B may potentially inform the success of pre‐service teacher training.
Simple, non‐mechanical and automatic calibration approach for axial‐scanning microscopy with an electrically tunable lens
Authors: Li Shengfu , Zhao Yu , Wen Weifent , Ma Yuncan , Liu Shouxian , Chen Guanghua , Ye Yan 
Published: April 2023

AbstractWe describe a simple and robust calibration approach for axial‐scanning microscopy that realizes axial focus shifts with an electrically tunable lens (ETL). We demonstrate the calibration approach based on a microscope with an ETL placed close to the rear stop of the objective lens. By introducing a target—consisted of repeating lines at one known frequency and placed at a ~45° angle to the imaging path, the calibration method captures multiple images at different ETL currents and calibrates the dependence of the axial focus shift on the ETL current by evaluating the sharpness of the captured images. It calibrates the dependence of the magnification of the microscope on the ETL current by measuring the period of the repeating lines in the captured images. The experimental results show that different from the conventional calibration procedure, the proposed scheme does not involve any mechanical scanning and can simultaneously calibrate the dependence of the axial focus shift and the magnification on the ETL current. This might facilitate imaging studies that require the measurement of fine structures in a 3D volume. We also show the calibration procedure can be used to estimate the radius of a conner‐arc sample, fabricated using laser micromachining. We believe that this easy‐to‐use calibration approach may facilitate use of ETLs for a variety of imaging platforms. It may also provide new insights for the development of novel 3D surface measurement methods.Research HighlightsThe proposed calibration scheme does not involve any mechanical scanning and can simultaneously calibrate the dependence of the axial focus shift and the magnification on the electrically tunable lens (ETL) current. It might facilitate imaging studies that require the measurement of fine structures in a 3D volume, and the use of ETLs for a variety of imaging platforms. It may also provide new insights for the development of novel 3D surface measurement methods.