bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia
Authors: Rausch Christian , Rothenberg-Thurley Maja , Dufour Annika , Schneider Stephanie , Gittinger Hanna , Sauerland Cristina , Görlich Dennis , Krug Utz , Berdel Wolfgang E. , Woermann Bernhard J. , Hiddemann Wolfgang , Braess Jan , von Bergwelt-Baildon Michael , Spiekermann Karsten , Herold Tobias , Metzeler Klaus H. 
Published: April 2023

AbstractThe revised 2022 European LeukemiaNet (ELN) AML risk stratification system requires validation in large, homogeneously treated cohorts. We studied 1118 newly diagnosed AML patients (median age, 58 years; range, 18–86 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 and compared ELN-2022 to the previous ELN-2017 risk classification. Key findings were validated in a cohort of 1160 mostly younger patients. ELN-2022 reclassified 15% of patients, 3% into more favorable, and 12% into more adverse risk groups. This was mainly driven by patients reclassified from intermediate- to adverse-risk based on additional myelodysplasia-related mutations being included as adverse-risk markers. These patients (n = 79) had significantly better outcomes than patients with other adverse-risk genotypes (5-year OS, 26% vs. 12%) and resembled the remaining intermediate-risk group. Overall, time-dependent ROC curves and Harrel’s C-index controlling for age, sex, and AML type (de novo vs. sAML/tAML) show slightly worse prognostic discrimination of ELN-2022 compared to ELN-2017 for OS. Further refinement of ELN-2022 without including additional genetic markers is possible, in particular by recognizing TP53-mutated patients with complex karyotypes as “very adverse”. In summary, the ELN-2022 risk classification identifies a larger group of adverse-risk patients at the cost of slightly reduced prognostic accuracy compared to ELN-2017.
Unveiling the complexity of spatiotemporal soliton molecules in real time
Authors: Guo Yuankai , Lin Wei , Wang Wenlong , Zhang Runsen , Liu Tao , Xu Yiqing , Wei Xiaoming , Yang Zhongmin 
Published: April 2023

AbstractObserving the dynamics of 3D soliton molecules can hold great opportunities for unveiling the mechanism of molecular complexity and other nonlinear problems. In spite of this fantastic potential, real-time visualization of their dynamics occurring on femtosecond-to-picosecond time scales is still challenging, particularly when high-spatiotemporal-resolution and long-term observation are required. In this work, we observe the real-time speckle-resolved spectral-temporal dynamics of 3D soliton molecules for a long time interval using multispeckle spectral-temporal measurement technology. Diverse real-time dynamics of 3D soliton molecules are captured for the first time, including the speckle-resolved birth, spatiotemporal interaction, and internal vibration of 3D soliton molecules. Further studies show that nonlinear spatiotemporal coupling associated with a large average-chirp gradient over the speckled mode profile plays a significant role in these dynamics. These efforts may shed new light on decomposing the complexity of 3D soliton molecules, and create an analogy between 3D soliton molecules and chemical molecules.
A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3
Authors: Ta Atri , Ricci-Azevedo Rafael , Vasudevan Swathy O. , Wright Skylar S. , Kumari Puja , Havira Morena S. , Surendran Nair Meera , Rathinam Vijay A. , Vanaja Sivapriya Kailasan 
Published: April 2023

AbstractType I interferons (IFNs) are consequential cytokines in antibacterial defense. Whether and how bacterial pathogens inhibit innate immune receptor-driven type I IFN expression remains mostly unknown. By screening a library of enterohemorrhagic Escherichia coli (EHEC) mutants, we uncovered EhaF, an uncharacterized protein, as an inhibitor of innate immune responses including IFNs. Further analyses identified EhaF as a secreted autotransporter—a type of bacterial secretion system with no known innate immune-modulatory function—that translocates into host cell cytosol and inhibit IFN response to EHEC. Mechanistically, EhaF interacts with and inhibits the MiT/TFE family transcription factor TFE3 resulting in impaired TANK phosphorylation and consequently, reduced IRF3 activation and type I IFN expression. Notably, EhaF-mediated innate immune suppression promotes EHEC colonization and pathogenesis in vivo. Overall, this study has uncovered a previously unknown autotransporter-based bacterial strategy that targets a specific transcription factor to subvert innate host defense.
Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy
Authors: Bhatia Vipul , Kamat Nikhil V. , Pariva Tiffany E. , Wu Li-Ting , Tsao Annabelle , Sasaki Koichi , Sun Huiyun , Javier Gerardo , Nutt Sam , Coleman Ilsa , Hitchcock Lauren , Zhang Ailin , Rudoy Dmytro , Gulati Roman , Patel Radhika A. , Roudier Martine P. , True Lawrence D. , Srivastava Shivani , Morrissey Colm M. , Haffner Michael C. , Nelson Peter S. , Priceman Saul J. , Ishihara Jun , Lee John K. 
Published: April 2023

AbstractSix transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen for therapeutic targeting in prostate cancer. Here, we report broad expression of STEAP1 relative to prostate-specific membrane antigen (PSMA) in lethal metastatic prostate cancers and the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrate reactivity in low antigen density, antitumor activity across metastatic prostate cancer models, and safety in a human STEAP1 knock-in mouse model. STEAP1 antigen escape is a recurrent mechanism of treatment resistance and is associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein combined with STEAP1 CAR T cell therapy enhances antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading.
Greater traditionalism predicts COVID-19 precautionary behaviors across 27 societies
Authors: Samore Theodore , Fessler Daniel M. T. , Sparks Adam Maxwell , Holbrook Colin , Aarøe Lene , Baeza Carmen Gloria , Barbato María Teresa , Barclay Pat , Berniūnas Renatas , Contreras-Garduño Jorge , Costa-Neves Bernardo , del Pilar Grazioso Maria , Elmas Pınar , Fedor Peter , Fernandez Ana Maria , Fernández-Morales Regina , Garcia-Marques Leonel , Giraldo-Perez Paulina , Gul Pelin , Habacht Fanny , Hasan Youssef , Hernandez Earl John , Jarmakowski Tomasz , Kamble Shanmukh , Kameda Tatsuya , Kim Bia , Kupfer Tom R. , Kurita Maho , Li Norman P. , Lu Junsong , Luberti Francesca R. , Maegli María Andrée , Mejia Marinés , Morvinski Coby , Naito Aoi , Ng’ang’a Alice , de Oliveira Angélica Nascimento , Posner Daniel N. , Prokop Pavol , Shani Yaniv , Solorzano Walter Omar Paniagua , Stieger Stefan , Suryani Angela Oktavia , Tan Lynn K. L. , Tybur Joshua M. , Viciana Hugo , Visine Amandine , Wang Jin , Wang Xiao-Tian 
Published: April 2023

AbstractPeople vary both in their embrace of their society’s traditions, and in their perception of hazards as salient and necessitating a response. Over evolutionary time, traditions have offered avenues for addressing hazards, plausibly resulting in linkages between orientations toward tradition and orientations toward danger. Emerging research documents connections between traditionalism and threat responsivity, including pathogen-avoidance motivations. Additionally, because hazard-mitigating behaviors can conflict with competing priorities, associations between traditionalism and pathogen avoidance may hinge on contextually contingent tradeoffs. The COVID-19 pandemic provides a real-world test of the posited relationship between traditionalism and hazard avoidance. Across 27 societies (N = 7844), we find that, in a majority of countries, individuals’ endorsement of tradition positively correlates with their adherence to costly COVID-19-avoidance behaviors; accounting for some of the conflicts that arise between public health precautions and other objectives further strengthens this evidence that traditionalism is associated with greater attention to hazards.
Neuronal growth on high-aspect-ratio diamond nanopillar arrays for biosensing applications
Authors: Losero Elena , Jagannath Somanath , Pezzoli Maurizio , Goblot Valentin , Babashah Hossein , Lashuel Hilal A. , Galland Christophe , Quack Niels 
Published: April 2023

AbstractMonitoring neuronal activity with simultaneously high spatial and temporal resolution in living cell cultures is crucial to advance understanding of the development and functioning of our brain, and to gain further insights in the origin of brain disorders. While it has been demonstrated that the quantum sensing capabilities of nitrogen-vacancy (NV) centers in diamond allow real time detection of action potentials from large neurons in marine invertebrates, quantum monitoring of mammalian neurons (presenting much smaller dimensions and thus producing much lower signal and requiring higher spatial resolution) has hitherto remained elusive. In this context, diamond nanostructuring can offer the opportunity to boost the diamond platform sensitivity to the required level. However, a comprehensive analysis of the impact of a nanostructured diamond surface on the neuronal viability and growth was lacking. Here, we pattern a single crystal diamond surface with large-scale nanopillar arrays and we successfully demonstrate growth of a network of living and functional primary mouse hippocampal neurons on it. Our study on geometrical parameters reveals preferential growth along the nanopillar grid axes with excellent physical contact between cell membrane and nanopillar apex. Our results suggest that neuron growth can be tailored on diamond nanopillars to realize a nanophotonic quantum sensing platform for wide-field and label-free neuronal activity recording with sub-cellular resolution.
Disentangling diagnostic object properties for human scene categorization
Authors: Wiesmann Sandro L. , Võ Melissa L.-H. 
Published: April 2023

AbstractIt usually only takes a single glance to categorize our environment into different scene categories (e.g. a kitchen or a highway). Object information has been suggested to play a crucial role in this process, and some proposals even claim that the recognition of a single object can be sufficient to categorize the scene around it. Here, we tested this claim in four behavioural experiments by having participants categorize real-world scene photographs that were reduced to a single, cut-out object. We show that single objects can indeed be sufficient for correct scene categorization and that scene category information can be extracted within 50 ms of object presentation. Furthermore, we identified object frequency and specificity for the target scene category as the most important object properties for human scene categorization. Interestingly, despite the statistical definition of specificity and frequency, human ratings of these properties were better predictors of scene categorization behaviour than more objective statistics derived from databases of labelled real-world images. Taken together, our findings support a central role of object information during human scene categorization, showing that single objects can be indicative of a scene category if they are assumed to frequently and exclusively occur in a certain environment.
Morphological and organic spectroscopic studies of a 44-million-year-old leaf beetle (Coleoptera: Chrysomelidae) in amber with endogenous remains of chitin
Authors: Mitchell Jerit L. , McKellar Ryan C. , Barbi Mauricio , Coulson Ian M. , Bukejs Andris 
Published: April 2023

AbstractThis study details the quality of preservation of amber deposits in the Eocene. Through Baltic amber crack-out studies using Synchrotron Micro-Computed Tomography and Scanning Electron Microscopy it was found that the cuticle of a specimen of leaf beetle (Crepidodera tertiotertiaria (Alticini: Galerucinae: Chrysomelidae)) is exceptionally well preserved. Spectroscopic analysis using Synchrotron Fourier Transform Infrared Spectroscopy suggests presence of degraded $$\upalpha$$
α
-chitin in multiple areas of the cuticle, and Energy Dispersive Spectroscopy supports the presence of organic preservation. This remarkable preservation is likely the result of several factors such as the favourable antimicrobial and physical shielding properties of Baltic amber as compared to other depositional media, coupled to rapid dehydration of the beetle early in its taphonomic process. We provide evidence that crack-out studies of amber inclusions, although inherently destructive of fossils, are an underutilised method for probing exceptional preservation in deep time.
Conservative management of early-stage endometrial cancer for fertility preservation: a survey study among Swedish gynecologists and gynecological oncologists
Authors: Iliadis Stavros I. , Gambadauro Pietro 
Published: April 2023

AbstractConservative management of endometrial cancer (CMEC) is viable for women with early-stage disease wishing to preserve fertility, but there is poor knowledge regarding clinicians’ attitudes towards treatment or guidelines adherence. This 55-item survey study investigated CMEC-related experience, practice and attitudes among clinically active Swedish gynecologists and gynecological oncologists, focusing on reproductive eligibility criteria. The survey consisted of a general and two specific subsets, selectively delivered to clinicians active in infertility (subset A) and endometrial cancer (subset B) care. Answers from 218 clinicians were included. More than half agreed on CMEC whereas only 5% explicitly disagreed. The majority supported a fertility work-up to substantiate reasonable chances to pregnancy and live birth. Most disagreed about CMEC in case of previous unsuccessful fertility treatments, while more than 1/3 disagreed about CMEC in known fertility problems, recurrent miscarriages or previous children. Over 50% of respondents in subset A (n = 107) found it applicable with fertility investigations such as ovarian reserve testing or, in case of male partner, semen analysis. Respondents in subset B (n = 165) agreed on items based on existing recommendations regarding the oncological management of CMEC, including the use of continuous progestins, hysteroscopic resection of macroscopic lesions, control biopsy with curettage or hysteroscopy after 6 months of treatment, pursuing pregnancy as soon as possible after complete response, and performing a hysterectomy once live birth is achieved. While many clinicians were familiar with CMEC, the overall experience is limited. Fertility specialists seem less involved than oncologists in patient care but there is broad support for fertility-related eligibility criteria.
Screening of single nucleotide polymorphisms within HLA region related to hematopoietic stem cell transplantation using MassARRAY technology
Authors: Tsai Shu-Hui , Chang Pi-Yueh , Wen Ying-Hao , Lin Wei-Tzu , Hsu Fang-Ping , Chen Ding-Ping 
Published: April 2023

AbstractA growing number of studies showed that single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA)-related genes were associated with the outcome of hematopoietic stem cell transplantation (HSCT). Thus, other SNPs located nearby the classical HLA genes must be considered in HSCT. We evaluated the clinical feasibility of MassARRAY by comparing to Sanger sequencing. The PCR amplicons with each one of the 17 loci that were related to the outcomes of HSCT published by our previous study were transferred onto a SpectroCHIP Array for genotyping by mass spectrometry. The sensitivity of MassARRAY was 97.9% (614/627) and the specificity was 100% (1281/1281), where the positive predictive value (PPV) was 100% (614/614) and the negative predictive value (NPV) was 99.0% (1281/1294). MassARRAY is high-throughput, which can accurately analyze multiple SNPs at the same time. Based on these properties, we proposed that it could be an efficient method to match the genotype between the graft and the recipient before transplantation.
Proteomics reveals specific biological changes induced by the normothermic machine perfusion of donor kidneys with a significant up-regulation of Latexin
Authors: Zaza Gianluigi , Neri Flavia , Bruschi Maurizio , Granata Simona , Petretto Andrea , Bartolucci Martina , di Bella Caterina , Candiano Giovanni , Stallone Giovanni , Gesualdo Loreto , Furian Lucrezia 
Published: April 2023

AbstractRenal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device. Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine samples were collected at T0 (urine produced in the first 15 min after the beginning of normothermic reperfusion), T30, T60 and T120. Multiple algorithms, support vector machine learning and partial least squares discriminant analysis were used to select the most discriminative proteins during NMP. Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 during NMP. Machine learning algorithms identified the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1 and F9) in the kidney and urine after NMP. Latexin (LXN), an endogenous carboxypeptidase inhibitor, resulted the most-upregulated protein at T120, and this result was confirmed by ELISA. In addition, functional analysis revealed that the most strongly upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins represented the complement system and coagulation cascade. Our proteomic analysis demonstrated that even brief periods of NMP induce remarkable metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.
Complete response to alectinib in ALK-fusion metastatic salivary ductal carcinoma
Authors: Adashek Jacob J. , Sapkota Surendra , de Castro Luna Rodrigo , Seiwert Tanguy Y. 
Published: April 2023

AbstractThe advent of next-generation sequencing (NGS) has allowed for the identification of novel therapeutic targets for patients with uncommon cancers. It is well known that fusion translocations are potent driver of cancer pathogenesis and can render tumors exquisitely sensitive to matching targeted therapies. Here we describe a patient with ALK-fusion positive widely metastatic salivary ductal carcinoma, who achieved a durable complete response from alectinib, a potent and specific ALK tyrosine kinase inhibitor. This case serves as another reminder that ALK-fusions can be targeted regardless of histology and can afford patients dramatic and durable benefit. It also emphasizes the need for insurance coverage for such beneficial therapies. While ALK fusions are exceedingly rare in salivary ductal carcinoma, the presence of multiple other targetable aberrations supports the recommendation for universal NGS testing for such tumors.
Reprogramming of human peripheral blood mononuclear cells into induced mesenchymal stromal cells using non-integrating vectors
Authors: Chen Wanqiu , Wang Chenguang , Yang Zhi-Xue , Zhang Feng , Wen Wei , Schaniel Christoph , Mi Xianqiang , Bock Matthew , Zhang Xiao-Bing , Qiu Hongyu , Wang Charles 
Published: April 2023

AbstractMesenchymal stromal cells (MSCs) have great value in cell therapies. The MSC therapies have many challenges due to its inconsistent potency and limited quantity. Here, we report a strategy to generate induced MSCs (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) with OCT4, SOX9, MYC, KLF4, and BCL-XL using a nonintegrating episomal vector system. While OCT4 was not required to reprogram PBMCs into iMSCs, omission of OCT4 significantly impaired iMSC functionality. The omission of OCT4 resulted in significantly downregulating MSC lineage specific and mesoderm-regulating genes, including SRPX, COL5A1, SOX4, SALL4, TWIST1. When reprogramming PBMCs in the absence of OCT4, 67 genes were significantly hypermethylated with reduced transcriptional expression. These data indicate that transient expression of OCT4 may serve as a universal reprogramming factor by increasing chromatin accessibility and promoting demethylation. Our findings represent an approach to produce functional MSCs, and aid in identifying putative function associated MSC markers.
Insights into the deactivation mechanism of a self-supported nickel electrode for 5-hydroxymethyl furfural electrooxidation: focus on the stability of the electrode as a whole
Authors: Liu Fangbing , Lin Nan , Xin Deyuan , Li Xinxin , Cong Linchuan , Han Fuyu , Lin Haibo 
Published: April 2023

Three routes were proposed based on the structure of a self-supported NiOx loaded nickel foam electrode under operating conditions, which are: catalytically active layer shedding, nickel matrix dissolution, and the accelerated shedding effect of OER.
Automatic textual description of colorectal polyp features: explainable artificial intelligence
Authors: Thijssen Ayla , Schreuder Ramon-Michel , Fonollà Roger , van der Zander Quirine , Scheeve Thom , Winkens Bjorn , Subramaniam Sharmila , Bhandari Pradeep , de With Peter , Masclee Ad , van der Sommen Fons , Schoon Erik 
Published: April 2023

AbstractComputer-aided diagnosis systems (CADx) can improve colorectal polyp (CRP) optical diagnosis. For integration into clinical practice, better understanding of artificial intelligence (AI) by endoscopists is needed. We aimed to develop an explainable AI CADx capable of automatically generating textual descriptions of CRPs. For training and testing of this CADx, textual descriptions of CRP size and features according to the Blue Light Imaging (BLI) Adenoma Serrated International Classification (BASIC) were used, describing CRP surface, pit pattern, and vessels. CADx was tested using BLI images of 55 CRPs. Reference descriptions with agreement by at least five out of six expert endoscopists were used as gold standard. CADx performance was analyzed by calculating agreement between the CADx generated descriptions and reference descriptions. CADx development for automatic textual description of CRP features succeeded. Gwet’s AC1 values comparing the reference and generated descriptions per CRP feature were: size 0.496, surface-mucus 0.930, surface-regularity 0.926, surface-depression 0.940, pits-features 0.921, pits-type 0.957, pits-distribution 0.167, and vessels 0.778. CADx performance differed per CRP feature and was particularly high for surface descriptors while size and pits-distribution description need improvement. Explainable AI can help comprehend reasoning behind CADx diagnoses and therefore facilitate integration into clinical practice and increase trust in AI.