bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary outcomes in IDH‐mutated acute myeloid leukemia: The impact of co‐occurring NPM1 mutations and venetoclax‐based treatment
Authors: Lachowiez Curtis A. , Reville Patrick K. , Kantarjian Hagop , Jabbour Elias , Borthakur Gautam , Daver Naval , Issa Ghayas , Furudate Ken , Tanaka Tomoyuki , Pierce Sherry , Tang Guilin , Patel Keyur P. , Medeiros Jeffrey , Abbas Hussein A. , Haddad Fadi , Hammond Daniel , Short Nicholas J. , Maiti Abhishek , Yilmaz Musa , Sasaki Koji , Takahashi Koichi , Pemmaraju Naveen , Konopleva Marina , Garcia‐Manero Guillermo , Ravandi Farhad , Kadia Tapan M. , Loghavi Sanam , DiNardo Courtney D. 
Published: August 2022

AbstractIsocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co‐occurring NPM1 mutations, which may influence treatment outcomes. Detailed analysis of IDH‐mutated AML treated with venetoclax and influence of co‐occurring NPM1 mutations remains unclear. This retrospective single‐center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co‐occurring NPM1 mutations in patients with IDH1 or IDH2‐mutated AML. 556 patients with IDH1, IDH2, and/or NPM1 mutated AML were included. Patients with IDH1mut AML (N = 119) were more likely to have older age, sAML, ELN‐adverse risk disease, and adverse‐risk cytogenetics compared to those with IDH2mut (N = 229) or IDHwt/NPM1mut AML (N = 208). In multivariate analysis, patients with IDH2mut (HR 0.61 [95%CI: 0.43–0.88], p value: .007) or IDHwt/NPM1mut (HR 0.65 [95% CI: 0.45–0.94], p value: .024) AML had a decreased risk of death versus IDH1mut AML. Venetoclax‐based lower‐intensity regimens partially abrogated the detrimental effect of IDH1mut with similar OS observed between IDH1mut/NPM1wt, IDH2mut/NPM1wt, and IDHwt/NPM1mut AML. With regards to the influence of IDHmut/NPM1mut cases, IC improved survival in IDH2mut/NPM1mut versus IDH2mut/NPM1wt AML (HR: 0.54 [95% CI: 0.2644–1.082], p value: .077), while venetoclax‐based therapy improved survival in IDH1mut/NPM1mut versus IDH1mut/NPM1wt AML (HR: 0.094 [95% CI: 0.01–0.74], p value: .0056). Differing outcomes were observed in IDH1mut versus IDH2mut or NPM1mut AML which were influenced by co‐occurring NPM1 mutations and partially abrogated with venetoclax‐based therapy. Given the differing biology and survival in IDH1mut AML, investigations incorporating molecularly targeted therapies such as IDH inhibitors remain warranted in this subgroup.
Bioorthogonal Lanthanide Molecular Probes for Near‐Infrared Fluorescence and Mass Spectrometry Imaging
Authors: Jin Guo‐Qing , Sun De‐en , Xia Xiaoqian , Jiang Zhi‐Fan , Cheng Bo , Ning Yingying , Wang Fuyi , Zhao Yao , Chen Xing , Zhang Jun‐Long 
Published: August 2022

AbstractWe report here the development of clickable and highly near‐infrared (NIR) fluorescent lanthanide (Ln) complexes for bioorthogonal labeling of biomolecules. These azide‐ or alkyne‐functionalized Ln complexes are hydrophilic and fluorogenic, exhibiting a strong increase of NIR fluorescence upon conjugation with biomolecules. Metabolic labeling of biomolecules with azide or alkyne, followed by click labeling with the Ln complexes, enables NIR fluorescence (NIRF) imaging of DNA, RNA, proteins, and glycans in cells. Furthermore, multicolor imaging is performed by combining click‐labeling with the Ln complexes and immunostaining. In addition, the Ln complexes is compatible with click‐expansion microscopy (click‐ExM), which enables high‐resolution NIRF imaging of cellular glycoproteins. Finally, the Ln complexes can be used for time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS) imaging, thus achieving the first example of dual‐modal imaging combining NIRF and SIMS microscopies.
Simultaneous and Spontaneous Oxidation and Reduction in Microdroplets by the Water Radical Cation/Anion Pair
Authors: Qiu Lingqi , Cooks R. Graham 
Published: August 2022

AbstractMicrodroplets show unique chemistry, especially in their intrinsic redox properties, and to this we here add a case of simultaneous and spontaneous oxidation and reduction. We report the concurrent conversions of several phosphonates to phosphonic acids by reduction (R−P → H−P) and to pentavalent phosphoric acids by oxidation. The experimental results suggest that the active reagent is the water radical cation/anion pair. The water radical cation is observed directly as the ionized water dimer while the water radical anion is only seen indirectly though the spontaneous reduction of carbon dioxide to formate. The coexistence of oxidative and reductive species in turn supports the proposal of a double‐layer structure at the microdroplet surface, where the water radical cation and radical anion are separated and accumulated.
Differential Peptide Multi‐Macrocyclizations at the Surface of a Helical Foldamer Template
Authors: Dengler Sebastian , Douat Céline , Huc Ivan 
Published: August 2022

AbstractHybrid sequences comprising a peptide with several Cys residues and an aromatic foldamer helix with several chloroacetamide functions at its surface were synthesized. Such products may in principle form numerous macromulticyclic thioether products by intramolecularly combining all Cys residues and all chloroacetamide functions. However, we show that the reactive sites on the structurally defined helix can be placed at such locations that the peptide selectively stitches itself to form a series of different macrocycles within mostly one preferred product. Reactions were monitored by HPLC and products with two, three or four macrocycles were identified using LC–MS and NMR. The series of selective macrocyclizations define a sort of reaction trail where reaction sites otherwise identical are involved successively because of their precise positioning in space. The trails can be predicted to a large extent based on structural considerations and the assumption that smaller macrocycles form faster.
Amino Acid‐triggered Water‐soluble NBD Derivatives for Differential Organelle Staining and the Role of the Chemical Moiety for their Specific Localization
Authors: Mandal Subhasis , Singh Arpana , Paul Subhojit , Ghosh Arnab , Sen Prosenjit 
Published: August 2022

AbstractApart from being the unit of proteins, amino acids have diverse roles. Here we have shown that amino acids guide the differential transportation of a dye molecule to the cellular organelles depending upon the property of their intrinsic functionality. We have conjugated the nitrobenzofurazan (NBD) moiety with two amino acids (lysine and histidine derivatives) with a linker. Both derivates are water‐soluble and biocompatible in nature. Surprisingly, we found that lysine‐conjugated NBD (NBD‐Lys) stains lipid droplets whereas histidine‐conjugated NBD (NBD‐His) stains lysosomes. We also measured the spectral properties of these two NBD conjugates. The results depict that both conjugates are extremely stable both in air and under inert atmosphere, and the fluorescence of the derivatives remains almost unaltered at different pH. Further by altering the functionality of the side chain, we established the contribution of each functional group towards this differential organelle targeting.
The factor structure of cognitive reflection, numeracy, and fluid intelligence: The evidence from the Polish adaptation of the Verbal CRT
Authors: Sobkow Agata , Olszewska Angelika , Sirota Miroslav 
Published: August 2022

AbstractThe Cognitive Reflection Test (CRT) is one of the most popular measures of individual differences in rational thought and decision making. To overcome the issue of overlap with numeracy, a novel measure of cognitive reflection less related to numeracy and math anxiety than Numerical CRT was developed—Verbal CRT. The present research had two main aims: first to investigate the generalizability of Verbal CRT in cultural contexts outside the United States/United Kingdom and second to test the factor structure linking traditional—numerical—CRT, Verbal CRT, numeracy, and fluid intelligence. In Studies 1a and 1b, we adapted and tested the validity and psychometric properties of Polish versions of tasks and scales. Next, using a large and diverse sample of Polish adults, we tested five models of the factor structure of cognitive abilities and thinking dispositions (Study 2). The most parsimonious and best‐fitted model contained three latent variables: Verbal CRT, numeracy (composed of the items from the Berlin Numeracy Test and traditional—numerical—CRT), and fluid intelligence. In line with previous research, our results show that Verbal CRT is a valid cognitive reflection measure that provides a clearer interpretation than traditional CRT, even in a different language and cultural context.
Near‐infrared‐induced drug release from antibody–drug double conjugates exerts a cytotoxic photo‐bystander effect
Authors: Takahashi Kazuomi , Yasui Hirotoshi , Taki Shunichi , Shimizu Misae , Koike Chiaki , Taki Kentaro , Yukawa Hiroshi , Baba Yoshinobu , Kobayashi Hisataka , Sato Kazuhide 
Published: August 2022

AbstractIdeal cancer treatments specifically target and eradicate tumor cells without affecting healthy cells. Therefore, antibody‐based therapies that specifically target cancer antigens can be considered ideal cancer therapies. Antibodies linked with small‐molecule drugs (i.e., antibody–drug conjugates [ADCs]) are widely used in clinics as antibody‐based therapeutics. However, because tumors express antigens heterogeneously, greater target specificity and stable binding of noncleavable linkers in ADCs limit their antitumor effects. To overcome this problem, strategies, including decreasing the binding strength, conjugating more drugs, and targeting tumor stroma, have been applied, albeit with limited success. Thus, further technological advancements are required to remotely control the ADCs. Here, we described a drug that is photo‐releasable from an ADC created via simple double conjugation and its antitumor effects both on target and nontarget tumor cells. Specifically, noncleavable T‐DM1 was conjugated with IR700DX to produce T‐DM1‐IR700. Although T‐DM1‐IR700 itself is noncleavable, with NIR‐light irradiation, it can release DM1‐derivatives which elicited antitumor effect in vitro mixed culture and in vivo mixed tumor model which are mimicking heterogeneous tumor‐antigen expression same as real clinical tumors. This cytotoxic photo‐bystander effect occurred in various types mixed cultures in vitro, and changing antibodies also exerted photo‐bystander effects, suggesting that this technology can be used for targeting various specific cancer antigens. These findings can potentially aid the development of strategies to address challenges associated with tumor expression of heterogeneous antigen.
Characterizing the most effective scaffolding approaches in engineering and technology education: A clustering approach
Authors: Belland Brian R. , Lee Eunseo , Zhang Anna Y. , Kim ChanMin 
Published: August 2022

AbstractThis study indicates the most effective combinations of scaffolding features within computer science and technology education settings. It addresses the research question, “What combinations of scaffolding characteristics, contexts of use, and assessment levels lead to medium and large effect sizes among college‐ and graduate‐level engineering and technology learners?” To do so, studies in which scaffolding led to a medium or large effect size within the context of technology and engineering education were identified within a scaffolding meta‐analysis data set. Next, two‐step cluster analysis in SPSS 24 was used to identify distinct groups of scaffolding attributes tailored to learning computer science at the undergraduate and graduate levels. Input variables included different scaffolding characteristics, the context of use, education level, and effect size. There was an eight‐cluster solution: five clusters were associated with large effect size, two with medium effect size, and one with both medium and large effect size. The three most important predictors were the context in which scaffolding was used, if and how scaffolding is customized over time and the decision rules that govern scaffolding change. Notably, highly effective scaffolding clusters are associated with most levels of each predictor.
Effects of GABAB receptor positive allosteric modulator BHF177 and IRS‐1 on apoptosis of hippocampal neurons in rats with refractory epilepsy via the PI3K/Akt pathway
Authors: Wang Peng , Nan Shanji , Zhang Yizhi , Fan Jia 
Published: August 2022

AbstractThe present study was conducted to determine the effects of the γ‐aminobutyric acid B (GABAB) receptor positive allosteric modulator BHF177 on refractory epilepsy (RE). An RE rat model was initially established via treatment with lithium‐pilocarpine. The RE rats were then treated with BHF177 or the GABAB receptor antagonist CGP46381, followed by recording of their seizure rate and assessment of their spatial learning in the Morris water maze test. Treatment of BHF177 reduced the seizure intensity, whereas this effect was revered upoj treatment with CGP46381. Immunohistochemistry revealed that BHF177 treatment diminished P‐glycoprotein (P‐gp) expression in the hippocampal tissues of RE rats. Next, we found that BHF177 activated GABAB receptor, resulting in upregulated expression of insulin receptor substrate 1 (IRS‐1) and PI3K, as well as antiapoptotic factors (Bcl‐2 and mTOR), along with suppression of the apoptosis factors Bax and cleaved caspase‐3 in the hippocampal tissues. Further, activation of GABAB receptors by BHF177 alleviated the inflammatory response in hippocampal tissues of RE rats, as evidenced by reduced VCAM‐1, ICAM‐1, and tumor necrosis factor‐α levels. Next, we treated primary cultured rat hippocampal neurons with BHF177 and the IRS‐1 selective inhibitor NT157. BHF177 inhibited hippocampal apoptosis in rat hippocampal neurons by regulating the IRS‐1/PI3K/Akt axis through crosstalk between GABAB and insulin‐like growth factor‐1 receptors. Collectively, our findings indicate that the BHF177 inhibited neuron apoptosis, thus protecting against RE through the IRS‐1/PI3K/Akt axis, which may present a new therapeutic channel for RE.
DNA methylation influences the CTCF‐modulated transcription of RASSF1A in lung cancer cells
Authors: Xie Bin , Peng Feng , He Fengping , Cheng Yixing , Cheng Jiangtao , Zhou Zhibing , Mao Wei 
Published: August 2022

AbstractRas‐association domain family 1A (RASSF1A) is one of the most methylated genes in lung cancer (LC). We investigate whether the high DNA methylation level of RASSF1A can relieve the resistance of RASSF1A to LC by inhibiting RASSF1A's transcription factor binding to RASSF1A. RASSF1A expression in tissues and cells was tested utilizing quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blot. RASSF1A expression and RASSF1A methylation level in LC cells exposed to 5‐Aza‐dc were assessed by qRT‐PCR and quantitative methylation‐specific PCR. The association between CTCF and RASSF1A was assessed using hTFtarget, ChIP, and luciferase reporter gene analysis. The effects of 5‐Aza‐dc, CTCF, and RASSF1A on cell biological behaviors and epithelial‐mesenchymal transition (EMT)‐related markers were assessed by cell function experiments and Western blot. Moreover, we constructed the xenograft tumor and pulmonary nodule metastasis models, and assessed tumor volume and weight. RASSF1A expression and pulmonary nodule metastasis were tested utilizing qRT‐PCR, Western blot, and H&E staining. RASSF1A was under‐expressed in LC tissues and cells. 5‐Aza‐dc enhanced RASSF1A level and weakened RASSF1A methylation level in LC cells. RASSF1A silencing neutralized 5‐Aza‐dc‐mediated repressing effects on LC cell biological function and EMT. The loss of CTCF binding to RASSF1A in LC cells was associated with DNA methylation. The effect of 5‐Aza‐dc on RASSF1A level, LC cell malignant behaviors, and EMT‐related factors were strengthened by CTCF upregulation. RASSF1A overexpression suppressed LC tumor growth and pulmonary nodule metastasis in vivo. DNA methylation blocked the modulation of RASSF1A expression by CTCF and relieved the resistance of RASSF1A to LC.
LncRNA KCNQ1OT1 contributes to hydrogen peroxide‐induced apoptosis, inflammation, and oxidative stress of cardiomyocytes via miR‐130a‐3p/ZNF791 axis
Authors: Xin Hong , Li Chengliang , Cai Tianzhi , Cao Jinlong , Wang Meixue 
Published: August 2022

AbstractIt has been reported that long noncoding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) played an important role in myocardial infarction (MI). However, the regulatory network behind KCNQ1OT1 in MI is largely unknown. Quantitative real time polymerase chain reaction (qRT‐PCR) was applied to detect the enrichment of KCNQ1OT1, microRNA‐130a‐3p (miR‐130a‐3p) and zinc finger 791 (ZNF791). The viability and apoptosis of AC16 cells were measured by (4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and flow cytometry. Enzyme‐linked immunosorbent assay (ELISA) was conducted to assess the inflammation and oxidative stress status of AC16 cells. The targeted relationship between miR‐130a‐3p and KCNQ1OT1 or ZNF791 was predicted by StarBase bioinformatic database, and dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to verify these predictions. Hydrogen peroxide (H2O2) stimulation caused a significant upregulation in the expression of KCNQ1OT1, while the level of miR‐130a‐3p showed an opposite phenomenon. KCNQ1OT1 was a crucial downstream component in H2O2‐mediated toxic effects, and KCNQ1OT1 accelerated H2O2‐induced toxic effects in AC16 cells. KCNQ1OT1 could sponge miR‐130a‐3p and down‐regulate its expression. MiR‐130a‐3p exerted opposite effects to KCNQ1OT1, and the depletion of miR‐130a‐3p attenuated the protective effects of KCNQ1OT1 intervention on AC16 cells exposed to H2O2. MiR‐130a‐3p could bind to ZNF791, and ZNF791 served as the target of miR‐130a‐3p to promote H2O2‐induced injury of AC16 cells. ZNF791 was modulated by KCNQ1OT1/miR‐130a‐3p signaling in H2O2‐treated AC16 cells. In all, lncRNA KCNQ1OT1 deteriorated H2O2‐mediated injury in cardiomyocytes through upregulating ZNF791 via serving as a molecular sponge for miR‐130a‐3p.
Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy
Authors: Liu Lin , Liu Zuoliang , Zeng Chunyun , Xu Yingtong , He Li , Fang Qing , Chen Zhiheng 
Published: August 2022

AbstractIn previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR‐mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine‐induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+‐free exposed for epileptiform activity induction. The real‐time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT‐mediated dUTP‐biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit‐8 assay. Immunofluorescent staining and green fluorescent protein‐light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+‐free‐induced seizure‐like neuron apoptosis, partially reversing the effect of Mg2+‐free on the mTOR signaling pathway and seizure‐like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+‐free‐induced seizure‐like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy‐induced brain injury.
A simplified cardiac damage staging predicts the outcome of patients undergoing TAVR—A multicenter analysis
Authors: Shamekhi Jasmin , Hasse Caroline , Veulemans Verena , Al‐Kassou Baravan , Piayda Kerstin , Maier Oliver , Zeus Tobias , Weber Marcel , Sedaghat Alexander , Zimmer Sebastian , Kelm Malte , Nickenig Georg , Sinning Jan‐Malte 
Published: August 2022

AbstractBackgroundA significant number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) suffer from extra‐aortic cardiac damage. Few studies have investigated strategies to quantify cardiac damage and stratify patients accordingly in different risk groups. The aim of this retrospective multicenter study was to provide a user‐friendly simplified staging system based on the proposed classification system of Généreux et al. as a tool to evaluate the prognosis of patients undergoing TAVR more easily. Moreover, we analyzed changes in cardiac damage after TAVR.MethodsWe assessed cardiac damage in patients, who underwent TAVR at the Heart Center Bonn or Düsseldorf, using pre‐ and postprocedural transthoracic echocardiography. Patients were assigned to the staging system proposed by Généreux et al. according to the severity of their baseline cardiac damage. Based on the established system, we created a simplified staging system to facilitate improved applicability. Finally, we compared clinical outcomes between the groups and evaluated changes in cardiac damage after TAVR.ResultsA total of 933 TAVR patients were included in the study. We found a significant association between cardiac damage and 1‐year all‐cause mortality (stage 0: 0% vs. stage 1: 3% vs. stage 2: 6.6%; p < 0.009). In multivariate analysis, cardiac damage was an independent predictor of 1‐year all‐cause mortality (hazard ratio: 2.0, 95% confidence interval: 1.1–3.8; p = 0.03).ConclusionsIn patients undergoing TAVR, cardiac damage is associated with enhanced mortality. A simplified staging system can help identify patients at high risk for an adverse outcome.
Otologic complications of temporomandibular joint arthrocentesis due to arteriovenous fistula
Authors: Fanti Joseph A. , Reddy Abhita , Greenbaum Evan , Qaisi Mohammed , Shah Biraj , Murphy James 
Published: August 2022

AbstractArteriovenous fistula (AVF) is a rare sequela following arthrocentesis of the temporomandibular joint. This case report discusses a constellation of symptoms, findings, and appropriate management of a patient with a superficial temporal AVF. Several findings in this case, including vertigo, nystagmus, and hearing loss, have not been previously documented in the literature.
Pallister–Hall syndrome diagnosed in a young man after an acute adrenal crisis
Authors: Grassa Anis , Yazidi Meriem , Marrakchi Jihene , Bel Hadj Sliman Chaima , Oueslati Ibtissem , Chihaoui Melika 
Published: August 2022

AbstractPallister–Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease. We report the case of an 18‐year‐old young man in whom the diagnosis of PHS was delayed until his hospitalization in the endocrinology department for acute adrenal insufficiency.