bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides During Rituximab Maintenance Therapy
Authors: Khoudour Nihel , Delestre Florence , Jabot‐Hanin Fabienne , Jouinot Anne , Nectoux Juliette , Letouneur Franck , Izac Brigitte , Vidal Michel , Guillevin Loïc , Puéchal Xavier , Charles Pierre , Terrier Benjamin , Blanchet Benoit 
Published: May 2023

ObjectiveInterindividual variability in response to rituximab remains unexplored in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides. Rituximab pharmacokinetics (PK) and pharmacodynamics (PD) as well as genetic polymorphisms could contribute to variability. This ancillary study of the MAINRITSAN 2 trial aimed to explore the relationship between rituximab plasma concentration, genetic polymorphisms in PK/PD candidate genes, and clinical outcomes.MethodsPatients included in the MAINRITSAN2 trial (ClinicalTrials.gov identifier: NCT01731561) were randomized to receive a 500‐mg fixed‐schedule rituximab infusion or an individually tailored regimen. Rituximab plasma concentrations at month 3 (CM3) were assessed. DNA samples (n = 53) were genotyped for single‐nucleotide polymorphisms within 88 putative PK/PD candidate genes. The relationship between PK/PD outcomes and genetic variants was investigated using logistic linear regression in additive and recessive genetic models.ResultsOne hundred and thirty‐five patients were included. The frequency of underexposed patients (<4 μg/ml) in the fixed‐schedule group was statistically lower compared to that in the tailored‐infusion group (2.0% versus 18.0%; P = 0.02, respectively). Low rituximab plasma concentration at 3 months (CM3 <4 μg/ml) was an independent risk factor for major relapse (odds ratio 6.56 [95% confidence interval (95% CI) 1.26–34.09]; P = 0.025) at month 28 (M28). A sensitivity survival analysis also identified CM3 <4 μg/ml as an independent risk factor for major relapse (hazard ratio [HR] 4.81 [95% CI 1.56–14.82]; P = 0.006) and relapse (HR 2.70 [95% CI 1.02–7.15]; P = 0.046). STAT4 rs2278940 and PRKCA rs8076312 were significantly associated with CM3 but not with major relapse onset at M28.ConclusionThese results suggest that drug monitoring could be useful to individualize the schedule of rituximab administration within the maintenance phase.
Establishment and validation of a prognostic nomogram for postoperative patients with gastric cardia adenocarcinoma: A study based on the Surveillance, Epidemiology, and End Results database and a Chinese cohort
Authors: Wang Lei , Ge Jingjing , Feng Liwen , Wang Zehua , Wang Wenjia , Han Huiqiong , Qin Yanru 
Published: May 2023

AbstractBackgroundGastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram.MethodsIn this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C‐index, calibration curve, time‐dependent ROC curve, and DCA curve. Kaplan–Meier survival curves were also generated to illustrate the differences in cancer‐specific survival (CSS) between the groups.ResultsThe results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer‐specific survival in the training cohort. Both the C‐index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high‐ and low‐risk groups were observed.ConclusionsRace, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.
LAG‐3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics
Authors: Adashek Jacob J. , Kato Shumei , Nishizaki Daisuke , Miyashita Hirotaka , De Pradip , Lee Suzanna , Pabla Sarabjot , Nesline Mary , Conroy Jeffrey M. , DePietro Paul , Lippman Scott , Kurzrock Razelle 
Published: May 2023

AbstractBackgroundLymphocyte activation gene 3 (LAG‐3) or CD223 is a transmembrane protein that serves as an immune checkpoint which attenuates T‐cell activation. Many clinical trials of LAG‐3 inhibitors have had modest effects, but recent data indicate that the LAG‐3 antibody relatlimab, together with nivolumab (anti‐PD‐1), provided greater benefit than nivolumab alone in patients with melanoma.MethodsIn this study, the RNA expression levels of 397 genes were assessed in 514 diverse cancers at a clinical‐grade laboratory (OmniSeq: https://www.omniseq.com/). Transcript abundance was normalized to internal housekeeping gene profiles and ranked (0–100 percentile) using a reference population (735 tumors; 35 histologies).ResultsA total of 116 of 514 tumors (22.6%) had high LAG‐3 transcript expression (≥75 percentile rank). Cancers with the greatest proportion of high LAG‐3 transcripts were neuroendocrine (47% of patients) and uterine (42%); colorectal had among the lowest proportion of high LAG‐3 expression (15% of patients) (all p < 0.05 multivariate); 50% of melanomas were high LAG‐3 expressors. There was significant independent association between high LAG‐3 expression and high expression of other checkpoints, including programmed death‐ligand 1 (PD‐L1), PD‐1, and CTLA‐4, as well as high tumor mutational burden (TMB) ≥10 mutations/megabase, a marker for immunotherapy response (all p < 0.05 multivariate). However, within all tumor types, there was inter‐patient variability in LAG‐3 expression level.ConclusionsProspective studies are therefore needed to determine if high levels of the LAG‐3 checkpoint are responsible for resistance to anti‐PD‐1/PD‐L1 or anti‐CTLA‐4 antibodies. Furthermore, a precision/personalized immunotherapy approach may require interrogating individual tumor immunograms to match patients to the right combination of immunotherapeutic agents for their malignancy.
Clinical characteristics and prognosis analysis of patients with de novo ASXL1‐mutated AML treated with the C‐HUNAN‐AML‐15 protocol: A multicenter study by the South China Pediatric AML Collaborative Group
Authors: Zeng Minhui , Chen Keke , Tian Xin , Zou Runying , Feng Xiaoqin , Li Chunfu , Li Jian , Zheng Mincui , Mai Huirong , Yang Lihua , He Yingyi , Xu Honggui , Wen Hong , He Xiangling 
Published: May 2023

AbstractBackgroundASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood.AimsThis study aimed to investigate the clinical characteristics and prognostic factors of ASXL1‐mutant pediatric AML from a large Chinese multicenter cohort.MethodsA total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1‐mut group, n = 487 for ASXL1‐wt group).ResultsASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1‐mut AML group than in the ASXL1‐wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5‐year overall survival (OS) and event‐free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1‐mut AML patients, a white blood cell (WBC) count ≥50 × 109/L had significantly poorer 5‐year OS and EFS than a WBC count <50 × 109/L (78.0% vs. 44.6%, p = 0.001; 74.8% vs. 44.6%, p = 0.003, respectively), while receiving hematopoietic stem cell transplantation (HSCT) had a higher 5‐year OS and EFS (84.5% vs. 48.5%, p = 0.024; 79.5% vs. 49.3%, p = 0.047, respectively). In the multivariate Cox regression analysis, patients with high‐risk AML undergoing HSCT tended to have a better 5‐year OS and EFS than those receiving chemotherapy as a consolidation (HR = 0.168 and 0.260, both p < 0.001), and WBC count ≥50 × 109/L or failure to achieve complete response after the first course were independent adverse predictors of OS and EFS (HR = 1.784 and 1.870, p = 0.042 and 0.018; HR = 3.242 and 3.235, both p < 0.001).ConclusionThe C‐HUANA‐AML‐15 protocol is a well‐tolerated and effective in the treatment of pediatric AML. ASXL1 mutation is not an independent adverse prognosis predictor for survival in AML, whereas ASXL1‐mut patients tend to have a poor prognosis if WBC count ≥50 × 109/L, but they can benefit from HSCT.
TFAM knockdown undermines SQSTM1 mRNA stability but retards autophagy flux and inhibits tumor cells proliferation under starvation conditions
Authors: Jiang Xu , Xu Ying , Yang Jingrui , Wang Jing , Gao Liu , Yu Li 
Published: May 2023

AbstractAlthough starvation stress can alter the homeostasis of mitochondria and promote autophagy, there is still a lack of research focusing on the connection between them. In this study, we found that, accompanied by the upregulation of autophagy flux, the membrane mitochondrial potential (MMP), the content of reactive oxygen species (ROS), the production of ATP, and the copy number of mitochondrial DNA (mt‐DNA) were changed when limiting amino acids supply. We screened and analyzed altered genes related to mitochondrial homeostasis under starvation stress and verified that the expression of mitochondrial transcription factor A (TFAM) was prominently upregulated. Inhibition of TFAM led to the change of mitochondrial function and homeostasis, caused the decrease of SQSTM1 mRNA stability and ATG101 protein level and restricted the autophagy process of cells under amino acid deficient conditions. In addition, the TFAM knockdown and starvation treatment aggravated the DNA damage and reduced proliferation rate of tumor cells. Therefore, our data shows the correlation between mitochondria homeostasis and autophagy, reveals the effect of TFAM on autophagy flux under starvation stress and provides experimental basis for the combined starvation therapy targeting mitochondria to inhibit tumor growth.
Asymmetric Catalytic Transformations of Aza‐ortho‐ and Aza‐para‐Quinone Methides
Authors: Zurro Mercedes , Maestro Aitor 
Published: May 2023

AbstractThe catalytic methodologies for the derivatization of aza‐QM have recently appeared in the literature and involve organocatalytic and organometallic approaches. This review aims at analyzing the diverse catalytic systems involving chiral NHC carbenes, phosphoric acids, phosphoramidites, phosphine and copper and palladium catalysis showing its applicability for the synthesis of a diverse away of N‐containing compounds which in many cases have biological activity.
Thin Layer Chromatography‐Freeze Surface‐Enhanced Raman Spectroscopy: A Powerful Tool for Monitoring Synthetic Reactions
Authors: Fukunaga Yu , Ogawa Rintaro , Homma Amane , Okada Tetsuo 
Published: May 2023

AbstractThin layer chromatography (TLC) is widely used to confirm the formation of the target compound in chemical synthesis. The key issue in TLC is spot identification as it primarily relies on retention factors. Coupling of TLC with surface‐enhanced Raman spectroscopy (SERS), which gives direct molecular information, is an appropriate choice, to overcome this challenge. However, interference from the stationary phase and impurities on the nanoparticles added for SERS measurements significantly degrades TLC‐SERS efficiency. It was found that freezing effectively eliminates such interferences and dramatically improves the performance of TLC‐SERS. In this study, TLC‐freeze SERS is applied to the monitoring of four chemically important reactions. The proposed method can identify the product and side‐products of similar structures, detect compounds with high sensitivity, and provide information of quantities that allows the reliable determination of the reaction time based on kinetic analysis.
Pushing the Boundary of Covalency in Lanthanoid‐Tellurium Bonds: Insights from the Synthesis, Molecular and Electronic Structures of Low‐Coordinate, Monomeric Europium(II) and Ytterbium(II) Tellurolates
Authors: Deka Rajesh , Dey Sourav , Guo Zhifang , Butcher Ray J. , Junk Peter C. , Turner David R. , Singh Harkesh B. , Deacon Glen B. 
Published: May 2023

AbstractOwing to the strict hard/soft dichotomy between the lanthanoids and tellurium atoms, and the strong affinity of lanthanoid ions for high coordination numbers, low‐coordinate, monomeric lanthanoid tellurolate complexes have remained elusive as compared to the lanthanoid complexes with lighter group 16 elements (O, S, and Se). This makes the development of suitable ligand systems for low‐coordinate, monomeric lanthanoid tellurolate complexes an appealing endeavor. In a first report, a series of low‐coordinate, monomeric lanthanoid (Yb, Eu) tellurolate complexes were synthesized by utilizing hybrid organotellurolate ligands containing N‐donor pendant arms. The reaction of bis[2‐((dimethylamino)methyl)phenyl] ditelluride,1and 8,8′diquinolinyl ditelluride,2withLn0metals (Ln=Eu, Yb) resulted in the formation of monomeric complexes [LnII(TeR)2(Solv)2] [R=C6H4‐2‐CH2NMe2] [3:Ln=Eu, Solv=tetrahydrofuran;4:Ln=Eu, Solv=acetonitrile;5:Ln=Yb, Solv=tetrahydrofuran;6:Ln=Yb, Solv=pyridine] and [EuII(TeNC9H6)2(Solv)n] (7: Solv=tetrahydrofuran, n=3;8: Solv=1,2‐dimethoxyethane, n=2), respectively. Complexes3–4and7–8represent the first sets of examples of monomeric europium tellurolate complexes. The molecular structures of complexes3–8are validated by single–crystal X‐ray diffraction studies. The electronic structures of these complexes were investigated using Density Functional Theory (DFT) calculations, which revealed appreciable covalency between the tellurolate ligands and lanthanoids.
Recent Advances in Activatable Probes for Molecular Imaging by Stimuli‐Controlled Disassembly
Authors: Huang Weijing , Yang Yanling , Ye Deju 
Published: May 2023

Comprehensive SummaryStimuli‐controlled disassembly process has shown promise to direct delivery of probes and/or spatial‐temporally control imaging signals for molecular imaging in vivo. Via the disassembly process, well defined nanoprobes with a stimulus‐responsive moiety can be controllably converted into small‐molecular imaging agents in response to a stimulus, leading to a switch in imaging signals. Moreover, the on‐site released small‐molecule probes could enhance penetration into the deep tissue for improved imaging of deep‐seated molecular targets. Therefore, such a stimuli‐controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects. In this review article, we first briefly introduce the general principle of stimuli‐controlled disassembly. We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process. Activatable probes by using multiple stimuli to control cascaded in situ self‐assembly and disassembly processes are also discussed. Finally, we close with a conclusion of current challenges and perspective in this field. We wish this review paper will give readers useful information on molecular imaging via the intelligent stimuli‐controlled disassembly process.
Bipolar cells containing protein kinase Cα mediate attentional facilitation of the avian retinal ganglion cells by the retinopetal signal
Authors: Uchiyama Hiroyuki , Matsutani Shinji , Ohno Hiroshi , Yamaoka Seiya , Mizokami Takuya , Sugimoto Shiho , Hirashima Yasuhiro 
Published: May 2023

AbstractBirds have a well‐developed retinopetal system projecting from the midbrain to the contralateral retina. The signal sent to the retina through the retinopetal system facilitates visual responses of the retinal ganglion cells (RGCs), and the retinopetal signals function as attentional signals during visual search. Thus, the retinopetal signal somehow reaches and facilitates visual responses of the RGCs. However, the tertiary neuron of the retinopetal system, the isthmo‐optic target cell (IOTC), is unlikely to contact most RGCs directly, because the IOTCs form axon terminals localized in the outermost sublayer (lamina 1) of the inner plexiform layer (IPL) where few RGC dendrites terminate. Therefore, some other intrinsic retinal neurons must be involved in the centrifugal attentional enhancement of visual responses of the RGCs. We investigated connections of the target cells of the IOTCs in chicken and quail, using light and electron microscopic immunohistochemistry. We show that axon terminals of the IOTC make synaptic contacts with protein kinase Cα (PKCα)‐immunoreactive (ir) bipolar cells (PKCα‐BCs) in lamina 1 of the IPL. Furthermore, with prolonged electrical stimulation of the isthmo‐optic nucleus (ION) on one side, whose neurons send their axons to the contralateral retina and make synaptic contacts there with IOTCs, phosphorylation of cAMP response element‐binding protein was observed in the PKCα‐BCs in the contralateral retina, but not in the ipsilateral retina. This suggests that electrical stimulation of ION activated PKCα‐BCs through synapses from IOTCs to PKCα‐BCs, thus stimulating transcription in PKCα‐BCs. Thus, centrifugal attentional signals may facilitate visual responses of RGCs via the PKCα‐BCs.
Impact of infections on the incidence of acute inflammatory demyelinating polyneuropathy in children
Authors: Gilbert Hannah , Abend Nicholas S. , Hutchinson Melissa , Messer Ricka , Moharir Mahendranath , Nash Kendall , Palaganas Jamie , Piantino Juan , Shah Samir S. , Hall Matt , Wells Elizabeth , Press Craig A. ,   Pediatric Neurohospitalist Work Group
Published: May 2023

AbstractObjectivesAcute inflammatory demyelinating polyneuropathy (AIDP) is the leading cause of acute flaccid paralysis in children and hypothesized to be triggered by antecedent infection. We sought to determine the association between AIDP and commonly acquired community infections in children. We utilized the reduction in these infections due to measures during coronavirus disease 2019 (COVID‐19) to serve as a natural experiment and determine their contribution to AIDP.MethodsThis cross‐sectional study used administrative and billing data from children's hospitals contributing to the Pediatric Health Information System. We included hospitalizations of children with a diagnosis of AIDP from (January 2017 through February 2021). Encounters for infection‐ (including respiratory, gastrointestinal, and COVID‐19) related diagnoses were measured as a marker of community incidence.ResultsA total of 1111 index encounters for AIDP were included. Pre‐COVID‐19, AIDP was not associated with respiratory or gastrointestinal infections, specifically, influenza or campylobacter. During the COVID‐19 period from March 2020 to February 2021, respiratory, gastrointestinal, and influenza infections decreased compared to expected (for the same time of year pre‐COVID‐19) by 59.6%–90.1%, 51.5%–68.9%, and 54.5%–97.9%, respectively. In contrast, AIDP hospitalizations and all hospitalizations only decreased by 11.5%–39.3% and 14.2%–25%, respectively. COVID‐19 was not positively associated with AIDP overall or at individual hospitals.InterpretationCommon community‐acquired infections including COVID‐19 were not strongly associated with hospitalizations for AIDP in children. AIDP persisted despite the dramatic reduction in infection‐related encounters during the pandemic. These results suggest that recent antecedent community‐acquired infections were not the primary driver of AIDP and that alternative triggers should be explored.
Cysteine‐Based Perfluorinated Derivatives: A Theoretical and Experimental Study**
Authors: Chalán‐Gualán Sisa , Ramos‐Tomillero Iván , Terencio Thibault , De Lima Lola , Navas‐León Daniela G. , Suárez Margarita , Santiago Vispo Nelson , Albericio Fernando , Rodríguez Hortensia 
Published: May 2023

AbstractCysteine‐based perfluoroaromatic (hexafluorobenzene (HFB) and decafluorobiphenyl (DFBP)) were synthesized and established as a chemoselective and available core to construct molecular systems ranging from small molecules to biomolecules with interesting properties. The DFBP was found more effective than HFB for the monoalkylation of decorated thiol molecules. As proof of concept of the potential application of perfluorinated derivatives as non‐cleavable linkers, some antibody‐perfluorinated conjugates were prepared via thiol through two different strategies, i) using thiol from reduced cystamine coupling to carboxylic acids from mAb by amide bond, and ii) using thiols from reduction of mAb disulfide bond. Conjugates cell binding analysis demonstrated that the bioconjugation does not affect the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated through spectroscopic characterization (FTIR and 19F NMR chemical shifts) and theoretical calculations. The comparison of calculated and experimental 19F NMR shifts and IR wavenumbers give excellent correlations, asserting as powerful tools in structurally identifying HFB and DFBP derivatives. Moreover, molecular docking was also developed to predict cysteine‐based perfluorated derivatives’ affinity against topoisomerase Il and cyclooxygenase 2 (COX‐2). The results suggested that mainly cysteine‐based DFBP derivatives could be potential topoisomerase II α and COX‐2 binders, becoming potential anticancer agents and candidates for anti‐inflammatory treatment.
Study on the Preparation and Morphology Mechanism of Micron‐Sized Hexagonal Flake Basic Zinc Chloride (Zn5(OH)8Cl2·H2O) by Ammonia Precipitation Method
Authors: Fan Tianbo , Zhao Yibo , Wang Xin an , Liu Sen , Li Xue , Guo Hongfan , Li Li 
Published: May 2023

AbstractThe chemical formula of basic zinc chloride is Zn5(OH)8Cl2 · H2O (denoted as ZHC). It is a new type of zinc source additive, widely used in the feed industry. In this article, micron‐sized hexagonal flake ZHC with a diameter of 10–60 µm is directly prepared by ammonia precipitation method using ZnCl2 as raw material. The products are characterized and analyzed by X‐ray diffraction, scanning electron microscopy, and laser particle size analyzer. The effects of reaction temperature, ammonia flow rate, aging time, and reactant concentration on the product morphology are studied. Under the optimum reaction conditions, the ZnCl2 concentration is 2.0 mol L−1, NH3 flow rate is 300 mL min−1, the reaction time is 1 h, the reaction temperature is 80 °C, and the aging time is 5 h. Lastly, the yield reaches 49.06%. The growth habit of ZHC is theoretically analyzed by the Morphology program. The calculation results are in good agreement with the experimental results. The change of (003) crystal plane exposure caused by temperature is an important reason for the non‐ideality of macroscopic morphology.