bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of ARI‐0001 CART19 cell therapy in patients with relapsed/refractory CD19‐positive acute lymphoblastic leukemia with isolated extramedullary disease
Authors: Ortiz‐Maldonado Valentín , Alonso‐Saladrigues Anna , Español‐Rego Marta , Martínez‐Cibrián Nuria , Faura Anna , Magnano Laura , Català Albert , Benítez‐Ribas Daniel , Giné Eva , Díaz‐Beyá Marina , Correa Juan Gonzalo , Rovira Montserrat , Montoro‐Lorite Mercedes , Martínez‐Roca Alexandra , Rodríguez‐Lobato Luis Gerardo , Cabezón Raquel , Cid Joan , Lozano Miquel , Garcia‐Rey Enric , Conde Nuria , Pedrals Georgina , Rozman María , Torrebadell Montserrat , Setoain Xavier , Rodríguez Sonia , Esteve Jordi , Pascal Mariona , Urbano‐Ispizua Álvaro , Juan Manel , Delgado Julio , Rives Susana 
Published: March 2022

AbstractWe evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B‐cell acute lymphoblastic leukemia (B‐ALL) treated with the CD19‐directed CAR T cells ARI‐0001 in two centers (adult and pediatric), including patients treated in the CART19‐BE‐01 trial and the consecutive compassionate use program. iEMD was detected by PET‐CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 106 ARI‐0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure‐related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%–99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%–94%) of them. Progression‐free and overall survival were 49% (95% CI: 30%–79%) and 61% (95% CI: 40%–92%) at 2 years. In conclusion, the use of ARI‐0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products.
Dining in Tuva: Social correlates of diet and mobility in Southern Siberia during the 2nd–4th centuriesCE
Authors: Milella Marco , Caspari Gino , Laffranchi Zita , Arenz Gabriele , Sadykov Timur , Blochin Jegor , Keller Marcel , Kapinus Yulija , Lösch Sandra 
Published: March 2022

AbstractObjectivesContemporary archeological theory emphasizes the economic and social complexity of Eurasian steppe populations. As a result, old notions of “nomadic” cultures as homogenously mobile and economically simple are now displaced by more nuanced interpretations. Large part of the literature on diet and mobility among Eurasian pastoralists is focused on the Bronze and Iron Ages. The underrepresentation of more recent contexts hampers a full discussion of possible chronological trajectories. In this study we explore diet and mobility at Tunnug1 (Republic of Tuva, 2nd–4th century CE), and test their correlation with social differentiation.Materials and MethodsWe compare demographic patterns (by age‐at‐death and sex) of carbon, nitrogen, and sulfur stable isotope ratios (δ13C, δ15N, and δ34S) among 65 humans and 12 animals from Tunnug1 using nonparametric tests and Bayesian modeling. We then compare isotopic data with data on perimortal skeletal lesions of anthropic origin and funerary variables.ResultsOur analyses show that: (1) diet at Tunnug1 was largely based on C4plants (likely millet) and animal proteins; (2) few individuals were nonlocals, although their geographic origin remains unclarified; (3) no differences in diet separates individuals based on sex and funerary treatment. In contrast, individuals with perimortal lesions show carbon and nitrogen stable isotope ratios consistent with a diet incorporating a lower consumption of millet and animal proteins.DiscussionOur results confirm the previously described socioeconomic variability of steppe populations, providing at the same time new data about the economic importance of millet in Southern Siberia during the early centuries CE.
Prolonged Unconsciousness is Common in COVID‐19 and Associated with Hypoxemia
Authors: Waldrop Greer , Safavynia Seyed A. , Barra Megan E. , Agarwal Sachin , Berlin David A. , Boehme Amelia K , Brodie Daniel , Choi Jacky M. , Doyle Kevin , Fins Joseph J. , Ganglberger Wolfgang , Hoffman Katherine , Mittel Aaron M. , Roh David , Mukerji Shibani S. , Der Nigoghossian Caroline , Park Soojin , Schenck Edward J. , Salazar‐Schicchi John , Shen Qi , Sholle Evan , Velazquez Angela G. , Walline Maria C. , Westover M. Brandon , Brown Emery N. , Victor Jonathan , Edlow Brian L. , Schiff Nicholas D. , Claassen Jan 
Published: March 2022

ObjectiveThe purpose of this study was to estimate the time to recovery of command‐following and associations between hypoxemia with time to recovery of command‐following.MethodsIn this multicenter, retrospective, cohort study during the initial surge of the United Statesʼ pandemic (March–July 2020) we estimate the time from intubation to recovery of command‐following, using Kaplan Meier cumulative‐incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID‐19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).ResultsFive hundred seventy‐one patients of the 795 patients recovered command‐following. The median time to recovery of command‐following was 30 days (95% confidence interval [CI] = 27–32 days). Median time to recovery of command‐following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command‐following was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46–0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85–0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non‐overlapping second surge cohort (N = 427, October 2020 to April 2021).InterpretationSurvivors of severe COVID‐19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life‐sustaining therapies. ANN NEUROL 2022;91:740–755
Pushing the Length Limit of Dihydrodiboraacenes: Synthesis and Characterizations of Boron‐Embedded Heptacene and Nonacene
Authors: Chen Cheng , Wang Ming‐Wei , Zhao Xing‐Yu , Yang Shuang , Chen Xing‐Yu , Wang Xiao‐Ye 
Published: March 2022

AbstractBoron‐embedded heteroacenes (boraacenes) have attracted enormous interest in organic chemistry and materials science. However, extending the skeleton of boraacenes to higher acenes (N≥6) is synthetically challenging because of their limited stability under ambient conditions. Herein, we report the synthesis of boron‐embedded heptacene (DBH) and nonacene (DBN) as the hitherto longest boraacenes. The former is highly stable (even after 240 h in tetrahydrofuran), while the latter is air‐sensitive with the half‐life (t1/2) of 11.8 min. The structures of both compounds are verified by single‐crystal X‐ray diffraction, revealing a linear backbone with an antiaromatic C4B2core. Photophysical characterizations associated with theoretical calculations indicate that both compounds exhibit highly efficient anti‐Kasha emissions. Remarkably, the air‐stableDBHmanifests an ultrahigh photoluminescence quantum yield (PLQY) of 98±2 % and can be chemically reduced to its radical anion and dianion states, implying the value of boron‐doped higher acenes as novel functional materials.
para‐Selective C−H Borylation of Aromatic Quaternary Ammonium and Phosphonium Salts
Authors: Lu Shuo , Zheng Tianyu , Ma Jiawei , Deng Zhangming , Qin Shengmeng , Chen Yu , Liang Yong 
Published: March 2022

AbstractAromatic ammonium and phosphonium salts are important synthetic intermediates and multifunctional materials, but para‐selective functionalization of the aromatic salts remains a challenge. Here we develop an ionic ligand based on our newly designed “biphenyl‐phenanthroline” skeleton and realize the Ir‐catalyzed para‐selective C−H borylation of seven types of aromatic quaternary ammonium and phosphonium salts. Gram‐scale transformation, late‐stage elaboration for drug molecule, and diversification of borylated products demonstrate the potential utility of this reaction. The mechanistic studies and computational analysis elucidate the origin of para‐selectivity.
Inhibition of Alkali Metal Reduction of 1‐Adamantanol by London Dispersion Effects
Authors: Mears Kristian L. , Stennett Cary R. , Fettinger James C. , Vasko Petra , Power Philip P. 
Published: March 2022

AbstractA series of alkali metal 1‐adamantoxide (OAd1) complexes of formula [M(OAd1)(HOAd1)2], where M=Li, Na or K, were synthesised by reduction of 1‐adamantanol with excess of the alkali metal. The syntheses indicated that only one out of every three HOAd1 molecules was reduced. An X‐ray diffraction study of the sodium derivative shows that the complex features two unreduced HOAd1 donors as well as the reduced alkoxide (OAd1), with the Ad1 fragments clustered together on the same side of the NaO3 plane, contrary to steric considerations. This is the first example of an alkali metal reduction of an alcohol that is inhibited from completion due to the formation of the [M(OAd1)(HOAd1)2] complexes, stabilized by London dispersion effects. NMR spectroscopic studies revealed similar structures for the lithium and potassium derivatives. Computational analyses indicate that decisive London dispersion effects in the molecular structure are a consequence of the many C−H⋅⋅⋅H−C interactions between the OAd1 groups.
A Water‐Soluble Highly Oxidizing Cobalt Molecular Catalyst Designed for Bioinspired Water Oxidation
Authors: Su Yun‐Fei , Luo Wen‐Zhi , Lin Wang‐Qiang , Su Yi‐Bing , Li Zi‐Jian , Yuan Yong‐Jun , Li Jian‐Feng , Chen Guang‐Hui , Li Zhaosheng , Yu Zhen‐Tao , Zou Zhigang 
Published: March 2022

AbstractHerein, we present a stable water‐soluble cobalt complex supported by a dianionic 2,2′‐([2,2′‐bipyridine]‐6,6′‐diyl)bis(propan‐2‐ol) ligand scaffold, which is a rare example of a high‐oxidation species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single‐site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high‐oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.
Polyethyleneimine‐condensed polystyrene resin: A specific adsorbent for Cu2+ over Ni2+
Authors: Meng Qi , He Qiang , Liu Jiang , Cao Yiwen , Yuan Dan , Teng Qiaoqiao 
Published: March 2022

AbstractA polyethyleneimine grafted polystyrene adsorption resin (PSFPA) was prepared by condensation reaction of formylated polystyrene resin (PSF) with polyethyleneimine (PEI). The material has been characterized by IR spectroscopy, CHN elemental, specific surface area and pore size and thermal gravimetric analyses. It showed a superb equilibrium adsorptive capacity of 2.92 mmol/g for Cu2+ at 318 K and no uptake of Ni2+ at all in neither single metal nor binary systems with Ni:Cu ratio high up to 100, suggesting a potential applicability of PSFPA in refining Ni electrolyte. The Cu adsorption/desorption behaviors were further detailedly studied in static and dynamic modes by investigating pH, temperature, and initial concentration effects. Kinetic studies indicated that the adsorption of Cu2+ by PSFPA conformed to pseudo‐second‐order kinetics, and the adsorption rate was controlled by intraparticle diffusion. The adsorption followed Langmuir isotherms and was identified as a spontaneous endothermic process.
Role of Glutaminase 2 in Promoting CD4+ T Cell Production of Interleukin‐2 by Supporting Antioxidant Defense in Systemic Lupus Erythematosus
Authors: Hisada Ryo , Yoshida Nobuya , Orite Seo Yeon K. , Umeda Masataka , Burbano Catalina , Scherlinger Marc , Kono Michihito , Krishfield Suzanne , Tsokos George C. 
Published: March 2022

ObjectiveGlutaminase (GLS) isoenzymes GLS1 and GLS2 catalyze the first step of glutaminolysis. GLS1 is requisite for Th17 cell differentiation, and its inhibition suppresses autoimmune disease in animals, but the function of GLS2 is not known. The aim of this study was to investigate the role of GLS2 in CD4+ T cell function and systemic lupus erythematosus (SLE) pathogenesis.MethodsWe measured reactive oxygen species (ROS) levels, lipid peroxidation, and mitochondrial mass and polarization by flow cytometry, interleukin‐2 (IL‐2) production by a dual luciferase assay, and CpG DNA methylation of Il2 by a real‐time polymerase chain reaction system. The impact of the overexpression of wild‐type GLS1, wild‐type GLS2, or mutated GLS2 at the PDZ domain–binding motif in CD4+ T cells was examined. Furthermore, GLS2 expression in CD4+ T cells from lupus‐prone mice and patients with SLE was analyzed by Western blotting.ResultsGLS2, but not GLS1, reduced ROS levels and lipid peroxidation and restored mitochondrial function in T cells. GLS2 promoted IL‐2 production through the demethylation of the Il2 promoter. Mutation of the PDZ domain–binding motif abated the ability of GLS2 to regulate IL‐2 and ROS levels. In lupus‐prone mice and patients with SLE, the expression of GLS2 was decreased in CD4+ T cells. Finally, GLS2 overexpression corrected ROS levels and restored IL‐2 production by CD4+ T cells from lupus‐prone mice and SLE patients.ConclusionOur findings suggest that GLS2 has a crucial role in IL‐2 production by CD4+ T cells by supporting antioxidant defense, and they offer a new approach to correcting IL‐2 production by T cells in SLE.
Cancer's second genome: Microbial cancer diagnostics and redefining clonal evolution as a multispecies process
Authors: Sepich‐Poore Gregory D. , Guccione Caitlin , Laplane Lucie , Pradeu Thomas , Curtius Kit , Knight Rob 
Published: March 2022

AbstractThe presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome—the metagenome—are manifold, but require careful consideration of microbial experimental idiosyncrasies that are distinct from host‐centric methods. Furthermore, the discoveries of intracellular and intra‐metastatic cancer bacteria necessitate fundamental changes in describing clonal evolution and selection, reflecting bidirectional interactions with non‐human residents. Reconsidering cancer clonality as a multispecies process similarly holds key implications for understanding metastasis and prognosing therapeutic resistance while providing rational guidance for the next generation of bacterial cancer therapies. Guided by these new findings and challenges, this Review describes opportunities to exploit cancer's metagenome in oncology and proposes an evolutionary framework as a first step towards modeling multispecies cancer clonality. Also see the video abstract here: https://youtu.be/-WDtIRJYZSs
Profile of cognitive impairment in late‐stage Parkinson's disease
Authors: Severiano e Sousa Catarina , Fabbri Margherita , Godinho Catarina , Moiron Simões Rita , Chendo Inês , Coelho Miguel , Pavão Martins Isabel , Ferreira Joaquim J. 
Published: March 2022

AbstractIntroductionThe profile of cognitive impairment associated with the late stages of Parkinson's disease (LSPD) is rarely reported. Its characterization is necessary to better understand the cognitive changes that occur as the disease progresses and to better contribute to its management.MethodsIn this cross‐sectional study, we characterized the cognitive profile of LSPD patients using the comprehensive assessment methodology proposed by the International Parkinson and Movement Disorders Society Task Force. The association of clinical and demographic variables with dementia diagnosis was also investigated using binary logistic regression analysis.ResultsEighty‐four LSPD patients were included (age 75.4 ± 6.9; disease duration 16.9 ± 7.5). Fifty‐four (64.3%) were classified as demented and presented a global impairment cognitive profile. In the nondemented group (N = 30), 25 (83.3%) LSPD patients met the diagnostic criteria for mild cognitive impairment, mostly with multiple domain impairment (96.0%) and a heterogeneous profile. Memory was the most frequent and severely impaired cognitive domain in both groups. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities were significantly associated with dementia diagnosis (p < .05).ConclusionsCognitive impairment in multiple domains was common in LSPD patients. The most frequent and prominent deficits were in the memory domain, with a strong interference from attention impairment. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities proved to be important determinants for dementia diagnosis.
Impact of severity of baseline thrombocytopenia on outcomes after percutaneous coronary interventions: Analysis from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program
Authors: Vallurupalli Srikanth , Hess Edward , Plomondon Mary E. , Park Ki , Waldo Stephen W. , Agarwal Shivkumar , Uretsky Barry F. 
Published: March 2022

AbstractObjectivesThe aim of this study was to evaluate the effect of the degree of severity of baseline thrombocytopenia (TCP) on outcomes after percutaneous coronary intervention (PCI)BackgroundThe association of TCP with clinical outcomes among patients undergoing coronary intervention has not been previously evaluated.MethodsUsing data from the US Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program, we identified patients undergoing PCI between October 1, 2007, to September 30, 2017. The cohort was then stratified by platelet count, as no TCP (platelet count >150,000/mcl), mild TCP (100–150,000/mcl), or moderate‐severe TCP (<100,000/mcl) and this was associated with clinical outcomes.ResultsThe cohort included 80,427 patients (98% male), of which 14.9% (13.2% mild, 1.7% moderate‐severe) suffered from TCP at the time of PCI. Compared with mild or no TCP, moderate‐severe TCP was associated with increased risk of post‐PCI pericardiocentesis (0.6% vs. 0.2% vs. 0.2%, p = 0.018) and in‐hospital mortality (1.5% vs. 0.7% vs. 0.7%) without a difference in postprocedure stroke (0.5% vs. 0.3% vs. 0.3%, p = 0.6). Over a median follow‐up of 1729 days, time‐to‐repeat revascularization was significantly shorter in moderate‐severe TCP (1080 vs. 1347 vs. 1467 days, p < 0.001) despite lower risk of revascularization. Both mild (adjusted HR: 1.11, 95% CI: 1.07–1.15, p < 0.001) and moderate‐severe TCP (HR: 1.55, 95% CI: 1.43–1.69, p < 0.001) were associated with increased all‐cause mortality compared with those without TCP.ConclusionsThrombocytopenia was associated with increased short‐ and long‐term adverse events among patients undergoing PCI. Any degree of TCP was associated with increased long‐term all‐cause mortality while moderate‐severe TCP was also associated with increased risk of periprocedural adverse events.
Individual patient data meta‐analysis of patients treated with a heparin‐bonded Viabahn in the femoropopliteal artery for chronic limb‐threatening ischemia
Authors: Groot Jebbink Erik , van Wijck Iris , Holewijn Suzanne , Iida Osamu , Spinelli Domenico , Saxon Richard R. , Zeller Thomas , Okhi Takao , Bosiers Marc , Reijnen Michel M. P. J. 
Published: March 2022

AbstractObjectivesThe aim of the study was to analyze available data on patients treated for chronic limb‐threatening ischemia (CLTI) with the heparin‐bonded Viabahn endoprosthesis.BackgroundThe patency of self‐expanding covered stents in patients with complex femoropopliteal lesions is encouraging. However, data were mostly derived in patients with intermittent claudication. Patients with CLTI often have more advanced disease and worse outcome.MethodsAfter the abstract screening, full‐text papers were checked. Authors were approached to consider joining the consortium. Data were sent anonymously, databases were merged and an individual patient data meta‐analysis was performed. Kaplan–Meier curves were used to calculate the freedom from amputations, the amputation‐free survival, and patency rates.ResultsSeven studies were enrolled, representing 161 limbs that were treated for CLTI. Median lesion length was 28.0 cm (interquartile range 25.0–33.0 cm) and 82.7% were chronic total occlusions. The technical success rate was 98.1% and the 30‐day mortality 1.9%. Through 2‐year follow‐up, the freedom‐from‐major‐amputations was 99.3%, with an amputation‐free survival of 78.8%. The freedom‐from‐loss‐of primary, primary‐assisted, and secondary patency was 70.4%, 71.8%, and 88.2%, respectively, at 1‐year and 59.5%, 62.7%, and 86.1% at 2‐year follow‐up, respectively. The reintervention‐free survival was 62.2% at a 2‐year follow‐up.ConclusionsTreatment of femoropopliteal disease in CLTI patients with the use of the heparin‐bonded Viabahn is safe and effective with favorable clinical outcomes and low amputation rates. Reinterventions are needed in a subset of the population to maintain endoprosthesis patency. Close follow‐up using duplex is recommended to detect potential edge stenosis, allowing treatment before device occlusion.
Toward bioeconomy of a multipurpose cereal: Cell wall chemistry of Sorghum is largely buffered against stem sugar content
Authors: Kanbar Adnan , Schäfer Daniela S. , Keller Judith , Nick Peter , Bunzel Mirko 
Published: March 2022

AbstractBackground and ObjectivesSorghum (Sorghum bicolor L. Moench) is a multipurpose crop with high potential for the bioeconomy. Ten sweet, grain and dual‐purpose sorghum genotypes were compared with respect to sugar‐related traits and cell wall composition.FindingsThe dual‐purpose hybrids Ganymed, Zerberus, and Tarzan performed better with respect to plant height, cane weight, and juice volume, but the sweet genotype KIT1 produced the highest sugar concentration (°Brix) in the stem. Analytical sugar data demonstrate genotypic differences in terms of sugar composition and concentrations, with sucrose being dominant. The monosaccharide composition of the stem cell wall polysaccharides showed surprisingly little genotypic variability. Variations in contents of lignin and cell wall‐bound hydroxycinnamate monomers were moderate.ConclusionsSweet, grain and dual‐purpose sorghum genotypes differ widely in terms of sugar‐related morphological parameters but are comparable with respect to their cell wall chemistry.Significance and NoveltyThe use of sorghum as a bioeconomy crop has mainly focused on the extraction of sugar for bioethanol production. However, besides cell wall polymers, the potential usage of hydroxycinnamates as platform molecules for the chemical industry may improve the valorization of the residues after sugar extraction. This application appears to be fairly independent of genotype, further increasing the potential of sorghum for the bioeconomy.