bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Binding of Sarilumab and Tocilizumab to IL‐6Rα and Effects of Receptor Occupancy on Clinical Parameters
Authors: Xu Christine , Rafique Ashique , Potocky Terra , Paccaly Anne , Nolain Patrick , Lu Qiang , Iglesias‐Rodriguez Melitza , St John Gregory , Nivens Michael C. , Kanamaluru Vanaja , Fairhurst Jeanette , Ishii Tomonori , Maldonado Rafael , Choy Ernest , Emery Paul 
Published: December 2020

AbstractWe evaluated interleukin‐6 (IL‐6) receptor‐α subunit (IL‐6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL‐6Rα receptor occupancy (RO) and C‐reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL‐6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL‐6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28‐joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL‐6Rα in vitro with 15‐ to 22‐fold higher affinity than tocilizumab, and inhibits IL‐6–mediated classical and trans signaling via membrane‐bound and soluble IL‐6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady‐state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28‐joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL‐6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.
The antibacterial and antiproliferative ability of kānuka, Kunzea ericoides, leaf extracts obtained by subcritical water extraction
Authors: Essien Sinemobong O , Young Brent , Baroutian Saeid 
Published: December 2020

AbstractBACKGROUNDSubcritical water kānuka leaf extracts contain high levels of polyphenols. However, whether these extracts can serve as natural antimicrobial and chemopreventive agents is still a question. This study aimed to evaluate the antibacterial and antiproliferative efficacy of SWE kanuka leaf extracts. Subcritical water extraction (SWE) was used to obtain natural extracts from kānuka leaves potentially rich in biologically active compounds. The antibacterial and antiproliferative capacities were assessed by broth microdilution assay and MTT‐assay, respectively. The assessed properties were compared to extraction from ethanol extraction (EE).ResultsThe screening results for antibacterial properties demonstrated that subcritical water kānuka leaf extracts were active against Escherichia coli (minimum conc. 0.8 mg/mL) and Staphylococcus aureus (minimum conc. 3.8 mg/mL). These extracts also exerted dose‐dependent antiproliferative effects on the viability of cancerous human cervical cell lines (Hep‐2 and RD cells) and mouse cell lines (L cells). The extraction temperature had significantly affected the extract's activities by enhancing neoformed compounds with beneficial effects.CONCLUSIONSSubcritical water extracts of kānuka demonstrated a better efficacy against bacterial growth and malignant cells viability in comparison to extracts obtained using conventional ethanol extraction. This SWE kānuka leaf product could be used in a range of applications where antimicrobial and antiproliferative properties are required. Further studies are needed to examine the mechanism and markers of these properties. © 2020 Society of Chemical Industry
BPDCN: When polychemotherapy does not compromise allogeneic CD123 CAR‐T cell cytotoxicity
Authors: Poussard Margaux , Philippe Laure , Fredon Maxime , Bôle‐Richard Elodie , Biichle Sabeha , Renosi Florian , Perrin Sophie , Kroemer Marie , Limat Samuel , Bonnefoy Francis , Daguindau Etienne , Deconinck Eric , Gruson Bérengère , Saas Philippe , Adotévi Olivier , Garnache‐Ottou Francine , Angelot‐Delettre Fanny 
Published: December 2020

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poor prognosis and no treatment consensus. Combining chemotherapy and immunotherapy is a promising strategy to enhance therapeutic effect. Before combining these therapies, the influence of one on the other has to be explored. We set up a model to test the combination of polychemotherapy ‐ named methotrexate, idarubicine, dexamethasone, and L‐asparaginase (MIDA) ‐ and CD123 CAR‐T cell therapy. We showed that CD123 CAR‐T cells exert the same effect on BPDCN models alone, or after MIDA regimen. These data support a preclinical rationale to use immunotherapy after a treatment with polychemotherapy for BPDCN patients.
Enzymatic diagnosis of neuronal lipofuscinoses in dried blood spots using substrates for concomitant tandem mass spectrometry and fluorimetry
Authors: Maeser Stefan , Petre Brindusa‐Alina , Ion Laura , Rawer Stephan , Kohlschütter Alfried , Santorelli Filippo M. , Simonati Alessandro , Schulz Angela , Przybylski Michael 
Published: December 2020

AbstractNeuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative diseases predominantly in childhood that are characterized by psychomotor deterioration, epilepsy, and early death of patients. The NCLs analyzed in the present study are caused by defects of the specific enzymes, CLN1 (palmitoyl protein thioesterase 1; PPT1), CLN2 (tripeptidyl peptidase 1; TPP1), and CLN10 (cathepsin D). Specific and sensitive diagnostic assays of NCLs were the main goal of this study. They are of increasing importance, particularly since enzyme replacement therapy (ERT) for NCL2 has recently become available for clinical treatment, and ERTs for further NCLs are under development. Here, we report specific and sensitive determinations for CLN1, CLN2, and CLN10 on dried blood spots by tandem mass spectrometry using multiple reaction monitoring mass spectrometry (MRM‐MS). Identical substrates suitable for (i) fluorimetric determination of single enzymes and (ii) for MRM‐MS determination of multiple enzymes were synthesized by chemical coupling of alkyl‐umbelliferone building blocks with the corresponding peptidyl‐substrate groups recognized by the target enzyme. Enzymatic determinations were performed both by fluorimetry and MRM‐MS in patients with NCL1, NCL2, and NCL10 and showed good agreement in single assays. Moreover, duplex and triplex determinations were successfully performed for NCL1, NCL2, and NCL10. Specific peptidyl‐(4‐alkyl‐umbelliferone) substrates were also synthesized for mass spectrometric determinations of different cathepsins (cathepsins‐D, ‐F, and ‐B), to provide a differentiation of proteolytic specificities.
Engaging endogenous opioid circuits in pain affective processes
Authors: Kimmey Blake A. , McCall Nora M. , Wooldridge Lisa M. , Satterthwaite Theodore D. , Corder Gregory 
Published: December 2020

AbstractThe pervasive use of opioid compounds for pain relief is rooted in their utility as one of the most effective therapeutic strategies for providing analgesia. While the detrimental side effects of these compounds have significantly contributed to the current opioid epidemic, opioids still provide millions of patients with reprieve from the relentless and agonizing experience of pain. The human experience of pain has long recognized the perceived unpleasantness entangled with a unique sensation that is immediate and identifiable from the first‐person subjective vantage point as “painful.” From this phenomenological perspective, how is it that opioids interfere with pain perception? Evidence from human lesion, neuroimaging, and preclinical functional neuroanatomy approaches is sculpting the view that opioids predominately alleviate the affective or inferential appraisal of nociceptive neural information. Thus, opioids weaken pain‐associated unpleasantness rather than modulate perceived sensory qualities. Here, we discuss the historical theories of pain to demonstrate how modern neuroscience is revisiting these ideas to deconstruct the brain mechanisms driving the emergence of aversive pain perceptions. We further detail how targeting opioidergic signaling within affective or emotional brain circuits remains a strong avenue for developing targeted pharmacological and gene‐therapy analgesic treatments that might reduce the dependence on current clinical opioid options.
Small shards and long distances — three cryptotephra layers from the Nahe palaeolake including the first discovery of Laacher See Tephra in Schleswig‐Holstein (Germany)
Authors: Krüger Sascha , van den Bogaard Christel 
Published: December 2020

ABSTRACTInvestigations of Lateglacial to Early Holocene lake sediments from the Nahe palaeolake (northern Germany) provided a high‐resolution palynological record. To increase the temporal resolution of the record a targeted search for cryptotephra was carried out on the basis of pollen stratigraphy. Three cryptotephra horizons were detected and geochemically identified as G10ka series tephra (a Saksunarvatn Ash), Vedde Ash and Laacher See Tephra. Here we present the first geochemically confirmed finding of the ash from the Laacher See Eruption in Schleswig‐Holstein—extending the so far detected fallout fan of the eruption further to the north‐west. These finds enable direct stratigraphical correlations and underline the potential of the site for further investigations.
Effects of mandibular setback surgery on the sleep architecture and respiratory function (Clinical observations)
Authors: Ogata Kinuko , Tanoue Ryuichiro , Mori Hiroyuki , Kotorii Nozomu , Kusukawa Jingo 
Published: December 2020

AbstractCephalometric analyses and full channel laboratory‐based polysomnography (PSG) were performed to clarify the relationship between mandibular setback surgery and the respiratory function at sleep and the sleep architecture. Thirty‐nine Japanese adults (male, n = 13; female, n = 26) with skeletal Class Ⅲ malocclusion who were treated with mandibular setback surgery were examined. All patients underwent lateral cephalography and full PSG before and at more than 6 months after advanced surgery. All radiographs were traced and the measurements were statistically analyzed. The anteroposterior airway width tended to decrease at all sites after mandibular setback, but no significant difference was observed. Among the full PSG data, the 5% oxygen desaturation index (ODI), wake time, and lighter stages of sleep (Stage N1, N2) were statistically significant parameter (P < .05).It was suggested that mandibular setback surgery tended to result in a worse respiratory function at sleep and worse sleep architecture, even if the patient did not develop obstructive sleep apnea syndrome (OSAS).
“I know my body better than you:” patient focus groups to inform a decision aid on oral corticosteroid use during pregnancy
Authors: Palmsten Kristin , Bredesen Dani , JaKa Meghan M. , Kumar Pritika C. , Ziegenfuss Jeanette Y. , Kharbanda Elyse O. 
Published: December 2020

AbstractPurposeThere is unmet need for decision support regarding medication use during pregnancy. We aimed to inform the development of a decision aid on oral corticosteroid (OCS) use during pregnancy through focus groups.MethodsWe invited patients from one health system who had a recent live birth and a condition for which OCSs may be prescribed (ie, asthma or other autoimmune disease) to participate in focus groups. We conducted conventional qualitative content analysis of verbatim transcripts of the focus groups using inductive coding.ResultsThere were 30 participants across five focus groups from May to June 2019. Women endorsed the need for patient‐provider discussions about OCS use during pregnancy in which the provider shares risks and benefits and the patient makes her decision. Furthermore, women generally expressed support for patient‐centered handouts about OCS use during pregnancy that the provider discusses with the patient. When considering whether to take OCSs in pregnancy, women had concerns about: the medication's impact on their baby (eg, miscarriage, birth defects, long‐term effects), themselves (eg, effects on mood, sleep, weight gain), pregnancy complications (eg, preterm birth, increased blood pressure), and lactation. Women wanted information on OCSs (eg, indications, length of treatment, and cost), alternative treatments, and risks of not taking OCSs.ConclusionsWe established patient need for a decision aid on OCS use during pregnancy that providers can discuss with patients. To address patient concerns, the aid should at a minimum describe the medication's impact on baby, including long‐term effects, maternal health, pregnancy complications, and lactation.
Correlates of school bullying victimization among Black/White biracial adolescents: Are they similar to their monoracial Black and White peers?
Authors: Hong Jun Sung , Yan Yueqi , Gonzalez‐Prendes A. Antonio , Espelage Dorothy L. , Allen‐Meares Paula 
Published: December 2020

AbstractGuided by the social‐ecological perspective, we examined familial, peer, and school‐related predictors of bullying victimization among a large sample of U.S. White, Black, and biracial adolescents. Data were drawn from the Health Behavior in School‐aged Children study, drawn from adolescents who self‐identified as White, Black, or biracial. Of the total sample, 3211 were White, 1188 were Black, and 175 were biracial. Adolescents completed measures of bullying victimization, perceptions of family relations, peer relationships, and school connectedness. Biracial students reported more bullying victimization than White and Black students. For biracial adolescents, family affluence off, and negative perceptions of other students were both found to be positively associated with victimization. For Whites, age, difficulty in talking with parents, parents sometimes like me to make my own decision, parents almost never like me to make my own decisions were negatively associated with victimization. On the other hand, talking with friends and negative perceptions of other students were positively associated with victimization. Among Blacks, age, and parents who almost never like me to make my own decisions were negatively associated with victimization. However, a parent who is almost never loving was positively associated with victimization. Implications for future research and school‐based practice are provided.
Effects of in vitro‐induced drug resistance on the virulence of Streptococcus
Authors: Ding Yue‐Xia , Wu Qun , Guo Yan , Li Man , Li Pei‐Feng , Ma Yi , Liu Wen‐Chao 
Published: December 2020

AbstractThis study aimed to evaluate the effects of in vitro‐induced drug resistance on the virulence of Streptococcus. Micro‐dilution method was used to determine the minimal inhibitory concentration (MIC). In vitro‐induced drug resistance was conducted for S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) by gradually increasing the antimicrobial concentration (strains were from IVDC, China). PCR was used to detect the resistance and virulence genes of the strains before and after resistance induction. Colony morphology was observed to compare the physiological and biochemical properties of the strains. A total of 88 clean‐grade Kunming mice (obtained from Inner Mongolia University, Hohhot, China) were used in half of the lethal dose (LD50) test for detecting the changes in virulence of strains. The results showed that S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) developed resistance against seven kinds of antibiotics, respectively. Resistance and virulence genes of CVCC3701 were changed when treated by the Penicillin‐inducing. The growth of the CVCC3701‐PEN was decreased compared to the CVCC3701. Virulence test in mice indicated that the LD50 of CVCC3701 before induction and CVCC3701‐PEN after induction were 5.45 × 106 and 5.82 × 108 CFU/ml, respectively. Compared with the untreated bacteria, the bacterial virulence was reduced 1.1 × 102 times after resistance induction. In conclusion, S. dysgalactiae (CVCC3701) is a susceptible strain of drug resistance to antibiotics, in vitro‐induced drug resistance reduced the virulence of CVCC3701, but the virulence is still existing and also could result in the death of mice. For public health safety, it must be alert to the emergence of drug resistance of Streptococcus in animal production.
Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors
Authors: Dageforde Leigh Anne , Vachharajani Neeta , Tabrizian Parissa , Agopian Vatche , Halazun Karim , Maynard Erin , Croome Kristopher , Nagorney David , Hong Johnny C. , Lee David , Ferrone Cristina , Baker Erin , Jarnagin William , Hemming Alan , Schnickel Gabriel , Kimura Shoko , Busuttil Ronald , Lindemann Jessica , Florman Sander , Holzner Matthew L. , Srouji Rami , Najjar Marc , Yohanathan Lavanya , Cheng Jane , Amin Hiral , Rickert Charles A. , Yang Ju Dong , Kim Joohyun , Pasko Jennifer , Chapman William C. , Majella Doyle Maria B. 
Published: December 2020

BACKGROUND:
Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA.

STUDY DESIGN:
Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis.

RESULTS:
Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001).

CONCLUSIONS:
Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.
Narrowband Magnetosonic Waves Near the Lower Hybrid Resonance Frequency in the Inner Magnetosphere: Wave Properties and Excitation Conditions
Authors: Ouyang Zhihai , Yuan Zhigang , Yu Xiongdong , Yao Fei 
Published: December 2020

AbstractIn this study, the excitation of narrowband fast magnetosonic (MS) waves near the lower hybrid resonance frequency (fLHR) has been investigated with observations from Van Allen Probes mission and linear growth theory. A typical wave event is first examined to show that these waves can be excited through linear instabilities driven by partial shell distributions of protons. Then it is found that these narrowband MS waves from 188 wave events observed by the Van Allen Probe A between January 1, 2013 to December 31, 2015 have central frequencies around 0.7fLHR with a bandwidth of 0.2fLHR. In addition, these waves are observed mainly in the dayside and dusk sectors outside the plasmapause, which is different from previously reported results. Moreover, the simultaneously observed energetic protons during wave activities show that the ratios of the ring speed Vr to the Alfvén speed VA mainly fall into the range of 0.8 < Vr/VA < 1, and this preferred condition for excitations of narrowband MS waves near fLHR is also verified by a parameter analysis of calculating linear wave growth rates combined with wave observations.
Van Allen Belt Punctures and Their Correlation With Solar Wind, Geomagnetic Activity, and ULF Waves
Authors: Joseph J. , Jaynes A. N. , Baker D. N. , Li X. , Kanekal S. G. 
Published: December 2020

AbstractWe investigate the rare events of sudden appearances of relativistic electrons (>700 keV), which are normally confined to the Van Allen belts, in the slot region. The frequency of occurrence of these events is on average 1–2 per year. To cope with the scarcity of events, in this study, we examine 21 years of trapped relativistic electron fluxes available from the POES and MetOp Space Environment Monitor (SEM‐2). Our statistical analysis shows that these events can occur even during moderate geomagnetic activity. Occurrence of these events correlates with high‐speed solar winds or interplanetary coronal mass ejections depending on the phase of the solar cycle. A strong correlation of these events is found with ultra‐low frequency (ULF) wave activity, which can be used to predict these events with more than 75% accuracy.
Capability of Superspheroids for Modeling PARASOL Observations Under Dusty‐Sky Conditions
Authors: Lin W. , Bi L. , Weng F. , Li Z. , Dubovik O. 
Published: December 2020

AbstractA comprehensive dust‐particle geometry model is highly required for accurate computations of optical parameters in radiative transfer simulations and relevant remote sensing applications. In this study, a superspheroidal model is proposed for simulating polarized radiation at the top of the atmosphere (TOA) under dusty‐sky conditions. The superspheroidal model has one more degree of freedom than the spheroidal model. Sensitivity studies are first conducted to investigate how the additional freedom in the superspheroidal dust model affects the polarized signals at the TOA followed by an examination of the impact of particle size, complex refractive index, and surface properties on these polarized signals. The applicability of the superspheroidal model is then assessed for 11 selected dust events in three main dust source regions (namely, North Africa, Middle East, and the Taklamakan Desert). Specifically, the normalized polarized radiance as observed by the Polarization and Anisotropy of Reflectances for Atmospheric Sciences coupled with Observations from a Lidar (PARASOL) are compared with simulations from an adding‐doubling vector radiative transfer model. It is found that the concave superspheroidal model with large roundness parameters achieves favorable performances in fitting the angular distribution of the PARASOL polarized radiance. The optimal roundness parameter is found to be 2.6–3.0 and is consistent with recent comparison of the simulated scattering matrices and their laboratory measurement counterparts. These findings support the potential applicability of the superspheroidal model for polarized remote sensing applications.