bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B‐cell lymphoma
Authors: Herrera Alex F. , Goy Andre , Mehta Amitkumar , Ramchandren Radhakrishnan , Pagel John M. , Svoboda Jakub , Guan Shanhong , Hill John S. , Kwei Kevin , Liu Emily A. , Phillips Tycel 
Published: October 2019

AbstractThis phase 1b/2, multicenter, open‐label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL). Patients were treated with once‐daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28‐day cycles in phase 1b without dose‐limiting toxicities, confirming the phase 2 dosing. Sixty‐one patients with FL (n = 27), germinal center B‐cell (GCB) DLBCL (n = 16), non‐GCB DLBCL (n = 16), and unspecified DLBCL (n = 2) were treated. Overall response rate (ORR) was 25% in all patients, 26% in patients with FL, 13% in patients with GCB DLBCL, and 38% in patients with non‐GCB DLBCL. Overall, median progression‐free survival was 4.6 months and median overall survival was 18.1 months; both were longer in patients with FL than in patients with DLBCL. The most frequent treatment‐emergent adverse events (AEs) in patients with FL and DLBCL, respectively, were diarrhea (16 [59%]; 16 [47%]), fatigue (12 [44%]; 16 [47%]), nausea (9 [33%]; 12 [35%]), peripheral edema (7 [26%]; 13 [38%]), decreased appetite (8 [30%]; 11 [32%]), neutropenia (6 [22%]; 11 [32%]), and vomiting (5 [19%]; 12 [35%]). Investigator‐defined immune‐related AEs were reported in 12/61 (20%) patients. Correlative analyses were conducted but did not identify any conclusive biomarkers of response. In FL, GCB DLBCL, and non‐GCB DLBCL, ibrutinib plus durvalumab demonstrated similar activity to single‐agent ibrutinib with the added toxicity of the PD‐L1 blockade; the combination resulted in a safety profile generally consistent with those known for each individual agent.
Arginine‐enveloped virus inactivation and potential mechanisms
Authors: Meingast Christa , Heldt Caryn L. 
Published: October 2019

AbstractArginine synergistically inactivates enveloped viruses at a pH or temperature that does little harm to proteins, making it a desired process for therapeutic protein manufacturing. However, the mechanisms and optimal conditions for inactivation are not fully understood, and therefore, arginine viral inactivation is not used industrially. Optimal solution conditions for arginine viral inactivation found in the literature are high arginine concentrations (0.7–1 M), a time of 60 min, and a synergistic factor of high temperature (≥40°C), low pH (≤pH 4), or Tris buffer (5 mM). However, at optimal conditions full inactivation does not occur over all enveloped viruses. Enveloped viruses that are resistant to arginine often have increased protein stability or membrane stabilizing matrix proteins. Since arginine can interact with both proteins and lipids, interaction with either entity may be key to understanding the inactivation mechanism. Here, we propose three hypotheses for the mechanisms of arginine induced inactivation. Hypothesis 1 describes arginine‐induced viral inactivation through inhibition of vital protein function. Hypothesis 2 describes how arginine destabilizes the viral membrane. Hypothesis 3 describes arginine forming pores in the virus membrane, accompanied by further viral damage from the synergistic factor. Once the mechanisms of arginine viral inactivation are understood, further enhancement by the addition of functional groups, charges, or additives may allow the inactivation of all enveloped viruses in mild conditions.
Carbon‐ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: Prospective observational study
Authors: Takayasu Yukihiro , Kubo Nobuteru , Shino Masato , Nikkuni Osamu , Ida Shota , Musha Atsushi , Takahashi Katsumasa , Hirato Junko , Shirai Katsuyuki , Saitoh Jun‐ichi , Yokoo Satoshi , Chikamatsu Kazuaki , Ohno Tatsuya , Nakano Takashi ,   for the Working Group on Head and Neck Tumors
Published: October 2019

AbstractThis study aimed to evaluate the efficacy of carbon‐ion radiotherapy in combination with chemotherapy using dacarbazine, nimustine, and vincristine (DAV therapy) in mucosal melanoma. Twenty‐one patients with clinically localized mucosal melanoma of the head and neck were enrolled. The primary endpoint was 3‐year overall survival (OS). Secondary endpoints included local control, progression‐free survival (PFS), and adverse event occurrence. Carbon‐ion radiotherapy with a dose of 57.6‐64.0 Gy (relative biological effectiveness) in 16 fractions was delivered concurrently with DAV therapy, and 2 cycles of adjuvant DAV therapy were administered every 6 weeks. The median follow‐up periods were 15.5 months for all patients, and 31.2 months for 12 surviving patients. All patients had locally advanced T4a or T4b disease in the rhino‐sinus area. In 16 patients (76.2%), 3 cycles of planned DAV therapy were completed. The 3‐year OS and PFS rates were 49.2% and 37.0% respectively. The 3‐year local control rate was 92.3%. Eleven patients (52%) developed distant metastasis, which was the most frequent pattern of the first failure. Commonly presenting acute grade 2‐3 toxicities associated with radiotherapy and chemotherapy were mucositis (11 patients [53%]) and leukopenia (9 patients [43%]), which improved with conservative therapy. None of the patients developed grade 3 or greater late toxicities. Carbon‐ion radiotherapy in combination with DAV therapy led to excellent local control for advanced mucosal melanoma within acceptable toxicities. The efficacy of additional DAV therapy in improving survival was weaker than expected as distant metastases still occurred frequently. Trial registration no. UMIN000007939.
Anaerobic Biodegradability of Digestates – Influence of and Correlations for Klason lignin
Authors: Mächtig Torsten , Casaretto René , Moschner Christian R. , Born Jens , Holm-Nielsen Jens Bo , Hartung Eberhard 
Published: October 2019

AbstractAppropriate evaluation of the process performance of biogas plants needs to consider the anaerobic biodegradability of the used biomass. Anaerobic biodegradability is limited by lignin, which is part in most substrates and, by extension, in digestates of biogas plants. Previous research has shown that the content of acid detergent lignin (ADL) in digestates can be predicted from measured gross calorific values (GCVs). The correlation of GCV of 34 digestate samples to an alternative measure for lignin, the Klason lignin (KL), is evaluated as well as the correlation of KL content and other chemical constituents to residual biomethane potential (BMP). Results indicate a very low correlation of chemical composition to GCV and BMP. A correlation of GCV to BMP was not observable. The results let conclude that evaluation of anaerobic biodegradability of digestates by measuring KL or predicting KL from GCV is not productive.
Validity and efficiency in analyzing ordinal responses with missing observations
Authors: She Xichen , Wu Changbao 
Published: October 2019

AbstractThis article addresses issues in creating public‐use data files in the presence of missing ordinal responses and subsequent statistical analyses of the dataset by users. The authors propose a fully efficient fractional imputation (FI) procedure for ordinal responses with missing observations. The proposed imputation strategy retrieves the missing values through the full conditional distribution of the response given the covariates and results in a single imputed data file that can be analyzed by different data users with different scientific objectives. Two most critical aspects of statistical analyses based on the imputed data set, validity and efficiency, are examined through regression analysis involving the ordinal response and a selected set of covariates. It is shown through both theoretical development and simulation studies that, when the ordinal responses are missing at random, the proposed FI procedure leads to valid and highly efficient inferences as compared to existing methods. Variance estimation using the fractionally imputed data set is also discussed.The Canadian Journal of Statistics48: 138–151; 2020 © 2019 Statistical Society of Canada
deltaTE: Detection of Translationally Regulated Genes by Integrative Analysis of Ribo‐seq and RNA‐seq Data
Authors: Chothani Sonia , Adami Eleonora , Ouyang John F. , Viswanathan Sivakumar , Hubner Norbert , Cook Stuart A. , Schafer Sebastian , Rackham Owen J. L. 
Published: October 2019

AbstractRibosome profiling quantifies the genome‐wide ribosome occupancy of transcripts. With the integration of matched RNA sequencing data, the translation efficiency (TE) of genes can be calculated to reveal translational regulation. This layer of gene‐expression regulation is otherwise difficult to assess on a global scale and generally not well understood in the context of human disease. Current statistical methods to calculate differences in TE have low accuracy, cannot accommodate complex experimental designs or confounding factors, and do not categorize genes into buffered, intensified, or exclusively translationally regulated genes. This article outlines a method [referred to as deltaTE (ΔTE), standing for change in TE] to identify translationally regulated genes, which addresses the shortcomings of previous methods. In an extensive benchmarking analysis, ΔTE outperforms all methods tested. Furthermore, applying ΔTE on data from human primary cells allows detection of substantially more translationally regulated genes, providing a clearer understanding of translational regulation in pathogenic processes. In this article, we describe protocols for data preparation, normalization, analysis, and visualization, starting from raw sequencing files. © 2019 The Authors.Basic Protocol: One‐step detection and classification of differential translation efficiency genes using DTEG.RAlternate Protocol: Step‐wise detection and classification of differential translation efficiency genes using RSupport Protocol: Workflow from raw data to read counts
Ocean warming and acidification alter the behavioral response to flow of the sea urchin Paracentrotus lividus
Authors: Cohen‐Rengifo Mishal , Agüera Antonio , Bouma Tjeerd , M'Zoudi Saloua , Flammang Patrick , Dubois Philippe 
Published: October 2019

AbstractOcean warming (OW) and acidification (OA) are intensively investigated as they pose major threats to marine organism. However, little effort is dedicated to another collateral climate change stressor, the increased frequency, and intensity of storm events, here referred to as intensified hydrodynamics. A 2‐month experiment was performed to identify how OW and OA (temperature: 21°C; pHT: 7.7, 7.4; control: 17°C‐pHT7.9) affect the resistance to hydrodynamics in the sea urchin Paracentrotus lividus using an integrative approach that includes physiology, biomechanics, and behavior. Biomechanics was studied under both no‐flow condition at the tube foot (TF) scale and flow condition at the individual scale. For the former, TF disk adhesive properties (attachment strength, tenacity) and TF stem mechanical properties (breaking force, extensibility, tensile strength, stiffness, toughness) were evaluated. For the latter, resistance to flow was addressed as the flow velocity at which individuals detached. Under near‐ and far‐future OW and OA, individuals fully balanced their acid‐base status, but skeletal growth was halved. TF adhesive properties were not affected by treatments. Compared to the control, mechanical properties were in general improved under pHT7.7 while in the extreme treatment (21°C‐pHT7.4) breaking force was diminished. Three behavioral strategies were implemented by sea urchins and acted together to cope with flow: improving TF attachment, streamlining, and escaping. Behavioral responses varied according to treatment and flow velocity. For instance, individuals at 21°C‐pHT7.4 increased the density of attached TF at slow flows or controlled TF detachment at fast flows to compensate for weakened TF mechanical properties. They also showed an absence of streamlining favoring an escaping behavior as they ventured in a riskier faster movement at slow flows. At faster flows, the effects of OW and OA were detrimental causing earlier dislodgment. These plastic behaviors reflect a potential scope for acclimation in the field, where this species already experiences diel temperature and pH fluctuations.
High‐throughput compound screen reveals mTOR inhibitors as potential therapeutics to reduce (auto)antibody production by human plasma cells
Authors: Tuijnenburg Paul , aan de Kerk Daan J. , Jansen Machiel H. , Morris Ben , Lieftink Cor , Beijersbergen Roderick L. , van Leeuwen Ester M.M. , Kuijpers Taco W. 
Published: October 2019

AbstractAntibody production by the B cell compartment is a crucial part of the adaptive immune response. Dysregulated antibody production in the form of autoantibodies can cause autoimmune disease. To date, B‐cell depletion with anti‐CD20 antibodies is commonly applied in autoimmunity, but pre‐existing plasma cells are not eliminated in this way. Alternative ways of more selective inhibition of antibody production would add to the treatment of these autoimmune diseases. To explore novel therapeutic targets in signaling pathways essential for plasmablast formation and/or immunoglobulin production, we performed a compound screen of almost 200 protein kinase inhibitors in a robust B‐cell differentiation culture system. This study yielded 35 small cell‐permeable compounds with a reproducible inhibitory effect on B‐cell activation and plasmablast formation, among which was the clinically applied mammalian target of rapamycin (mTOR) inhibitor rapamycin. Two additional compounds targeting the phosphoinositide 3‐kinase‐AKT‐mTOR pathway (BKM120 and WYE‐354) did not affect proliferation and plasmablast formation, but specifically reduced the immunoglobulin production. With this compound screen we successfully applied a method to investigate therapeutic targets for B‐cell differentiation and identified compounds in the phosphoinositide 3‐kinase‐AKT‐mTOR pathway that could specifically inhibit immunoglobulin production only. These drugs may well be explored to be of value in current B‐cell‐depleting treatment regimens in autoimmune disorders.
Internalized equality and protest against injustice: The role of disadvantaged group members’ self‐respect in collective action tendencies
Authors: Renger Daniela , Eschert Silke , Teichgräber Mimke L. , Renger Sophus 
Published: October 2019

AbstractRecent research shows that self‐respect (defined as seeing yourself as a person with equal rights) predicts assertive but not aggressive responses to injustice in interpersonal contexts. The present research focuses on the antecedents of self‐respect and its consequences for collective action tendencies among members of disadvantaged groups. Across three studies (N = 227, N = 454, N = 131) using different contexts and samples (discrimination of Muslims in Germany; women regarding gender inequality), experiences with equality‐based respect (defined as being treated as someone of equal worth) predicted self‐respect. Moreover, across all three studies, self‐respect predicted intentions for cooperative or normative but not support for hostile or non‐normative protest. The results demonstrate the potential of self‐respect for facilitating collective action in the face of injustice while still enabling positive intergroup relations.
Optimization and field application of water jet for coal bed methane stimulation
Authors: Yang Xuelin , He Lipeng , Lu Tingkan , Liu Yanbao , Li Xuelong , Cao Jie , Luo Guang , Yang Huiming 
Published: October 2019

AbstractNowadays, the water jet technique has been more frequently used for coal bed methane stimulation. As the ultimate component of the water jet system, the nozzle has important influence on the rock breaking ability of water jet. To optimize the nozzle, a simplified model for impinging water jet was established. The effects of geometric structure (cylindrical, conical, and conical‐straight) and parameters (outlet diameter d, conical angle α, and length L) on the flow field of the impinging water jet are simulated through computational fluid dynamics software Fluent14.0. Besides, the effects of inlet pressure (Pin) and target distances (S) on the jet dynamics are also discussed based on the simulation results. The results show that the jet dynamic parameters including dynamic pressure, velocity, and impinging pressure vary with different nozzles. The jet dynamic parameters linearly increase with the inlet pressure, while they first increase then decrease with the increase in target distance. Additionally, the optimal nozzle designed based on the numerical simulation was used in the field test, and the results indicate that this technique can effectively improve the gas drainage efficiency.
An die Spitze der Bewegung!
Authors: Vowe Gerhard , Henn Philipp 
Published: October 2019

AbstractOnline‐Medien, Suchmaschinen und soziale Netzwerke verändern längst die politische Kommunikation und damit auch politische Entscheidungsprozesse. Nicht weniger als ein neuer Strukturwandel der Öffentlichkeit vollzieht sich, den es zu gestalten gilt.
Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention
Authors: Spooner Rachel K. , Wiesman Alex I. , Proskovec Amy L. , Heinrichs‐Graham Elizabeth , Wilson Tony W. 
Published: October 2019

AbstractThe ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of “higher order” attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top‐down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention‐reorienting task to investigate top‐down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time–frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60–80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole‐brain voxel‐wise correlations between validity difference scores (i.e., attention reorienting trials—nonreorienting trials) in frontal theta activity and movement‐locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top‐down modulation of movement‐related gamma responses during attentional reorienting and movement execution.
Prospective evaluation of oral premalignant lesions using a multimodal imaging system: a pilot study
Authors: Yang Eric C. , Vohra Imran S. , Badaoui Hawraa , Schwarz Richard A. , Cherry Katelin D. , Jacob Justin , Rodriguez Jessica , Williams Michelle D. , Vigneswaran Nadarajah , Gillenwater Ann M. , Richards‐Kortum Rebecca R. 
Published: October 2019

AbstractBackgroundMultimodal optical imaging, incorporating reflectance and fluorescence modalities, is a promising tool to detect oral premalignant lesions in real‐time.MethodsImages were acquired from 171 sites in 66 patient visits for clinical evaluation of oral lesions. An automated algorithm was used to classify lesions as high‐ or low‐risk for neoplasia. Biopsies were acquired at clinically indicated sites and those classified as high‐risk by imaging, at the surgeon's discretion.ResultsTwenty sites were biopsied based on clinical examination or imaging. Of these, 12 were indicated clinically and by imaging; 58% were moderate dysplasia or worse. Four biopsies were indicated by imaging evaluation only; 75% were moderate dysplasia or worse. Finally, four biopsies were indicated by clinical evaluation only; 75% were moderate dysplasia or worse.ConclusionMultimodal imaging identified more cases of high‐grade dysplasia than clinical evaluation, and can improve detection of high grade precancer in patients with oral lesions.
Favorable modulation of osteoblast cellular activity on Zr‐modified Co–Cr–Mo alloy: The significant impact of zirconium on cell–substrate interactions
Authors: Gong Na , Montes Ivan , Nune Krishna C. , Misra R. Devesh Kumar , Yamanaka Kenta , Mori Manami , Chiba Akihiko 
Published: October 2019

AbstractCobalt‐chromium‐molybdenum alloys exhibit good mechanical properties (yield strength: ~530 MPa, ultimate tensile strength: ~1114 MPa, elongation‐to‐failure: ~47.3%, and modulus: ~227 GPa) and corrosion resistance. In recent years, from the perspective of osseointegration, they are considered to be lower in rank in comparison to the widely used titanium alloys. We elucidate here the significant and favorable modulation of cellular activity of Zr‐modified Co–Cr–Mo alloys. The average grain size of Co–Cr–Mo alloy samples with and without Zr was 104 ± 27 and ~53 ± 11 μm, respectively. The determining role of small addition of Zr (0.04 wt. %) to the Co–Cr–Mo alloys in favorable modulation of cellular activity was accomplished by combining cellular biology and materials science and engineering. Experiments on the influence of Zr addition to Co–Cr–Mo alloys clearly demonstrated that the cell adhesion, spread and cell–substrate interactions were enhanced in the presence of Zr. The spread/growth rate of cells was ~120% on the Co–Cr–Mo alloy and 190% per day on the Co–Cr–Mo–Zr alloy. While the % area covered by the cells increased from ~5.1 to ~33.6% on Co–Cr–Mo alloy and ~19.2 to ~47.8% on Co–Cr–Mo–Zr alloy after 2 and 24 hr of incubation. Similarly, the cell density increased from ~1354 to ~3424 cells/cm2 on Co–Cr–Mo alloy and ~3583 to ~7804 cells/cm2 on Co–Cr–Mo–Zr alloy after 2 and 24 hr of incubation. Additionally, stronger vinculin focal adhesion contact and signals associated with actin stress fibers together with extracellular matrix protein, fibronectin, were noted.