bluuebunny/crossref_metadata_2025_split huggingface dataset:
RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma
Authors: Zinzani Pier Luigi , Rodgers Thomas , Marino Dario , Frezzato Maurizio , Barbui Anna Maria , Castellino Claudia , Meli Erika , Fowler Nathan H. , Salles Gilles , Feinberg Bruce , Kurukulasuriya Nuwan C. , Tillmanns Sascha , Parche Stephan , Dey Debarshi , Fingerle-Rowson Günter , Ambarkhane Sumeet , Winderlich Mark , Nowakowski Grzegorz S. 
Published: August 2021

Abstract

Purpose:
Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination.

Patients and Methods:
Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide–treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score–based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates. The primary endpoint was investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS).

Results:
Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4–77.5) was observed for the combination therapy versus 34.2% (23.7–46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90–8.14); P &lt; 0.0001]. Higher CR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4–51.4) vs. 13.2% (6.5–22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data.

Conclusions:
RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL.
Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care
Authors: Chakraborty Saptarshi , Ecker Brett L. , Seier Ken , Aveson Victoria G. , Balachandran Vinod P. , Drebin Jeffrey A. , D'Angelica Michael I. , Kingham T. Peter , Sigel Carlie S. , Soares Kevin C. , Vakiani Efsevia , Wei Alice C. , Chandwani Rohit , Gonen Mithat , Shen Ronglai , Jarnagin William R. 
Published: August 2021

Abstract

Purpose:
The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management.

Experimental Design:
The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome.

Results:
Colorectal genomic subtype prediction was primarily influenced by mutations in APC and PIK3CA, tumor mutational burden, and DNA mismatch repair (MMR)–deficiency signature. Pancreatic genomic-subtype prediction was dictated by KRAS gene alterations, particularly KRAS G12D, KRAS G12R, and KRAS G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the MDM2 gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability.

Conclusions:
The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.
Spatial UMAP and Image Cytometry for Topographic Immuno-oncology Biomarker Discovery
Authors: Giraldo Nicolas A. , Berry Sneha , Becht Etienne , Ates Deniz , Schenk Kara M. , Engle Elizabeth L. , Green Benjamin , Nguyen Peter , Soni Abha , Stein Julie E. , Succaria Farah , Ogurtsova Aleksandra , Xu Haiying , Gottardo Raphael , Anders Robert A. , Lipson Evan J. , Danilova Ludmila , Baras Alexander S. , Taube Janis M. 
Published: August 2021

Abstract

Multiplex immunofluorescence (mIF) can detail spatial relationships and complex cell phenotypes in the tumor microenvironment (TME). However, the analysis and visualization of mIF data can be complex and time-consuming. Here, we used tumor specimens from 93 patients with metastatic melanoma to develop and validate a mIF data analysis pipeline using established flow cytometry workflows (image cytometry). Unlike flow cytometry, spatial information from the TME was conserved at single-cell resolution. A spatial uniform manifold approximation and projection (UMAP) was constructed using the image cytometry output. Spatial UMAP subtraction analysis (survivors vs. nonsurvivors at 5 years) was used to identify topographic and coexpression signatures with positive or negative prognostic impact. Cell densities and proportions identified by image cytometry showed strong correlations when compared with those obtained using gold-standard, digital pathology software (R2 &gt; 0.8). The associated spatial UMAP highlighted “immune neighborhoods” and associated topographic immunoactive protein expression patterns. We found that PD-L1 and PD-1 expression intensity was spatially encoded—the highest PD-L1 expression intensity was observed on CD163+ cells in neighborhoods with high CD8+ cell density, and the highest PD-1 expression intensity was observed on CD8+ cells in neighborhoods with dense arrangements of tumor cells. Spatial UMAP subtraction analysis revealed numerous spatial clusters associated with clinical outcome. The variables represented in the key clusters from the unsupervised UMAP analysis were validated using established, supervised approaches. In conclusion, image cytometry and the spatial UMAPs presented herein are powerful tools for the visualization and interpretation of single-cell, spatially resolved mIF data and associated topographic biomarker development.
Characterizing Sex Differences in Physical Frailty Phenotypes in Heart Failure
Authors: Denfeld Quin E. , Habecker Beth A. , Camacho S. Albert , Roberts Davis Mary , Gupta Nandita , Hiatt Shirin O. , Medysky Mary E. , Purnell Jonathan Q. , Winters-Stone Kerri , Lee Christopher S. 
Published: August 2021

Background:
Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this sex difference are poorly understood. The purpose of this study was to characterize sex differences in physical frailty phenotypes in HF.

Methods:
We prospectively enrolled adults with class I–IV HF. Physical frailty was measured with the frailty phenotype criteria. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Body composition was measured using dual-energy x-ray absorptiometry. Simple comparative statistics and stepwise regression modeling were used.

Results:

The average age of the sample (n=115) was 63.6±15.7 years, 49% were women, and 73% had nonischemic cause. Forty-three percent of the sample was physically frail. Women had a 4.6 times greater odds of being physically frail compared with men, adjusting for covariates (odds ratio=4.63 [95% CI, 1.81–11.84],
P
=0.001). Both physically frail men and women were characterized by more type 2 diabetes, higher comorbidity burden, and worse dyspnea symptoms. Physically frail women had significantly worse symptoms compared with non–physically frail women but no difference in body composition characteristics. Physically frail men had significantly lower appendicular muscle mass, higher percent fat, lower hemoglobin, and more depressive symptoms compared with non–physically frail men.

Conclusions:
Women are significantly more likely to be physically frail compared with men in HF. Physical frailty in both women and men is characterized by comorbidities and worse symptoms; physical frailty in men is characterized by worse physiological characteristics.
When Is a Moabite a Moabite? Selectivity, Stereotypes, and Identity in the Gemeindegesetz, Deut. 23:2–9 [Eng 1–8]
Authors: Timmer Daniel C. 
Published: August 2021

Abstract
This article argues that the Gemeindegesetz’s exclusion of Ammonites and Ammonites from the qahal-YHWH, like its inclusion of Edomites and Egyptians, is not based on ethnobiology or essentialist ethnicity. It draws on social identity and stereotyping theory to explore the text’s characterization of these different groups, and proposes that the salience of moral-behavioral features subordinates but does not efface ethnic and other factors. This interpretation is also integrated with approaches to identity for Israelites and non-Israelites elsewhere in Deuteronomy.
Milieux marchands et institutions du commerce : La question du droit d’étape à Mayence de 1797 à 1814
Authors: Garner Guillaume 
Published: August 2021

Résumé
Cet article étudie les débats sur l’abolition du droit d’étape de Mayence et Cologne entre 1797 et 1814. Lorsque les Français ont conquis la rive gauche du Rhin, ils proclament leur intention de libéraliser le commerce et la navigation sur le Rhin, en même temps qu’ils abolissent les privilèges dans les quatre nouveaux départements du Rhin. Ceci a relancé un débat ancien sur le droit d’étape : tandis que les chambres de commerce de Cologne et Mayence le défendent comme un moyen de police de la navigation et du commerce, les milieux marchands de villes allemandes (Francfort, Düsseldorf) et de certaines villes françaises (Coblence) demandent son abolition au nom de la liberté économique et des principes de la Révolution française. L’article analyse les raisons pour lesquelles le gouvernement français maintient et confirme, de la signature de la Convention de l’octroi du Rhin en 1804 jusque 1813, ce qui constitue un privilège.
Impacts of ocean currents on the South Indian Ocean extratropical storm track through the relative wind effect
Authors: Seo Hyodae , Song Hajoon , O’Neill Larry W. , Mazloff Matthew R. , Cornuelle Bruce D. 
Published: August 2021

AbstractThis study examines the role of the relative wind (RW) effect (wind relative to ocean current) in the regional ocean circulation and extratropical storm track in the South Indian Ocean. Comparison of two high-resolution regional coupled model simulations with/without the RW effect reveals that the most conspicuous ocean circulation response is the significant weakening of the overly energetic anticyclonic standing eddy off Port Elizabeth, South Africa, a biased feature ascribed to upstream retroflection of the Agulhas Current (AC). This opens a pathway through which the AC transports the warm and salty water mass from the subtropics, yielding marked increases in sea surface temperature (SST), upward turbulent heat flux (THF), and meridional SST gradient in the Agulhas retroflection region. These thermodynamic and dynamic changes are accompanied by the robust strengthening of the local low-tropospheric baroclinicity and the baroclinic wave activity in the atmosphere. Examination of the composite lifecycle of synoptic-scale storms subjected to the high THF events indicates a robust strengthening of the extratropical storms far downstream. Energetics calculations for the atmosphere suggest that the baroclinic energy conversion from the basic flow is the chief source of increased eddy available potential energy, which is subsequently converted to eddy kinetic energy, providing for the growth of transient baroclinic waves. Overall, the results suggest that the mechanical and thermal air-sea interactions are inherently and inextricably linked together to substantially influence the extratropical storm tracks in the South Indian Ocean.
Direct Solar Viewing Calibration Concept for Future CERES-, GERB-, or Libera-Type Earth Orbital Climate Missions
Authors: Matthews G. 
Published: August 2021

Abstract
Better predictions of global warming can be enabled by tuning legacy and current computer simulations to Earth radiation budget (ERB) measurements. Since the 1970s, such orbital results exist, and the next-generation instruments such as one called “Libera” are in production. Climate communities have requested that new ERB observing system missions like these have calibration accuracy obtaining significantly improved calibration SI traceability and stability. This is to prevent untracked instrument calibration drifts that could lead to false conclusions on climate change. Based on experience from previous ERB missions, the alternative concept presented here utilizes directly viewing solar calibration, for cloud-size Earth measurement resolution at <1% accuracy. However, it neglects complex already used calibration technology like solar diffusers and onboard lights, allowing new lower cost/risk unconsidered spectral characterizing concepts to be introduced for today’s technology. Also in contrast to near future ERB concepts already being produced, this enables in-flight wavelength dependent calibration of Earth-observing telescopes using direct solar views, through narrowband filters continuously characterized on-orbit.
Snowfall Model Validation Using Surface Observations and an Optimal Estimation Snowfall Retrieval
Authors: Hellmuth Franziska , Kokkvoll Engdahl Bjørg Jenny , Storelvmo Trude , David Robert O. , Cooper Steven J. 
Published: August 2021

AbstractIn the winter, orographic precipitation falls as snow in the mid- to high latitudes where it causes avalanches, affects local infrastructure, or leads to flooding during the spring thaw. We present a technique to validate operational numerical weather prediction model simulations in complex terrain. The presented verification technique uses a combined retrieval approach to obtain surface snowfall accumulation and vertical profiles of snow water at the Haukeliseter test site, Norway. Both surface observations and vertical profiles of snow are used to validate model simulations from the Norwegian Meteorological Institute’s operational forecast system and two simulations with adjusted cloud microphysics. Retrieved surface snowfall is validated against measurements conducted with a double-fence automated reference gauge (DFAR). In comparison, the optimal estimation snowfall retrieval produces +10.9% more surface snowfall than the DFAR. The predicted surface snowfall from the operational forecast model and two additional simulations with microphysical adjustments (CTRL and ICE-T) are overestimated at the surface with +41.0%, +43.8%, and +59.2%, respectively. Simultaneously, the CTRL and ICE-T simulations underestimate the mean snow water path by −1071.4% and −523.7%, respectively. The study shows that we would reach false conclusions only using surface accumulation or vertical snow water content profiles. These results highlight the need to combine ground-based in situ and vertically profiling remote sensing instruments to identify biases in numerical weather prediction.
Management of small perforated corneal ulcers: Training model in mammalian eye to enhance surgical skills of residents
Authors: Bafna Rahul Kumar , Tripathi Manasi , Asif Mohamed Ibrahime , Agarwal Rinky , Lata Suman , Kumar Sushil , Sharma Namrata 
Published: August 2021

Purpose: To demonstrate a training technique on the mammalian eye for optimum Cyanoacrylate Tissue adhesive application in cases of perforated corneal ulcers. Methods: A full-thickness defect simulating a perforation was created on the goat’s eye cornea to teach the technique of cyanoacrylate glue application in cases of corneal perforations to novice surgeons. Results: This training model on the mammalian eye was tested by 10 residents at our centre. All the 10 candidates involved in our series were newly joined Cornea fellows with proficient skill in cataract surgeries and minor ophthalmic procedures such as suture removal, chalazion excision, pterygium removal and administration of an intravitreal injection. None of the candidates had prior experience of corneal surgeries. Each resident made an average of 4.4 attempts to seal the corneal defect, obtain a regular corneal surface and form the anterior chamber. Conclusion: This training model helps in mastering one of the skills of corneal surgeries.
Emotional Intelligence, Organizational Social Architecture, and Black Male Leadership
Authors: Rudel Enin M. , Derr Brandi , Ralston Miranda , Williams Terrence B. , Young Aprille 
Published: August 2021

The Problem The leadership of Black male leaders is an under-studied topic in the leadership literature and more so in the field of human resource development. Moreover, traditional and contemporary leadership theories are universalized and have not adequately captured social and emotional issues encountered by leaders within their social identity location. A closer examination of this phenomenon is needed to close the gap in the human resource development literature as well as contemporary leadership theory. The Solution A qualitative study was used to examine the experiences of Black male leaders in an organizational setting using the frameworks of emotional intelligence and social architecture. Findings suggest that emotional intelligence explains why Black male leaders desire mentorship, need increased organizational support for psychological safety, use specialized strategies to deal with social and emotional distress, face barriers to acculturation into the workplace culture, draw on authentic leadership skills to face obstructions to leadership, and use code switching to navigate multiple identities. Recommendations are made for more inclusive mentoring programs that consider the needs of this underrepresented group. The Stakeholders HRD researchers, scholars, educators, practitioners, organizational leaders and others involved in diversity, equity, and inclusion work.
Improvements in lung function with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler versus dual therapies in patients with COPD: a sub-study of the ETHOS trial
Authors: Rabe Klaus F. , Martinez Fernando J. , Singh Dave , Trivedi Roopa , Jenkins Martin , Darken Patrick , Aurivillius Magnus , Dorinsky Paul 
Published: August 2021

Background: In the phase III, 52-week ETHOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF), at two inhaled corticosteroid dose levels, resulted in significantly lower moderate/severe exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) and budesonide/formoterol fumarate (BFF). Here, we report results from the ETHOS pulmonary function test (PFT) sub-study, which assessed lung function in a subset of ETHOS patients. Methods: ETHOS (NCT02465567) was a randomized, double-blind, multi-center, parallel-group study in patients with moderate to very severe COPD who had experienced ⩾1 moderate/severe exacerbation in the previous year. Patients received BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF 18/9.6 µg, or BFF 320/9.6 µg twice daily via a single metered dose Aerosphere inhaler for 52 weeks. A subset of patients participated in the 4-hour PFT sub-study; primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV1) versus GFF and FEV1 area under the curve from 0 to 4 hours (AUC0–4) versus BFF at week 24. Results: The PFT modified intent-to-treat population included 3088 patients (mean age 64.4 years; mean reversibility post-albuterol 16.7%; mean post-albuterol FEV1% predicted 42.8). BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved morning pre-dose trough FEV1 at week 24 versus GFF ( p ⩽ 0.0035 for both). Improvements in trough FEV1 were also observed at week 52 for BGF 320/18/9.6 µg and 160/18/9.6 µg versus GFF ( p ⩽ 0.0005 for both). For FEV1 AUC0–4 at week 24, BGF 320/18/9.6 µg and 160/18/9.6 µg showed significant improvements versus BFF ( p < 0.0001 for both). Improvements were maintained at week 52 ( p < 0.0001). Conclusions: BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved trough FEV1 versus GFF and FEV1 AUC0–4 versus BFF at week 24. The lung function benefits with both doses of BGF were maintained following 52 weeks of treatment. The reviews of this paper are available via the supplemental material section.
Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma
Authors: Thudium Mueller Karen , Grupp Stephan A. , Maude Shannon L. , Levine John E. , Pulsipher Michael A. , Boyer Michael W. , August Keith J. , Myers G. Doug , Tam Constantine S. , Jaeger Ulrich , Foley Stephen Ronan , Borchmann Peter , Schuster Stephen J. , Waller Edmund K. , Awasthi Rakesh , Potthoff Bernd , Warren Andy , Waldron Edward R. , McBlane Fraser , Chassot-Agostinho Andrea , Laetsch Theodore W. 
Published: August 2021

AbstractTisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-γ in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 &lt; 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses &lt;1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.