bluuebunny/crossref_metadata_2025_split huggingface dataset:
219 CD47 and phosphatidylserine contribute to the interaction between antigen presenting cells and the allogeneic cell-based relapse vaccine DCP-001
Authors: Zuo Haoxiao , Singh Satwinder Kaur , Lierop Marie-José Van , Kaspers Jorn , Bos Remco , Kamermans Alwin , Vries Helga E de , Gruijl Tanja de , Kruisbeek Ada , Manting Erik , Singh Satwinder Kaur 
Published: November 2021

BackgroundDCP-001 is a cancer relapse vaccine derived from the DCOne® human leukemic cell line. During manufacturing, DCOne® cells are shifted towards a mature dendritic cell (mDC) phenotype, combining an endogenous tumor antigen repertoire (e.g. WT-1, RHAMM and PRAME) with a mDC costimulatory profile and providing the basis for the highly immunogenic vaccine DCP-001. In a phase I clinical study in acute myeloid leukemia (AML), DCP-001 demonstrated to be safe and to induce multifunctional antitumor immune responses.1 It has also been reported that DCP-001 induces antitumor immunity against multiple myeloma cells in peripheral blood mononuclear cells (PBMC) from multiple myeloma patients and that DCP-001 antigenic material is transferred to host antigen presenting cells (APC), possibly via extracellular vesicles.2 However, the possibility of direct interactions between DCP-001 and host APC has not yet been investigated.MethodsTo further elucidate the mode of action of DCP-001, we studied the interactions of DCP-001 with human PBMC and isolated immature monocyte-derived DCs (iMoDC) in in vitro co-culture studies. A human skin explant model was used to determine uptake of DCP-001 by migrating skin DCs after intradermal injection.ResultsWe found that DCP-001 stimulates the secretion of various proinflammatory cytokines (IL-1β, GM-CSF, IFN-γ, IL-2, TNF-α, and IL-6) and chemokines (IL-8 and RANTES) in PBMC. In addition, we demonstrate that DCP-001 is efficiently taken up by iMoDC via direct cell-cell interactions and that this phagocytic process is influenced by ”eat-me” and ”don’t eat me” signaling pathways. Blocking of the ”eat-me” signals calreticulin and phosphatidylserine inhibited the uptake of DCP-001, whereas blockade of the ”don’t eat me” signal CD47 enhanced DCP-001 uptake. After intradermal injection of DCP-001 in an ex-vivo human skin model, its uptake by skin-emigrating DCs was demonstrated as well as simultaneous activation of these DCs.ConclusionsOur data suggest a key role for host antigen presenting cells in the triggering of immune responses upon DCP-001 vaccination. In addition, the data provide rationale for potential combination therapies based on DCP-001 and inhibitors of the CD47 pathway.Referencesvan de Loosdrecht AA, et al. A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia. Cancer Immunol Immunother 2018;67(10):1505–1518.Leaf RK, et al. DCOne as an allogeneic cell-based vaccine for multiple myeloma. J Immunother 2017;40(9):315–322.
292 Ex vivo profiling of PD-1 blockade using an organotypic tissue slice model in solid tumors
Authors: Ding Lina , Sullivan Kristin , Zhou Chensheng , Trillo-Tinoco Jimena , Lewin Anne , King Catherine , Nelson David , Chen Benjamin , Bowden Michaela 
Published: November 2021

BackgroundTumor explant models provide a powerful ex vivo tool to evaluate complex biological mechanisms in a controlled environment. Ex vivo models retain much of the original tumor biology, heterogeneity, and tumor microenvironment, and therefore provide a useful preclinical platform and functional approach to assess drug responses rapidly and directly.MethodsTo explore mechanisms of resistance to cancer immunotherapy, we established an organotypic tissue slice Air-Liquid Interface (ALI) ex vivo system utilizing surgical tumor specimens from patients to assess the impact of the clinically utilized anti-PD-1 antibody nivolumab (OPDIVO). In the present study, we built a real-world patient cohort comprised of six tumor types: non-small cell lung cancer, melanoma, pancreatic ductal adenocarcinoma, breast cancer, prostate cancer, and colorectal cancer. We assessed tissue morphology, histology, PD-L1 IHC (CPS and TPS), CD8 T cell topology, proliferation in the tumor and stromal compartments, and secretome profiling.ResultsOur tumor slice model highly recapitulated features of the original tumor, including tumor architecture, immune phenotypes, and the prognostic markers. To identify responses to aPD-1 treatment, we compared baseline values for the cultured tumor slices with values at different timepoints post treatment. Secretome profiling of tissue explant supernatants using a panel of 94 analytes, revealed alterations to cytokines produced in the tumor microenvironment in response to aPD-1 treatment. We found that soluble expression patterns were associated with T-cell patterns (inflamed, excluded and desert) and PD-L1 score (CPS and TPS) in tumor tissues. These cytokines mediate critical functions across the immune cell cycle. Ongoing efforts to characterize T cell activation, exhaustion, tumor intrinsic responses and microenvironment composition using Imaging Mass Cytometry will be presented.ConclusionsIn this study, we demonstrated the feasibility of using fresh, surgically resected human tumors to test aPD-1 responses in an ex vivo system. Further, this model system has the potential to drive discovery and translational efforts by evaluating mechanisms of resistance to cancer immunotherapy and evaluate new single agent or combination therapies in the ex vivo setting.
380 GS-3583, a novel FLT3 agonist Fc fusion protein, expands conventional dendritic cells in healthy volunteers
Authors: Rajakumaraswamy Nishanthan , Dauki Anees , Kuhne Michelle , Trowe Torsten , Weng Winnie , Lin Kai-Wen , Elboudjwarej Emon , Carr Brian , Worth Angela , Vashishtha Anshu , Schwabe Christian , Othman Ahmed 
Published: November 2021

BackgroundConventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T cells and their recruitment to tumor microenvironment (TME). However, cDC1s are often underrepresented in the TME. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L), a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to expansion of cDC1s in the periphery which can then be recruited into the TME. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T cell mediated anti-tumor activity. We sought to evaluate the pharmacodynamic (PD) effect of a single dose of GS-3583 in healthy volunteers alongside its safety. Herein, we present the updated results of the study.MethodsThis was a first-in-human, placebo-controlled study of GS-3583 in healthy volunteers to evaluate the safety, pharmacokinetics (PK), and PD of escalating single doses (ranging from 75 micrograms to 2000 micrograms) of GS-3583. The study was blinded to the subjects and the investigator. Each dose cohort enrolled 8–12 healthy subjects who received GS-3583 or placebo as single IV infusion at 3:1 ratio. Subjects were observed in the phase 1 unit for 15 days and then for 12 weeks as outpatients. As part of the PD evaluation, we investigated the changes in the number of cDC1 and cDC2 cells.ResultsAs of 2nd July 2021, selected safety, PK and PD data from all 4 cohorts were available. GS-3583 was well tolerated and all subjects had been discharged. To date, there have been no serious or grade 3 or higher adverse events. Preliminary PK analysis suggested dose-dependent increase in GS-3583 exposure (AUC and Cmax). Preliminary PD analysis shows that administration of GS-3583 resulted in temporary, dose-dependent increases in cDC1/cDC2 cells that peaked between days 5–11 (higher doses resulted in later peaks) and returned to baseline within 3 weeks of drug administration (table 1, figure 1).Abstract 380 Table 1Selected subject characteristics and pharmacodynamic resultsAbstract 380 Figure 1A) Comparison of cDC1 cell quantitative changes in cohorts 1–4; B) Comparison of cDC2 cell quantitative changes in cohorts 1–4ConclusionsGS-3583 infusion was well tolerated and induced dose dependent expansion of dendritic cells in the periphery in healthy volunteers. In patients with cancer, this increase in dendritic cells can be utilized to enhance anti-tumor therapeutic effects of immuno-oncology therapies.AcknowledgementsFunding provided by Gilead Sciences, Inc.Ethics ApprovalThe study received study site IRB/Ethics Committee approval prior to enrollment of subjects.
Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage
Authors: Liu Hanhan , Schwarting Julian , Terpolilli Nicole Angela , Nehrkorn Kathrin , Plesnila Nikolaus 
Published: November 2021

Background and Purpose:

Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia resulting in high acute mortality and severe chronic neurological deficits. Spasms of the pial and intraparenchymal microcirculation (microvasospasms) contribute to acute cerebral ischemia after SAH; however, the underlying mechanisms remain unknown. We hypothesize that free iron (Fe
3+
) released from hemolytic red blood cells into the subarachnoid space may be involved in microvasospasms formation.

Methods:
Male C57BL/6 mice (n=8/group) received 200 mg/kg of the iron scavenger deferoxamine or vehicle intravenously and were then subjected to SAH by filament perforation. Microvasospasms of pial and intraparenchymal vessels were imaged three hours after SAH by in vivo 2-photon microscopy.

Results:
Microvasospasms occurred in all investigated vessel categories down to the capillary level. Deferoxamine significantly reduced the number of microvasospasms after experimental SAH. The effect was almost exclusively observed in larger pial arterioles (>30 µm) covered with blood.

Conclusions:

These results provide proof-of-principle evidence that Fe
3+
is involved in the formation of arteriolar microvasospasms after SAH and that arteriolar and capillary microvasospasms are triggered by different mechanisms. Deciphering the mechanisms of Fe
3+
-induced microvasospasms may result in novel therapeutic strategies for SAH patients.
Miriam Tildesley and the Anthropological Politics of Standardizing Racial Measurements
Authors: Clever Iris 
Published: November 2021

Abstract
This article examines to what extent nationalist and sexist sentiment and international politics shaped attempts to universalize measurement practices in physical anthropology. On the one hand, racial scientists were interested in creating an international community with a universalized methodology and developing a global taxonomy of human races. On the other hand, they chauvinistically guarded their localized practices from outside influences. By following the standardization efforts of British biometrician Miriam Tildesley, a female racial scientist adamant on unifying a research field largely dominated by men from different countries, this article argues that intersecting forces of nationalism, internationalism, and sexism shaped anthropological practices in the early twentieth century.
Islamic Law, Slavery, and Feelings
Authors: de la Puente Cristina 
Published: November 2021

Abstract
This article studies a fourth/tenth-century notarial model to limit and place conditions on (istirʿāʾ) the manumission of an unruly and bad-tempered female slave. The text is part of al-Wathāʾiq wa-l-sijillāt, a notarial manual compiled by Cordoban scholar Ibn al-ʿAṭṭār (d. 399/1009), the earliest edited Andalusi work of this genre. Although it is part of a chapter on slavery and, more specifically, of a section dedicated to the manumission of slaves, it is not a generic notarial text dealing with the manumission of female slaves. The document is not a manumission form, but one that complements and limits a manumission; in fact, its aim is to impede or overturn the process. The article studies this notarial model in three different contexts: (1) Andalusi kutub al-wathāʾiq, (2) Mālikī legal literature on slavery and (3) notarial model reservation testimonies. Even if, at first glance, it appears to be an unusual legal document, when analysing other Mālikī sources we observe that the text is part of a well-documented tradition with widely accepted legal justification. This model is nevertheless exceptional from a procedural point of view because its legal arguments are based on feelings and refer specifically to the slave’s personality, temperament and behaviour as the factors that motivated the legal act.
The Sidama Quest for Self-Rule: The Referendum on Regional Statehood Under the Ethiopian Federation
Authors: Tronvoll Kjetil 
Published: November 2021

Abstract
The Sidama of southern Ethiopia has a long history of struggle to reclaim self-rule, which was lost with the forceful incorporation of their territory into the Ethiopian empire in 1893. With the fall of the military junta in 1991, the new government reconfigured the country into a multinational (ethnic) federation. Years of protests and turmoil led to the consolidation of a nationalist movement demanding the constitutional right to conduct a referendum on the establishment of a separate Sidama regional state under the federation. The process was marred by demonstrations and incidents of violence, but the vote itself was conducted peacefully with an overwhelming 97.7 per cent ‘yes’ vote. Sidama regional state was eventually formed, but the political leadership initially advocating for its establishment was marginalised due to the centralising policies of the federal government party restricting the principles of the constitutional multinational federalism.
Embracing Inclusivity through Pedagogical Practices: Case Studies from Singapore Science Lessons
Authors: Teo Tang Wee , Pua Ching Yee 
Published: November 2021

Abstract
This paper examines the pedagogical practices in three case studies of elementary science lessons that took place in classrooms or laboratories to make connections to the discourse about inclusivity in science teaching. Using the Singapore Teaching Practice as a reference, we analyzed the pedagogical practices enacted during three lessons where specific intervention strategies were undertaken during the lessons to address the needs of students with dyslexia. Using event-oriented inquiry, nine (including one emergent) pedagogical practices were adapted by the science teachers. The findings also suggested differences in the outcomes from enacting the same pedagogical practices in different teaching situations. This study contributes to the literature by offering a situated definition of ‘pedagogical practices’, a dynamic construct in the existing literature, in the context of inclusive education. Suggestions on ways to adapt the nine pedagogical practices to enhance the reflexivity of teachers in inclusive science teaching are offered.
Between Political and Economic Imperialism: Russia’s Shifting Global Strategy
Authors: Matveev Ilya 
Published: November 2021

Abstract
Russia experienced both economic and geopolitical expansion in the 2000s. During this time, the Kremlin and big business worked in tandem to assert Russian influence in post-Soviet space. However, the annexation of Crimea and Russia’s involvement in the war in Eastern Ukraine in 2014 marked a new period that severed the state’s geopolitical strategy and the interests of big capital. While the state continues to engage in open and covert military action, the activity of Russian business abroad has sharply diminished. Relying on David Harvey’s concepts of territorial and capitalist logics of power, the article explores the interplay between political and economic imperialism during Putin’s 20 years in power and situates Russia within today’s global imperialist landscape. I find that the Kremlin’s geopolitical and geoeconomic shift in 2014 can ultimately be explained by the strategic orientation of the country’s leadership, in particular, the deeply ingrained emphasis on security and ‘hard power’. However, the turn away from economic imperialism was also structurally determined by the exhaustion of the country’s economic engine that no longer generates surplus capital in need of a ‘spatial fix’.
Intensification of Tilted Tropical Cyclones over Relatively Cool and Warm Oceans in Idealized Numerical Simulations
Authors: Schecter David A. 
Published: November 2021

Abstract
A cloud-resolving model is used to examine the intensification of tilted tropical cyclones from depression to hurricane strength over relatively cool and warm oceans under idealized conditions where environmental vertical wind shear has become minimal. Variation of the SST does not substantially change the time-averaged relationship between tilt and the radial length scale of the inner core, or between tilt and the azimuthal distribution of precipitation during the hurricane formation period (HFP). By contrast, for systems having similar structural parameters, the HFP lengthens superlinearly in association with a decline of the precipitation rate as the SST decreases from 30° to 26°C. In many simulations, hurricane formation progresses from a phase of slow or neutral intensification to fast spinup. The transition to fast spinup occurs after the magnitudes of tilt and convective asymmetry drop below certain SST-dependent levels following an alignment process explained in an earlier paper. For reasons examined herein, the alignment coincides with enhancements of lower–middle-tropospheric relative humidity and lower-tropospheric CAPE inward of the radius of maximum surface wind speed rm. Such moist-thermodynamic modifications appear to facilitate initiation of the faster mode of intensification, which involves contraction of rm and the characteristic radius of deep convection. The mean transitional values of the tilt magnitude and lower–middle-tropospheric relative humidity for SSTs of 28°–30°C are respectively higher and lower than their counterparts at 26°C. Greater magnitudes of the surface enthalpy flux and core deep-layer CAPE found at the higher SSTs plausibly compensate for less complete alignment and core humidification at the transition time.
Mechanisms of Rainfall Biases in Two CORDEX-CORE Regional Climate Models at Rainfall Peaks over Central Equatorial Africa
Authors: Tamoffo Alain T. , Amekudzi Leonard K. , Weber Torsten , Vondou Derbetini A. , Yamba Edmund I. , Jacob Daniela 
Published: November 2021

Abstract
Two regional climate models (RCMs) participating in the CORDEX–Coordinated Output for Regional Evaluations (CORDEX-CORE) project feature a dipole-type rainfall bias during March–May (MAM) and September–November (SON) over central equatorial Africa (CEA), consisting of positive bias in west central equatorial Africa (WCEA) and negative bias in east central equatorial Africa (ECEA). One is the Regional Model version 2015 (REMO2015) and the other is the fourth version of the Regional Climate Model (RegCM4-v7). RCMs are nested in three Earth system models (ESMs) from phase 5 of the Coupled Model Intercomparison Project (CMIP5), and in the reanalysis ERA-Interim, at ∼25-km spacing grid resolution. This study highlights misrepresented underlying physical processes associated with these rainfall biases through a process-based evaluation. Both RCMs produce a weaker Congo basin cell, associated with a weaker land–ocean zonal surface pressure gradient. Consequently, less water vapor enters the region, and little is transported from WCEA to ECEA, resulting in higher moisture availability in the west than in the east. This leads to an unevenly distributed moisture across the region, favoring a stronger atmospheric instability in WCEA where the moist static energy (MSE) anomalously increases through an enhanced latent static energy (LSE). Moisture arrives at a slower pace in ECEA, associated with the weak cell’s strength. The intensity of ascent motions in response to the orographic constraint is weak to destabilize atmospheric stability in the lower layers, necessary for initiating deep convection. Therefore, the convection is shallow in ECEA related to underestimating the MSE due to the reduced LSE.
Comparative Efficacy of the KTP Laser and Cold Steel in Office-Based Surgery for Oropharyngeal Papilloma
Authors: Ma Jingru , Zhao Xiaoyun , Zhen Ruiqing , Mao Wenjing , Wu Xiufa , Fang Rui , He Peijie , Wei Chunsheng 
Published: November 2021

Objective: This study aims to compare the efficacy of the potassium-titanyl-phosphate (KTP) laser and cold steel surgery in treating oropharyngeal papilloma. Methods: Between 2017 and 2020, we enrolled 242 patients with oropharyngeal papilloma who were treated with either the KTP laser (n = 160) or cold steel surgery (n = 82). Patient charts were reviewed for demographic data (age and gender), pathology, anatomical location of lesions, operative duration, pain rating, residual disease, and recurrence. Results: The oropharyngeal papillomas were successfully removed in all patients, except one with a significant pharyngeal reflex. There was no significant difference in the average time for lesion resection between KTP laser and cold steel group (18.11 ± 13.96 s vs 19.43 ± 16.91 s, P > .05). However, all patients who underwent cold steel surgery experienced bleeding during the operation and required postoperative observation (about 20 min), making the total procedure time longer than that of the KTP laser procedure, which did not cause any intraoperative bleeding or require postoperative observation. After KTP laser treatment, the pain rating was .49 ± .98, whereas after cold steel surgery, it was .74 ± 1.12 ( P = .058). Twenty-five samples were sent for human papillomavirus (HPV) testing, and one tested positive for both HPV 6 and 11 strains, while another tested positive for HPV 16. No residual disease or recurrence was observed at the treatment sites after a long period of follow-up (M = 15.35 ± 10.79 mo; range = 6-39 mo). Conclusion: The KTP laser provided a better hemostasis effect and a good surgical field of vision during the operation, allowing the surgeon to complete the procedure in less time. No significant difference in terms of pain rating, incision recovery, and postoperative recurrence between the KTP laser treatment and cold steel surgery.
Mental Health Effects of Hurricane Sandy on Older Adults
Authors: Corley Samantha S. , Ornstein Katherine A. , Rasul Rehana , Lieberman-Cribbin Wil , Maisel Hayley , Taioli Emanuela , Schwartz Rebecca M. 
Published: November 2021

Objectives To examine whether hurricane exposure, lack of access to medical care (LAMC), and displacement during Hurricane Sandy were associated with PTSD and other mental health (MH) symptoms among older adult New York residents. Methods Participants ( N = 411) were ≥60 years old at the time of survey data collection (1–4 years post-Sandy). Outcomes included PTSD, depression, and anxiety symptoms and stress. Hurricane exposure, displacement, and LAMC were primary predictors. Results Older adults with greater hurricane exposure had increased PTSD, anxiety, and stress symptoms. LAMC had a strong association (ORadj = 4.11) with PTSD symptoms but was not associated with other MH symptoms. Displacement was not associated with MH outcomes. Discussion This is the first study to examine exposure, displacement, and LAMC together and to examine their varying impacts on different MH outcomes among older adults post-hurricane. Findings support the importance of disaster preparedness interventions tailored to the MH needs of community-dwelling older adults.