bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A26: Tetravalency endows anti-CD27 antibodies with enhanced co-stimulatory activity and anti-tumour immune responses
Authors: Widdess Marcus A , Chan H. T. Claude , Penfold Christine A , Mockridge C Ian , Inzhelevskaya Tatyana , Metcalfe Hannah J , Cragg Mark S , Al-Shamkhani Aymen 
Published: December 2022

Abstract
Immunostimulatory antibodies targeting co-stimulatory TNFRSF members have shown promise in pre-clinical cancer models, but this has not translated into clinical success, primarily due to lack of efficacy. Oligomerisation of the co-stimulatory molecule CD27 by its trimeric membrane-bound ligand activates NF-κB and AP1 signalling leading to enhanced CD8 T cell responses in both humans and mice. Targeting CD27 with bivalent mAb may lead to sub-optimal receptor oligomerisation and inefficient T cell activation. Here we present a general approach to improve the potency of anti-CD27 mAb. We engineered tetravalent forms of anti-CD27 antibodies targeting both mouse and human CD27 by attaching two additional Fab fragments to the N-terminus of the of the IgG VH domain. These tetravalent mAb had greater avidity to CD27 and were more potent than their bivalent counterparts in stimulating NF-κB activation and T cell proliferation in vitro, with optimal responses requiring antibody crosslinking by FcγRIIb. In addition, confocal microscopy of hCD27-GFP fusion protein expressing Jurkat T cells showed that tetravalent anti-hCD27 mAb triggered receptor clustering more efficiently than the equivalent bivalent mAb, as evidenced by the increased number of receptor clusters on the cell surface. Importantly, tetravalent anti-CD27 mAb induced greater CD8 T cell responses than the bivalent mAb in a vaccination model and was more efficacious in suppressing tumour growth in vivo. This work demonstrates that the agonistic activity of anti-CD27 mAb can be significantly improved by tetravalency and suggest that this approach could be utilised to enhance the therapeutic activity of mAb targeting other members of the TNFRSF.
Citation Format: Marcus A Widdess, H. T. Claude Chan, Christine A Penfold, C Ian Mockridge, Tatyana Inzhelevskaya, Hannah J Metcalfe, Mark S Cragg, Aymen Al-Shamkhani. Tetravalency endows anti-CD27 antibodies with enhanced co-stimulatory activity and anti-tumour immune responses [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A26.
Abstract A53: Intranasal nanoparticulate PLGA cancer vaccine administration prevents secondary lung metastasis
Authors: Donkor Michael A , Choe Jamie , Quinn Byron , Jones Harlan P 
Published: December 2022

Abstract
The lung is one of the most frequent sites of cancer metastasis. Because metastatic lung disease is usually associated with poor survivorship, decreasing secondary lung metastasis will decrease morbidity and mortality associated with cancer. Mitigating tumor immunosurveillance at metastatic sites such as the lung is essential for tumor progression and metastasis. As such, tumors developing elsewhere in the body take advantage of the natural tolerogenicity of the lung to establish immunosuppressive niches via tumor burden induce pre-metastatic niche formation to support lung metastasis. Here we tested the ability of an intranasal nano-vaccine administration to prevent the seeding of tumor cells in the lungs by pre-emptying tumor burden induced immunosuppression. Our hypothesis is that intranasal administration of cancer nano-vaccine will prevent secondary lung metastasis from an existing primary tumor. Because breast cancer is the one of the primary tumors with high propensity to metastasize to the lung, we used the syngeneic mouse breast tumor model to test our hypothesis. Our results showed that intranasal administration of our engineered nano-vaccine protected the lungs of female BALB/c mice from secondary lung metastasis after orthotopic implantation of murine 4T1 tumors. The protection was as a result of nano-vaccine induced antitumor immunity in the lungs. Mice that received the intranasal nano-vaccine had increased frequency of effector T-cells and increase accumulation of lung resident memory T-cell in their lungs. This coincided with increased frequency of IFN-g and granzyme B producing CD8+ T-cells following ex-vivo restimulation of lymphocytes from the lungs of previously immunized mice with tumor cell. These results demonstrate that cancer vaccines can still be part of an integrated cancer therapy where they can be used as a prophylactic approach to prevent secondary lung metastasis.
Citation Format: Michael A Donkor, Jamie Choe, Byron Quinn, Harlan P Jones. Intranasal nanoparticulate PLGA cancer vaccine administration prevents secondary lung metastasis [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A53.
Abstract A62: Three pronged strategy to enhance pharmacological effectiveness of pHLA targeting TcEs
Authors: Sabarth Nicolas , Adam Paul , Kumar Sandeep , Liu Yanyun , Konopitzky Renate , Boettcher Jark , Panavas Tadas 
Published: December 2022

Abstract
T-cell engagers redirect T cells to a tumor specific target leading to lysis of tumor cells with demonstrated therapeutic benefit in hematological and solid tumors. Most T-cell engagers in development focus on surface exposed tumor antigens as targets. However, HLA/peptide complex directed (TCR mimic) T cell engagers enable targeting of tumour associated intracellular proteins and therefore broaden the cancer antigen space for T cell engagers. Potency and specificity are key attributes for the design of TCR mimic T cell engagers. Here, we employed a three pronged strategy to enhance pharmacological effectiveness of pHLA targeting TcEs: i) innovative bispecific formats employing avidity effect ii) TCRm affinity maturation by pHLA-Fv model based library design and phage display iii) pHLA-Fv crystal structure based affinity maturation in silico. The different strategies and combinations thereof enabled and improved lysis of tumor cells by T cell engager and informed on the structure-function relation of TCR mimic T cell engager.
Citation Format: Nicolas Sabarth, Paul Adam, Sandeep Kumar, Yanyun Liu, Renate Konopitzky, Jark Boettcher, Tadas Panavas. Three pronged strategy to enhance pharmacological effectiveness of pHLA targeting TcEs [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A62.
Abstract A68: Listeria monocytogenes-based vaccines to mediate targeted ablation of the tumor-associated vasculature in colorectal cancer
Authors: Anderson Trevor S , Wooster Amanda L , Oladejo Mariam , Wood Laurence , Lowe Devin 
Published: December 2022

Abstract
Anti-cancer vaccines are consequential and useful tools in eliciting long-term immune responses against tumor-associated antigens (TAAs). Attenuated listeria monocytogenes represents one such vaccine modality for inducing durable immune-driven responses against MHC class I/II presented antigens. Rather than direct this form of therapy against the dynamic assortment of targets expressed directly by tumor cells, we have instead conjugated listeria-based listeriolysin O (LLO) to RGS5, a critical molecule for cancer angiogenesis. Intriguingly, RGS5 is upregulated by pericytes in nascent blood vessels within the tumor microenvironment, and the destabilization of such blood vessel networks can effectively induce regressions of vascularized tumors like colon cancer. Our initial in vivo studies in mice immunized with the RGS5-LLO vaccine demonstrated significant protection against the aggressive colon cancer line MC38. Such findings provide the rationale for continuing efforts in developing a listeria-based therapeutic regimen against RGS5 and understanding the mechanistic interplay between vaccine-directed immune cells and tumor-derived blood vessels in this model.
Citation Format: Trevor S Anderson, Amanda L Wooster, Mariam Oladejo, Laurence Wood, Devin Lowe. Listeria monocytogenes-based vaccines to mediate targeted ablation of the tumor-associated vasculature in colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A68.
Clinician and Algorithmic Application of the 2019 and 2022 Society of Cardiovascular Angiography and Intervention Shock Stages in the Critical Care Cardiology Trials Network Registry
Authors: Patel Siddharth M. , Berg David D. , Bohula Erin A. , Baird-Zars Vivian M. , Barnett Christopher F. , Barsness Gregory W. , Chaudhry Sunit-Preet , Daniels Lori B. , van Diepen Sean , Ghafghazi Shahab , Goldfarb Michael J. , Jentzer Jacob C. , Katz Jason N. , Kenigsberg Benjamin B. , Lawler Patrick R. , Miller P. Elliott , Papolos Alexander I. , Park Jeong-Gun , Potter Brian J. , Prasad Rajnish , Singam N. Sarma V. , Sinha Shashank S. , Solomon Michael A. , Teuteberg Jeffrey J. , Morrow David A. ,   on behalf of the CCCTN Investigators
Published: December 2022

Background:
Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined.

Methods:
The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria.

Results:

Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C–E: 19.0% to 83.7% and 14.6% to 52.2%, respectively;
P
trend
<0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%;
P
trend
<0.001).

Conclusions:
Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.
The conservation paradox of an introduced population of a threatened species: spadefoot toads in the coastal dunes of the Netherlands
Authors: Koster Stephanie , Prins Nienke , Dufresnes Christophe , France James , de Visser Manon C. , Struijk Richard P.J.H. , Wielstra Ben 
Published: December 2022

Abstract
Species that are threatened in their native range may actually prosper as introduced populations. To investigate how such introduced populations were established involves determining from where within the natural range the founder individuals originated. This can be accomplished through mtDNA barcoding. The common spadefoot toad (Pelobates fuscus) naturally occurs in the south and east of the Netherlands and has shown a rapid decline. Yet, a flourishing introduced population was recently discovered in the coastal dunes in the west of the country. We use mtDNA barcoding to determine the provenance of the introduced population. We sampled both native and introduced populations from the Netherlands and compared our sequences to haplotypes from across the entire distribution range. The mtDNA haplotypes found in the introduced population are distinct from those naturally occurring in the Netherlands and point towards an origin in the Pannonian Basin, on the boundary between Central and Southeastern Europe. Paradoxically, the thriving P. fuscus population in the Dutch coastal dunes should be considered a conservation risk to local biodiversity, even though within the native range in the Netherlands the species is severely threatened. Our study illustrates the complicated conservation questions associated with species that are both native and invasive.
A New Inscription of the Pāṇḍuvaṃśins of Dakṣiṇa Kosala
Authors: Ali Daud , Zhang Diana Shuheng 
Published: December 2022

Abstract
This is the first notice, edition, and translation of a royal order in Sanskrit, engraved on a set of three copper-plates kept in the permanent collection of the Philadelphia Museum of Art. The inscription is dated to the seventh year of the reign of Nannarāja I, king of the Pāṇḍuvaṃśin lineage active in Dakṣiṇa Kosala in the sixth and seventh centuries CE. The inscription provides important new information about a family of engravers, probably relocated from Śarabhapura to Sirpur, who served both the Śarabhapurīya and Pāṇḍuvaṃśin courts. The plates further suggest that Nannarāja I, as the first Pāṇḍuvaṃśin king of South Kosala, continued the epigraphic traditions of the Śarabhapurīyas, whom he may have served with his father Indrabala in his early career before the conflicts which brought him to power.
‘Tis Pity She’s (Still) a Whore: Mary Magdalene in The Chosen
Authors: Burnette-Bletsch Rhonda 
Published: December 2022

Abstract
Early Jesus films reveled in the traditional, historically inaccurate interpretation of Mary Magdalene as a penitent prostitute. While films produced since the 1980s are less heavy-handed in explicitly sexualizing or shaming Mary, promiscuity remains her most persistent trait. Traces of the penitent prostitute are detectable in The Chosen, a crowd-funded evangelical series on the life of Jesus which foregrounds Mary as a disciple. Her story arc in The Chosen mirrors that of the prostitute protagonist in Redeeming Love (2022), another evangelical film based on Francine River’s fictional adaptation of the Hosea/Gomer story. Both works adhere closely to what film scholar, Russell Campbell, identifies as the ‘martyr’ character type and ‘love story’ narrative structure commonly found in cinematic depictions of sex work. Ultimately, these films reinscribe patriarchal ideology when the woman is rescued and reformed by a virtuous man at risk of his own reputation.
The Alfaẓ al-Mishnah Commentary by R. Saadiah Gaon
Authors: Fuchs Uziel 
Published: December 2022

Abstract
This article presents a commentary on the Mishna composed by R. Saadiah Gaon, who served as head of the Sura yeshivah in Baghdad at the beginning of the 10th century. The commentary is a Hebrew-Arabic glossary defining difficult words in the Mishnah. The commentary is well referenced in writings from early periods, and a large portion of the manuscript was recently identified in the Cairo Genizah. I present a number of proofs that R. Saadiah Gaon authored the commentary and show that many adaptions were made to this commentary in several manuscripts. This unpublished commentary is the earliest systematic commentary on rabbinic literature.
On the Date of Composition of the Book of Commandments by the Qaraite Levi b. Yefet
Authors: Vidro Nadia 
Published: December 2022

Abstract
The Book of Commandments of the influential Qaraite scholar Levi b. Yefet is traditionally dated 1006/7 CE. This date is based on the Hebrew translation of the Book of Commandments and is irreconcilable with a calendrical characteristic of this year provided by Levi b. Yefet. In this article I propose to revise the date of composition of the Book of Commandments to 1009 CE. This date is given in a copy of the Arabic original of the code and is calendrically consistent. I also discuss events in the calendar of Palestinian Qaraites that prompted Levi b. Yefet to mention the year in which he was writing and that took place due to irregular weather patterns.
Using Hydraulic Theory to Monitor Dense Overflows in a Parabolic Channel
Authors: Saberi Atousa , Pratt Lawrence J. , Haine Thomas W. N. , Helfrich Karl R. 
Published: December 2022

Abstract
Deep ocean passages are advantageous sites for long-term monitoring of deep transport and other physical properties relevant to climate. Rotating hydraulic theory provides potential for simplifying monitoring strategy by reducing the number of quantities that need to be measured. However, the applicability of these theories has been limited by idealizations such as restriction to zero or uniform potential vorticity (pv) and to channels with rectangular cross sections. Here the relationship between the flow characteristics in a canonical sea strait and its upstream condition is studied using uniform pv rotating hydraulic theory and a reduced-gravity shallow-water numerical model that allows for variation in pv. The paper is focused mainly on the sensitivity of the hydraulic solution to the strait geometry. We study the dynamics of channels with continuously varying (parabolic) cross sections to account for the rounded nature of sea-strait topographies and potentially improve monitoring strategies for realistic channel geometries. The results show that far enough from the channel entrance, the hydraulically controlled flow in the strait is insensitive to the basin circulation regardless of parabolic curvature. The controlled transport relation is derived for the case of uniform pv theory. Comparing the model to theory, we find that the measurement of the wetted edges of the interface height at the critical section can be used to estimate the volume flux. Based on this finding, we suggest three monitoring strategies for transport estimation and compare the estimates with the observed values at the Faroe Bank Channel. The results showed that the estimated transports are within the range of observed values.

Significance Statement
The paper investigates the relationship between the flow characteristics in an idealized sea strait and its upstream condition using rotating hydraulic theory and numerical modeling. We study the dynamics of channels with continuously varying (parabolic) cross sections to account for the rounded nature of sea-strait topographies and potentially improve monitoring strategies for realistic channel geometries. We suggest three monitoring strategies for transport estimation and apply the methods to the Faroe Bank Channel. Our estimates of dense water transport are within the range of observed values. This is significant, because the suggested monitoring strategies only require 1–3 measurements to estimate the transport at a given passage and can be used to guide observing systems.
Did the COVID-19 Pandemic Impact the Caliber of Trainees Taken During Match 2021? A Survey of General Surgery Residency Program Directors
Authors: Ferry Andrew M. , Asaad Malke , Rajesh Aashish , Grush Andrew E. , Elmorsi Rami , Burns Heather R. , Mohan Vamsi C. , Bauer David F. , Maricevich Renata S. 
Published: December 2022

Background The cancellation of clinical rotations (CRs) and implementation of virtual interviews (VIs) profoundly affected the residency selection process leading up to the 2021 NRMP Match. The authors investigated how these changes influenced the caliber of applicants taken by general surgery (GS) residency programs from the perspectives of program directors (PDs). Methods A 14 question, web-based electronic survey was emailed to PDs of ACGME-accredited GS residency programs. Questions sought program characteristics and PDs’ perspectives regarding potential differences in subjective characteristics and clinical skills demonstrated by their 2021 Match class relative to previous resident classes. Results A total of 75 PDs (27.2%) responded to our survey. Most respondents observed no changes in residents’ fit with their program (72.0%), communication skills (68.0%), responsiveness to clinical instruction and feedback (73.3%), work ethic (73.3%), and rotation evaluations (68.0%). Only 21.3% of PDs believed that VIs negatively impacted their ability to accurately assess applicant intangibles. Conversely, 56.0% of PDs reported that the cancellation of CRs in 2020 negatively affected residents’ clinical competency at the start of residency. At 1-year following the 2021 NRMP Match, 30.7% of PDs reported that the clinical skills exhibited by their 2021 Match class were poorer than previous resident classes. Discussion Our findings suggest that VIs limited selection committees’ ability to accurately assess applicant’s subjective characteristics to a lesser degree than previously described in the literature. Canceled CRs adversely affected the 2021 Match Class’s clinical skills at the start of residency and at 1 year following the 2021 NRMP Match.
Prevalence and sociocultural correlates of post-traumatic stress disorder and complex PTSD among Chinese community health service users in Hong Kong
Authors: Fung Hong Wang , Wong Emily Nga Man , Lam Stanley Kam Ki , Chien Wai Tong , Hung Suet Lin , Ross Colin A. , Cloitre Marylene 
Published: December 2022

Objectives: Complex post-traumatic stress disorder (CPTSD) is a newly recognized trauma disorder in ICD-11. Little is known about the prevalence and correlates of CPTSD in primary care settings. Its cultural aspects also remained minimally explored. This study investigated the prevalence and sociocultural correlates of PTSD and complex PTSD among Chinese community health service users in Hong Kong. Methods: This study investigated ICD-11 PTSD and CPTSD in a sample of adults ( N = 376) who had recently received services from Registered Chinese Medicine Practitioners in Hong Kong. Traditional Chinese medicine service is part of primary care services in Chinese societies. Participants completed self-report measures of CPTSD, trauma exposure, perceived family support, perceived caregiver’s Chinese traditionality/modernity, participation (social activities and occupational productivity), depression and pain. Results: The past-month prevalence of ICD-11 PTSD and CPTSD was 5.6% and 18.4%, respectively, in our sample. Chi-square tests and one-way ANOVAs revealed that participants with CPTSD were younger and reported more trauma, lower family support, lower levels of social participation and productivity, more depressive symptoms and pain, and more social welfare and mental health service usages than those without PTSD. We found that perceived caregiver’s Chinese modernity (e.g. egalitarianism) was negatively correlated with CPTSD symptoms. Apart from age, non-betrayal trauma had the strongest association with classical PTSD symptoms, while betrayal trauma and perceived family support had the strongest association with disturbances in self-organization symptoms. Conclusion: This study provides the first data regarding the prevalence and correlates of ICD-11 PTSD and CPTSD among community health service users in Hong Kong. PTSD and CPTSD are common but often unrecognized mental health problems which are associated with more impairments and more service needs.