bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A006: Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy
Authors: Sharma Priya Chandramohan , Patel Digna , Dalai Sarat K 
Published: December 2023

Abstract
Autologous cell-based therapy is a preferred approach for Cancer immunotherapy. However, generating potent NK cells and antigen experienced T cells has been a challenge. To address this issue, we have developed a strategy of using the combination of IL-12 and IL-15 to activate CD4+ T cells, CD8+ T cells and NK cells. IL-12 and IL-15 possess distinct roles but both are potent inflammatory cytokines. IL-12 is a vital promoter of Th1 differentiation via activation of signal transducer and activator of transcription 4 (STAT4), while IL-15 is essential for developing innate immune response as well as contributing to the maintenance of memory CD8+ T cells. Substantial in vivo and in vitro data have been reported to support the role of IL-15 as a T cell growth factor. These activities of IL-12 and IL-15 make them ideal for combinatorial immunotherapy of cancer. However, the short half-life (~ 1hr) and poor bioavailability limits the therapeutic use of IL-15. To overcome these limitations, we have designed chimeric IL-15-IgG2 (Indian Patent Application No. 201721010096A) with an objective of augmenting the generation of memory T cells as well as reactivating them during the antigenic challenge. Our stable chimeric IL-15 has a half-life of &gt;40 Hrs. In humans, IL-12 is needed for DCs to provoke rapid IFN-g production by NK cells, IL-15 seems essential for the NK cell proliferation. In the present study, we are testing the potential of chimeric IL-15 individually and in combination with native hIL-12 as an activator of CD4+ T cells, CD8+ T cells and NK cells. The combination of both cytokines shows potent release of IFN-g as well as activation of the T-cell subsets and NK cells. In our future studies we will use these pre-activated cells for adoptive transfer in cancer immunotherapy. Detailed findings will be reported during the conference.
Citation Format: Priya Chandramohan Sharma, Digna Patel, Sarat K Dalai. Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A006.
Abstract A015: Rapid mitochondrial reactive oxygen species production precedes NF-κB activation and pro-inflammatory responses in macrophages
Authors: Zaniani Parinaz Tavakoli , Balomenos Dimitrios 
Published: December 2023

Abstract
Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, we performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, MAPK activation by regulating TRAF-6 ubiquitination, and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies, targeting early mROS production and control extreme inflammation in the context of sepsis and other inflammatory diseases.
Citation Format: Parinaz Tavakoli Zaniani, Dimitrios Balomenos. Rapid mitochondrial reactive oxygen species production precedes NF-κB activation and pro-inflammatory responses in macrophages [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A015.
Abstract A034: VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity
Authors: Rezaei Reza , Azad Taha , Petryk Julia , Bell John C. 
Published: December 2023

Abstract
This research introduces VV-iVP55, a conditionally replicating vaccinia virus platform, as a promising alternative to thymidine kinase (Tk) deleted oncolytic vaccinia viruses. The unique feature of VV-iVP55 is its growth control using doxycycline, a trait not found in conventional Tk-deleted viruses. Laboratory studies revealed that VV-iVP55 achieves higher virus titers and lower cell viability in B16-F10 and MC38 syngeneic models compared to Tk-deleted viruses. Notably, VV-iVP55 demonstrated lower toxicity in immunocompromised mice upon doxycycline withdrawal, unlike Tk-deleted viruses that showed significant toxicity. In vivo efficacy studies further highlighted the superiority of VV-iVP55 over Tk-deleted viruses in CT26 and B16 subcutaneous models, as well as MC38 subcutaneous and intraperitoneal models. An immune microenvironment analysis conducted six days post-intratumoral injection revealed beneficial alterations induced by VV-iVP55, such as increased T and B cell content in the tumor and reduced MDSCs in both the tumor and spleen. Moreover, VV-iVP55 was linked to a significant change in T cell differentiation. Unlike the PBS and Tk viruses, which showed almost complete differentiation towards effector T cells, VV-iVP55 maintained a substantial population of T cells in naive and transition phases, significantly in both CD4 and CD8 T cells. This likely led to lower expression of exhaustion markers PD1, TIM3, TIGIT, and LAG3, suggesting less exhaustion and more potential for immune response. In summary, VV-iVP55 emerges as a powerful alternative to Tk-deleted oncolytic vaccinia viruses, offering enhanced immunogenicity, controlled toxicity, and preserved oncolytic properties.
Citation Format: Reza Rezaei, Taha Azad, Julia Petryk, John C. Bell. VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A034.
Abstract B032: CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy
Authors: Cha Junha , Kim Dahee , Kim Gamin , Cho Jae-Won , Sung Euijeong , Baek Seungbyn , Hong Min Hee , Kim Chang Gon , Sim Nam Suk , Hong Hyun Jun , Lee Jung Eun , Hemberg Martin , Park Seyeon , Yoon Sun Ock , Ha Sang-Jun , Koh Yoon Woo , Kim Hye Ryun , Lee Insuk 
Published: December 2023

Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) is a prevalent subtype of head and neck cancer representing one of the largest diagnosed malignancies worldwide. A distinct subtype of OPSCC induced by Human Papilloma Virus (HPV) is well known to favor beneficial clinical outcomes in cancer treatment compared to HPV-negative OPSCCs. However, HPV-positive OPSCCs in the context of immunotherapy remains unclear, as no distinct benefits are observed in clinical trials. In this study, we performed single-cell RNA and T cell receptor sequencing analyses of 20 tumor samples to dissect the cellular and molecular factors associated with viral infection and immunotherapy outcome. We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. This finding suggests heterogeneity of malignant cells negates immunotherapy response in HPV-positive OPSCCs. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed significant association with dampened antitumor activity in HPV-positive OPSCC patients, which may explain their clinical heterogeneity. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Validation in an independent cohort confirms enhanced tertiary lymphoid structure activity in HPV-positive OPSCCs. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade confirmed an inverse correlation between the density of CD161+ Trm and changes in tumor size. These results suggest that targeted inhibition of CD161 in Trm may augment immunotherapy efficacy in HPV-positive oropharyngeal cancers.
Citation Format: Junha Cha, Dahee Kim, Gamin Kim, Jae-Won Cho, Euijeong Sung, Seungbyn Baek, Min Hee Hong, Chang Gon Kim, Nam Suk Sim, Hyun Jun Hong, Jung Eun Lee, Martin Hemberg, Seyeon Park, Sun Ock Yoon, Sang-Jun Ha, Yoon Woo Koh, Hye Ryun Kim, Insuk Lee. CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B032.
Abstract B054: Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma
Authors: Vosahlikova Sarka , Holicek Peter , Moserova Irena , Orsulic Sandra , Mikyskova Romana , Hensler Michal , Kasikova Lenka , Lanickova Tereza , Novotny Ondrej , Reinis Milan , Drozenova Jana , Ryska Ales , Rob Lukas , Halaska Michael J , Cibula David , Spisek Radek , Fucikova Jitka 
Published: December 2023

Abstract
Epithelial ovarian carcinoma (EOC) is among the top five causes of cancer-related death in women. Most women with EOC achieve indeed complete remission after primary or interval cytoreductive surgery combined with chemotherapy based on a platinum-taxane doublet. Homologous recombination (HR) defects imposed by germline or somatic BRCA1 DNA repair-associated (BRCA1) or BRCA2 mutations are not only key determinants of platinum sensitivity in EOC patients but also provide a strong rationale for maintenance therapy based on poly(ADP-ribose) polymerase (PARP) inhibitors, which is generally associated with improved progression-free survival (PFS). Besides direct cytotoxic and cytostatic properties, PARPi have been shown to mediate multipronged immunostimulatory effects, largely reflecting their ability to inhibit DNA repair in malignant cells and indicating the possibility to synergy with immune-check point inhibitors (ICIs). Here, using multiparametric flow cytometry, multiplex immunostaining, single cells transcriptomics and functional studies in experimental syngeneic BR5-Akt mouse model and EOC tumor samples, we discuss PARPi immunomodulatory activity, with a specific focus on molecular and cellular pathways that can be harnessed to develop superior combinatorial regimens for clinical management. Thus, PARPi might enhance the mutational load of EOCs as consequence of unrepaired DNA damage and DAMPs exposure, favoring T cell infiltration, but also appear to drive robust type I IFN secretion downstream of cyclic GMP-AMP synthase and stimulator of IFN response cGAMP interactor 1 activation. In addition, the combination of PARPi with ICIs positively regulate the balance between adaptive anti-tumor immunity and innate myeloid components and significantly improve the cytotoxic T cell profile as shown in both experimental mice model and HGSOC tumor samples. We surmise that rationally designed combinations of PARPi and immunotherapeutic agents might be critical to unlock immunosuppression in the EOC microenvironment in support of clinical efficacy.
Citation Format: Sarka Vosahlikova, Peter Holicek, Irena Moserova, Sandra Orsulic, Romana Mikyskova, Michal Hensler, Lenka Kasikova, Tereza Lanickova, Ondrej Novotny, Milan Reinis, Jana Drozenova, Ales Ryska, Lukas Rob, Michael J Halaska, David Cibula, Radek Spisek, Jitka Fucikova. Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B054.
L’authenticité des généalogies des immigrés andalous au Maroc et dans les régences ottomanes à l’époque moderne entre revendications et refus
Authors: Ben el Haj Soulami Jaafar 
Published: December 2023

Abstract
Although al-Andalus was historically the territory of the Umayyads par excellence, certain branches of the Alid families (enemies of the Umayyads) settled there, especially in the 4th / 10th century. Over the centuries, other non-Idrisid branches also settled in al-Andalus, where the presence of these ašrāf branches was noted until the end of the Middle Ages. With the forced Christianization of all Andalusians from around 1500 in the Kingdom of Granada, and from 1523 in the Kingdom of Valencia, these branches suffered the systematic loss of family documents justifying their membership of the Prophet’s family, especially with the ransacking of Arab heritage papers. Forced into exile in 1609, in a mass exodus ordered by the Hispanic monarchy, the Andalusians found themselves exiled in the Muslim countries of North Africa, bereft of any written genealogical justification. Oral tradition was all that remained to justify their claim. They claimed the noble genealogy of the Prophet, but often to no avail, as the indigenous North African Muslims generally denied them this claim for lack of convincing justification.
Le pouvoir du chérif : perspectives sahariennes (XVIIIe/XIXe siècles)
Authors: Warscheid Ismail 
Published: December 2023

Abstract
This article studies the integration of Cherifian lineage groups into the social fabric of two oasis societies in western Sahara, Touat in southern Algeria and Oualata in Mauritania, during the 18th and 19th centuries. The aim is to consider the šarīf as a social actor distinct from “maraboutic” groups. We argue that Saharan šurafāʾ have a power that, although legitimized by the prestige of the genealogical link with the Prophet, can be articulated independently of the authority conferred by the status of scholar or “saint” (walī). Their power seems to rest primarily on their commitment as community leaders and, above all, on their ability to impose themselves in power relations between lineage groups, including through use of force of arms.
Eschatology, Divination, and Gassendi’s Encounter with Spanish-Netherlandish Natural Philosophy (1629)
Authors: Broecke Steven Vanden 
Published: December 2023

Abstract
Scholars have tended to focus on Gassendi’s relations with the mathematical, natural-philosophical, and erudite interlocutors he encountered in the Republic. This sits uneasily with the fact that Gassendi’s time in the Spanish Netherlands was about three times as long as his stay in the Republic (i.e., six weeks vs. two weeks). Drawing on the deep engagement with eschatology and divination of Gassendi’s close friend Govaert Wendelen (1580–1667) in the period between 1626 and 1632, this paper raises two questions. First, which natural-philosophical culture did Gassendi encounter in the Spanish Netherlands? Second, which similarities and divergences between Gassendi and his interlocutors does this encounter allow us to discern more clearly?
Zoonoses in Unconventional Companion Animals
Authors: Bursee Lukas J. 
Published: December 2023

Abstract
The keeping of unconventional companion animals represents a special area of animal husbandry. While formerly reserved for zoological institutions, nowadays more and more unconventional companion animals can be found in the care of private owners. Due to the special nature and requirements of these animals, there are people who demand legal restrictions of these husbandries. One point often mentioned in this regard is the risks of zoonoses, which are said to be higher than with classical companion animals. Considering this argument, a conflict emerges between private rights of companion animal owners and the interests of public safety. With the help of a balancing of interests, this conflict can be examined more closely and an initial assessment of the justification for restrictions can be made.
Acquired brown syndrome in a child with acute rheumatic fever
Authors: Assayag Elishai , Totah Hashem , Drabkin Elena , Reich Ehud , Rabinovich Ronen , Rappoport Daniel 
Published: December 2023

Purpose To describe a rare case of acquired Brown syndrome (ABS) associated with acute rheumatic fever (ARF). Case Report a healthy 9-year-old girl developed polyarthritis, carditis, and elevated inflammatory markers 10 days after suffering from a sore throat. She was diagnosed with ARF and was treated with systemic antibiotics and high-dose non-steroidal anti-inflammatory drug (NSAID). After 2 weeks, despite improvement of ARF symptoms, the patient presented with binocular vertical diplopia, periorbital pain, and limited elevation in adduction of the left eye. Imaging revealed a thickened trochlea-superior oblique tendon complex, and ABS due to trochleitis was diagnosed. The patient underwent a successful regional corticosteroid injection as a second-line treatment, and within a month, all signs and symptoms of ABS resolved. Conclusions ABS is an infrequent yet possible manifestation of ARF.
Predicting Mortality Following Odontoid Fracture Fixation in Elderly Patients: CAADS-16 Score
Authors: ElNemer William , Solomon Eric , Raad Micheal , Jain Amit , Lee Sang Hun 
Published: December 2023

Study Design Retrospective Review of a National Database. Introduction By utilizing a national database, this study aims to quantify the predictors of 30-day mortality after odontoid fixation and guide appropriate management for patients in whom the choice between operative and non-operative management is unclear. Methods The American College of Surgeons National Surgical Quality Improvement Database was queried using Current Procedural Terminology (CPT) codes and International Classification of Disease (ICD) codes to identify patients 60 or older who underwent surgical fixation of an odontoid fracture from 2005 to 2020. Risk factors for mortality significant in univariate and subsequent multivariate analysis were used to develop a scoring system to predict post-operative mortality. Results 608 patients were identified. Patients were split into a non-mortality 30 days post-op group, and into a mortality 30 days post-op group. The following risk factors were included in the scoring system: functional dependency, disseminated cancer, albumin less than 3.5, WBC count greater than 16 k, anterior surgical approach, and pre-op SIRS. Using a cutoff value of 2, the CAAD-16 score had a sensitivity and specificity of 82% and 81%, respectively. The ASA score, cutoff at 4, showed a sensitivity and specificity of 64% and 75% respectively. Conclusions This sample of 294 patients represents one of the largest samples of odontoid fracture fixation patients available in the literature and comes from a nationally representative database. We structure relevant risk factors into the CAADS-16 score, which has the potential to be a clinically relevant tool to prevent short-term postoperative mortality.
Exclusive Benefits of Sustained MRD-Negative in High-Risk Multiple Myeloma
Authors: Ren Liang , Xu Tianhong , Wang Wenjing , Yang Yang , Wang Yawen , Maihemaiti Aziguli , Lan Tianwei , Li Panpan , Zhou Chi , Wang Pu , Liu Peng 
Published: December 2023

Introduction: Achievement of minimal residual disease (MRD) negativity is now recognized as a strong prognostic indicator for favorable clinical outcomes in multiple myeloma (MM) patients. Nonetheless, the optimal duration of MRD-negativity as a surrogate endpoint across different levels of sensitivity remains unclear. Additionally, it is imperative to explore whether sustained MRD-negativity holds the same prognostic value for MM patients with varying risk stratifications.
Methods: In this study, 587 newly diagnosed MM patients were assessed for MRD using multiparameter flow cytometry (sensitivity of 10^-5 or 10^-6) at Zhongshan Hospital Fudan University between January 2014 and Janyary 2022. Patients were categorized as MRD-negativity not obtained (NON-MRD), obtained and sustained (SUS-MRD), or obtained and lost (LOS-MRD) based on their MRD status at given landmark point(4, 6, 12, 18, 24, and 36 months) after initiation of anti-myeloma treatment. The impact of MRD-negativity on survival outcomes was analyzed at increasing landmark times. Univariate and multivariate regression analyses were performed to examine the prognostic implications of time-dependent MRD status on overall survival in the context of different risk-stratification systems which were identified by versions of International Staging System (ISS).
Results: A total of1718 MRD tests were performed on MM patients, the median number was 3. Among survival analyses at differnet landmark time, MM patients at 12 months showed greatest separation in subsequent survival between 3 groups no matter the sensitivity of 10^-5 or 10^-6 ( p=0.032, p=0.03). Pooled analysis indicated that patients who were in SUS-MRD category with a sensitivity ≥10^-5 had superior overall survival (OS) at 12 months landmark point ( p&lt;0.001), with comparable survival between patients in Non-MRD and LOS-MRD category ( p=0.096, Figure 1). SUS-MRD group of MM patients at 12 months did not show better OS than the rest part patients in low-risk subgroup(ISS/R-ISS/R2-ISS=I, p=0.73, p=0.28, p=0.41,respectively). Among high-risk subgroup (ISS/R-ISS=III, R2-ISS=IV), landmark survival analyses at 12 months indicated that SUS-MRD benefited patients most, as shown the greatest OS in the SUS-MRD part ( p=0.013, p=0.011, p=0.056,respectively). Multivariate cox regression analysis showed that SUS-MRD was an independent favorable variable for patients in the ISS/R-ISS=III group ( p=0.021, HR:0.429; p=0.002, HR: 0.161).
Conclusions: No matter the sensitivity of 10^-5 or 10^-6, the sustained of MRD negative lasts for 12 months is a robust marker of superior survival outcomes. MM patients who lost MRD negative has similar OS with those constant MRD positive in the long term. Benefit of Sustained MRD negative in MM limited to high risk subgroup MM patients.