bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA26: Understanding the impact of COVID in cancer patients through the COVID-19 and Cancer (CCC-19) and other COVID consortiums
Authors: Rini Brian I.
Published: December 2020

SARS-CoV-2 and the resulting disease, COVID-19, has led to a global pandemic with broad impact on the delivery of medical care. Cancer patients may be especially vulnerable to both infection and adverse outcomes from COVID due to a number of factors including advanced age, immunosuppression from disease and/or anticancer therapy, and heightened interaction with the medical system. Several cohort studies have been launched to more fully understand risk factors for death and other adverse outcomes in patients with active or remote cancer. CCC-19 is a cohort study involving more than 100 institutions that enter data into a REDCaP database regarding patient demographics, cancer type and treatment details, and outcome of COVID infection. All patients have documented SARS-CoV-2 PCR positive and/or clinical symptoms consistent with COVID, in addition to an ongoing or past history of invasive malignancy. The initial analysis of this cohort study (n=928; Kuderer et al., Lancet 2020) demonstrated a 13% mortality rate and revealed several factors associated with an increased mortality including advanced age, male gender, greater number of comorbidities, worse ECOG performance status, and progressive cancer. Recent cancer surgery and receipt of cytotoxic or other systemic anticancer therapy was not associated with worse outcome, although small patient numbers in some subsets precluded definitive conclusions. At present, there are approximately 3,000 patients entered into this database and updated analyses will be presented. In addition to this effort, a number of other societies have created similar databases including ASH, ASCO, and ESMO. These complementary efforts will allow a global assessment of the impact of COVID on cancer patients including mortality and adverse outcomes in addition to cancer-specific outcomes. Last, the NCI COVID-19 in Cancer Patients Study (NCCAPS) is a prospective study in patients with active cancer and recent SARS-CoV-2 infection. This 2,000-patient study is open to accrual and will prospectively define both the impact of COVID on cancer and also cancer status and treatment on COVID outcome. In addition, biospecimen collection in this study will examine genetic predisposition, cytokine and coagulopathic parameters, and serologic outcomes. Collectively, these retrospective and prospective efforts will enable a more granular understanding of COVID in cancer patients to enable both appropriate cancer care delivery and improvement in outcomes in cancer patients with COVID infection.

Citation Format: Brian I. Rini, (on behalf of the CCC-19 Consortium). Understanding the impact of COVID in cancer patients through the COVID-19 and Cancer (CCC-19) and other COVID consortiums [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA26.
Abstract PO-079: COVID-19 in relation to hematologic events and mortality in subset of inpatient cancer patients
Authors: Gadde Saikrishna , Badari Ambuga , Cole John , Manjunath Nikhil
Published: December 2020

COVID-19 is a newly diagnosed entity that has been identified for about 6 months. With the US now being the prevalent nation affected, we aimed to identify factors that were relevant to survival and hematologic events in COVID patients. Our group had primarily been assessing COVID-19-confirmed patients as per PCR at Ochsner Medical Center in Louisiana; we primarily studied patients who were admitted between January 2020 to May 2020. Main events that are currently being studied include factors such as mortality, length of stay, and bleeding or thrombotic events. Secondary endpoints included factors such as influence on blood type and also amount of transfusions required by these patients. Our overall analysis of 1,773 patients yielded a number of 60 patients whom we were able to identify as having an active cancer diagnosis. This disproportionate number of patients may be related to factors such as reluctance to visit the hospital among cancer patients, a phenomenon noted similarly in Cardiology, where the number of admissions for cardiac causes had declined suddenly during this pandemic timeline. One half of our population was African American and included an even proportion of males and females. The age range of patients was between 35-93 years. The most common malignancies that were noted to co-occur with COVID-19 in our population seemed to be lung, prostate, and hematologic malignancies. Although final analyses regarding mortality are to be completed, the proportion of patients who had died with a diagnosis of cancer was around 50% per collection of our current data. Twenty three out of 60 (38%) patients required blood transfusions. In comparison to other reports that had reported bleeding events and thrombotic events, our report revealed a much lower rate of bleeding events (5/60) and thrombotic events (5/60). We plan to repeat our analysis to assess for any confounders in identifying these events, as noted, since some earlier literature had reported between one quarter to two thirds of patients having a thrombotic event. Our analysis also looks at other descriptive variables such as use of anticoagulant and antiplatelet agents, absolute counts of neutrophils and lymphocytes, platelets, and coagulation markers. Also, our assessment includes a study in assessment of any delays noted in chemotherapy dates for these patients.

Citation Format: Saikrishna Gadde, Ambuga Badari, John Cole, Nikhil Manjunath. COVID-19 in relation to hematologic events and mortality in subset of inpatient cancer patients [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-079.
Abstract IA30: Targeting MYC deregulation in cancer
Authors: Lueg Gregor A. , Faronato Monica , Gorelik Andrii , Grocin Andrea G. , Llorian-Sopena Miriam , Chakravarty Probir , Brzezicha Bernadette , Janz Martin , Garnett Mathew J. , Calado Dinis P. , Tate Edward W.
Published: December 2020

Human N-myristoyltransferase (NMT) 1 and 2 catalyze N-terminal protein myristoylation, a modification that regulates membrane trafficking and interactions of >100 proteins. NMT has been proposed as a target in cancer, but a rationale for selectivity is lacking due to the complex impact of NMT inhibition (NMTi) on multiple cellular pathways. Here, large-scale screens of hundreds of cancer cell lines against a panel of potent and selective NMTi were combined with systems-level analyses to reveal that NMTi is synthetically lethal with deregulated MYC or MYCN. Synthetic lethality is mediated by post-transcriptional failure in (NADH) Complex I protein synthesis followed by mitochondrial dysfunction in MYC-deregulated cancer cells. We observed that NMT inhibitors blocked the growth of patient-derived tumors with deregulated MYC, without overt toxicity. This mechanistic framework supports NMTi as a novel targeted therapeutic approach and provides a new paradigm in which targeting of a constitutive protein modification is synthetically lethal in MYC-deregulated cancers.

Citation Format: Gregor A. Lueg, Monica Faronato, Andrii Gorelik, Andrea G. Grocin, Miriam Llorian-Sopena, Probir Chakravarty, Bernadette Brzezicha, Martin Janz, Mathew J. Garnett, Dinis P. Calado, Edward W. Tate. Targeting MYC deregulation in cancer [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA30.
Abstract IA40: Defining precursors in low-grade lymphomas that seed second lymphomas
Authors: Louissaint Abner , Weinstock David
Published: December 2020

Most patients with low-grade lymphoma will achieve a clinical remission (CR) with standard chemoimmunotherapy. Yet, relapse from minimal residual disease (MRD), either as low-grade or high-grade disease, remains the leading cause of death. Several studies have provided consistent evidence showing the strong prognostic value of measurable MRD using flow cytometry, PCR, next-generation sequencing, or other approaches. While MRD includes the malignant cells that remain in a patient who achieves CR, not all MRD cells may have the functional capability to proliferate into relapse. We recently introduced a nomenclature to more precisely distinguish cells included within MRD. In this nomenclature, M-REC (Minimal-RElapsable Cancer) denotes fully transformed cells capable of driving a relapse; MN-REC (Minimal Non-RElapsable Cancer) denotes fully-transformed cells incapable of driving a relapse; and MRP (Minimal Residual Precursors) denotes residual cells that harbor somatic and/or phenotypic alterations but are not fully malignant, such as those causing a dysplastic “field-effect” in cancers like those of the bladder, head and neck, or esophagus. Studies that defined the genetic phylogeny of lymphoma using diagnostic, relapsed, and transformed B-cell lymphomas from the same patients have identified examples where MRPs repeatedly evolve into clinical lymphomas. This conflicts with the traditional model of cancer evolution, in which “relapses” result from M-RECs that persist after therapy. There are two immediate implications to this paradigm-shifting concept: 1) Many “relapses” are actually second lymphomas, and 2) defining and targeting the vulnerabilities of MRPs may be essential for improving lymphoma-free survival among patients who achieve a CR. It is important to note that the vulnerabilities of MRD may differ within the bone marrow, blood, lymph node, and other sites, so sampling of each is essential. To make this possible, we have advanced two strategies. First, we have established xenografts of human follicular lymphoma explants within immunocompromised mice that capture both malignant and nonmalignant cellular components, as well as predictable transformation to large-cell lymphoma in vivo. Second, we have initiated rapid autopsies of patients with disseminated lymphoma to obtain specimens from multiple organs and thereby define the heterogeneity of environmental niches that support the persistence of MRD.

Citation Format: Abner Louissaint, David Weinstock. Defining precursors in low-grade lymphomas that seed second lymphomas [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA40.
Abstract PO-04: Noncoding mutations in mantle cell lymphoma disrupt regulation of HNRNPH1 by alternative splicing
Authors: Coyle Krysta M. , Qureshi Quratulain , Pararajalingam Prasath , Thomas Nicole , Audas Timothy E. , Morin Ryan D.
Published: December 2020

Non-Hodgkin lymphomas (NHL) are a collection of cancers with each malignancy having distinct clinical management and prognosis. Mantle cell lymphoma (MCL) is particularly genetically heterogeneous and is considered incurable. Through a combination of exome, genome, and targeted sequencing of MCL tumors, we identified recurrent mutations in HNRNPH1 (heterogeneous nuclear ribonucleoprotein H1). These mutations are largely intronic or silent and are associated with a putative cis regulatory region involving a single exon. In RNA-seq data from matched cases, we identified variable representation of two distinct HNRNPH1 isoforms. Based on the reading frame of the affected exons, canonical splicing is predicted to produce a functional protein, while alternative splicing introduces a premature termination codon leading to nonsense-mediated decay. We observed a significantly higher proportion of canonical transcripts in MCL tumors bearing HNRNPH1 mutations, leading us to conclude that mutations in HNRNPH1 significantly alter its splicing. Furthermore, increased canonical splicing results in higher HNRNPH1 protein abundance as determined by immunohistochemical analysis of an MCL tissue microarray. HNRNPH1 mutation status and splicing ratio are associated with shorter survival of MCL patients. We developed an in vitro reporter minigene and introduced three specific mutations corresponding to the patient-identified mutations in HNRNPH1. These mutations lead to an increase in canonical splicing and translation of the HNRNPH1 minigene-derived peptide. Additionally, when HNRNPH1 is overexpressed, we observe a decrease of this peptide, implicating HNRNPH1 in the regulation of its own splicing. This is supported by preliminary data indicating that HNRNPH1 binds its own RNA. Beyond its own splicing, HNRNPH1 is likely also involved in the splicing of additional splicing factors. Overexpression of HNRNPH1 affects the splicing of SRSF3 and HNRNPDL, and many other targets are likely to be identified. This work elucidates a functional role for recurrent noncoding HNRNPH1 mutations and implicates HNRNPH1 expression and splicing of its downstream targets in lymphomagenesis. We continue to explore trans regulatory targets of HNRNPH1 using in vitro and cell-based models. While splicing is a growing field of interest in lymphoma biology, the unique pattern and consequences of these largely silent mutations specifically implicate alternative splicing as an oncogenic mechanism in MCL.

Citation Format: Krysta M. Coyle, Quratulain Qureshi, Prasath Pararajalingam, Nicole Thomas, Timothy E. Audas, Ryan D. Morin. Noncoding mutations in mantle cell lymphoma disrupt regulation of HNRNPH1 by alternative splicing [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-04.
Abstract PO-20: Molecular characterization of a mouse model of peripheral T-cell lymphoma with Tfh and Th2 features
Authors: Kuczynski Elizabeth , Morlino Giulia , Peter Alison , Calado Dinis , Sinclair Charles , Carnevalli Larissa
Published: December 2020

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of malignancies with an aggressive clinical course. Molecular and immunophenotypic analysis have linked PTCL subgroups to derivation from differentiated T cells, including T follicular helper (Tfh), Th1, and Th2 cells. Effective therapies for these PTCLs are undefined and tumor models are limited. We developed a novel mouse model of PTCL and applied it to evaluate responses to therapy. An in vivo transplantable cell line was isolated by passaging a splenic lymphoma arising from a mouse with B cell-specific Blimp1-deletion (Cγ1-Cre Blimp1fl/fl) into C57bl/6J mice. Lymphomas were profiled by flow cytometry, immunohistochemistry, RNA, and exome sequencing. Mice intravenously inoculated with lymphoma cells developed disseminated disease affecting primarily lymphoid tissues and the liver. Model latency to welfare endpoint was 3-4 weeks. Transplantable cells expressed multiple T-cell lineage markers, were CD8 negative and CD4 positive, but gradually downregulated CD4 with passaging. Lymphoma cells (“mPTCL”) also expressed a single TCRvβ chain, suggesting origin from a T helper cell clone. Immunophenotypically, mPTCL stably expressed Tfh markers ICOS, PD-1, CD40L, and low BCL6, and thus was potentially classifiable as a surrogate PTCL of Tfh phenotype. However, the transcriptome of purified mPTCL or spleens indicated a resemblance to Th2 cells and corresponding PTCL-GATA3 subtype (a PTCL-not otherwise specified). In accord with Tfh and Th2 helper function, B cells in the tumor microenvironment had an activated phenotype but were nonexpansive. Investigation into oncogenic pathways in mPTCL revealed a predicted deleterious mutation in Ctnnb1 (β-catenin) and enrichment for Myc-activated, cell cycle regulation, and DNA damage response genes. In vivo, mPTCL progression was significantly and potently delayed by monotherapy inhibition of ataxia telangiectasia and Rad3-related (ATR), a kinase central to resolving replication stress. Taken together, we established a novel model of PTCL with overlapping Tfh and Th2 features. Our findings in this model suggest the use of a DNA damage response inhibitor as a potential treatment strategy for aggressive PTCL-GATA3 lymphomas.

Citation Format: Elizabeth Kuczynski, Giulia Morlino, Alison Peter, Dinis Calado, Charles Sinclair, Larissa Carnevalli. Molecular characterization of a mouse model of peripheral T-cell lymphoma with Tfh and Th2 features [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-20.
Abstract PO-21: Investigating the role of exosomes derived from chemotherapy-resistant leukemia cells as mediators of cellular plasticity
Authors: Garnica Taismara , Lesbon Jéssika , Rochetti Arina , Payton Chantell , Muirhead Rhona , Pang Lisa , Argyle David , da Silveira Juliano , Fukumasu Heidge
Published: December 2020

Adult T-cell leukemia/lymphoma (ATLL) is a type of cancer with aggressive and rapid progression and has been linked to infection with the human T-cell lymphotropic virus type 1 (HTLV-1). Standard treatment consists of chemotherapy, radiation therapy, and stem-cell transplant, but the development of chemoresistance is common. Despite major advances in understanding the pathogenesis of the disease, patients who do not respond or achieve only transient responses remain a challenge for clinicians. Exosomes are small extracellular vesicles (30-150 nm in diameter) involved in intercellular communication and biologic material transference (including mRNA, miRNA, lipids, and metabolites) between the cells. Exosomes are an emerging key to understanding cancer cell communication and signaling pathway activation during the chemoresistance process. Our hypothesis is that exosomes secreted by chemoresistant (CR) ATLL cells can drive phenotypic changes in nonresistant ATLL cells. For this purpose, we induced chemoresistance using the CHOP protocol (dexamethasone, doxorubicin, and vincristine cocktail) in Jurkat cells (human acute T-cell leukemia/lymphoma). We determined IC50 values as 1 nM of dexamethasone, 0.05 μM of doxorubicin, and 1 nM of vincristine. Acquisition of chemoresistance was demonstrated by increased cell viability after treatment using IC50 of drugs cocktail. We found that Jurkat-CR have slower doubling time compared to respective naïve cells, 26 hours and 21 hours to CR-Jurkat and naïve, respectively. Exosomes derived from the putative chemoresistant were isolated and used to treat their respective naïve cells. There was an increase in cell proliferation after the exosome's treatment comparing to control for Jurkat (P<0.0035). However, there was no difference in proliferation comparing the treatment using exosomes derived from naïve cells and those derived from CR cells (P=0.91). The cell proliferation was higher after 78 hours of exosomes' treatment (P<0.001). Those results are preliminary data. Despite the differences in proliferation related to exosomes treatment, further experiments are required to prove our initial hypothesis.

Citation Format: Taismara Garnica, Jéssika Lesbon, Arina Rochetti, Chantell Payton, Rhona Muirhead, Lisa Pang, David Argyle, Juliano da Silveira, Heidge Fukumasu. Investigating the role of exosomes derived from chemotherapy-resistant leukemia cells as mediators of cellular plasticity [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-21.
Abstract PO-22: Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma
Authors: Razzaghi Raud , Agarwal Shreya , Kotlov Nikita , Plotnikova Olga , Nomie Krystle , Huang Da Wei , Wright George W. , Li Moyi , Takata Katsuyoshi , Yao Chen , O'Shea John J. , Phelan James D. , Pittaluga Stefania , Scott David W. , Muppidi Jagan R.
Published: December 2020

Fas is highly expressed on germinal center (GC) B cells, and mutations of FAS have been reported in diffuse large B-cell lymphoma (DLBCL); however, the function of Fas in the GC remains controversial. Although GC-derived DLBCL has better overall outcomes to therapy than other DLBCL types, some cases are refractory and the molecular basis for this is often unknown. We show that Fas is a strong cell-intrinsic regulator of GC B cells that promotes B-cell death in the light zone likely via T follicular helper (Tfh) cell-derived Fas ligand. In the absence of Fas, GCs were more clonally diverse due to an accumulation of cells that did not demonstrably bind antigen. We found that FAS alterations occurred most commonly in the GC-derived genetic subtype of DLBCL, EZB. FAS alterations in EZB were associated with inferior outcomes and an enrichment of Tfh cells. Alterations in FAS co-occurred with deficiency in HVEM and PD-1 ligands that regulate the Tfh-B cell interaction and were associated with increased diversity of B-cell receptor variable genes across samples. This work shows that Fas is critically required for GC homeostasis and suggests that loss of Tfh-mediated counterselection in the GC contributes to lethality in a distinct subtype of GC-derived lymphoma.

Citation Format: Raud Razzaghi, Shreya Agarwal, Nikita Kotlov, Olga Plotnikova, Krystle Nomie, Da Wei Huang, George W. Wright, Moyi Li, Katsuyoshi Takata, Chen Yao, John J. O'Shea, James D. Phelan, Stefania Pittaluga, David W. Scott, Jagan R. Muppidi. Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-22.
Abstract PO-29: Conserved and unique transcriptional programs in human and canine non-Hodgkin lymphomas inform the judicious applications for the spontaneous canine model of disease
Authors: Sarver Aaron L. , Modiano Jaime F.
Published: December 2020

Non-Hodgkin lymphomas (NHL) represent a diverse group of tumors that are common in both humans and dogs. Extensive work has documented driver genes and inferred the cell of origin for many subtypes of human NHL, and emerging data suggest that the driver events are distinct for the corresponding subtypes of canine NHL. This raises important questions about how and when spontaneous canine NHLs can or should be considered as models for human NHLs. Here, we show the application of bioinformatics tools that allow us to systematically reduce the dimensionality of complex transcriptional patterns across independent datasets, platforms, and species, and that are capable of identifying conserved and unique traits, as well as outcome associations. The application of these tools to human and canine NHL datasets shows that, for example, the gene expression cluster that defines the germinal center-B-cell (GCB)-like subtype is exclusively present in human samples, but not in dog samples. Conversely, we confirm that non-GCB subtypes (activated B-cell [ABC] or ABC-like) include a heterogeneous group of subtypes defined by expression of shared and species-specific gene clusters, including resident or infiltrating cells that mold the stromal and immune microenvironments. Moreover, we are able to expand this approach to other subtypes of NHL to discern the contributions from stromal transcriptional programs and from lymphocyte transcriptional programs by including samples in the analyses where stromal cells were depleted. Overall, our comparative genomic approach will enhance our understanding of the conserved and species-specific events that underlie the molecular etiology of NHL, informing when spontaneous canine NHL subtypes should be considered as independent, unrelated conditions and improving and refining when and how they can be used as a relevant spontaneous model of human NHL.

Citation Format: Aaron L. Sarver, Jaime F. Modiano. Conserved and unique transcriptional programs in human and canine non-Hodgkin lymphomas inform the judicious applications for the spontaneous canine model of disease [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-29.
Abstract PO-60: The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte-predominant Hodgkin lymphoma patients: A propensity-matched analysis of the Surveillance, Epidemiology, and End Results database
Authors: Wang Shijie , Jia Mingfang , Han Jianglong , Zhang Rui , Huang Kejie , Qiao Yunfeng , Chen Ping , Fu Zhenming
Published: December 2020

Background: The stage-specific roles of radiotherapy (RT) alone, chemotherapy alone, and chemoradiotherapy (CRT) for patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated.

Methods: We analyzed patients with NLPHL in all stages enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching was performed to ensure well-balanced characteristics between the comparison groups. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazard ratio (HR), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses.

Results: For early-stage patients, RT alone was found to be associated with the improved survival of 10 months to 15 months and the deceased HR of 60% to 80%. Chemotherapy alone also had survival benefits (improved OS = 12.1 months; improved CSS = 5.3 months). However, not all of these improvements were statistically significant. CRT was associated with the best survival: the mean OS was significantly improved by 20 months and the HR was reduced by more than 80%, both before and after PS matching (PSM) (P < 0.05). For advanced-stage patients, none of RT alone, chemotherapy alone, and CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long-term survival (RMST120m: neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104m vs. 111m vs. 108m). Subgroup analysis showed that the efficacy of RT alone in patients with early-stage NLPHL was significantly different between younger people and older people (age < 40: HR, 95% CI = 5.70, 0.34 - 94.2, P = 0.224; age ≧ 40: HR, 95% CI = 0.06, 0.01 - 0.32, P = 0.001; P for interaction = 0.005).

Conclusions: The results from the large SEER database suggested that CRT was associated with the best survival of patients with the early-stage NLPHL. More effective treatment strategies for patients with advanced-stage NLPHL remain to be further studied.

Citation Format: Shijie Wang, Mingfang Jia, Jianglong Han, Rui Zhang, Kejie Huang, Yunfeng Qiao, Ping Chen, Zhenming Fu. The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte-predominant Hodgkin lymphoma patients: A propensity-matched analysis of the Surveillance, Epidemiology, and End Results database [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-60.
Role of Inherited Thrombophilia Risk Factors in Patients with CKD-5 Receiving Haemodialysis
Authors: Liapi Dimitra , Sfiridaki Aikaterini , Livadiotaki Aikaterini , Alegakis Athanasios , Stylianou Kostas , Manika Ioanna , Renieri Vassia , Daphnis Eugene , Alexandrakis Michael
Published: December 2020

Background: The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. Objectives: The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. Methods: A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. Results: The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (p > 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; p = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. Conclusion: The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.
A Bitter Pill to Swallow: Pseudoachalasia Secondary to Oesophageal Deviation Resulting from Mediastinal Shift and Left Atrial Enlargement after Left Lower Lobectomy
Authors: Surmont Magali M.V.P. , Aerts Maridi , Kunda Rastislav , Kindt Sébastien
Published: December 2020

Pseudoachalasia, also known as secondary achalasia, is a rare clinical condition mimicking idiopathic achalasia but unrelated to primary loss of nitrergic innervation. It has mostly been attributed to malignancy infiltrating the oesophageal wall, but several other benign underlying pathologies have been reported. Because of similar manometric appearance, high-resolution manometry (HRM) of the oesophagus alone cannot distinguish between idiopathic achalasia and pseudoachalasia. Misdiagnosis can result in ineffective treatment by dilatation or even more invasive therapy. This is the first case-report of pseudoachalasia secondary to oesophageal deviation resulting from mediastinal shift and left atrial enlargement following prior left lower lobectomy. HRM, the gold standard for the diagnosis of achalasia, confirmed the incomplete relaxation of the lower oesophageal sphincter (LES) in absence of normal oesophageal peristalsis. However, additional workup with CAT scan and cardiac ultrasound identified an anatomical shift by the extrinsic mass effect resulting from the atrial enlargement, but without contrast retention at the LES.
Promoting Speech Intelligibility in Autism Spectrum Disorder through the Implementation of Phonologically Similar Stimuli
Authors: Petinou Kakia
Published: December 2020

Objectives: The study focused on promoting expressive phonological skills in 1 Greek-speaking child with autism spectrum disorder (ASD) and comorbid speech sound disorder (SSD). Based on the phonological neighborhood density framework, it was hypothesized that the experimental manipulation through clinical implementation of phonologically overlapping stimuli would yield positive expressive phonology gains relevant to ASD. Participant and Methods: A multiple-baseline single-subject design was implemented. Three baseline sessions measured expressive phonology variables. Sixteen biweekly 30-min intervention sessions were carried out for a period of 2 months. Dependent variables included phonetic inventory size, proportion of consonants correct, occurrences of phonological processes, and percentage of whole word matches elicited via specific word probe stimuli. The Intelligibility in Context Scale was completed by the child’s teacher prior to the initiation of intervention and at a follow-up session. Experimental stimuli were grouped together in phonologically dense cohorts. Results: Comparison between pre-test and post-test measures revealed expressive phonology gains across all measured variables. Follow-up session results showed generalization of expressive phonology gains on untreated targets. Conclusions: Significant expressive phonology gains were achieved through the implementation of phonologically similar word stimuli within a systematic intervention protocol with the implementation of specific word-level variables. The findings supported this treatment approach for a child with ASD and SSD, while providing evidence for the phonological density advantage from a cross-linguistic perspective.
Fewer Cancer Cases in 4 Countries of the WHO European Region in 2018 through Increased Alcohol Excise Taxation: A Modelling Study
Authors: Rovira Pol , Kilian Carolin , Neufeld Maria , Rumgay Harriet , Soerjomataram Isabelle , Ferreira-Borges Carina , Shield Kevin D. , Sornpaisarn Bundit , Rehm Jürgen
Published: December 2020

Introduction: Prevention of cancer has been identified as a major public health priority for Europe, and alcohol is a leading risk factor for various types of cancer. This contribution estimates the number of cancer cases that could have potentially been averted in 2018 in 4 European countries if an increase in alcohol excise taxation had been applied. Methods: Current country and beverage-specific excise taxation of 4 member states of the WHO European Region (Germany, Italy, Kazakhstan, and Sweden) was used as a baseline, and the potential impacts of increases of 20, 50, and 100% to current excise duties were modelled. A sensitivity analysis was performed, replacing the current tax rates in the 4 countries by those levied in Finland. The resulting increase in tax was assumed to be fully incorporated into the consumer price, and beverage-specific price elasticities of demand were obtained from meta-analyses, assuming less elasticity for heavy drinkers. Model estimates were applied to cancer incidence rates for the year 2018. Results: In the 4 countries, >35,000 cancer cases in 2018 were caused by alcohol consumption, with the highest rate of alcohol-attributable cancers recorded in Germany and the lowest in Sweden. An increase in excise duties on alcohol would have significantly reduced these numbers, with between 3 and 7% of all alcohol-attributable cancer cases being averted if taxation had been increased by 100%. If the 4 countries were to adopt an excise taxation level equivalent to the one currently imposed in Finland, an even higher proportion of alcohol-attributable cancers could be avoided, with Germany alone experiencing 1,600 fewer cancer cases in 1 year. Discussion/Conclusion: Increasing excise duties can markedly reduce cancer incidence in European countries.
Surgimento e consolidação da Semana Internacional de Arqueologia Discentes MAE/USP: uma reflexão
Authors: Brandão Kelly , Oliveira Aline Feitoza de , Gaspar Melian , Da Silva Maurício André , Panuzio Renato Saad , Estevam Renata , Nobre Emerson , Hirata Elaine Farias Veloso
Published: December 2020

Este artigo discute e reflete sobre a criação e consolidação da Semana Internacional de Arqueologia Discentes MAE/USP (SIA), que surgiu em 2007 e passou a ocorrer com frequência bianual. Organizada de forma aberta e colaborativa por discentes do Museu, a SIA se tornou um espaço de articulação, troca de conhecimentos e experiências, que desempenha um papel fundamental na formação de futuros profissionais engajados com a ciência e a gestão do patrimônio arqueológico no cenário nacional da Arqueologia. Ao longo das várias edições, o evento se profissionalizou e ganhou a marca internacional, com a criação de um protocolo dinâmico e democrático para que estudantes possam exercer trabalhos conjuntos e de maior inserção institucional. Uma organização feita por discentes e voltada para pessoas interessadas em geral, a SIA potencializou seu espírito aberto e o diálogo crescente com os diferentes coletivos humanos que vem demandando novas práticas e posturas do fazer arqueológico. Por meio de entrevistas, questionários, análises da documentação e nossa experiência pessoal, trazemos aqui um olhar sobre a história da SIA e seu papel na trajetória acadêmica de discentes e no Museu como um todo. Esperamos que essa reflexão possa contribuir com o estímulo para a continuidade e surgimento de outros eventos semelhantes pelo país.
lado humano da Arqueologia Forense: entrevista com Criméia Almeida
Authors: Almeida Criméia Alice Schmidt , Albuquerque João Pedro Silva de , Oliveira Aline Feitoza de , Calazans Marília Oliveira , Ramos Rebeca Righetti
Published: December 2020

Criméia Alice Schmidt Almeida participou da VI Semana Internacional de Arqueologia Discentes do Museu de Arqueologia e Etnologia da Universidade de São Paulo, na mesa de debate sobre Arqueologia da Repressão e Resistência: Materialidade e Patrimônio em Áreas de Conflito. Após sua fala, foi proposta uma entrevista para entender sua trajetória, sua aproximação com os campos da Arqueologia e Antropologia e seu contato com equipes internacionais e impressões sobre atuação de arqueólogos nos trabalhos de buscas e identificações desenvolvidos no Brasil. A entrevista permitiu reforçar a importância da troca entre as equipes técnicas e as famílias de pessoas desaparecidas.
Arqueologias indigenas: una mirada desde el Sur
Authors: Ayala Patricia
Published: December 2020

Este artículo es una reflexión sobre lo que se ha ido conformado en las últimas décadas como Arqueologías Indígenas. Enfatizo el sentido plural de este concepto porque, si bien se ha tratado de responder a la pregunta de qué son las Arqueologías Indígenas?, qué es lo que las caracteriza y diferencia de otras arqueologías alternativas?, se ha concluido que engloba una serie de aproximaciones teóricas y practicas, cuyos mayores ejes transversales - aunque no los únicos - se refieren a construir una arqueología con, por y para los pueblos indígenas, así como a generar una línea de trabajo que apueste por su descolonización y la construcción de metodologías colaborativas. Para ello se comparan y evalúan las experiencias Norte y Sud America.
A covariate-constraint method to map brain feature space into lower dimensional manifolds
Authors: Renard Félix , Heinrich Christian , Bouthillon Marine , Schenck Maleka , Schneider Francis , Kremer Stéphane , Achard Sophie
Published: December 2020

Human brain connectome studies aim to both explore healthy brains, and extract and analyze relevant features associated with pathologies of interest. Usually this consists of modeling the brain connectome as a graph and using graph metrics as features. A fine brain description requires graph metrics computation at the node level. Given the relatively reduced number of patients in standard cohorts, such data analysis problems fall in the high-dimension, low-sample-size framework. In this context, our goal is to provide a machine learning technique that exhibits flexibility, gives the investigator an understanding of the features and covariates, allows visualization and exploration, and yields insight into the data and the biological phenomena at stake. The retained approach is dimension reduction in a manifold learning methodology; the originality is that the investigator chooses one (or several) reduced variables. The proposed method is illustrated in two studies. The first one addresses comatose patients; the second one compares young and elderly populations. The method sheds light on the differences between brain connectivity graphs using graph metrics and potential clinical interpretations of these differences.
Demystifying Moral Damages in International Investment Arbitration
Authors: Weber Simon
Published: December 2020

Claims for compensation of material damages in investment arbitration are well known – they are part of every dispute. Tribunals deal extensively with such claims and do not accord much attention to another type of damages: moral damages. Until today, no uniform solution has been found. There seems to be stark disagreement between arbitral tribunals on how to deal with a claim for moral damages. This article sheds light on moral damages and proposes a possible solution under international law. To this end, it introduces the concept of moral damages and its history in international disputes. After having set out such general overview, it then applies the concept to investment arbitration by analysing five issues arbitral tribunals have been faced with when confronted by a claim for moral damages. Finally, it comments on the most prominent awards and provides an outlook for a possible solution.
Reparation Modalities at the Extraordinary Chambers in the Courts of Cambodia (ECCC)
Authors: Perez-Leon-Acevedo Juan-Pablo
Published: December 2020

In the last decade, the ECCC has ordered reparations for victims of the Khmer Rouge’s mass atrocities committed in Cambodia during the 1970s. Various scholars have examined those reparations ordered by the ECCC. Yet, this is the first academic piece to assess the ECCC’s reparation modalities under the UN Reparation Principles, which contain key standards on reparations for victims of atrocities. Overall, the ECCC has ordered important rehabilitation, satisfaction and guarantees of non-repetition measures to redress victims’ harm. This is a meaningful current development with regard to reparations for victims of atrocities. However, the ECCC’s reparation law and practice exhibits some important deficits under the UN Reparation Principles. At the ECCC, restitution and compensation are excluded and the range of guarantees of non-repetition has been limited. Nonetheless, these deficits must be considered within the ECCC’s mandate as an internationalised criminal court.
Res judicata and the Admissibility of Applications before the African Court on Human and Peoples’ Rights: a Fresh Look at Dexter Eddie Johnson v. Republic of Ghana
Authors: Nkhata Mwiza Jo
Published: December 2020

In Dexter Eddie Johnson v. Republic of Ghana, the African Court on Human and Peoples’ Rights (the Court), for only the second time in its history, applied Article 56(7) of the African Charter on Human and Peoples’ Rights (the Charter) to declare a case inadmissible. The Court reasoned that the case was inadmissible since the applicant had first approached, and obtained a determination, from the United Nations Human Rights Committee before lodging his case with the Court. This article analyses the Court’s decision and attempts to unpack the Court’s interpretation and application of the doctrine of res judicata, which is the essence of the requirement in Article 56(7) of the Charter.
¿Dónde están los Judíos en la “Vida Americana?”: Art, Politics, and Identity on Exhibit
Authors: Shandler Jeffrey
Published: December 2020

Vida Americana: Mexican Muralists Remake American Art, 1925–1945, an exhibition that opened at the Whitney Museum of American Art in February, 2020, proposed to remake art history by demonstrating the profound impact Mexican painters had on their counterparts in the United States, inspiring American artists “to use their art to protest economic, social, and racial injustices.” An unexamined part of this chapter of art history concerns the role of radical Jews, who constitute almost one half of the American artists whose work appears in the exhibition. Rooted in a distinct experience, as either immigrants or their American-born children, these Jewish artists had been making politically charged artworks well before the Mexican muralists’ arrival in the United States. Considering the role of left-wing Jews in this period of art-making would complicate the curatorial thesis of Vida Americana. Moreover, the exhibition’s lack of attention to Jews in creating and promoting this body of work raises questions about how the present cultural politics of race may have informed the analysis of this chapter of art history.
Ideophones in Moro
Authors: Naser Angelo Ali , Rose Sharon
Published: December 2020

This article presents a descriptive study of ideophones in Moro, addressing both their structural characteristics and usage, with data from the Thetogovela dialect. We describe their sound patterns, word categorization and placement within sentences, and discuss their meaning and conventionalization. Moro ideophones convey a wide range of sensory meanings, including sound, touch, movement and visual patterns. They are uninflected and typically appear utterance finally, most closely resembling adverbs. Ideophones are often introduced by support verbs, including ‘do’, ‘be’ and ‘eat’, the latter for visual patterns. Ideophones may exhibit reduplication, which in some cases can correspond to pluractionality. The main distinctive sound pattern of Moro ideophones is a wider distribution of obstruents, as well as a performative use of expressive duration and phonation.
Property concepts in Tabaq: More than one road can lead to Rome
Authors: Schneider-Blum Gertrud , Hellwig Birgit
Published: December 2020

In this paper, we investigate the interplay between the morphosyntactic class of adjectives, the semantics of property concepts, and the function of noun modification in Tabaq, a Kordofan Nubian language (Nilo-Saharan phylum) spoken in the north-west of the Nuba Mountains in Sudan. Tabaq has a small class of adjectives containing few semantic types, and playing only a limited role with respect to the core function of adjectives: the modification of nouns. By contrast, a large number of descriptive modifiers is derived from two other word classes, verbs and nouns, and this paper describes the different ways of coding property concepts in Tabaq.
Verbal and verbless copular clauses in Moro
Authors: Jenks Peter
Published: December 2020

Moro has a rich array of copular clause constructions which show clear contrasts in their syntactic makeup. One class of copular clauses contain verbal heads, others are headed by non-verbal predicates that bear some inflectional morphology which is shared with verbs, while a final group of copular clauses lack any words which could be identified as verbs. I show that verbal and verb-like copular clauses always contain a predicative core. On the other hand, verbless copular clauses lack predicative semantics, serving the functions of identification or equation. I provide a simple syntactic analysis which accounts for the morphosyntactic distribution of the different types of clauses.
Latinx Boys and Juvenile Delinquency
Authors: Van Wyk Judy A.
Published: December 2020

This study examines Latinx boys in the juvenile justice system and addresses acculturation theory to assess whether or not adjudicated foreign-born Latinx boys are more delinquent than others before adjudication, and whether or not these boys are a bigger burden on the juvenile justice system than others. The present study addresses data and methodological issues that plague the current research using the Ocean Tides Database containing multi-year (1975–2019) cross sectional data for 1,083 adjudicated boys. Multivariate analyses confirm that Latinx immigrant youth who are delinquent pose no greater threats to the American public either before or after adjudication than US-born citizens or other immigrants do. There is minimal support for acculturation theory in explaining behavioral differences between first and second-generation Latinx immigrants.
Slave Christologies: Augustine and the Enduring Trouble with the “Form of a Slave” (Phil 2:5–7)
Authors: Elia Matthew
Published: December 2020

This essay finds in the thought of Augustine of Hippo a key moment in the development of a strand of the Western theological tradition I will call slave Christologies: theological accounts of the person and work of Jesus Christ that, drawing from the Philippians hymn (Phil 2:5–11), symbolically identify his body with the body of the enslaved, and in so doing, weave the order of slaveholding into the texture of Christian thought. I approach the political and theological implications of this tradition under the pressure of a twofold haunting: of the perennial, if hard to specify, interplay between ideas and forms of life, between the symbolic and the social; and of the contingent, specific historical afterlife of racial slavery which provides the conditions for contemporary Christian thought.