bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA03: PARP inhibitor and platinum resistance in ovarian cancer-genome wide CRISPR screens
Authors: Chowdhury Dipanjan 
Published: September 2020

Abstract
High-grade serous ovarian carcinoma (HGSOC) patients with germline mutations in BRCA1/2 exhibit high sensitivity and improved outcome to platinum-based drugs and PARP inhibitors. Three PARP inhibitors (olaparib, rucaparib, niraparib) have recently gained FDA approval for the treatment of HGSOCs. However, de novo and acquired resistance to these agents is common even in the BRCA mutation carriers and pose a significant, unsolved clinical challenge. Here we identify multiple gene complexes involved in PARPi resistance through a loss-of-function CRISPR screen. High-confidence hits include previously identified 53BP1, PARP1, shieldin complex, and ATMIN/DYNLL1 complex. Only for DYNLL1 does low expression correlate with worse outcome in BRCA1-mutant ovarian cancer patients; incidentally, all these patients had platinum-based therapy. In BRCA1-defective HGSOC patients, DNA end resection is greatly compromised and contributes to the loss of HR and PARP inhibitor sensitivity. DNA end resection is a vital process that initiates homologous recombination (HR)-mediated repair of double-stranded DNA breaks and consequently influences genome stability. Loss of DYNLL1 allows DNA end resection and restores HR in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and PARP inhibitors. In primary ovarian carcinomas low BRCA1 expression correlates with increased chromosomal aberrations, and the junction sequences of somatic structural variants indicate the loss of HR. Concurrent decrease in DYNLL1 expression in BRCA1-low ovarian cancers “rescued” this phenotype with reduced genomic alterations and increased homology at putative lesions. From the mechanistic standpoint, we observed that DYNLL1 limits nucleolytic degradation of DNA ends by interacting with the DNA end resection machinery (MRN complex, BLM helicase, and DNA2) in cells. The impact of DYNLL1 on end resection can be recapitulated in vitro; this is dependent on direct interaction with MRE11. Furthermore, DYNLL1 mutants that do not interact with MRE11 phenocopy the PARPi resistance phenotype of DYNLL1/BRCA1-deficient cells. Therefore, we infer that DYNLL1 is an important antiresection factor that significantly influences genomic stability and response to DNA-damaging chemotherapy in ovarian cancer patients.
Citation Format: Dipanjan Chowdhury. PARP inhibitor and platinum resistance in ovarian cancer-genome wide CRISPR screens [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA03.
Abstract IA06: The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative
Authors: Birrer Michael J. , Wenzel Lari , Miller Austin , Lankes Heather , Ramirez Nilsa , Parmigiani Giovanni , Mok Samuel , Nephew Kenneth , Conrads Thomas , Coukos George , Maxwell George L. , Fulci Giulia , Scroggins Mary 
Published: September 2020

Abstract
In 2019 there will be 22,500 new cases of ovarian cancer, resulting in approximately 14,000 deaths. Ovarian cancer remains the highest case fatality rate of any gynecologic cancer. Despite significant improvement in the surgical and chemotherapeutic managements of ovarian cancer patients, the overall survival has not changed in 30 years. However, these new therapies have resulted in a significant improvement in median survival, resulting in increasing numbers of patients surviving greater than 10 years with disease. The clinical and molecular features of these unique patients remain uncharacterized. The Department of Defense Ovarian Cancer Research Program (DOD OCRP) funded the creation of our interdisciplinary Long-term Survivor Consortium (LTSC), composed of 6 research sites including MDACC, UAB, IU, UCI, Ludwig Cancer Research, and University Hospitals of Canton Vaud (CHUV) and INOVA, a bioinformatic center at DFCI, and administrative centers at UCI and UAB. The purpose of the consortium is to identify characteristics and predictors of long-term survival in advanced ovarian cancer patients. The consortium is overseen by both a scientific and advocacy advisory board to guide direction and efforts. 285 specimens of advanced-stage high-grade serous ovarian cancers with full clinical annotation including greater than 12 years of follow-up were analyzed for this project. In addition, 340 early-stage high-grade ovarian cancers were available for one of the AIMs of the project. These latter samples were obtained through the creation of an international consortium funded by the DOD OCRP. All specimens were first reviewed for tumor context by H&E staining to determine percentage of tumor. The scientific platforms include whole transcriptome, microRNAs, global proteomics, immune profiling, and methylation. All specimens were analyzed on each individual platform and the results will be integrated in a global process. In parallel with these efforts, a systematic analysis of quality of life of patients at the time of diagnosis and later during the course of their disease based upon patient-reported outcome surveys has been undertaken. These data will also be integrated with genomic results to produce signatures that can further characterize long-term survivors of ovarian cancer.
Citation Format: Michael J. Birrer, Lari Wenzel, Austin Miller, Heather Lankes, Nilsa Ramirez, Giovanni Parmigiani, Samuel Mok, Kenneth Nephew, Thomas Conrads, George Coukos, George L. Maxwell, Giulia Fulci, Mary Scroggins. The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA06.
Abstract IA15: Modeling the tumor microenvironment of high-grade serous ovarian cancer
Authors: Balkwill Frances 
Published: September 2020

Abstract
Using biopsies of metastatic high-grade serous ovarian cancer (HGSOC) that ranged from minimal to extensive disease, we defined RNA and protein profiles that evolved with changes in cellularity, architecture, and tissue modulus. This gave new insights into host response to cancer as well as leukocyte, cytokine, and matrisome regulation in the tumor microenvironment (TME). Although we had studied a single metastatic site, we identified an extracellular matrix (ECM) gene expression signature, which we named the matrix index, that significantly associated with increased stiffness and disease score. High matrix index distinguished patients with a shorter overall survival in ovarian and twelve other primary cancers, suggesting a common matrix response to human cancer. We used this “deconstruction” analysis of a human TME to build 3D multicellular cultures of human HGSOC cells, primary omental fibroblasts, mesothelial cells, and adipocytes. These cultures reproduce the prognostic matrix index signature, as confirmed by RNAseq and immunofluorescence, of the human cancer biopsies. Using these 3D models, we can study regulation of the matrisome and cancer cell invasion. Similarly, we have conducted multilevel analysis of orthotopic mouse models of HGSOC metastases with relevant oncogenic mutations. This analysis identified significant correlations between the transcriptome, host cell infiltrates, immune response, matrisome, vasculature, and tissue modulus of mouse and human TMEs, with several stromal and malignant cell targets in common. However, each mouse model showed distinct differences and potential vulnerabilities that enabled us to predict response to chemotherapy and an anti-IL-6 antibody. The transcriptional profiles of the mouse tumors that differed in chemotherapy response were able to classify chemotherapy-sensitive and -refractory patient tumors. We believe that these 3D human and mouse models provide useful preclinical tools and may help identify subgroups of HGSOC patients most likely to respond to specific therapies.
Citation Format: Frances Balkwill. Modeling the tumor microenvironment of high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA15.
Abstract IA26: Combined PARP and immune checkpoint inhibition in ovarian cancer
Authors: Konstantinopoulos Panagiotis A. 
Published: September 2020

Abstract
Ovarian cancer (OC) is one of the few malignancies in which immunotherapy with immune checkpoint inhibitors exhibits only modest activity and currently has no FDA-approved indication. Therefore, the development of strategies to improve the efficacy of immune checkpoint blockade is a high priority in this disease. Recent studies in OC models have demonstrated that PARP inhibitors (PARPi), besides their direct cytotoxic effects, exhibit antitumor immunity that occurs in a STING-dependent manner and is augmented by immune checkpoint blockade. Based on these studies, combined PARP and immune checkpoint inhibition represents an active area of clinical investigation in OC. The goal of this presentation is to outline the preclinical data behind combined PARP and immune checkpoint inhibition in OC, highlight preliminary results as well as ongoing clinical trials of PARPi/immune checkpoint inhibitor combinations in both first-line and recurrent disease, and discuss emerging biomarkers of response.
Citation Format: Panagiotis A. Konstantinopoulos. Combined PARP and immune checkpoint inhibition in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA26.
Clientelism and Democracy
Authors: Sommer Jamie M. 
Published: September 2020

Abstract
Carbon dioxide (CO2) emissions are rapidly increasing across the world. While national governments are usually seen as having the power, authority, and ability to make significant reductions in their CO2 outputs, cross-national research rarely focuses on the institutional structures of states that moderate their CO2 emissions. Previous research that focuses on internal state factors largely focus on democracy and find wildly conflicting results. This research argues that clientelism is a missing piece of the puzzle in explaining how democracy impacts CO2 emissions. Building on the extant contradictory research, the present study uses two-way fixed effects regression analysis for 150 nations from 1971-2014 to understand how the interaction between clientelism and democracy impacts CO2 emissions. The findings reveal that controlling for clientelism reduces CO2 outputs more in high-income and low-income nations with higher levels of participatory democracy. However, the interaction is not statistically significant for all nations, nor for middle-income nations. These results suggest that reducing clientelist relationships in nations with high- and low-incomes, but not middle incomes will make participatory democracies more effective at reducing CO2 emissions.
Confessionalization, Symphony, or Democratization?
Authors: Tsvietkova Yulianna V. 
Published: September 2020

Abstract
This article analyzes modern religious life in Ukraine, specifically the relations between religious organizations and government bodies in state and social domains. Particular attention is given to the concrete territorial and historical evolution of state Christian doctrines and church relations in Ukrainian lands. The article also examines the main problems and conflicts regarding the registration and functioning of the largest religious organizations in the country, and relations between them. Special attention is paid to the role that religious organizations play in the democratic processes, and to their effect on the relations between state and church. These relations have unfolded against the background of the political events of the last 15 years in Ukraine and the region: internal social conflicts, the general trend toward pro-European democratization, and the Russian-Ukrainian conflict.
Chemosensory Dysfunction in COVID‐19: Prevalences, Recovery Rates, and Clinical Associations on a Large Brazilian Sample
Authors: Brandão Neto Deusdedit , Fornazieri Marco Aurélio , Dib Caroline , Di Francesco Renata Cantisani , Doty Richard L. , Voegels Richard Louis , de Rezende Pinna Fabio 
Published: September 2020

ObjectiveOur study aimed to measure the percentage of reported olfactory or taste losses and their severity, recovery time, and association with other features in a large cohort of patients with COVID‐19.Study DesignProspective survey.SettingQuaternary medical center and online survey.MethodsThe perceived chemosensory capacities of 655 patients with confirmed COVID‐19 were assessed with 11‐point category rating scales (0, no function; 10, normal function). Patients were contacted in hospital, by phone calls, or by internet regarding their ability to smell or taste, and 143 were interviewed by phone 1 to 4 months later to assess the recovery of their chemosensory abilities.ResultsThe prevalence of self‐reported olfactory, general taste, and taste quality–specific disturbances (sweet, sour, bitter, and salty) in the patients with COVID‐19 were 82.4% (95% CI, 79.5%‐85.3%), 76.2% (95% CI, 72.9%‐79.4%), and 52.2% (95% CI, 48.3%‐56.1%), respectively. The majority reported anosmia (42.9%). The presence of chemosensory symptoms was not associated with COVID‐19 severity. At a median time >2 months after the onset of symptoms, rates of total and partial olfaction recovery were 53.8% and 44.7%, while complete or partial return to previous taste function was 68.3% and 27.6%. Less than 5% of the patients reported no chemosensory function improvement at all.ConclusionThe prevalence of self‐reported chemosensory dysfunction is high among patients with COVID‐19. Almost all patients seem to recover a significant part of their smell and taste abilities in the first 4 months after the onset of symptoms.
Conversion to hemi-shoulder arthroplasty or reverse total shoulder arthroplasty after failed plate osteosynthesis of proximal humerus fractures: a retrospective study
Authors: Han Xiulan , Zhuang Jintao , Yu Weiguang , Gao Yixin , Zhao Mingdong , Ye Junxing , Han Guowei , Zeng Xianshang 
Published: September 2020

Objective To assess the clinical outcomes of hemi-shoulder arthroplasty (HSA) versus reverse total shoulder arthroplasty (RTSA) following failed plate osteosynthesis of proximal humerus fractures in elderly patients. Methods This retrospective study identified all patients that had a documented failed plate osteosynthesis of proximal humeral fractures treated with revision HSA or RTSA. Follow-up occurred at 1, 3, 6 and 12 months after surgery and every year thereafter. The primary outcomes were the American Shoulder and Elbow Surgeons (ASES) scores, Simple Shoulder Test (SST) scores, visual analogue scale (VAS) pain scores and the University of California, Los Angeles Shoulder Rating Scale (UCLA SRS) scores. The secondary outcome was the rate of major complications. Results A total of 126 patients (126 shoulders) were enrolled in the study. At the final follow-up, the RTSA group had significantly greater improvements in ASES, SST and UCLA SRS scores than the HSA group. The RTSA group had significantly larger decreases in the VAS pain score compared with the HSA group. The rate of major complications was significantly higher in the HSA group than in the RTSA group (44.4% versus 27.5%, respectively). Conclusion RTSA provided superior functional outcomes compared with HSA, with a lower rate of major complications after a follow-up period of at least 5 years.
A Review of Drug-Drug Interactions for Biologic Drugs Used in the Treatment of Psoriasis
Authors: Armanious Miriam , Vender Ronald 
Published: September 2020

Biologic drugs are increasingly being prescribed for the treatment of psoriasis. Very little information is available in the literature regarding potential drug interactions with these medications. This paper serves as a guide for prescribers to be aware of possible interactions between biologic drugs approved for the treatment of psoriasis in North America and concomitant therapies. Objective To provide an overview of reported drug interactions between biologic drugs and concomitant therapies. Methods Reports of potential drug interactions were compiled through a search of Micromedex, drug monographs (Canadian, American, and European), as well as a PubMed search of each biologic drug with the term “drug interaction.” Conclusion Generally, caution should be exercised when multiple immunosuppressive therapies are prescribed due to increased risk of infection. However, this is more the result of a synergistic effect as opposed to a true drug interaction. There have been cases where multiple biologic therapies have been concomitantly used without adverse events, as their mechanisms involved different pathways. The sources used to compile this guide were often comprised of low levels of evidence, reinforcing the idea that further studies are required to better direct prescribers.
Wood-Related Open-Globe Injuries
Authors: Pfister Tyler , Bohnak Carisa , Patel Shriji 
Published: September 2020

Purpose: This work evaluates the clinical characteristics, visual outcomes, and complications of patients treated for open-globe injuries (OGIs) caused by wooden objects. Methods: A retrospective review of medical records was conducted on patients presenting to a tertiary trauma center with an OGI between January 2005 and December 2017. Medical records were isolated for wounds caused by wooden objects. Patient demographics were recorded, with presenting visual acuity (VA), physical examination findings, and wound characteristics. After primary globe repair, secondary complications, need for additional surgery, and visual outcomes were noted until final examination. Main outcome measures were final VA and secondary complications. The Ocular Trauma Score (OTS) was computed and assessed for clinical relevance related to visual outcomes. Results: Thirty-two patients met the inclusion criteria, with 15 (47%) being injured by plant material. Thirty of the patients were men (94%). A large portion of patients presented with hand motion or worse vision (48%), and there were high rates of hyphema (59%), vitreous hemorrhage (31%), retinal detachment (28%), and endophthalmitis (9%). Two patients eventually required enucleation. At last follow-up, 19 patients achieved 20/100 VA or better (59.4%), which correlated with their OTS ( P < .001). Conclusions: Despite the high clinical severity of wood OGIs, the potential for visual recovery remains high. The OTS appropriately assesses the severity of injuries and the likely prognosis in this cohort of patients.
The prevalence of headache disorders in children and adolescents in Mongolia: a nationwide schools-based study
Authors: Luvsannorov Otgonbayar , Anisbayar Tsengunmaa , Davaasuren Munkhzul , Baatar Otgonzaya , Batmagnai Khaliunaa , Tumurbaatar Khulan , Enkhbaatar Sarantuya , Uluduz Derya , Şaşmaz Tayyar , Solmaz Elif Tuğçe , Steiner Timothy J. 
Published: September 2020

Abstract
Background
The Global Campaign against Headache collects data from children (7–11 years) and adolescents (12–17 years) both to inform health and education policies and to contribute to the Global Burden of Disease (GBD) study. This survey in Mongolia was part of this global enquiry.

Methods
Following the generic protocol for the global enquiry, this was a schools-based cross-sectional survey. Self-completed structured questionnaires were administered, within classes, in seven schools in four districts of the Capital city and three rural areas of Mongolia, selected to represent the country’s diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache (UdH).

Results
Of 4515 potential participants, 4266 completed the questionnaire (children 2241 [52.5%], adolescents 2025 [47.5%]; males 2107 [49.4%], females 2159 [50.6%]). Children were therefore slightly over-represented, although overall mean age was 11.3 ± 3.3 years (range: 6–17; median 11). The non-participation proportion was 4.5%. Observed lifetime prevalence of headache was 81.0%. Gender- and age-adjusted 1-year prevalence was 59.4% (migraine: 27.3%; tension-type headache [TTH]: 16.1%; UdH: 6.6%; all headache on ≥15 days/month: 4.2%; probable medication-overuse headache: 0.7%). All headache types except UdH were more prevalent among females than males, and all were more prevalent among adolescents than children, although UdH represented a higher proportion of all headache in children (13.0%) than in adolescents (10.0%). Headache yesterday was reported by 15.9% of the sample, 26.0% of those with headache.

Conclusions
At least in adolescents, headache in Mongolia is no less common than in adults. The clear difference from similar studies in other countries was a lower prevalence of UdH, perhaps a consequence of reporting bias in a non-troublesome headache (mild and short-lasting by definition). This study informs policy in Mongolia and, with no similar study yet from elsewhere in Western Pacific Region, makes an important contribution to the global enquiry.
The prevalence of headache disorders in children and adolescents in Ethiopia: a schools-based study
Authors: Zewde Yared Zenebe , Zebenigus Mehila , Demissie Hanna , Tekle-Haimanot Redda , Uluduz Derya , Şaşmaz Tayyar , Bozdag Fatma , Steiner Timothy J. 
Published: September 2020

Abstract
Background
The Global Burden of Disease (GBD) study establishes headache as the second-highest cause of disability worldwide. Because most headache data in GBD are from adults, leading to underestimation of headache-attributed burden, a global schools-based programme within the Global Campaign against Headache is contributing data from children (7–11 years) and adolescents (12–17 years). This national study in Ethiopia is the first in this programme reported from sub-Saharan Africa.

Methods
A cross-sectional survey following the generic protocol for the global study was conducted in six schools (urban and rural), in Addis Ababa city and three regions of Ethiopia. Structured questionnaires were self-completed under supervision by pupils within their classes. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH).

Results
Of 2349 potential participants, 2344 completed the questionnaire (1011 children [43.1%], 1333 adolescents [56.9%]; 1157 males [49.4%], 1187 females [50.6%]), a participation proportion of 99.8%. Gender- and age-adjusted 1-year prevalence of headache was 72.8% (migraine: 38.6%; tension-type headache: 19.9%; UdH: 12.3%; all headache on ≥15 days/month: 1.2%; probable medication-overuse headache: 0.2%). Headache was more prevalent in females (76.2%) than males (71.0%), a finding reflected only in migraine among the headache types. Headache was more prevalent among adolescents (77.6%) than children (68.4%), reflected in all types except migraine, although prevalence of UdH fell sharply after age 14 years to 3.9%.
For headache overall, findings matched those in Turkey and Austria, obtained with the same questionnaire, but the high prevalence of migraine, not increasing with age, was surprising. The study highlighted diagnostic difficulties in young people, especially when poorly educated, with migraine diagnoses driven by improbably high proportions reporting nausea (44.8%) and vomiting (28.0%) as usual symptoms accompanying their headaches.

Conclusions
Headache is very common in children and adolescents in Ethiopia. This has major public-health implications, since half the country’s population are aged under 18 years.