tbuckley/cabot-search huggingface dataset:
Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth
Authors: Joseph Niyibizi, Marie-Hélène Mayrand, François Audibert, Patricia Monnier, Paul Brassard, Louise Laporte, Julie Lacaille, Monica Zahreddine, Marie-Josée Bédard, Isabelle Girard, Diane Francoeur, Ana Maria Carceller, Jacques Lacroix, William Fraser, François Coutlée, Helen Trottier, Helen Trottier, Marie-Hélène Mayrand, François Coutlée, Patricia Monnier, Louise Laporte, Joseph Niyibizi, Monica Zahreddine, Ana Maria Carceller, Paul Brassard, Jacques Lacroix, Diane Francoeur, Marie-Josée Bédard, Isabelle Girard, François Audibert, William Fraser
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. <h3>Objective</h3> To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. <h3>Design, Setting, and Participants</h3> The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. <h3>Exposures</h3> Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. <h3>Main Outcomes and Measures</h3> The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. <h3>Results</h3> The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. <h3>Conclusions and Relevance</h3> The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.
The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation
Authors: Zhiwei Fan, Changyue Wu, Miaomiao Chen, Yongying Jiang, Yuanyuan Wu, Renfang Mao, Yihui Fan
Journal: Acta Pharmaceutica Sinica B (2021)

The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around
Mobile app care utility: Patients and caregivers perception.
Authors: Ingrid Oakley-Girvan, Reem Yunis, Elaine Kurtovich, Sara Aghaee, Ai Kubo, Maya Ramsey, Michelle Longmire, Elad Neeman, Raymond Liu
Journal: Journal of Clinical Oncology (2021)

157 Background: There is increasing appreciation for the insight provided by combining low-burden home-based remote digital measurements with patient and observer reported outcomes. In this study, we assessed perspectives of cancer patients and their caregivers on the utility of a mobile app combined with a smartwatch for collection of specific outcomes and to provide clinically actionable data. Methods: In a decentralized clinical trial we consented and enrolled (10/12/2020-4/30/2021) dyads that consisted of a cancer patient and their informal caregiver. All participants had to own an Apple iPhone 6 or higher. Patients were provided with an Apple watch 3 or 4 and downloaded a patient informed mobile app (DigiBioMarC). Caregivers only download a caregiver informed mobile app (TOGETHERCare). Participants were asked to use their respective app for 28 days during which time specific surveys and activity requests were delivered through the mobile app; digital measures of physical activity were collected via the smartwatch. At the end of the app usage period, questions were asked in a video interview about the patient and caregiver perspectives on use of their respective apps and what they believed could be impacted if their doctor were to receive the app information. Respondents could select Strongly Agree, Agree, Neutral, Disagree, or Strongly Disagree. Results: Fifty-four dyads were enrolled; four were unable to continue due to a decline in health. Questions were drafted and IRB approved in time to be asked of 45 dyads. The Table lists some results and the percent of respondents that selected Strongly Agree or Agree. Conclusions: Patients and caregivers reported that both apps would encourage them to take better care of themselves/be more physically active and would improve emotional wellbeing. A high proportion of respondents also felt the apps would improve communication with their doctor and provide early important information for the doctor to act upon compared to usual care. Additional work in a large randomized trial is planned to evaluate specific care outcomes. [Table: see text]
P04.10 <i>CDKN2A</i> mutational status is associated with venous thromboembolism in patients with glioblastoma
Authors: M Y Kapteijn, F H J Kaptein, M A M Stals, S G van Duinen, M J B Taphoorn, L Dirven, J A F Koekoek, F A Klok, H H Versteeg, J T Buijs
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Patients with glioblastoma have a high risk of developing venous thromboembolism (VTE). However, the underlying genetic risk factors remain largely unknown. Therefore, the aim of our study was to discover whether genetic aberrations in glioblastoma associate with VTE. MATERIAL AND METHODS In this retrospective cohort study, all patients diagnosed with glioblastoma between February 2017 and August 2020 in two hospitals (Leiden University Medical Center and Haaglanden Medical Center) were included (n=341). Targeted DNA next-generation sequencing (NGS) had been performed of all glioblastomas for diagnostic purposes and included tumor mutational status of the genes ATRX, BRAF, CIC, FUBP1, H3F3A, IDH1, IDH2, PIK3CA, PTEN and TP53 and amplification/gain or deletion of BRAF, CDKN2A, EGFR, NOTCH1 and PTEN. Through extensive chart review, we collected data on VTE events (deep vein thrombosis and/or pulmonary embolism) three months before until two years after glioblastoma diagnosis, which were adjudicated by an independent investigator. Patients with cerebral vein thrombosis (n=3) and low quality NGS data (n=1; minimum reads/samples: &amp;lt;1.5M and/or minimum depth: &amp;lt;100 reads) were excluded. Cox regression analysis and competing risk analysis (CICR) were performed to compare patients that developed VTE with patients that did not. RESULTS Of the 337 patients, 215 had died, 26 were diagnosed with VTE and 37 were lost to follow-up. CDKN2A deletion was found to associate most significantly with VTE (HR: 2.65, 95%CI: 1.18–5.94, p=0.018). Competing risk analysis confirmed this finding, demonstrating a 12-month adjusted cumulative incidence of 12.7% (95%CI: 7.5–19.3) compared to 5.2% (95%CI: 2.5–9.2) in patients with CDKN2A wild-type (p=0.013). No significant association was found between any of the investigated genes, including CDKN2A deletion, and death. CONCLUSION This study demonstrates that CDKN2A deletion is associated with VTE in glioblastoma patients. Therefore, CDKN2A mutational status may be a promising predictor to identify patients with glioblastoma at high risk of VTE, who may benefit from thromboprophylaxis.
The nematode C. elegans senses airborne sound
Authors: Adam J. Iliff, Can Wang, Elizabeth A. Ronan, Alison E. Hake, Yuling Guo, Xia Li, Xinxing Zhang, Maohua Zheng, Jianfeng Liu, Karl Grosh, R. Keith Duncan, X.Z. Shawn Xu
Journal: Neuron (2021)

Unlike olfaction, taste, touch, vision, and proprioception, which are widespread across animal phyla, hearing is found only in vertebrates and some arthropods. The vast majority of invertebrate species are thus considered insensitive to sound. Here, we challenge this conventional view by showing that the earless nematode C. elegans senses airborne sound at frequencies reaching the kHz range. Sound vibrates C. elegans skin, which acts as a pressure-to-displacement transducer similar to vertebrate eardrum, activates sound-sensitive FLP/PVD neurons attached to the skin, and evokes phonotaxis behavior. We identified two nAChRs that transduce sound signals independently of ACh, revealing an unexpected function of nAChRs in mechanosensation. Thus, the ability to sense airborne sound is not restricted to vertebrates and arthropods as previously thought, and might have evolved multiple times independently in the animal kingdom, suggesting convergent evolution. Our studies also demonstrate that animals without ears may not be presumed to be sound insensitive.
OS14.4.A The Neuroplastic Potential of the Human Brain before and After Glioma Surgery: Towards “Interventional Neurorehabilitation
Authors: A Poologaindran, R Romero-Garcia, M Hart, I Young, T Santarius, S Price, R Sinha, C Profyris, C Profyris, Y Erez, C Teo, M Sughrue, J Suckling
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The human brain is a highly neuroplastic ‘complex’ network: it self-organises without a hard blueprint, adapts to evolving circumstances, and can withstand insults. However, similar to other naturally occurring networks, brain networks can only endure a finite amount of damage before cognitive processes are affected. In this study, we first sought to establish the brain networks governing domain-general cognition (DGC) in healthy individuals across the lifespan. We then sought to map, track, and potentially rehabilitate networks governing DGC through connectomics and non-invasive brain stimulation (NIBS) when damaged by low-grade gliomas (LGG) and surgical oncology. METHODS Using MRI and cognitive data from n=629 individuals (aged 18–88, Female= 51%), we assessed the structural, functional, and topological relevance of the spatially-distributed multiple-demand (MD) system for DGC. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectomic and cognitive data at multiple time points: pre-surgery and post-surgery Day 1, Month 3, Month 12. In an independent cohort of n=34 patients, we sought to establish the safety profile for “interventional neurorehabilitation”: connectome-driven NIBS in the acute post-operative period to accelerate cognitive recovery. RESULTS In healthy individuals, the MD system across multiple scales of biological organisation was positively associated with higher-order cognition (Catell’s fluid intelligence). In our patients, pre-operative LGG infiltration into the structural MD system was negatively associated with the number of long-term cognitive deficits, suggesting a functional reorganisation. Mixed-effects modelling demonstrated the resilience of the functional MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed increased perioperative modularity can distinguish patients with long-term cognitive improvements at one-year follow-up. Finally, NIBS within two weeks post-craniotomy had a 90% (n=31/34) recruitment rate into the trial. There were no seizures or serious complications due to NIBS in this patient population. Transient headaches and tingling were reported in a minority of patients. CONCLUSION For the first time, we elucidate long-term cognitive and network trajectories following LGG surgery while establishing a positive safety-profile for NIBS in the acute post-operative period. We argue that “mesoscale” brain mapping serves as a robust biomarker for intervention-related plasticity for future clinical trials. While we performed these experiments in the context of neurosurgery, connectomics and NIBS could be adopted across diverse neuro-oncological care pathways (i.e. chemotherapy/radiation).
Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small cell lung cancer (NSCLC).
Authors: Stephanie Ossowski, Elad Neeman, Charles Borden, Amy Ying Ju Lin, Raymond Liu
Journal: Journal of Clinical Oncology (2021)

244 Background: Next generation sequencing (NGS) is a crucial component of evaluation of newly diagnosed patients with metastatic non-small cell lung cancer (NSCLC) to determine appropriate first line treatment. Delays in NGS can lead to psychologic distress for patients and can affect choices in first line therapy, especially for patients with underlying targetable mutations. While more data is needed to benchmark turnaround time for NGS results, guidelines and expert consensus suggest time from diagnosis to treatment should be 15 days and turnaround time for genomic testing 10-14 days. This study was aimed at reducing time to NGS results in a large integrated health care system. Methods: Through the ASCO Quality Training Program, we reviewed electronic medical records of 25 patients with newly diagnosed, untreated metastatic NSCLC from 12/2018 to 9/2020 and determined number of days from pathological diagnosis to NGS results. We reviewed process maps for oncology, pathology, the internal data management division, and a genomic testing company to determine factors leading to significant preventable delays. Since 11/2020, we created an automated weekly report using CoPath to identify new pathological diagnoses of potential metastatic NSCLC. The oncology department reviewed these cases weekly and NGS orders were placed for patients with metastatic NSCLC. Eleven additional patients with newly diagnosed metastatic NSCLC were included in the prospective cohort. Results: Demographic characteristics are noted in Table. Our intervention reduced median time from pathological diagnosis to NGS results from 24 to 19 days. Median time from biopsy results to NGS order was reduced from 7 to 1 day. Time from specimen being sent from pathology to NGS vendor was a median of 6 days in both cohorts. Total time from pathological diagnosis to appropriate treatment was reduced from a median of 33 to 25 days. Conclusions: Delays in time to NGS results can be reduced by improved communication between departments and simple, automated interventions to ensure results are efficiently released to an oncologist. Additional Plan-Do-Study-Act cycles are currently being developed to further reduce time from biopsy results to NGS results. [Table: see text]
P13.03 Sex-specific influence of androgen receptor gene expression on survival of glioblastoma patients
Authors: M Łysiak, M Trybuła, A Malmström, M Mudaisi, C Bratthäll, M Strandeus, P Milos, M Hallbeck, P Söderkvist
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The mRNA and protein expression of androgen receptor (AR) are upregulated in glioblastoma (GBM) and studies show that use of AR antagonists leads to apoptosis of GBM cells in vitro and reduction of tumor volume in a mouse model. With increased prevalence of GBM among males, the role and genetic alterations of AR are worth investigating, especially taking into account the location of AR on chromosome X and possible sex differences associated with it. MATERIAL AND METHODS Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 106 fresh frozen GBM samples (34 females and 72 males) collected at Linköping University Hospital. This cohort was also subjected to AR promoter methylation analysis, where 17 CpG sites were the target of pyrosequencing. Methylation levels were then correlated with mRNA gene expression, independently for each sex, using Pearson correlation coefficient. Gene expression of AR was also analyzed in The Cancer Genome Atlas cohort of primary IDH wild type GBM (135 females and 219 males) and association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomization by maximally selected rank statistics. RESULTS DNA amplifications, as well as deletions of the AR were detected, with a higher frequency of alterations found in females (26.4% vs. 8.3%). AR gene expression correlated with methylation levels of two CpG sites in females (chrX:67543271, chrX:67543762) and three different CpG sites in males (chrX:67543889, chrX:67543895, chrX:67543899). There was no difference in the AR expression between males and females in neither of the cohorts, but significantly higher AR expression was found in the classical subtype of GBM in TCGA. Survival analysis of the TCGA cohort revealed the opposite effect of AR expression on OS of males and females, with high AR expression correlating with shorter OS in females (13.6 vs.15.7 months, p=0.035) and longer OS in males (16.6 vs. 12.2 months, p=0.04). Additional gene set enrichment analysis of these samples showed that high AR expression was strongly correlated with DNA repair but only in the male group. CONCLUSION Our results show that high AR mRNA expression in GBM exhibits different effects on patients’ survival depending on their sex, despite common occurrence of high AR expression and CN changes in males and females. The reasons for potential protective influence of AR in males remain unclear and require further investigations.
PL03.4.A Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period
Authors: M Coomans, L Dirven, N Aaronson, B Baumert, M van den Bent, A Bottomley, A Brandes, O Chinot, C Coens, T Gorlia, U Herrlinger, F Keime-Guibert, A Malmström, F Martinelli, R Stupp, A Talacchi, W Wick, J Reijneveld, M Taphoorn
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Maintenance of functioning and wellbeing during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period. MATERIAL AND METHODS We included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period. RESULTS 5539 patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9%-29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on ≥1 scale. Median deterioration-free survival period ranged between 3.8–5.4 months, and median time-to-deterioration between 8.2–11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period. CONCLUSION HRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients’ functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signalled.
KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state
Authors: Jin-Woo Lee, Jin Hur, Yoo-Wook Kwon, Cheong-Whan Chae, Jae-Il Choi, Injoo Hwang, Ji-Yeon Yun, Jin-A Kang, Young-Eun Choi, Young Hyun Kim, Sang Eun Lee, Cheol Lee, Dong Hyun Jo, Heeyoung Seok, Byong Seung Cho, Sung Hee Baek, Hyo-Soo Kim
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. Methods Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. Results KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. Conclusions KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.