tbuckley/cabot-search huggingface dataset:
Avian Neo-Sex Chromosomes Reveal Dynamics of Recombination Suppression and W Degeneration
Authors: Hanna Sigeman, Maria Strandh, Estelle Proux-Wéra, Verena E Kutschera, Suvi Ponnikas, Hongkai Zhang, Max Lundberg, Lucile Soler, Ignas Bunikis, Maja Tarka, Dennis Hasselquist, Björn Nystedt, Helena Westerdahl, Bengt Hansson
Journal: Molecular Biology and Evolution (2021)

How the avian sex chromosomes first evolved from autosomes remains elusive as 100 million years (My) of divergence and degeneration obscure their evolutionary history. The Sylvioidea group of songbirds is interesting for understanding avian sex chromosome evolution because a chromosome fusion event ∼24 Ma formed "neo-sex chromosomes" consisting of an added (new) and an ancestral (old) part. Here, we report the complete female genome (ZW) of one Sylvioidea species, the great reed warbler (Acrocephalus arundinaceus). Our long-read assembly shows that the added region has been translocated to both Z and W, and whereas the added-Z has retained its gene order the added-W part has been heavily rearranged. Phylogenetic analyses show that recombination between the homologous added-Z and -W regions continued after the fusion event, and that recombination suppression across this region took several million years to be completed. Moreover, recombination suppression was initiated across multiple positions over the added-Z, which is not consistent with a simple linear progression starting from the fusion point. As expected following recombination suppression, the added-W show signs of degeneration including repeat accumulation and gene loss. Finally, we present evidence for nonrandom maintenance of slowly evolving and dosage-sensitive genes on both ancestral- and added-W, a process causing correlated evolution among orthologous genes across broad taxonomic groups, regardless of sex linkage.
Analysis of reasons for Emergency Department (ED) visits and subsequent hospital admissions in patients with solid malignancies: A retrospective study from a cancer center in rural Maine.
Authors: Anannya Patwari, Vineel Bhatlapenumarthi, Courtney Brann, Jackson Waldrip, Victoria Caruso, Abigail Hatch, Adam Curtis, Catherine Chodkiewicz
Journal: Journal of Clinical Oncology (2021)

241 Background: Reducing ED visits in patients with cancer is cost saving and is particularly relevant during the COVID pandemic. We aim to identify patterns of ED visits among various cancer patients and reduce preventable ED visits and hospital admissions. Methods: We analyzed the number of ED visits and hospital admissions that occurred in patients with breast, lung, and Gastrointestinal (GI) cancers between July1 2019 and October31 2020 including demographics, stage, treatment type preceding the month of ED visit, reason, time of the day, day of the week the visit occurred. Results: 308 patients had 519 ED visits, 111 breast cancer patients had 184, 102 lung cancer patients had 186 and 95 GI cancer patients had 149 ED visits. 38% had &gt; 1 visit. 51%, (37% breast, 60% Lung and 58 % GI cancer) had stage 4 disease at the time of visit. There were no visits in the month of May 2020. 275 (53%) visits required hospital admissions, 60% of ED visits in lung cancer, 54% in GI and 46 % in breast cancer patients required hospitalization. Most common reason for ED visits in breast cancer patients was fall/injury (20%), with median age of 71 years, none were cancer/ chemotherapy induced. Among lung and GI cancer patients respiratory (24%) and GI related (24%) symptoms were the most common reasons respectively, majority were cancer/chemotherapy related. Most common symptoms requiring hospital admissions were respiratory 21%, GI 18%, cardiac 12%. 11% and 9% of ED visits were due to fall/injury and cancer related pain, of these 3.6% and 9% resulted in hospital admissions respectively. Lung and GI cancer patients were more likely to be referred to the ED from the oncologist office (23%) than breast cancer patients (11%). Conclusions: Reasons for ED visits vary by tumor types and some may be preventable. Fall/injury in breast cancer patients and cancer related pain in lung and GI cancer patients were frequent reasons for preventable ED visits. In lung and GI cancer patients, cancer/chemotherapy related respiratory, GI symptoms are felt to be less avoidable since they may be related to disease progression or presenting symptoms. We have initiated several strategies such as ‘’systematic physical therapy assessment’’ of our breast cancer patients over age 70 to reduce ED visits due to fall/injury. We are developing strategies to involve palliative care early to reduce the number of ED visits related to cancer related pain We now have “call us first campaign” to assess and intervene before going to ED since most visits occurred during working hours.[Table: see text]
Serious complications and recurrences after pelvic organ prolapse surgery for 2,309 women in the VIGI-MESH registry
Authors: T. Charles, R. De Tayrac, S. Campagne-Loiseau, M. Cosson, P. Ferry, X. Deffieux, J-P. Lucot, L. Wagner, P. Debodinance, C. Saussine, A-C. Pizzoferrato, C. Carlier-Guérin, T. Thubert, L. Panel, P-O. Bosset, E. Nkounkou, R. Ramanah, T. Boisramé, C. Raiffort, A. Chavériat, A. Fauconnier, X. Fritel
Journal: European Urology (2021)
Real-world outcomes in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab.
Authors: Gurjyot K. Doshi, Nicholas J. Robert, Liwei Chen, Philip K Chan, Viviana Del Tejo, Brian Stwalley, Stephen Huo, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2021)

305 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, was approved by the US Food and Drug Administration in April 2018 for the treatment of intermediate- or poor-risk advanced renal cell carcinoma (RCC), and the treatment paradigm has changed dramatically over the past few years. This real-world study examined treatment patterns and sequences, treatment response, safety, and survival outcomes with this novel first-line (1L) combination therapy among patients diagnosed with metastatic RCC (mRCC) in a community oncology practice setting. Methods: A retrospective analysis of the US Oncology Network’s iKnowMed medical data examined adult patients with an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognosis of intermediate- or poor-risk clear cell mRCC who received 1L NIVO+IPI between April 1, 2018, and March 31, 2020. Baseline demographic and clinical characteristics, treatment patterns, and treatment sequence were examined descriptively. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), time to treatment discontinuation (TTD), and time to treatment response (TTR) were analyzed using the Kaplan–Meier method. Treatment-related adverse events (TRAEs) and healthcare resource utilization were also analyzed. Results: A total of 193 adults with stage IV mRCC treated with 1L NIVO+IPI were identified. Median age (range) was 63 (30.0–89.0) years, 73.1% were male, 69.4% were white, 56.7% were IMDC intermediate risk, and 60.6% had a documented Eastern Cooperative Oncology Group performance status of 0 or 1. Median follow-up time (range) was 9.7 (0.1–24.7) months. Median PFS (95% CI) was 17.1 (12.6–21.2) months, and the 1-year landmark PFS rate was 58.3% (50.4–65.4). At 12 months, the OS rate (95% CI) was 75.4% (67.8–81.4). The ORR (95% CI) was 43.2% (34.6–52.1) among patients with a response assessment; the median TTR (range) was 2.8 (0.3–4.1) months and median DoR was not reached. Median TTD (95% CI) was 5.8 (4.5–7.5) months. Among the 63 (31.3%) patients who received second-line therapy, 50.8% received cabozantinib and 12.7% received pazopanib. TRAEs were reported in 47.2% of patients—the most frequently reported were fatigue (13.5%), rash (10.4%), diarrhea (6.7%), nausea (6.2%), colitis (3.6%), and pruritus (3.6%). The treatment-related hospitalization rate was 5.5% and the emergency department visit rate was 3.1%. Conclusions: This real-world study supports the clinical efficacy of 1L NIVO+IPI for patients with mRCC. Our findings also suggest that the NIVO+IPI combination was generally well tolerated in the real-world setting, with low rates of adverse events and healthcare resource utilization.
Open-source concealed EEG data collection for Brain-computer-interfaces - neural observation through OpenBCI amplifiers with around-the-ear cEEGrid electrodes
Authors: Michael Thomas Knierim, Christoph Berger, Pierluigi Reali
Journal: Brain-Computer Interfaces (2021)

(2021). Open-source concealed EEG data collection for Brain-computer-interfaces - neural observation through OpenBCI amplifiers with around-the-ear cEEGrid electrodes. Brain-Computer Interfaces: Vol. 8, No. 4, pp. 161-179.
Heart rate: Activity mismatch as a prognostic marker of survival in metastatic non-small cell lung cancer (NSCLC).
Authors: Sonam Puri, Yeonjung Jo, Benjamin Haaland, Kathleen Claire Kerrigan, Shiven B. Patel, Adriana M Coletta, Kelly Moynahan, Laura Cannon, Matthew Gumbleton, Nicole Hillman, Kelsey Embrey, Wallace L. Akerley
Journal: Journal of Clinical Oncology (2021)

190 Background: Performance status (PS) is the foundation for clinical trial eligibility criteria and the basis for treatment decisions in the treatment of NSCLC, but it is limited by subjectivity and potential miscommunication between patient, physician, and family. Activity trackers use is widespread and offers the potential to collect a broad range of patient generated data (steps, activity, heart rate, calories, sleep, etc.) to supplement the assessment of PS while minimizing subjectivity. Here we evaluated a clinical observation that elevated heart rate at rest is prognostic of survival. Methods: Patients with metastatic NSCLC were asked to participate in a prospective, observational study of potential prognostic survival factors that included wearing a FitBit tracker with a goal to measure HR-Activity mismatch measured by 2 parameters: 1) Heart Rate-Activity Mismatch (HAM) by percent of time when HR is high and activity is moderate or low over a day; 2) inappropriate HR (iHR) is the ratio of time with elevated HR/sedentary minutes average over a week. Correlation and regression analyses were performed for the initial 55 patients enrolled prior to COVID restrictions using data limited to the average of 7 days with wear &gt; 500 minutes closest to date of consent. Results: We enrolled 55 patients with metastatic NSCLC. There were 35 females and 20 males with a median age of 67 years. A majority of patients were never (38%, n = 21) or former smokers (40%, n = 22); adenocarcinoma (83%, n = 83%) was the most common histology. 30% (n = 17) patients were on 2 nd or greater line of therapy. 52 were included for survival analysis and 21 expired with median survival 226 days (149, NA). As average daily steps increased by 1000, the hazard of death decreased by a factor of 0.65 (95% CI: 0.45, 0.93, p = 0.018). As daily average distance increased by 1 mile, the hazard of death decreased by 0.55 (95% CI: 0.33, 0.91, p = 0.019). For HAM, the risk of death increased by 1.14 (95% CI: 1, 1.13, p = 0.046) for every 10% increase in HAM. For iHR &lt; 1 (i.e. high HR when sedentary), the risk of death was 2.84 (95% CI: 1.05, 7.67, p = 0.04) compared those with iHR &gt; 1. Steps, Distance, HAM and iHR were not statistically different by gender. Conclusions: Tracker-based measures of steps/distance and HR-Activity are prognostic of survival in NSCLC and may be useful to supplement evaluation of PS in clinical trials and practice.
Oncology value based payment models: Where are the savings opportunities?
Authors: Era Kim Oh, Jon Maguire, Tracy E. Spinks, Kristen K. McNiff Landrum, Jennifer Malin
Journal: Journal of Clinical Oncology (2021)

69 Background: Oncology practices are increasingly participating in value-based payment (VBP) arrangements; however, there is limited information on where practices have the greatest impact on reducing medical costs. Methods: United Healthcare (UHC) conducted a pilot to evaluate a VBP consisting of an episode fee, eliminating drug margin, and shared savings. The pilot was limited to members with breast, lung or colon cancer enrolled in UHC’s commercial plans. We compared total medical cost (TMC) per 120-day episode calculated from paid claims amounts for the pilot practices with a concurrent national cohort for the performance period (9/2015-9/2019) and a baseline period (1/2013-3/2015) using a difference-in-differences technique with a generalized linear regression model, adjusting for age, gender, cancer type and stage (adjuvant vs. metastatic), comorbidities, cancer surgery, radiation therapy, novel therapy, duration of therapy, and region. We categorized claims into 6 categories and estimated the impact of the VBP on costs: chemotherapy/drugs, radiation therapy, cancer surgery, cancer diagnostics, other cancer-related and other non-cancer related. In addition, we evaluated the difference in acute inpatient admission rates. Results: Patient treated in the pilot practices contributed 2,647 episodes of a total of 73,352 episode during the performance period, weighted equally between adjuvant and metastatic disease (Table). The adjusted TMC per 120-day episode was $36,434 for the national cohort and $37,215 for the participating clinics at baseline and $50,773 and $41,416, respectively during the performance period, resulting in an average decrease in TMC of $9,687 or a 20% reduction; although this varied significantly by stage and cancer type. The relative decrease in medical costs by category ranged from 13% for chemotherapy/drugs to 33% for cancer surgery and an increase in costs associated with cancer diagnostics of 7%; however, chemotherapy/drug were still associated with the largest absolute decrease in costs ($2,941). Practices participating in the pilot had a 24.7% decrease in the number of acute inpatient admissions and 12.6% decrease in the number of inpatient admission days; however, this did not reach statistical significance. Conclusions: Overall, practices participating in a VBP pilot with a commercial health plan decreased TMC per episode by 20% with savings across all cost categories except for cancer diagnostics.[Table: see text]
Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity
Authors: Clément Anfray, Francesco Mainini, Elisabeth Digifico, Akihiro Maeda, Marina Sironi, Marco Erreni, Achille Anselmo, Aldo Ummarino, Sara Gandoy, Francisco Expósito, Miriam Redrado, Diego Serrano, Alfonso Calvo, Marvin Martens, Susana Bravo, Alberto Mantovani, Paola Allavena, Fernando Torres Andón
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer and hinder the antitumoral efficacy of most treatments currently applied in the clinic. Previous studies have evaluated the antitumoral immune response triggered by (TLR) agonists, such as poly(I:C), imiquimod (R837) or resiquimod (R848) as monotherapies; however, their combination for the treatment of cancer has not been explored. This study investigates the antitumoral efficacy and the macrophage reprogramming triggered by poly(I:C) combined with R848 or with R837, versus single treatments. Methods TLR agonist treatments were evaluated in vitro for toxicity and immunostimulatory activity by Alamar Blue, ELISA and flow cytometry using primary human and murine M-CSF-differentiated macrophages. Cytotoxic activity of TLR-treated macrophages toward cancer cells was evaluated with an in vitro functional assay by flow cytometry. For in vivo experiments, the CMT167 lung cancer model and the MN/MCA1 fibrosarcoma model metastasizing to lungs were used; tumor-infiltrating leukocytes were evaluated by flow cytometry, RT-qPCR, multispectral immunophenotyping, quantitative proteomic experiments, and protein–protein interaction analysis. Results Results demonstrated the higher efficacy of poly(I:C) combined with R848 versus single treatments or combined with R837 to polarize macrophages toward M1-like antitumor effectors in vitro. In vivo, the intratumoral synergistic combination of poly(I:C)+R848 significantly prevented tumor growth and metastasis in lung cancer and fibrosarcoma immunocompetent murine models. Regressing tumors showed increased infiltration of macrophages with a higher M1:M2 ratio, recruitment of CD4 + and CD8 + T cells, accompanied by a reduction of immunosuppressive CD206 + TAMs and FOXP3 + /CD4 + T cells. The depletion of both CD4 + and CD8 + T cells resulted in complete loss of treatment efficacy. Treated mice acquired systemic antitumoral response and resistance to tumor rechallenge mediated by boosted macrophage cytotoxic activity and T-cell proliferation. Proteomic experiments validate the superior activation of innate immunity by poly(I:C)+R848 combination versus single treatments or poly(I:C)+R837, and protein–protein-interaction network analysis reveal the key activation of the STAT1 pathway. Discussion These findings demonstrate the antitumor immune responses mediated by macrophage activation on local administration of poly(I:C)+R848 combination and support the intratumoral application of this therapy to patients with solid tumors in the clinic.
Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
Authors: Lin Chen, Jie Deng, Ailing Yu, Yuhan Hu, Bo Jin, Pengyuan Du, Jianhong Zhou, Lei Lei, Yuan Wang, Serhii Vakal, Xingyi Li
Journal: Bioactive Materials (2021)

Boosting transcorneal permeability and pharmacological activity of drug poses a great challenge in the field of ocular drug delivery. In the present study, we propose a drug-peptide supramolecular hydrogel based on anti-inflammatory drug, dexamethasone (Dex), and Arg-Gly-Asp (RGD) motif for boosting transcorneal permeability and pharmacological activity via the ligand-receptor interaction. The drug-peptide (Dex-SA-RGD/RGE) supramolecular hydrogel comprised of uniform nanotube architecture formed spontaneously in phosphate buffered saline (PBS, pH = 7.4) without external stimuli. Upon storage at 4 °C, 25 °C, and 37 °C for 70 days, Dex-SA-RGD in hydrogel did not undergo significant hydrolysis, suggesting great long-term stability. In comparison to Dex-SA-RGE, Dex-SA-RGD exhibited a more potent in vitro anti-inflammatory efficacy in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages via the inhibition of nuclear factor кB (NF-κB) signal pathway. More importantly, using drug-peptide supramolecular hydrogel labeled with 7-nitro-2,1,3-benzoxadiazole (NBD), the Dex-SA-K(NBD)RGD showed increased performance in terms of integrin targeting and cellular uptake compared to Dex-SA-K(NBD)RGE, as revealed by cellular uptake assay. On topical instillation in rabbit's eye, the proposed Dex-SA-K(NBD)RGD could effectively enhance the transcorneal distribution and permeability with respect to the Dex-SA-K(NBD)RGE. Overall, our findings demonstrate the performance of the ligand-receptor interaction for boosting transcorneal permeability and pharmacological activity of drug.
제5차 대한간학회 춘계학술대회 초록집 : 포스터 전시 순서 ; 반티증후군: 항응고요법으로 치료한 간문맥 및 상장간막정맥 혈전증
Authors: 곽성재 ( Gwag Seong Jae ), 고상원 ( Go Sang Won ), 박수현 ( Park Su Hyeon ), 여미애 ( Yeo Mi Ae ), 김형건 ( Kim Hyeong Geon ), 이명석 ( Lee Myeong Seog ), 김우중 ( Kim U Jung )
Journal: Clinical and Molecular Hepatology (1999)
A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models
Authors: Eric S. Lightcap, Pengfei Yu, Stephen Grossman, Keli Song, Mithun Khattar, Kristina Xega, Xingyue He, James M. Gavin, Hisashi Imaichi, James J. Garnsey, Erik Koenig, Hongru Zhang, Zhen Lu, Pooja Shah, Yu Fu, Michael A. Milhollen, Beryl A. Hatton, Jessica Riceberg, Vaishali Shinde, Cong Li, James Minissale, Xiaofeng Yang, Dylan England, Richard A. Klinghoffer, Steve Langston, Katherine Galvin, Gary Shapiro, Sai M. Pulukuri, Serge Y. Fuchs, Dennis Huszar
Journal: Science Translational Medicine (2021)

TAK-981, a first-in-class small-molecule SUMOylation inhibitor, activates type I interferon signaling to promote antitumor immune responses in mice.
Association of Online Risk Factors With Subsequent Youth Suicide-Related Behaviors in the US
Authors: Steven A. Sumner, Brock Ferguson, Brian Bason, Jacob Dink, Ellen Yard, Marci Hertz, Brandon Hilkert, Kristin Holland, Melissa Mercado-Crespo, Shichao Tang, Christopher M. Jones
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The association between online activities and youth suicide is an important issue for parents, clinicians, and policy makers. However, most information exploring potential associations is drawn from survey data and mainly focuses on risk related to overall screen time. <h3>Objective</h3> To evaluate the association between a variety of online risk factors and youth suicide-related behavior using real-world online activity data. <h3>Design, Setting, and Participants</h3> A matched case-control study was conducted from July 27, 2019, to May 26, 2020, with the sample drawn from more than 2600 US schools participating in an online safety monitoring program via the Bark online safety tool. For 227 youths having a severe suicide/self-harm alert requiring notification of school administrators, cases were matched 1:5 to 1135 controls on location, the amount of follow-up time, and general volume of online activity. <h3>Exposures</h3> Eight potential online risk factors (cyberbullying, violence, drug-related, hate speech, profanity, sexual content, depression, and low-severity self-harm) through assessment of text, image, and video data. <h3>Main Outcomes and Measures</h3> Severe suicide/self-harm alert requiring notification of school administrators; severe suicide alerts are statements by youths indicating imminent or recent suicide attempts and/or self-harm. <h3>Results</h3> The 1362 participants had a mean (SD) age of 13.3 (2.41) years; 699 (51.3%) were male. All 8 online risk factors studied exhibited differences between case and control populations and were significantly associated with subsequent severe suicide/self-harm alerts when examining total direct and indirect pathways. These associations ranged from an adjusted odds ratio (aOR) of 1.17 (95% CI, 1.09-1.26) for drug-related content to an aOR of 1.82 (95% CI, 1.63-2.03) for depression-related content. When considering the total number of different types of online risk factors among the 8 measured, there was an exponentially larger risk of severe suicide/self-harm alerts; youths with 5 or more of the 8 risk factors present in their online activity had a more than 70-fold increased odds of subsequently having a severe suicide/self-harm alert (aOR, 78.64; 95% CI, 34.39-179.84). <h3>Conclusions and Relevance</h3> The findings of this study suggest that many discrete types of risk factors are identifiable from online data and associated with subsequent youth suicide-related behavior. Although each risk factor carries a specific association with suicide-related behavior, the greatest risk is evident for youths demonstrating multiple types of online risk factors.
ACC/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with atrial fibrillation
Authors: Robert L. McNamara, Lawrence M. Brass, Joseph P. Drozda, Alan S. Go, Jonathan L. Halperin, Charles R. Kerr, Samuel Lévy, David J. Malenka, Suneet Mittal, Frank Pelosi, Yves Rosenberg, Daniel Stryer, D.George Wyse, Martha J. Radford, David C. Goff, Frederick L. Grover, Paul A. Heidenreich, David J. Malenka, Eric D. Peterson, Rita F. Redberg
Journal: Journal of the American College of Cardiology (2004)