tbuckley/cabot-search huggingface dataset:
Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance)
Authors: Jonathan E. Rosenberg, Karla A. Ballman, Susan Halabi, Pamela J. Atherton, Amir Mortazavi, Christopher Sweeney, Walter M. Stadler, Benjamin A. Teply, Joel Picus, Scott T. Tagawa, Sreedhar Katragadda, Daniel Vaena, Jamal Misleh, Christopher Hoimes, Elizabeth R. Plimack, Thomas W. Flaig, Robert Dreicer, Dean Bajorin, Olwen Hahn, Eric J. Small, Michael J. Morris
Journal: Journal of Clinical Oncology (2021)

The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP).Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity.With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm.The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.
A long-term retaining molecular coating for corneal regeneration
Authors: Yi Zhang, Chenglin Li, Qiuwen Zhu, Renjie Liang, Chang Xie, Shufang Zhang, Yi Hong, Hongwei Ouyang
Journal: Bioactive Materials (2021)

Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide. There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility. Here we demonstrate a strategy of a protein coating for corneal injury regeneration. We synthesize an o-nitrosobenzaldehyde group (NB)-modified gelatin (GelNB), which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating. The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration, thereby effectively accelerating corneal repair and regeneration. The histological structure of the regenerated cornea is more similar to the native cornea. This molecular coating can be used conveniently as an eye drop solution, which makes it a promising strategy for corneal regeneration.
46P Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) plus chemotherapy in HER2-positive early breast cancer (EBC): Safety results from the adjuvant phase of the randomised, open-label, multicentre phase III (neo)adjuvant FeDeriCa study
Authors: S-A. Im, A.R. Tan, A. Mattar, R. Colomer, D. Stroyakovskii, Z. Nowecki, M. De Laurentiis, J-Y. Pierga, K.H. Jung, C. Schem, C. Aguila, T. Badovinac Crnjevic, S. Heeson, M. Shivhare, A. Alexandrou, E. Restuccia, C. Jackisch
Journal: Annals of Oncology (2021)
Abstract 17191: Virtual Fractional Flow Reserve Computed Through Design of Experiments Has Significant Correlation With Pressure Wire Fractional Flow Reserve
Authors: Javad Hashemi, Narayana Sarma Singam, Travis R Huffman, Robert E Berson, Shahab Ghafghazi
Journal: Circulation (2019)

Introduction: Fractional Flow Reserve (FFR) is the gold standard for quantification of coronary stenosis. Recently, computational fluid dynamics (CFD) methods have been used to compute virtual FFR ...
Abstract 027: Individual-level Fine Particulate Air Pollution Is Associated With Arrhythmia In Adolescents
Authors: Fan He, Julio Fernandez-Mendoza, Jeff D Yanosky, Vernon M Chinchilli, Laila Al-Shaar, Duanping Liao
Journal: Circulation (2021)

Introduction: Fine particulate (PM 2.5 ) exposure has been related to higher propensity of arrhythmias in adults. However, the association between PM 2.5 exposure and arrhythmia in adolescents remains unclear. Hypothesis: PM 2.5 exposure is related to an acute increase in numbers of arrhythmic heartbeats in adolescents. Methods: We used data collected from 421 adolescents in the Penn State Child Cohort (PSCC) follow-up examination for this report. From each participant, we obtained 24-hour beat-to-beat ECG data using a 12-lead Holter ECG. From which, arrhythmias, including premature ventricular contraction (PVC) and premature atrial contraction (PAC), were identified. The number of PVCs and PACs every 30 minutes were analyzed with individual-level 30-minute average PM 2.5 concentrations obtained by using a personal minute-by-minute PM 2.5 monitor for 24 hours in parallel to the ECG. Thus, each participant contributed 48 30-minute segments of arrhythmia and PM 2.5 data. Polynomial distributed lag models within a framework of a negative binomial model were used to assess the segment-specific and cumulative effect of PM 2.5 concentration on numbers of PVC and PAC, adjusting for age, race, sex, BMI percentile, temperature, and humidity. Results: The mean (SD) age of PSCC was 16.9 (2.2) years, with 54% males, and 78% whites. The 30-minute mean (SD) of PM 2.5 concentration was 14.4 (45.4) μg/m 3 , while PVC and PAC counts were 0.2 (2.0) and 0.5 (4.0). As shown in the table, 10 μg/m 3 increases in PM 2.5 concentration 0.5-2.0 hours prior to the ECG measures (lags 1-3) each were associated with 2% increase in PVC counts (all p&lt;0.05). Cumulatively, a 10 μg/m 3 increment in PM 2.5 was associated with a 5% (1% - 10%) increase in PVC counts within 2 hours after exposure. PM 2.5 was not related to PAC counts. Conclusion: Individual-level exposure to PM 2.5 is associated with an acute increased number of ventricular arrhythmia in population-based adolescents. The time course of the effect of PM 2.5 on ventricular arrhythmia is within 2 hours after exposure.
Lower step rate is associated with a higher risk of bone stress injury: a prospective study of collegiate cross country runners
Authors: Stephanie A Kliethermes, Mikel R Stiffler-Joachim, Christa M Wille, Jennifer L Sanfilippo, Pedro Zavala, Bryan C Heiderscheit
Journal: British Journal of Sports Medicine (2021)

Objectives To determine if running biomechanics and bone mineral density (BMD) were independently associated with bone stress injury (BSI) in a cohort of National Collegiate Athletic Association Division I cross country runners. Methods This was a prospective, observational study of 54 healthy collegiate cross country runners over three consecutive seasons. Whole body kinematics, ground reaction forces (GRFs) and BMD measures were collected during the preseason over 3 years via motion capture on an instrumented treadmill and total body densitometer scans. All medically diagnosed BSIs up to 12 months following preseason data collection were recorded. Generalised estimating equations were used to identify independent risk factors of BSI. Results Univariably, step rate, centre of mass vertical excursion, peak vertical GRF and vertical GRF impulse were associated with BSI incidence. After adjusting for history of BSI and sex in a multivariable model, a higher step rate was independently associated with a decreased risk of BSI. BSI risk decreased by 5% (relative risk (RR): 0.95; 95% CI 0.91 to 0.98) with each one step/min increase in step rate. BMD z-score was not a statistically significant risk predictor in the final multivariable model (RR: 0.93, 95% CI 0.85 to 1.03). No other biomechanical variables were found to be associated with BSI risk. Conclusion Low step rate is an important risk factor for BSI among collegiate cross country runners and should be considered when developing comprehensive programmes to mitigate BSI risk in distance runners.
Disparities in COVID-19 Vaccination Coverage Between Urban and Rural Counties — United States, December 14, 2020–April 10, 2021
Authors: Bhavini Patel Murthy, Natalie Sterrett, Daniel Weller, Elizabeth Zell, Laura Reynolds, Robin L. Toblin, Neil Murthy, Jennifer Kriss, Charles Rose, Betsy Cadwell, Alice Wang, Matthew D. Ritchey, Lynn Gibbs-Scharf, Judith R. Qualters, Lauren Shaw, Kathryn A. Brookmeyer, Heather Clayton, Paul Eke, Laura Adams, Julie Zajac, Anita Patel, Kimberley Fox, Charnetta Williams, Shannon Stokley, Stephen Flores, Kamil E. Barbour, LaTreace Q. Harris
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Approximately 60 million persons in the United States live in rural counties, representing almost one fifth (19.3%) of the population.* In September 2020, COVID-19 incidence (cases per 100,000 population) in rural counties surpassed that in urban counties (1). Rural communities often have a higher proportion of residents who lack health insurance, live with comorbidities or disabilities, are aged ≥65 years, and have limited access to health care facilities with intensive care capabilities, which places these residents at increased risk for COVID-19-associated morbidity and mortality (2,3). To better understand COVID-19 vaccination disparities across the urban-rural continuum, CDC analyzed county-level vaccine administration data among adults aged ≥18 years who received their first dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine, or a single dose of the Janssen COVID-19 vaccine (Johnson & Johnson) during December 14, 2020-April 10, 2021 in 50 U.S. jurisdictions (49 states and the District of Columbia [DC]). Adult COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%) overall and among adults aged 18-64 years (29.1% rural, 37.7% urban), those aged ≥65 years (67.6% rural, 76.1% urban), women (41.7% rural, 48.4% urban), and men (35.3% rural, 41.9% urban). Vaccination coverage varied among jurisdictions: 36 jurisdictions had higher coverage in urban counties, five had higher coverage in rural counties, and five had similar coverage (i.e., within 1%) in urban and rural counties; in four jurisdictions with no rural counties, the urban-rural comparison could not be assessed. A larger proportion of persons in the most rural counties (14.6%) traveled for vaccination to nonadjacent counties (i.e., farther from their county of residence) compared with persons in the most urban counties (10.3%). As availability of COVID-19 vaccines expands, public health practitioners should continue collaborating with health care providers, pharmacies, employers, faith leaders, and other community partners to identify and address barriers to COVID-19 vaccination in rural areas (2).
DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells
Authors: Francisco J Cueto, Carlos del Fresno, Paola Brandi, Alexis J. Combes, Elena Hernández-García, Alfonso R Sánchez-Paulete, Michel Enamorado, Christian P Bromley, Manuel J Gomez, Ruth Conde-Garrosa, Santos Mañes, Santiago Zelenay, Ignacio Melero, Salvador Iborra, Matthew F. Krummel, David Sancho
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Conventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet. Methods B16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s. Results Here, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice following Flt3L gene therapy. This improved antitumor immunity was associated with Batf3 -dependent enhanced accumulation of CD8 + T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, including Ccl5 expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover, FLT3LG and CCL5 or CCR5 gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth. Conclusion DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.
53P Incidence of febrile neutropenia (FN), adherence and compliance to granulocyte colony-stimulating factor (G-CSF) on-body injector (OBI) versus other FN prophylaxis in patients receiving myelosuppressive chemotherapy: Subgroup analysis in breast cancer patients
Authors: R. Mahtani, G.H. Lyman, R. Rifkin, D. Dale, A. Brookhart, S. Lewis, L. Decosta, T. Lawrence, R. Belani, J. Crawford
Journal: Annals of Oncology (2021)
Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics and Suicide and All-Cause Mortality in Patients With Newly Diagnosed Schizophrenia
Authors: Cheng-Yi Huang, Su-Chen Fang, Yu-Hsuan Joni Shao
Journal: JAMA Network Open (2021)

Schizophrenia is generally considered to be among the most severe psychiatric disorders because of the excessive mortality associated with it. Research to find means to reduce this excessive mortality is warranted.To investigate associations of long-acting injectable antipsychotics (LAIs) with all-cause, natural-cause, and suicide mortality risks as well as the impacts of early use of LAIs in patients with newly diagnosed schizophrenia.This cohort study used data from the Taiwan National Health Insurance Research Database to construct a population-based cohort of patients with schizophrenia who received oral antipsychotics (OAPs) from January 1, 2002, to December 31, 2017. Within this cohort, the LAI group was defined as patients who switched to LAIs and were prescribed LAIs at least 4 times within 1 year. The LAI group was propensity matched 1:1 to patients who continued receiving OAPs of the same compounds. All patients were followed up until switching the antipsychotic administration route, death, or the end of the study (December 31, 2018), whichever occurred first. Data analysis was performed from January 2002 to December 2018.All-cause mortality, natural-cause mortality, suicide mortality, and suicide attempts.In total, 2614 patients who switched to LAIs (median [interquartile range] {IQR} age, 30 [23-39] years) and 2614 who received OAPs (median [IQR] age, 30 [23-39] years) were included (1333 male patients [51.0%] in each group). During the 16-year follow-up period (median [IQR] follow-up of 14 [10-17] years), patients who switched to LAIs had lower risks of all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.54-0.81), natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93) compared with patients who received the corresponding OAPs. A 47% lower suicide mortality risk (aHR, 0.53; 95% CI, 0.30-0.92) was observed in patients who switched to LAIs within the first 2 years of OAP initiation.These findings suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Furthermore, early treatment with LAIs within the first 2 years of OAP initiation was associated with a decrease in suicide mortality risk. Thus, LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia.
Biomaterials from the sea: Future building blocks for biomedical applications
Authors: Mei-chen Wan, Wen Qin, Chen Lei, Qi-hong Li, Meng Meng, Ming Fang, Wen Song, Ji-hua Chen, Franklin Tay, Li-na Niu
Journal: Bioactive Materials (2021)

Marine resources have tremendous potential for developing high-value biomaterials. The last decade has seen an increasing number of biomaterials that originate from marine organisms. This field is rapidly evolving. Marine biomaterials experience several periods of discovery and development ranging from coralline bone graft to polysaccharide-based biomaterials. The latter are represented by chitin and chitosan, marine-derived collagen, and composites of different organisms of marine origin. The diversity of marine natural products, their properties and applications are discussed thoroughly in the present review. These materials are easily available and possess excellent biocompatibility, biodegradability and potent bioactive characteristics. Important applications of marine biomaterials include medical applications, antimicrobial agents, drug delivery agents, anticoagulants, rehabilitation of diseases such as cardiovascular diseases, bone diseases and diabetes, as well as comestible, cosmetic and industrial applications.
T‐Cell Immunoglobulin and Mucin Domain‐Containing Protein‐4 Is Critical for Kupffer Cell Homeostatic Function in the Activation and Resolution of Liver Ischemia Reperfusion Injury
Authors: Ming Ni, Jing Zhang, Rebecca Sosa, Hanwen Zhang, Han Wang, Dan Jin, Kaitlyn Crowley, Bita Naini, F. Elaine Reed, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski, Xuehao Wang, Yuan Zhai
Journal: Hepatology (2021)

Liver ischemia reperfusion injury (IRI) remains an unresolved clinical problem. This study dissected roles of liver-resident macrophage Kupffer cells (KCs), with a functional focus on efferocytosis receptor T-cell immunoglobulin and mucin domain-containing protein-4 (TIM-4), in both the activation and resolution of IRI in a murine liver partial warm ischemia model.Fluorescence-activated cell sorting results showed that TIM-4 was expressed exclusively by KCs, but not infiltrating macrophages (iMФs), in IR livers. Anti-TIM-4 antibody depleted TIM-4+ macrophages in vivo, resulting in either alleviation or deterioration of liver IRI, which was determined by the repopulation kinetics of the KC niche with CD11b+ macrophages. To determine the KC-specific function of TIM-4, we reconstituted clodronate-liposome-treated mice with exogenous wild-type or TIM-4-deficient KCs at either 0 hour or 24 hours postreperfusion. TIM-4 deficiency in KCs resulted in not only increases in the severity of liver IRI (at 6 hours postreperfusion), but also impairment of the inflammation resolution (at 7 days postreperfusion). In vitro analysis revealed that TIM-4 promoted KC efferocytosis to regulate their Toll-like receptor response by up-regulating IL-10 and down-regulating TNF-α productions.TIM-4 is critical for KC homeostatic function in both the activation and resolution of liver IRI by efferocytosis.
Abstract 005: Violent Crime, Physical Inactivity, And Obesity: Examining Differences In Spatial Relationships By Racial/ethnic Composition Of Community Residents
Authors: Chelsea R Singleton, Fikriyah Winata, Oluwafikayo S Adeyemi, Kaustubh V Parab, Susan Aguiñaga
Journal: Circulation (2021)

Introduction: Violent crime (e.g., homicide, aggravated assault) is a major public health issue that disproportionately affects communities of color in large urban centers. Studies have reported that residents in high crime communities are less likely to engage in physical activity. There is limited understanding of how violent crime influences physical inactivity and obesity at the community level. We aimed to address this gap by examining differences in spatial relationships between violent crime rate, physical inactivity, and obesity by racial/ethnic composition of community residents in Chicago, IL. Hypothesis: We assessed the hypothesis that violent crime rate is associated with the prevalence of physical inactivity and obesity at the census tract level in Chicago, IL. Methods: We conducted an ecological assessment of 2018 census tract data obtained from various sources. We used data from the City of Chicago to calculate per capita violent crime rate (number of incidents per 1,000 residents) for all census tracts (N = 801). Data on physical inactivity and obesity prevalence (%) were acquired from the CDC. Socio-demographic data (i.e., % Non-Hispanic (NH) White, % NH Black, % Hispanic, median household income) were obtained from the census bureau. We examined spatial lag and error models to determine if violent crime rate is associated with % physical inactivity and % obesity after controlling for socio-demographic characteristics and amenity availability (i.e., per capita outdoor parks and grocery stores). Stratified models were examined to identify differences in associations among majority NH White, NH Black, and Hispanic census tracts (defined as ≥ 50% representation). Results: NH Black census tracts (n = 278) had significantly higher rates of violent crime, physical inactivity, and obesity than Hispanic (n = 169) and NH White tracts (n = 240). Overall, violent crime rate was positivity associated with % physical inactivity (p&lt;0.001) but not % obesity (p=0.77) in Chicago after controlling for covariates. Stratified models revealed that violent crime rate was positively associated with % physical inactivity (p&lt;0.001) and % obesity (p=0.01) among NH Black tracts. Violent crime rate was not associated with % physical inactivity or % obesity among Hispanic and NH White census tracts. Conclusions: Racial/ethnic composition of residents appears to influence census-tract level associations between violent crime rate, physical inactivity, and obesity. Violent crime appears to be more relevant to physical inactivity and obesity in Chicago’s NH Black communities compared to Hispanic and NH White communities.