tbuckley/cabot-search huggingface dataset:
Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study
Authors: Karen A. Autio, Christopher A. Klebanoff, David Schaer, John Sae Wook Kauh, Susan F. Slovin, Matthew Adamow, Victoria S. Blinder, Manisha Brahmachary, Michelle Carlsen, Elizabeth Comen, Daniel C. Danila, Thompson N. Doman, Jeremy C. Durack, Josef J. Fox, Jill S. Gluskin, David M. Hoffman, Suhyun Kang, Praneet Kang, Jonathan Landa, Philomena F. McAndrew, Shanu Modi, Michael J. Morris, Ruslan Novosiadly, Dana E. Rathkopf, Rachel Sanford, Sonya C. Chapman, Courtney M. Tate, Danni Yu, Phillip Wong, Heather L. McArthur
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. Patients and Methods: Patients with advanced refractory metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) were treated with LY3022855 intravenously in 6-week cycles in cohorts: (A) 1.25 mg/kg every 2 weeks (Q2W); (B) 1.0 mg/kg on weeks 1, 2, 4, and 5; (C) 100 mg once weekly; (D)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. Results: Thirty-four patients (22 MBC; 12 mCRPC) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five patients with MBC (23%; duration, 82–302 days) and three patients with mCRPC (25%; duration, 50–124 days). Two patients with MBC (cohort A) had durable stable disease &amp;gt;9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. Conclusions: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease &amp;gt;9 months was observed in two patients with MBC.
Intermediate care--Hospital-at-Home in chronic obstructive pulmonary disease: British Thoracic Society guideline
Journal: Thorax (2006)

Intermediate care is a treatment model which bridges the interface between hospital and community care. It often involves cooperation between hospital doctors, general practitioners, nurses, physiotherapists and other healthcare professionals. A specific subtype of intermediate care is Hospital-at-Home (HaH), where active treatment is provided by healthcare professionals in the patient's home for a condition that otherwise would require hospital care, always for a limited period. In 2003 a Cochrane systematic review concluded that HaH was a safe and effective treatment approach for selected patients with exacerbations of chronic obstructive pulmonary disease (COPD), and suggested that one in four patients presenting to hospital as an emergency would be suitable for home treatment with nursing support,1 although some felt that this was an underestimate of eligibility for HaH (Stevenson, 2005). In 2004 the National Institute for Clinical Excellence (NICE) COPD guidelines2 included appraisal of HaH in exacerbations of COPD. A distinction was made between HaH (where hospital admission was avoided) and assisted or early discharge schemes (where a short initial admission was followed by home care). We suggest that it is illogical to exclude cases of early or assisted discharge from HaH and, in this guideline, we will consider HaH as a treatment modality which encompasses both admission avoidance and early supported discharge. The NICE guideline identified four randomised controlled trials (RCTs) and one service evaluation which were applicable to admission avoidance for patients with exacerbations of COPD, and one RCT related to early supported discharge. The evidence statements can be summarised as follows:
Combined weekly docetaxel (D) and gemcitabine (G) for relapsed ovarian cancer (OC) and peritoneal cancer (PC): A multi-institutional phase II study
Authors: R. T. Morris, D. E. Cohn, J. Fowler, L. A. Solomon, A. Vay, S. Seward, L. Heilbrun, D. Smith, A. R. Munkarah
Journal: Journal of Clinical Oncology (2009)

5565 Background: Both D and G have demonstrated single-agent activity in OC and PC. The purpose of this study was to prospectively evaluate the efficacy and toxicity for patients (pts) with relapsed platinum-sensitive (Plat-S) and platinum-resistant (Plat-R) OC or PC treated with combination weekly D and G. Methods: Eligibility criteria included women recurrent or refractory to first line platinum based therapy, a performance status of 2 or better, and adequate renal and hepatic function. Only one prior regimen (including maintenance therapy) was allowed. D (40 mg/m2) and G (800 mg/m2) were administered on days 1 and 8 of a 21 day cycle until progression. Best response was defined by RECIST criteria. Granulocyte stimulating factor prophylaxis was not allowed. There were 2 separate 2-stage designs used, one for each stratum: Plat-R and Plat-S, separately for a total planned sample of 62 pts. The primary endpoint was overall response rate (ORR). This study was approved by each center's institutional review board. Results: Thirty pts were enrolled prior to terminating accrual due to lagging enrollment. The median age was 57.5 years (range 41–80). One pt was diagnosed with PC; the remaining 29 had OC. Twenty-seven (90%) pts were response evaluable. The ORR was 59% (90% confidence interval: 0.44 - 0.73). Six pts (22%) achieved a complete response (CR), 10 pts (37%) achieved a partial response (PR) and one pt (4%) had stable disease. Progressive disease was noted in 10 pts (37%). Plat-S pts (n = 16) had a 69% ORR (CR = 31%, PR = 38%) and Plat-R pts (n = 11) had an ORR of 45% (CR = 9%, PR = 36%). Median overall survival was 12.7 months (Plat-S = 14.2 mos. and Plat-R = 6.7 mos.). Toxicity data were evaluable for 29 (97%) pts. Twelve pts (41%) experienced grade 3 or 4 neutropenia; two of these pts also had documented infections. Three pts had grade 3 anemia and 6 (21%) had grade 3 thrombocytopenia. Dose reductions were uncommon (n = 2, 7%). Twelve pts (41%) were hospitalized at least once during treatment. Conclusions: Weekly D and G combination therapy demonstrates significant activity and moderate toxicity in both Plat-S and Plat-R disease. This non-platinum combination deserves further evaluation and may be considered in pts with Plat-S and Plat-R OC and PC. No significant financial relationships to disclose.
Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection
Authors: Hongzhao Li, Robert W. Omange, Binhua Liang, Nikki Toledo, Yan Hai, Lewis R. Liu, Dane Schalk, Jose Crecente-Campo, Tamara G. Dacoba, Andrew B. Lambe, So-Yon Lim, Lin Li, Mohammad Abul Kashem, Yanmin Wan, Jorge F. Correia-Pinto, Michael S. Seaman, Xiao Qing Liu, Robert F. Balshaw, Qingsheng Li, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo
Journal: Journal of Clinical Investigation (2020)

After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with vaccine efficacy. The PCS vaccine did not induce immune activation or inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune microenvironment generated by the PCS vaccine was predictive of vaccine efficacy. Our study demonstrates, for the first time to our knowledge, that a vaccine which targets only viral maturation, but lacks full-length Env and Gag immunogens, can prevent intravaginal infection in a stringent macaque/SIV challenge model. Targeting HIV maturation thus offers a potentially novel approach to developing an effective HIV vaccine.
Repeatability of [<sup>18</sup>F] fluoro-deoxyglucose positron emission tomography (FDG-PET) in a multicenter phase I oncology study in patients with gastrointestinal malignancies
Authors: L. M. Velasquez, G. Kollia, W. Hayes, S. Galbraith
Journal: Journal of Clinical Oncology (2009)

2530 Background: FDG-PET is used to monitor response in multi-center oncology clinical trials. This study assessed the repeatability of select semi-quantitative standardized uptake values (SUV) as measured by double baseline FDG-PET studies in a multi-center phase I oncology trial. Methods: Double baseline FDG-PET studies were acquired on 62 sequentially enrolled patients. Tumor metabolic activity was assessed by SUV mean , SUV max , SUV peak and SUV 70% . Compliance with image acquisition guidelines and quality assurance (QA) standards were assessed as to their effect on SUV repeatability. Summary statistics for baseline absolute differences relative to the average of baseline values and repeatability analysis were performed for all patients (full dataset) and a subset with scans that passed QA (QA dataset), analyzed in both a multi-observer (site-reported) and single-observer (central-read) setting. Intra-subject precision of baseline measurements was assessed by repeatability coefficients, intra-subject coefficients of variation, and confidence intervals for all SUV parameters. Results: No statistically significant difference was noted between the two baseline measurements for any of the SUV parameters. Mean baseline differences for SUV mean , SUV max , SUV peak and SUV 70% were not statistically significant for either dataset, in the multi- or the single-observer setting. The intra-subject coefficient of variation of the SUV parameters ranged from 11–14% (QA dataset) to 16% (full dataset). The 95% repeatability coefficients for individual patient differences, ranged from (-25%, 34%) to (-34%, 52%) for all SUV parameters. Conclusions: Repeatability results of double baseline FDG-PET scans were similar for all SUV parameters assessed in a variety of analysis settings. The variability was acceptable even in the absence of close compliance with current consensus recommendations, supporting the use of FDG-PET imaging as a robust tumor assessment tool in multi-center oncology clinical trials. The results of this study suggest thresholds for determining metabolic response may be on the order of -35%, 50%, allowing increased confidence that a true change from baseline has occurred. [Table: see text]
3D Printing, Computational Modeling, and Artificial Intelligence for Structural Heart Disease
Authors: Dee Dee Wang, Zhen Qian, Marija Vukicevic, Sandy Engelhardt, Arash Kheradvar, Chuck Zhang, Stephen H. Little, Johan Verjans, Dorin Comaniciu, William W. O’Neill, Mani A. Vannan
Journal: JACC. Cardiovascular imaging (2020)
A novel recombinant tandem repeat DNA vaccine targeting at MUC1
Authors: W. Wu, D. Jin, W. Lou, J. Fan, D. Wang, X. Qin
Journal: Journal of Clinical Oncology (2009)

3066 Background: Tandem repeat (TR) is the key epitope of mucin 1 (MUC1) for inducing cytotoxic T lymphocytes (CTL) to kill the tumor cells specifically. A novel recombinant TR DNA vaccine was constructed to study its induced immune responses. Methods: A recombinant human TR (rhTR) gene encoding a single TR polypeptide of MUC1 was synthesized and cloned into the multiple cloning sites of plasmid pcDNA3.1/Myc-his (+) A to construct the recombinant plasmid pcDNA3.1-TR/Myc-his (+) A (pTR plasmid). Expression of pTR plasmid was confirmed by transfection assay and Western blot analysis. C57BL/6 (H-2 b ) mice were immunized with pTR plasmid (n=15) by tibial muscle injection. Mice inoculated with the empty vector (EV group, n=15) and 0.9% NaCl solution (NS group, n=15) were used as vector and blank control respectively. Four weeks later, all mice were immunized again. Specific antibody detection and cytotoxic assay were used to evaluate the vaccine-induced TR specific immune responses. Results: DNA sequencing confirmed that the pTR plasmid was exactly constructed. Transfection assay and Western blot analysis found that the transfected COS7 cells expressed TR polypeptide of MUC1 48 hours after transfection. Cytotoxic assay showed that immunization with pTR plasmid into C57BL/6 mice resulted in more efficient induction of CTL specific cytolysis against TR polypeptide than that of EV group and NS group (p&lt;0.01). Vaccine immunized mice had a higher equivalent concentration of anti-TR specific antibodies (2324μg/ml±238μg/ml) than that of EV group (1896μg/ml±533μg/ml, p&lt;0.01) and NS group (1736μg/ml±142μg/ml, p&lt;0.01). Conclusions: The novel recombinant TR DNA vaccine targeting at MUC1 was exactly constructed, immunization with which could induce TR specific CTL response and antibodies response in mice. No significant financial relationships to disclose.
International consensus statement: methods for recording and reporting of epidemiological data on injuries and illnesses in golf
Authors: Andrew Murray, Astrid Junge, Patrick Gordon Robinson, Mario Bizzini, Andre Bossert, Benjamin Clarsen, Daniel Coughlan, Corey Cunningham, Tomas Drobny, Francois Gazzano, Lance Gill, Roger Hawkes, Tom Hospel, Robert Neal, Jonathan Lavelle, Antony Scanlon, Patrick Schamash, Bruce Thomas, Mike Voight, Mark Wotherspoon, Jiri Dvorak
Journal: British Journal of Sports Medicine (2020)

Epidemiological studies of injury in elite and recreational golfers have lacked consistency in methods and definitions employed and this limits comparison of results across studies. In their sports-generic statement, the Consensus Group recruited by the IOC (2020) called for sport-specific consensus statements. On invitation by International Golf Federation, a group of international experts in sport and exercise medicine, golf research and sports injury/illness epidemiology was selected to prepare a golf-specific consensus statement. Methodological stages included literature review and initial drafting, online feedback from the consensus group, revision and second draft, virtual consensus meetings and completion of final version. This consensus statement provides golf-specific recommendations for data collection and research reporting including: (i) injury and illness definitions, and characteristics with golf-specific examples, (ii) definitions of golf-specific exposure measurements and recommendations for the calculation of prevalence and incidence, (iii) injury, illness and exposure report forms for medical staff and for golfers, and (iv) a baseline questionnaire. Implementation of the consensus methodology will enable comparison among golf studies and with other sports. It facilitates analysis of causative factors for injuries and illness in golf, and can also be used to evaluate the effects of prevention programmes to support the health of golfers.
THU0259 The risk factors for pain in lower extremities joints in university students of physical culture
Authors: J Flicinski, M Brzosko, K Prajs, H Przepiera-Bedzak
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Musculoskeletal pain is a very common complaint. Its prevalence increases with age but it is experienced also by young individuals. In a previous study concerning prevalence of musculoskeletal pain in joints of upper and lower extremities among university students of physical culture it was found that it occurred within the year in 45,9% of the whole group. Students complained of pain the most frequently in lower extremities joints (35,0%) while pain in upper extremities joints was reported by 20,87% of them. This study is a further step to find the most important factors influencing the occurrence of pain in lower extremities joints in this group. <h3>Objectives</h3> To determine the risk factors of the occurrence of pain in lower extremities joints in university students of physical culture. <h3>Methods</h3> The study was performed on 503 university students of physical culture, mean age 22,6 yrs (20–28 yrs), 218 women and 285 men. The subjects received a questionnaire concerning questions about musculoskeletal disorders in last 12 months. A reported joint pain had to last for at least 24 h to be considered as relevant. The questionnaire included also question about psycho-social factors, families, smoking habits and many other aspects of everyday life. The questionnaire was responded by 95,8% of students. The potential relationship of the investigated 27 variables was assessed in multivariate logistic regression model and then the role of significant variables was counted as relative risk with 95% of confidence interval in univariate logistic regression model. For statistical evaluation of the data STATA 5.0 software was used. <h3>Results</h3> Multivariate logistic regression has revealed that in women only stress related to personal problems (OR 2,3; CI 1,3–4,1), treatment for any long-lasting disease (OR 6,12; CI 1,9–20,1), frequent headaches (OR 2,1; CI 1,1–3,7) were significantly related to reporting pain in lower extremities joints. In male students reporting joint pain in lower extremities was significantly associated with body height (there was less pain for tall subjects, OR 0,4; CI 0,2–0,8), conflict with lecturers or teachers (OR 2,0; CI 1,2–3,5) and also with bringing up children (OR 3,0; CI 0,9–9,8). In both male and female students there were other risk factors of back pain like abdominal pain, conflicts with fellow students or smoking however the were not independent ones in multivariate logistic regression. <h3>Conclusion</h3> In female and male students pain in lower extremities joints was associated with some other health problems or with stress. In males also bringing up children influenced significantly occurrence of pain in lower extremities joints.
Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2
Authors: Anne L Wyllie, John Fournier, Arnau Casanovas-Massana, Melissa Campbell, Maria Tokuyama, Pavithra Vijayakumar, Joshua L Warren, Bertie Geng, M Catherine Muenker, Adam J Moore, Chantal B F Vogels, Mary E Petrone, Isabel M Ott, Peiwen Lu, Arvind Venkataraman, Alice Lu-Culligan, Jonathan Klein, Rebecca Earnest, Michael Simonov, Rupak Datta, Ryan Handoko, Nida Naushad, Lorenzo R Sewanan, Jordan Valdez, Elizabeth B White, Sarah Lapidus, Chaney C Kalinich, Xiaodong Jiang, Daniel J Kim, Eriko Kudo, Melissa Linehan, Tianyang Mao, Miyu Moriyama, Ji E Oh, Annsea Park, Julio Silva, Eric Song, Takehiro Takahashi, Manabu Taura, Orr-El Weizman, Patrick Wong, Yexin Yang, Santos Bermejo, Camila D Odio, Saad B Omer, Charles S Dela Cruz, Shelli Farhadian, Richard A Martinello, Akiko Iwasaki, Nathan D Grubaugh, Albert I Ko
Journal: New England Journal of Medicine (2020)

In this letter, the investigators report that saliva specimens and nasopharyngeal swab specimens had similar sensitivity in the detection of SARS-CoV-2 RNA in both symptomatic and asymptomatic persons.
Ivacaftor modifies cystic fibrosis neutrophil phenotype in subjects with R117H residual function CFTR mutations
Authors: Gareth R. Hardisty, Sheonagh M. Law, Suzanne Carter, Brenda Grogan, Pradeep K. Singh, Edward F. McKone, Robert D. Gray
Journal: European Respiratory Journal (2020)

CFTR modulation leads to changes in neutrophil phenotype even in patients with residual function CFTR mutations https://bit.ly/2EUk7xH
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: R. J. Collier, A. M. Pappenheimer
Journal: The Journal of Experimental Medicine (1964)

Intracellular levels of ATP, GTP, and hexose phosphates have been determined in HeLa cells at intervals after exposure to saturating doses of diphtheria toxin. Toxin causes no significant change in the level of any of these phosphorylated intermediates either in the presence or absence of glucose over a period of at least 5 to 6 hours. It is concluded that the inhibition of protein synthesis which occurs in HeLa cells at about 2 hours after the addition of saturating doses of toxin, does not result from an effect of toxin on energy metabolism.
Clinical characteristics and survival of 5283 esophageal cancer patients: A multicenter study from eighteen hospitals across six regions in China
Authors: Yutong He, Di Liang, Lingbin Du, Tiantian Guo, Yanyu Liu, Xibin Sun, Ning Wang, Min Zhang, Kuangrong Wei, Baoen Shan, Wanqing Chen
Journal: Cancer Communications (2020)

Abstract Objective This study aimed to investigate the potential determining epidemiological and clinical risk factors affecting the survival of esophageal cancer (EC) patients across multiple hospitals in China. Methods This was a multicenter study comprising of newly diagnosed EC cases from Beijing, Hebei, Henan, Hubei, Zhejiang, and Guangdong Province of China. Their baseline characteristics and treatment methods data were collected from their medical records. The EpiData software was used for data quality control. The Kaplan‐Meier method was used to estimate their overall survival (OS), and the Cox's proportional hazard regression model was used to estimate hazard ratios (HR) and 95% confidence interval (CI). Results The 3‐ and 5‐year OS rates of the 5283 investigated EC patients were 49.98% and 39.07%, respectively. Their median survival was 36.00 months. The median survival time of females was longer than that of males (females vs. males: 45.00 vs. 33.00, P &lt; 0.001). The 5‐year OS rate of patients who never‐smoked was higher than that of smokers (never‐smokers vs smokers: 40.73% vs. 37.84%, P = 0.001). There was no significant difference in the 5‐year OS rate between drinkers and never‐drinkers (drinkers vs never‐drinkers: 34.22% vs. 29.65%, P = 0.330). In multivariate analysis, pathological stage (stage II: HR = 1.80, 95% CI = 1.40‐2.31; stage III: HR = 2.62, 95% CI = 2.06‐3.34; stage IV: HR = 3.90, 95% CI = 2.98‐5.09), poor differentiation/undifferentiated (HR = 1.34, 95% CI = 1.11‐1.63), not married status (HR = 2.45, 95% CI = 1.49‐4.04), production and service personnel (HR = 1.36, 95% CI = 1.01‐1.83) and farming/fishing (HR = 1.40, 95% CI = 1.12‐1.76) were independent prognostic risk factors for poor EC survival. Tumors in the thoracic or abdominal part of the esophagus, female and family history of any cancer were independent factors predictive of a good EC OS. Conclusion Gender, marital status, occupation, family history of any cancer, tumor topographical site, differentiation status, and pathological stage were associated with the survival rate of EC. This study reveals important clinical characteristics of esophageal cancer patients in China and provides helpful information for their clinical management and surveillance.
Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications
Authors: Juan R. Rey, Juan Caro‐Codón, Sandra O. Rosillo, Ángel M. Iniesta, Sergio Castrejón‐Castrejón, Irene Marco‐Clement, Lorena Martín‐Polo, Carlos Merino‐Argos, Laura Rodríguez‐Sotelo, Jose M. García‐Veas, Luis A. Martínez‐Marín, Marcel Martínez‐Cossiani, Antonio Buño, Luis Gonzalez‐Valle, Alicia Herrero, José L. López‐Sendón, José L. Merino
Journal: European Journal of Heart Failure (2020)