tbuckley/cabot-search huggingface dataset:
Is the COVID-19 lockdown nudging people to be more active: a big data analysis
Authors: Ding Ding, Borja del Pozo Cruz, Mark A Green, Adrian E Bauman
Journal: British Journal of Sports Medicine (2020)

The COVID-19 pandemic has brought unparalleled destruction to global health, social and economic systems. To control the spread of COVID-19, most countries have enforced a societal-level lockdown. This mass disruption of civil life provides opportunities for observational ‘natural experiments’, mandating lifestyle changes overnight. Big data, such as Google Trends (GT), have been used to identify outbreaks1 and monitor risk communication strategies,2 public awareness3 and misinformation4 during COVID-19. The real-time nature of data, together with ubiquitous internet access and Google’s dominance of online search traffic, has uniquely positioned GT as a useful tool for ‘nowcasting’ social trends and lifestyle changes.5 

An area of life significantly impacted by COVID-19 lockdown is physical activity. Closure of gyms and restrictions on ‘non-essential’ travel may lead to declines in overall physical activity. Conversely, changing circumstances may interrupt ‘automatic’ behavioural patterns through ‘habit discontinuity’6 leading to formation of new health habits, as demonstrated by previous research on residential relocation.7 Here, we used GT data to explore community interest in physical activity before and during COVID-19 outbreaks in Australia, the UK and the USA.

We extracted GT data of nation-level online queries for the topic ‘exercise’, which included all related search terms sharing the same concept, such as ‘workouts’ and ‘fitness training’ (online supplementary file). GT normalises search data within a defined time frame and geography on a scale of …
PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis
Authors: E. G. Garcia, A. Veloso, M. L. Oliveira, J. R. Allen, S. Loontiens, D. Brunson, D. Do, C. Yan, R. Morris, S. Iyer, S. P. Garcia, N. Iftimia, W. Van Loocke, F. Matthijssens, K. McCarthy, J. T. Barata, F. Speleman, T. Taghon, A. Gutierrez, P. Van Vlierberghe, W. Haas, J. S. Blackburn, D. M. Langenau
Journal: Leukemia (2020)
Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors
Authors: Meijia Yang, Xin Tang, Zongliang Zhang, Lei Gu, Heng Wei, Shasha Zhao, Kunhong Zhong, Min Mu, Cheng Huang, Caiying Jiang, Jianguo Xu, Gang Guo, Liangxue Zhou, Aiping Tong
Journal: Theranostics (2020)

Purpose: Given that heterogeneous expression and variants of antigens on solid tumors are responsible for relapse after chimeric antigen receptor (CAR)-T cell therapy, we hypothesized that combinatorial targeting two tumor-associated antigens would lessen this problem and enhance the antitumor activity of T cells. Methods:The co-expression level of CD70 and B7-H3 was analyzed in multiple tumor tissue samples.Further, two putative antigens were identified in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis database.Two CD70 targeted CARs with different antigen binding domain, truncated CD27 and CD70 specific single-chain antibody fragment (scFv), were designed to screen a more suitable target-antigen binding moiety.Accordingly, we designed a bivalent tandem CAR (TanCAR) and further assessed the anti-tumor efficacy of TanCAR-T cells in vitro and in vivo.Results: Our results indicated that co-expression of CD70 and B7-H3 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma as well as melanoma.The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70 + tumor cells.TanCAR-T cells induced enhanced ability of cytolysis and cytokine release over unispecific CAR-T cells when encountering tumor cells expressing two target-antigens.Further, low doses of TanCAR-T cells could also effectively control the lung cancer and melanoma xenografts and improved overall survival of the treated animals.Conclusion: TanCAR-T cells targeting CD70 and B7-H3 exhibit enhanced antitumor functionality and improve the problem of antigenic heterogeneity and variant in the treatment against solid tumor and melanoma.
Maintenance tobramycin primarily affects untargeted bacteria in the CF sputum microbiome
Authors: Maria T Nelson, Daniel J Wolter, Alexander Eng, Eli J Weiss, Anh T Vo, Mitchell J Brittnacher, Hillary S Hayden, Sumedha Ravishankar, Gilbert Bautista, Anina Ratjen, Marcella Blackledge, Sharon McNamara, Laura Nay, Cheryl Majors, Samuel I Miller, Elhanan Borenstein, Richard H Simon, John J LiPuma, Luke R Hoffman
Journal: Thorax (2020)

The most common antibiotic used to treat people with cystic fibrosis (PWCF) is inhaled tobramycin, administered as maintenance therapy for chronic Pseudomonas aeruginosa lung infections. While the effects of inhaled tobramycin on P. aeruginosa abundance and lung function diminish with continued therapy, this maintenance treatment is known to improve long-term outcomes, underscoring how little is known about why antibiotics work in CF infections, what their effects are on complex CF sputum microbiomes and how to improve these treatments.To rigorously define the effect of maintenance tobramycin on CF sputum microbiome characteristics.We collected sputum from 30 PWCF at standardised times before, during and after a single month-long course of maintenance inhaled tobramycin. We used traditional culture, quantitative PCR and metagenomic sequencing to define the dynamic effects of this treatment on sputum microbiomes, including abundance changes in both clinically targeted and untargeted bacteria, as well as functional gene categories.CF sputum microbiota changed most markedly by 1 week of antibiotic therapy and plateaued thereafter, and this shift was largely driven by changes in non-dominant taxa. The genetically conferred functional capacities (ie, metagenomes) of subjects' sputum communities changed little with antibiotic perturbation, despite taxonomic shifts, suggesting functional redundancy within the CF sputum microbiome.Maintenance treatment with inhaled tobramycin, an antibiotic with demonstrated long-term mortality benefit, primarily impacted clinically untargeted bacteria in CF sputum, highlighting the importance of monitoring the non-canonical effects of antibiotics and other treatments to accurately define and improve their clinical impact.
Prevalence and resistance rates of infections with enterococci in patients with cirrhosis
Authors: T. Bucsics, M. Emich, M.-C. Nackenhorst, E. Berger, P. Schwabl, M. Mandorfer, B. Scheiner, A. Ferlitsch, T. Reiberger, M. Trauner
Journal: Journal of Hepatology (2018)
Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma
Authors: Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, Philippe Merle, Joong-Won Park, Thomas Yau, Stephen L. Chan, Jean-Frederic Blanc, Vincent C. Tam, Albert Tran, Vincenzo Dadduzio, David W. Markby, Rajesh Kaldate, Ann-Lii Cheng, Anthony B. El-Khoueiry, Ghassan K. Abou-Alfa
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes. Patients and Methods: Serum AFP was measured every 8 weeks by blinded, centralized testing. Outcomes were analyzed by baseline AFP bifurcated at 400 ng/mL and by on-treatment AFP response (≥20% decrease from baseline at Week 8). The optimal cutoff for change in AFP at Week 8 was evaluated using maximally selected rank statistics. Results: Median OS for cabozantinib versus placebo was 13.9 versus 10.3 months [HR, 0.81; 95% confidence interval (CI), 0.62–1.04] for patients with baseline AFP &amp;lt;400 ng/mL, and 8.5 versus 5.2 months (HR, 0.71; 95% CI, 0.54–0.94) for patients with baseline AFP ≥400 ng/mL. Week 8 AFP response rate was 50% for cabozantinib versus 13% for placebo. In the cabozantinib arm, median OS for patients with and without AFP response was 16.1 versus 9.1 months (HR, 0.61; 95% CI, 0.45–0.84). AFP response was independently associated with longer OS. The optimal cutoff for association with OS in the cabozantinib arm was ≤0% change in AFP at Week 8 [AFP control; HR 0.50 (95% CI, 0.35–0.71)]. HRs for PFS were consistent with those for OS. Conclusions: Cabozantinib improved outcomes versus placebo across a range of baseline AFP levels. On-treatment AFP response and control rates were higher with cabozantinib than placebo, and were associated with longer OS and PFS with cabozantinib.
Sounds for a Waking Coma Patient
Authors: Sherry Green
Journal: Annals of Internal Medicine (2020)

On Being a Patient7 July 2020Sounds for a Waking Coma PatientSherry Green, MSSherry Green, MSTillamook, Oregon (S.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0704 Audio Reading - “Sounds for a Waking Coma Patient” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Sounds for a Waking Coma Patient” by Sherry Green, MS Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The most important sound in the world, to my mind, is the rhythmic huffing of a ventilator in an intensive care unit, its demanding thrusts filling and holding a patient to life. That was the sound I awoke from my coma to hear. I was alone in a darkened room with a window that looked into another small room. Someone was moving inside that room just out of sight. A clock ticked high on a wall: 3:00. Was it morning or afternoon? Someone in the distance coughed. I was so lonely. Then I heard a pop can open, still off ... Author, Article, and Disclosure InformationAffiliations: Tillamook, Oregon (S.G.)Corresponding Author: Sherry Green, MS; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Sounds for a Waking Coma Patient” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Sounds for a Waking Coma Patient” by Sherry Green, MS Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 7 July 2020Volume 173, Issue 1Page: 69KeywordsComaH1N1LungsRunningSepsisShouldersSleepStrokeVentilatorsWalking ePublished: 7 July 2020 Issue Published: 7 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving <sup>177</sup>Lu-PSMA-617 Radioligand Therapy
Authors: Robert Seifert, Konstantin Seitzer, Ken Herrmann, Katharina Kessel, Michael Schäfers, Jens Kleesiek, Matthias Weckesser, Martin Boegemann, Kambiz Rahbar
Journal: Theranostics (2020)

Rationale: PSMA-PET-CT enables measuring molecular expression of prostate-specific membrane antigen (PSMA) in vivo, which is the target molecule of 177 Lu-PSMA-617 (Lu-PSMA) therapy.However, the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear; especially with regard to coexistence of high and low PSMA expressing metastases.To this end, this retrospective single arm study elucidates the correlation of PSMA expression and overall survival in patients treated with Lu-PSMA therapy.Additionally, PET based criteria to define low PSMA expression were explored.Methods: Eighty-five patients referred to Lu-PSMA therapy were included in the analysis.Pretherapeutic 68 Ga-PSMA-PET-CT scans were available for all patients.SUVmax of the highest PSMA expressing metastasis (PSMAmax), SUVmax of the lowest PSMA expressing metastasis (PSMAmin), and average SUVmax of all metastases (PSMAaverage) amongst other PET parameters were measured for each patient.A log-rank cutoff-finder was used to determine low (lowPSMAaverage) and high (highPSMAaverage) average PSMA expression as well as low (lowPSMAmin) and high (highPSMAmin) minimal PSMA expression.Results: PSMAaverage was a significant prognosticator of overall survival in contrast to PSMAmax (HR: 0.959; p = 0.047 vs. HR: 0.992; p = 0.231).Optimal log rank cut-offs were: PSMAaverage = 14.3;PSMAmin = 10.2.Patients with low average PSMA expression (lowPSMAaverage) had significantly shorter survival compared to those with high average expression (highPSMAaverage) (5.3 vs. 15.1 months; p < 0.001; HR: 3.738, 95%CI = 1.953-7.154;p < 0.001).Patients with low PSMA expressing metastases (lowPSMAmin) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMAmin) (p = 0.003; 7.9 months vs. 21.3;HR: 4.303, 95%CI = 1.521-12.178;p = 0.006).Patients that were classified as highPSMAaverage but with lowPSMAmin had an intermediate overall survival (11.4 months; longer compared to lowPSMAaverage, 5.3 months, p = 0.002; but shorter compared to highPSMAmin, 21.3 months, p = 0.02). Conclusion:Low average PSMA expression is a negative prognosticator of overall survival.Absence of low PSMA expressing metastases is associated with best overall survival and the maximum PSMA expression seems not suited to prognosticate overall survival.Low PSMA expression might therefore be a negative prognosticator for the outcome of patients treated with Lu-PSMA therapy.Future studies are warranted to elucidate the degree of low PSMA expression tolerable for Lu-PSMA therapy.
Independent, external validation of clinical prediction rules for the identification of extended-spectrum β-lactamase-producing Enterobacterales, University Hospital Basel, Switzerland, January 2010 to December 2016
Authors: Isabelle Vock, Lisandra Aguilar-Bultet, Adrian Egli, Pranita D Tamma, Sarah Tschudin-Sutter
Journal: Eurosurveillance (2020)

Background Algorithms for predicting infection with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) on hospital admission or in patients with bacteraemia have been proposed, aiming to optimise empiric treatment decisions. Aim We sought to confirm external validity and transferability of two published prediction models as well as their integral components. Methods We performed a retrospective case–control study at University Hospital Basel, Switzerland. Consecutive patients with ESBL-producing Escherichia coli or Klebsiella pneumoniae isolated from blood samples between 1 January 2010 and 31 December 2016 were included. For each case, three non-ESBL-producing controls matching for date of detection and bacterial species were identified. The main outcome measure was the ability to accurately predict infection with ESBL-PE by measures of discrimination and calibration. Results Overall, 376 patients (94 patients, 282 controls) were analysed. Performance measures for prediction of ESBL-PE infection of both prediction models indicate adequate measures of calibration, but poor discrimination (area under receiver-operating curve: 0.627 and 0.651). History of ESBL-PE colonisation or infection was the single most predictive independent risk factor for ESBL-PE infection with high specificity (97%), low sensitivity (34%) and balanced positive and negative predictive values (80% and 82%). Conclusions Applying published prediction models to institutions these were not derived from, may result in substantial misclassification of patients considered as being at risk, potentially leading to wrong allocation of antibiotic treatment, negatively affecting patient outcomes and overall resistance rates in the long term. Future prediction models need to address differences in local epidemiology by allowing for customisation according to different settings.
The efficacy and safety of CAR-T cell therapy in patients with refractory ALL and concomitant HBV infection
Authors: Peilong Lai, Xiaomei Chen, Le Qin, Zhiwu Jiang, Chenwei Luo, Xin Huang, Sujing Wu, Wei Ling, Yulian Wang, Jinghua Wang, Chenxin Deng, Lisi Huang, Lingji Zeng, Zesheng Lu, Liye Zhong, Pengjun Liao, Minming Li, Dongmei Chen, Suxia Geng, Ping Wu, Zhaoyang Tang, Duanqing Pei, Xin Du, Peng Li, Jianyu Weng
Journal: Leukemia (2020)
Temporal Trend in Young-Onset Type 2 Diabetes—Macrovascular and Mortality Risk: Study of U.K. Primary Care Electronic Medical Records
Authors: Digsu N. Koye, Joanna Ling, John Dibato, Kamlesh Khunti, Olga Montvida, Sanjoy K. Paul
Journal: Diabetes Care (2020)

OBJECTIVE To evaluate temporal prevalence trend, cardiometabolic risk factors, and the risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality (ACM) in incident young- and usual-onset type 2 diabetes. RESEARCH DESIGN AND METHODS From the U.K. primary care database, 370,854 people with a new diagnosis of type 2 diabetes from 2000 to 2017 were identified. Analyses were conducted by age- group (18–39, 40–49, 50–59, 60–69, 70–79 years) and high-/low-risk status without history of ASCVD at diagnosis, with subjects with two or more of current smoking, high systolic blood pressure, high LDL cholesterol (LDL-C), or chronic kidney disease classified as high risk. RESULTS The proportion of people aged &amp;lt;50 years at diagnosis increased during 2000–2010 and then stabilized. The incidence rates of ASCVD and ACM declined in people aged ≥50 years but did not decrease in people &amp;lt;50 years. Compared with people aged ≥50 years, those aged 18–39 years at diagnosis had a higher proportion of obesity (71% obese) and higher HbA1c (8.6%), and 71% had high LDL-C, while only 18% were on cardioprotective therapy. Although 2% in this age-group had ASCVD at diagnosis, 23% were identified as high risk. In the 18–39-year age-group, the adjusted average years to ASCVD/ACM in high-risk individuals (9.1 years [95% CI 8.2–10.0]/9.3 years [8.1–10.4]) were similar to the years in those with low risk (10.0 years [9.5–10.5]/10.5 years [9.7–11.2]). However, individuals aged ≥50 years with high risk were likely to experience an ASCVD event 1.5–2 years earlier and death 1.1–1.5 years earlier compared with low-risk groups (P &amp;lt; 0.01). CONCLUSIONS Unlike usual-onset, young-onset type 2 diabetes has similar cardiovascular and mortality risk irrespective of cardiometabolic risk factor status at diagnosis. The guidelines on the management of young-onset type 2 diabetes for intensive risk factor management and cardioprotective therapies need to be urgently reevaluated through prospective studies.
Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study
Authors: Tomoko Kobayashi, Shintaro Iwama, Yoshinori Yasuda, Norio Okada, Takayuki Okuji, Masaaki Ito, Takeshi Onoue, Motomitsu Goto, Mariko Sugiyama, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Kenji Yokota, Tetsunari Hase, Masahiro Morise, Naozumi Hashimoto, Masahiko Ando, Yasushi Fujimoto, Hideharu Hibi, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Yoshinori Hasegawa, Hiroshi Arima
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM). Methods A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint. Results Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p&lt;0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p&lt;0.05). Conclusions In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone. Clinical trials registration UMIN000019024.
Surgery for benign prostatic obstruction
Authors: Giuseppe Magistro, Christian G Stief
Journal: The Lancet (2020)

Almost all men have some form of benign prostatic hyperplasia as they age, often resulting in lower urinary tract symptoms due to benign prostatic obstruction. Most patients with bothersome lower urinary tract symptoms are treated with drugs (eg, α blockers or 5α-reductase inhibitors) and surgery is usually reserved for patients who do not respond to drug treatment. Both the safety issues of medication and surgery-related morbidity must be weighed against the efficacy of these treatments. The main reasons for discontinuation of drug treatment are serious adverse effects, such as postural hypotension, asthenia, dizziness, and impairment of sexual function, or loss of efficacy over time.
COVID-19 and the Chemical Senses: Supporting Players Take Center Stage
Authors: Keiland W. Cooper, David H. Brann, Michael C. Farruggia, Surabhi Bhutani, Robert Pellegrino, Tatsuya Tsukahara, Caleb Weinreb, Paule V. Joseph, Eric D. Larson, Valentina Parma, Mark W. Albers, Linda A. Barlow, Sandeep Robert Datta, Antonella Di Pizio
Journal: Neuron (2020)