tbuckley/cabot-search huggingface dataset:
Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates — United States, March 1–December 31, 2020
Authors: Gery P. Guy, Florence C. Lee, Gregory Sunshine, Russell McCord, Mara Howard-Williams, Lyudmyla Kompaniyets, Christopher Dunphy, Maxim Gakh, Regen Weber, Erin Sauber-Schatz, John D. Omura, Greta M. Massetti, Moriah Bailey, Amanda Brown, Ryan Cramer, Catherine Clodfelter, Robin Davison, Sebnem Dugmeoglu, Arriana Fitts, Siobhan Gilchrist, Rachel Hulkower, Alexa Limeres, Dawn Pepin, Adebola Popoola, Morgan Schroeder, Michael A. Tynan, Chelsea Ukoha, Michael Williams, Christopher D. Whitson, Gi Jeong, Lisa Landsman, Amanda Moreland, Julia Shelburne
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

CDC recommends a combination of evidence-based strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Because the virus is transmitted predominantly by inhaling respiratory droplets from infected persons, universal mask use can help reduce transmission (1). Starting in April, 39 states and the District of Columbia (DC) issued mask mandates in 2020. Reducing person-to-person interactions by avoiding nonessential shared spaces, such as restaurants, where interactions are typically unmasked and physical distancing (≥6 ft) is difficult to maintain, can also decrease transmission (2). In March and April 2020, 49 states and DC prohibited any on-premises dining at restaurants, but by mid-June, all states and DC had lifted these restrictions. To examine the association of state-issued mask mandates and allowing on-premises restaurant dining with COVID-19 cases and deaths during March 1-December 31, 2020, county-level data on mask mandates and restaurant reopenings were compared with county-level changes in COVID-19 case and death growth rates relative to the mandate implementation and reopening dates. Mask mandates were associated with decreases in daily COVID-19 case and death growth rates 1-20, 21-40, 41-60, 61-80, and 81-100 days after implementation. Allowing any on-premises dining at restaurants was associated with increases in daily COVID-19 case growth rates 41-60, 61-80, and 81-100 days after reopening, and increases in daily COVID-19 death growth rates 61-80 and 81-100 days after reopening. Implementing mask mandates was associated with reduced SARS-CoV-2 transmission, whereas reopening restaurants for on-premises dining was associated with increased transmission. Policies that require universal mask use and restrict any on-premises restaurant dining are important components of a comprehensive strategy to reduce exposure to and transmission of SARS-CoV-2 (1). Such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States (3,4).
Abstract 4948: Decrease in Poor Responders on Switching From Clopidogrel to Prasugrel: Results From the SWitching Anti Platelet (SWAP) Study
Authors: Jorge F Saucedo, Dominick J Angiolillo, Roger DeRaad, Andrew L Frelinger, Paul A Gurbel, Timothy M Costigan, Joseph A Jakubowski, Clement K Ojeh, Mark B Effron
Journal: Circulation (2009)

Background: The SWAP study, a prospective double-blind study in patients with a recent history of acute coronary syndrome (ACS), demonstrated that switching from a stable maintenance dose (MD) of clopidogrel (Clop) 75 mg/day to prasugrel (Pras) 10 mg/day, with or without a 60 mg loading dose (LD), resulted in significantly lower platelet aggregation by one week. This analysis reports on a secondary objective of the SWAP study evaluating the effect of switching from Clop to Pras on thienopyridine poor response rates. Methods: Poor response to Pras and Clop was evaluated in 100 patients (Placebo LD/Clop 75mg/day, n=33; Placebo LD/Pras 10mg/day, n=36; Pras 60 mg LD/Pras 10mg/day, n=31). Poor responders were defined as patients with maximum platelet aggregation (MPA) &gt;65% to 20 μ M ADP assessed by light transmittance aggregometry performed prior to randomization and at 2 hr, 24 hrs, and 7 days following start of study drug. Results: Prior to randomization, the Clop poor response rate was 27%. Poor responder rates in each group at 2 hrs, 24 hrs, and 7 days post study drug initiation are shown in the Figure . At 2 hrs and 24 hrs, there were no poor responders in patients receiving a LD of Pras. At the end of the 7-day MD period, the poor responder rate in the combined Pras groups (with and without LD) was significantly lower compared with Clop (5% vs. 21%; p=0.014). Conclusions: In patients with recent ACS, switching from Clop to Pras MD is associated with reduced poor response rates (or frequency of high platelet reactivity), while Pras LD overcomes any poor response seen with Clop.
simATAC: a single-cell ATAC-seq simulation framework
Authors: Zeinab Navidi, Lin Zhang, Bo Wang
Journal: Genome biology (2021)

Abstract Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identifies regulated chromatin accessibility modules at the single-cell resolution. Robust evaluation is critical to the development of scATAC-seq pipelines, which calls for reproducible datasets for benchmarking. We hereby present the simATAC framework, an R package that generates scATAC-seq count matrices that highly resemble real scATAC-seq datasets in library size, sparsity, and chromatin accessibility signals. simATAC deploys statistical models derived from analyzing 90 real scATAC-seq cell groups. simATAC provides a robust and systematic approach to generate in silico scATAC-seq samples with known cell labels for assessing analytical pipelines.
Digital biomarker of mental fatigue
Authors: Vincent Wen-Sheng Tseng, Nachiappan Valliappan, Venky Ramachandran, Tanzeem Choudhury, Vidhya Navalpakkam
Journal: npj Digital Medicine (2021)

Abstract Mental fatigue is an important aspect of alertness and wellbeing. Existing fatigue tests are subjective and/or time-consuming. Here, we show that smartphone-based gaze is significantly impaired with mental fatigue, and tracks the onset and progression of fatigue. A simple model predicts mental fatigue reliably using just a few minutes of gaze data. These results suggest that smartphone-based gaze could provide a scalable, digital biomarker of mental fatigue.
Gene-expression correlates of the oscillatory signatures supporting human episodic memory encoding
Authors: Stefano Berto, Miles R. Fontenot, Sarah Seger, Fatma Ayhan, Emre Caglayan, Ashwinikumar Kulkarni, Connor Douglas, Carol A. Tamminga, Bradley C. Lega, Genevieve Konopka
Journal: Nature Neuroscience (2021)
Predicting sentinel node positivity in patients with melanoma: external validation of a risk‐prediction calculator (the Melanoma Institute Australia nomogram) using a large European population‐based patient cohort*
Authors: M.A. El Sharouni, A.H.R. Varey, A.J. Witkamp, T. Ahmed, V. Sigurdsson, P.J. van Diest, R.A. Scolyer, J.F. Thompson, S.N. Lo, C.H. van Gils
Journal: British Journal of Dermatology (2021)

Background A nomogram to predict sentinel node (SN) positivity [the Melanoma Institute Australia (MIA) nomogram] was recently developed and externally validated using two large single-institution databases. However, there remains a need to further validate the nomogram's performance using population-based data. Objectives To perform further validation of the nomogram using a European national patient cohort. Methods Patients with cutaneous melanoma who underwent SN biopsy in the Netherlands between 2000 and 2014 were included. Their data were obtained from the Dutch Pathology Registry. The predictive performance of the nomogram was assessed by discrimination (C-statistic) and calibration. Negative predictive values (NPVs) were calculated at various predicted probability cutoffs. Results Of the 3049 patients who met the eligibility criteria, 23% (691) were SN positive. Validation of the MIA nomogram (including the parameters Breslow thickness, ulceration, age, melanoma subtype and lymphovascular invasion) showed a good C-statistic of 0·69 (95% confidence interval 0·66–0·71) with excellent calibration (R2 = 0·985, P = 0·40). The NPV of 90·1%, found at a 10% predicted probability cutoff for having a positive SN biopsy, implied that by using the nomogram, a 16·3% reduction in the rate of performing an SN biopsy could be achieved with an error rate of 1·6%. Validation of the MIA nomogram considering mitotic rate as present or absent showed a C-statistic of 0·70 (95% confidence interval 0·68–0·74). Conclusions This population-based validation study in European patients with melanoma confirmed the value of the MIA nomogram in predicting SN positivity. Its use will spare low-risk patients the inconvenience, cost and potential risks of SN biopsy while ensuring that high-risk patients are still identified.
Clinical and Economic Effects of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission
Authors: A. David Paltiel, Amy Zheng, Paul E. Sax
Journal: Annals of Internal Medicine (2021)

The value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood.To define performance standards and predict the clinical, epidemiologic, and economic outcomes of nationwide, home-based antigen testing.A simple compartmental epidemic model that estimated viral transmission, portrayed disease progression, and forecast resource use, with and without testing.Parameter values and ranges as informed by Centers for Disease Control and Prevention guidance and published literature.U.S. population.60 days.Societal; costs included testing, inpatient care, and lost workdays.Home-based SARS-CoV-2 antigen testing.Cumulative infections and deaths, number of persons isolated and hospitalized, and total costs.Without a testing intervention, the model anticipates 11.6 million infections, 119 000 deaths, and $10.1 billion in costs ($6.5 billion in inpatient care and $3.5 billion in lost productivity) over a 60-day horizon. Weekly availability of testing would avert 2.8 million infections and 15 700 deaths, increasing costs by $22.3 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.5 billion) and workdays lost ($14.0 billion), yielding incremental cost-effectiveness ratios of $7890 per infection averted and $1 430 000 per death averted.Outcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios, with large reductions in infections, mortality, and hospitalizations. Costs per death averted are roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5 to $17 million).Analysis was restricted to at-home testing. There are uncertainties concerning test performance.High-frequency home testing for SARS-CoV-2 with an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy.National Institutes of Health.
Phase III study evaluating efficacy and safety of MK-6482 + lenvatinib versus cabozantinib for second- or third-line therapy in patients with advanced renal cell carcinoma (RCC) who progressed after prior anti-PD-1/L1 therapy.
Authors: Robert J. Motzer, Yanfang Liu, Rodolfo F. Perini, Yayan Zhang, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2021)

TPS372 Background: There is an unmet need for treatment options in the second-line or later setting following anti–PD-1/L1 or VEGF tyrosine kinase inhibitor (TKI) therapy in patients with advanced RCC. Hypoxia-inducible factor (HIF)-2α is a transcription factor that has been established as an oncogenic driver in clear cell RCC (ccRCC). Promising antitumor activity has been reported for the first-in-class small molecular HIF-2α inhibitor, MK-6482, in heavily pretreated patients with ccRCC and patients with VHL disease–associated RCC. HIF-2α also regulates VEGF gene expression and plays a role in resistance to anti-VEGF therapy. Therefore, combining MK-6842 with a VEGF receptor TKI, such as lenvatinib, is an attractive treatment option in the advanced RCC setting. Methods: This is a randomized, open-label, active-controlled, multicenter phase III trial evaluating the efficacy and safety of MK-6482 + lenvatinib compared with cabozantinib in patients with advanced ccRCC who have progressed on prior anti–PD-1/L1 therapy (NCT04586231). Eligibility criteria include age ≥18 years; histologically confirmed, unresectable, locally advanced or metastatic ccRCC; disease progression on or after first- or second-line systemic treatment with an anti–PD-1/L1 therapy (monotherapy or in combination with other agent[s]) for locally advanced or metastatic disease, the immediately preceding line of treatment must be an anti–PD-1/L1 therapy; no more than 2 prior systemic regimens, with only 1 prior anti–PD-1/L1 therapy; measurable disease per RECIST v1.1; and Karnofsky performance status ≥70%. Patients must provide tissue for biomarker analysis. Approximately 708 patients will be randomly assigned in a 1:1 ratio to receive MK-6482 120 mg orally once daily (QD) + lenvatinib 20 mg orally QD or cabozantinib 60 mg orally QD. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The stratification factors are International mRCC Database Consortium prognostic scores (0, 1-2, or 3-6), number of prior lines of therapy (1 or 2), and geographic region (North America, Western Europe, or rest of the world). Imaging will be assessed by CT or MRI every 8 weeks through week 80, then every 12 weeks thereafter. The dual primary end points are progression-free survival per RECIST v1.1 as assessed by blinded independent central review (BICR) and overall survival. Secondary end points are objective response rate and duration of response per RECIST v1.1 as assessed by BICR, and safety. Safety and tolerability will be evaluated using a tiered approach. Clinical trial information: NCT04586231 .
Immune System Investigation Using Parasitic Helminths
Authors: Bonnie Douglas, Oyebola Oyesola, Martha M. Cooper, Avery Posey, Elia Tait Wojno, Paul R. Giacomin, De'Broski R. Herbert
Journal: Annual Review of Immunology (2021)

Coevolutionary adaptation between humans and helminths has developed a finely tuned balance between host immunity and chronic parasitism due to immunoregulation. Given that these reciprocal forces drive selection, experimental models of helminth infection are ideally suited for discovering how host protective immune responses adapt to the unique tissue niches inhabited by these large metazoan parasites. This review highlights the key discoveries in the immunology of helminth infection made over the last decade, from innate lymphoid cells to the emerging importance of neuroimmune connections. A particular emphasis is placed on the emerging areas within helminth immunology where the most growth is possible, including the advent of genetic manipulation of parasites to study immunology and the use of engineered T cells for therapeutic options. Lastly,we cover the status of human challenge trials with helminths as treatment for autoimmune disease, which taken together, stand to keep the study of parasitic worms at the forefront of immunology for years to come.
riboCIRC: a comprehensive database of translatable circRNAs
Authors: Huihui Li, Mingzhe Xie, Yan Wang, Ludong Yang, Zhi Xie, Hongwei Wang
Journal: Genome biology (2021)

Abstract riboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive repository of computationally predicted ribosome-associated circRNAs; a manually curated collection of experimentally verified translated circRNAs; an evaluation of cross-species conservation of translatable circRNAs; a systematic de novo annotation of putative circRNA-encoded peptides, including sequence, structure, and function; and a genome browser to visualize the context-specific occupant footprints of circRNAs. It represents a valuable resource for the circRNA research community and is publicly available at http://www.ribocirc.com .
Abstract 13476: Spatial Risk Factors Impact Cardiovascular Mortality: Analysis From the Golestan Cohort Study
Authors: Michael Hadley, Mahdi Nalini, Samrachana Adhikari, Jackie Szymonifka, Arash Etemadi, Farin Kamangar, Masoud Khoshnia, Jesse McChane, Akram Pourshams, Hossein Poustchi, Sadaf G Sepanlou, Paolo Boffetta, Reza Malekzadeh, Rajesh Vedanthan
Journal: Circulation (2019)

Introduction: Spatial risk factors are increasingly recognized to predict cardiovascular events independently of traditional risk factors. However, these spatial risk factors have been studied only...
Colin Dollery: clinical pharmacologist and moderniser, who embraced technology
Authors: Chris Mahony
Journal: BMJ (2021)

Colin Dollery, professor of clinical pharmacology and medicine and consultant clinical pharmacologist, who has died aged 89, endured “a dark night of the soul” before defying his father’s wishes to study medicine but was disdainful of the bowtie wearing Sir Lancelot Spratt imitators he believed dominated the profession.

By the mid-point of a career spanning six decades, Dollery could legitimately lay claim to having fathered clinical pharmacology as a subspecialty. By that point he had also played a key part in developing the drugs that transformed hypertension from a mass killer in the West to a condition routinely treated in primary care.

His career reflected a passion for “the science of medicine” and the central role of pharmacology in clinical care. As well as training and supporting a generation of future professors of clinical pharmacology and pharma industry leaders, Dollery was chair and then president of the International Union of Pharmacology and advised the UK government and the World Health Organization. He was a driving force behind the first world conference on clinical pharmacology in 1980.

The son of an Oxford educated chemistry teacher, Dollery moved from the grammar school in Lincoln where his father …
Benign Adrenal Nodule Mimicking Lymphoma Differentially Diagnosed by 18F-FDG and 18F-FGln PET/CT
Authors: Xiaoxia Xu, Hua Zhu, Hank F. Kung, Nan Li, Zhi Yang
Journal: Clinical Nuclear Medicine (2021)

18F-FDG and 18F-(2S,4R)4-fluoroglutamine (18F-FGln) PET/CT were performed in a 58-year-old woman with suspected small intestinal malignancy for differential diagnosis and staging. 18F-FDG and 18F-FGln PET images showed consistent intense hypermetabolic lesion activity in part of the small intestine. Moreover, 18F-FDG/PET demonstrated a focal of increased radiotracer uptake in left adrenal lesion, which did not show abnormal activity on 18F-FGln/PET. The postoperative pathology confirmed that it was a peripheral T-cell lymphomas of the intestine, and the adrenal lesion was considered benign after continuous CT follow-up for more than 2 years.
Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status
Authors: William J. Sandborn, Laurent Peyrin-Biroulet, Ala I. Sharara, Chinyu Su, Irene Modesto, Rajiv Mundayat, L. Mert Gunay, Leonardo Salese, Bruce E. Sands
Journal: Clinical Gastroenterology and Hepatology (2021)

Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status.Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open.Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort.Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612).
Health Care Utilization and Outcomes Associated with Accidental Poisonous Mushroom Ingestions — United States, 2016–2018
Authors: Jeremy A.W. Gold, Emily Kiernan, Michael Yeh, Brendan R. Jackson, Kaitlin Benedict
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Accidental consumption of poisonous mushrooms can result in serious illness and death (1).Reports of severe poisonings from consumption of foraged mushrooms for food or hallucinogenic purposes increased during 1999-2016 (2), and approximately 7,500 poisonous mushroom ingestions were reported annually to poison control centers across the United States (1).To estimate the frequency of emergency department (ED) visits, hospitalizations, and severe adverse outcomes associated with accidental poisonous mushroom ingestion in the United States, CDC analyzed 2016 data from the Healthcare Cost and Utilization Project's* Nationwide Emergency Department Sample (HCUP-NEDS) and National Inpatient Sample (HCUP-NIS) databases as well as 2016-2018 data from three IBM MarketScan sources: