tbuckley/cabot-search huggingface dataset:
A stage-specific cancer chemotherapy strategy through flexible combination of reduction-activated charge-conversional core-shell nanoparticles
Authors: Lingfei Han, Yingming Wang, Xiaoxian Huang, Bowen Liu, Lejian Hu, Congyu Ma, Jun Liu, Jingwei Xue, Wei Qu, Fulei Liu, Feng Feng, Wenyuan Liu
Journal: Theranostics (2019)

Precision medicine has increased the demand for stage-specific cancer chemotherapy. Drugs with different properties are needed for different stages of tumor development, which is, inducing rapid destruction in the early stage and facilitating deep penetration in the advanced stage. Herein, we report a novel reduction-activated charge-conversional core-shell nanoparticle (CS NP) formula based on ring-closing metathesis of the thiamine disulfide system (TDS) to deliver the chemotherapeutic agent-gambogic acid (GA). Methods: The shell consisted of hyaluronic acid-all-trans retinoid acid with a disulfide bond as the linker (HA-SS-ATRA). The core was selected from poly (γ-glutamic acid) with different grafting rates of the functional group (Fx%) of TDS. GA/CF100%S NPs, with the strongest reduction-responsive drug release, and GA/CF60%S NPs with the strongest penetration have been finally screened. On this basis, a stage-specific administration strategy against a two-stage hepatocellular carcinoma was proposed. Results: The developed CS NPs have been confirmed as inducing reduction-activated charge conversion from about -25 to +30 mV with up to 95% drug release within 48 h. The administration strategy, GA/CF100%S NPs for the early-stage tumor, and sequential administration of GA/CF60%S NPs followed by GA/CF100%S NPs for the advanced-stage tumor, achieved excellent tumor inhibition rates of 93.86±2.94% and 90.76±6.43%, respectively. Conclusions: Our CS NPs provide a novel platform for charge conversion activated by reduction. The stage-specific administration strategy showed great promise for cancer therapy.
Proposals to Lower Medication Costs—Reply
Authors: Robert M. Califf, Andrew Slavitt
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
What is sentimentalism? What is rationalism?
Authors: Antti Kauppinen
Journal: Behavioral and Brain Sciences (2019)

Abstract May argues successfully that many claims about the causal influence of affect on moral judgment are overblown. But the findings he cites are compatible with many of the key arguments of philosophical sentimentalists. His account of rationalism, in turn, relies on an overly broad notion of inference, and leaves open crucial questions about how we reason to moral conclusions.
ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver‐Related Cirrhosis
Authors: Luis Calzadilla‐Bertot, Eduardo Vilar‐Gomez, Vincent Wai‐Sun Wong, Manuel Romero‐Gomez, Rocio Aller‐de la Fuente, Grace Lai‐Hung Wong, Marlen Castellanos, Mohammed Eslam, Archita P. Desai, Gary P. Jeffrey, Jacob George, Naga Chalasani, Leon A. Adams
Journal: Hepatology (2020)

Nonalcoholic fatty liver disease (NAFLD) is an increasingly important cause of liver cirrhosis and subsequent complications. We retrospectively developed and validated a model to predict hepatic decompensation in patients with NAFLD and cirrhosis and compared this with currently available models.Baseline variables from an international cohort of 299 patients with biopsy-proven NAFLD with compensated cirrhosis were examined to construct a model using competing risk multivariate regression and Akaike/Bayesian information criteria. Validation was performed in 244 patients with biopsy-proven NAFLD cirrhosis from the United States. Prognostic accuracy was compared with the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and albumin-bilirubin (ALBI)-FIB-4 score using time-dependent area under the curve (tAUC) analysis. During a median follow-up of 5.6 years (range 2.4-14.1) and 5.4 years (range 1.5-13.8), hepatic decompensation occurred in 81 and 132 patients in the derivation and validation cohorts, respectively. In the derivation cohort, independent predictors of hepatic decompensation (Aspartate aminotransferase/alanine aminotransferase ratio, Bilirubin, International normalized ratio, type 2 Diabetes, and Esophageal varices) were combined into the ABIDE model. Patients with a score ≥4.1 compared with those with a score <4.1 had a higher risk of decompensation (subhazard ratio, 6.7; 95% confidence interval [CI], 4.0-11.2; P < 0.001), a greater 5-year cumulative incidence (37% vs. 6%, P < 0.001), and shorter mean duration to decompensation (3.8 vs 6.7 years, P < 0.001). The accuracy of the ABIDE model at 5 years was good in the derivation (tAUC, 0.80; 95% CI, 0.73-0.84) and validation cohorts (0.78; 95% CI, 0.74-0.81) and was significantly more accurate than the NFS (0.72), FIB-4 (0.74), MELD (0.69), CTP (0.72), and ALBI-FIB-4 (0.73) (all P < 0.001).In patients with NAFLD and compensated cirrhosis, ABIDE, a predictive model of routine clinical measures, predicts future hepatic decompensation.
In situ thermal ablation of tumors in combination with nano-adjuvant and immune checkpoint blockade to inhibit cancer metastasis and recurrence
Authors: Xiao Han, Rui Wang, Jun Xu, Qian Chen, Chao Liang, Jiawen Chen, Jiayue Zhao, Jiacheng Chu, Qin Fan, Edikan Archibong, Lixin Jiang, Chao Wang, Zhuang Liu
Journal: Biomaterials (2019)
Sixty seconds on . . . NHS passports
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Mercifully, this is not the latest head scratching pronouncement about the UK’s future relationship with Europe, but rather a new scheme allowing trainees and locum staff to obtain a special ‘“NHS passport” to let them move more easily across different sites.

NHS England thinks so. It hopes that removing the need for two day inductions and other admin, …
Translational cancer research comes of age in Latin America
Authors: A. S. Llera, O. L. Podhajcer, M. M. Breitenbach, L. Santini, B. Muller, A. Daneri-Navarro, C. A. Velázquez, N. Artagaveytia, J. Gómez, M. S. Frech, T. Brown, T. Gross
Journal: Science Translational Medicine (2015)

The U.S.–Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations.
A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function
Authors: Shiran Hoogi, Vasyl Eisenberg, Shimrit Mayer, Astar Shamul, Tilda Barliya, Cyrille J. Cohen
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Tumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co-inhibitory receptor expressed by T and NK cells which, upon binding to its ligand (e.g., CD155), can diminish cytokine production and effector function. Additionally, the absence of positive co-stimulation at the tumor site can further dampen T-cell response. <h3>Methods</h3> As T-cell genetic engineering has become clinically-relevant in the recent years, we devised herein a strategy aimed at enhancing T-cell anti-tumor function by diverting T-cell coinhibitory signals into positive ones using a chimeric costimulatory switch receptor (CSR) composed of the TIGIT exodomain fused to the signaling domain of CD28. <h3>Results</h3> After selecting an optimized TIGIT-28 CSR, we co-transduced it along with tumor-specific TCR or CAR into human T-cells. TIGIT-28-equipped T-cells exhibited enhanced cytokine secretion and upregulation of activation markers upon co-culture with tumor cells. TIGIT-28 enhancing capability was also demonstrated in an original in vitro model of T-cell of hypofunction induction upon repetitive antigen exposure. Finally, we tested the function of this molecule in the context of a xenograft model of established human melanoma tumors and showed that TIGIT-28-engineered human T-cells demonstrated superior anti-tumor function. <h3>Conclusion</h3> Overall, we propose that TIGIT-based CSR can substantially enhance T-cell function and thus contribute to the improvement of engineered T cell-based immunotherapy.
How Old Is Too Old to Be President?
Authors: Rebecca Voelker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Assisted dying: Quebec court strikes down imminent death requirement in Canada’s law
Authors: Owen Dyer
Journal: BMJ (2019)

Quebec’s Superior Court has ruled in favour of two plaintiffs who were denied medical assistance in dying because their conditions did not imminently threaten to end their lives.

Assisted dying laws in both Canada and Quebec stipulate that only patients facing “reasonably foreseeable” death may access medical assistance in dying. But this requirement contravenes Canada’s charter of rights and freedoms, ruled Justice Christine Baudouin. She gave the federal and provincial governments six months to amend their laws before those provisions are suspended. Both governments said that they would study the ruling before deciding whether to appeal.

The plaintiffs, Nicole Gladu and Jean Truchon, both of Montreal, were granted immediate permission to access medical assistance …
10 Years History of Cost-Effectiveness for 209 Newly Diagnosed Multiple Myeloma Patients at a Single-Institute in Japan
Authors: Kenshi Suzuki, Tomofumi Yamamoto, Masahiro Ikeda, Tomomi Takei, Nobuhiro Tsukada, Tadao Ishida, Arimi Ueda, Daiju Ichikawa, Maiko Matsushita, Yutaka Hattori
Journal: Blood (2016)
Association of Emergency Clinicians' Assessment of Mortality Risk With Actual 1-Month Mortality Among Older Adults Admitted to the Hospital
Authors: Kei Ouchi, Tania Strout, Samir Haydar, Olesya Baker, Wei Wang, Rachelle Bernacki, Rebecca Sudore, Jeremiah D. Schuur, Mara A. Schonberg, Susan D. Block, James A. Tulsky
Journal: JAMA Network Open (2019)

The accuracy of mortality assessment by emergency clinicians is unknown and may affect subsequent medical decision-making. To determine the association of the question, "Would you be surprised if your patient died in the next one month?" (known as the surprise question) asked of emergency clinicians with actual 1-month mortality among undifferentiated older adults who visited the emergency department (ED). This prospective cohort study at a single academic medical center in Portland, Maine, included consecutive patients 65 years or older who received care in the ED and were subsequently admitted to the hospital from January 1, 2014, to December 31, 2015. Data analyses were conducted from January 2018 to March 2019. Treating emergency clinicians were required to answer the surprise question, "Would you be surprised if your patient died in the next one month?" in the electronic medical record when placing a bed request for all patients who were being admitted to the hospital. The primary outcome was mortality at 1 month, assessed from the National Death Index. The secondary outcomes included accuracies of responses by both emergency clinicians and admitting internal medicine clinicians to the surprise question in identifying older patients with high 6-month and 12-month mortality. The full cohort included 10 737 older adults (mean [SD] age, 75.9 [8.8] years; 5532 [52%] women; 10 157 [94.6%] white) in 16 223 visits treated in the ED and admitted to the hospital. There were 5132 patients (31.6%) with a Charlson Comorbidity Index score of 2 or more. Mortality rates were 8.3% at 1 month, 17.2% at 6 months, and 22.5% at 12 months. Emergency clinicians stated that they would not be surprised if the patient died in the next month for 2104 patients (19.6%). In multivariable analysis controlling for age, sex, race, admission diagnosis, and comorbid conditions, the odds of death at 1 month were higher in patients for whom clinicians answered that they would not be surprised if the patient died in the next 1 month compared with patients for whom clinicians answered that they would be surprised if the patient died in the next 1 month (odds ratio, 2.4 [95% CI, 2.2-2.7]; P < .001). However, the diagnostic test characteristics of the surprise question were poor (sensitivity, 20%; specificity, 93%; positive predictive value, 43%; negative predictive value, 82%; accuracy, 78%; area under the receiver operating curve of the multivariable model, 0.73 [95% CI, 0.72-0.74; P < .001]). This study found that asking the surprise question of emergency clinicians may be a valuable tool to identify older patients in the ED with a high risk of 1-month mortality. The effect of implementing the surprise question to improve population-level health care for older adults in the ED who are seriously ill remains to be seen.
Abstract 14896: Does Echocardiography/Doppler Reliably Predict Elevated LVEDP?
Authors: David M Cameron, David Bach, Vallerie McLaughlin, Melvyn Rubenfire, Scott Visovatti
Journal: Circulation (2015)

Introduction: Heart failure with preserved ejection fraction is a common cause of group 2 pulmonary hypertension (PH). The utility of echocardiography (echo)/ Doppler for identification of elevated left ventricular end-diastolic pressure (LVEDP) specifically among patients with PH is not well defined. Methods: 161 patients referred to Pulmonary Hypertension Clinic were retrospectively studied. Included patients underwent echo/Doppler and had catheter measurement of LVEDP or pulmonary capillary wedge pressure within a 3-month period, had normal sinus rhythm at the time of the TTE, and had unchanged diuretic and PH regimens during the examination interval. The ability of echo to predict elevated LVEDP (&gt; 15 mm Hg) based on American Society of Echocardiography (ASE) / European Association of Echocardiography (EAE) guidelines was evaluated, and a new model was developed for better prediction of elevated LVEDP with echo data using univariate linear regression and multi-variable logistic regression; receiver operating characteristics were analyzed. Results: Of 161 patients, 81 (51%) had LVEDP &gt; 15 mm Hg on invasive testing; mean PAP was 37.8 ± 14.3 mmHg and PVR was 4.6 ±3.8 WU. Doppler E/A, E/e’ (septal, lateral, average), e’/a’ (lateral and average), LA volume, and LA diameter had significant correlation with LVEDP (p values &lt; 0.05). There was poor test performance of both the ASE/EAE model and the experimental model (area under the ROC 0.7, p &lt; 0.001). Only echo/Doppler grade III had a mean LVEDP significantly different from other grades (p value &lt; 0.05). Conclusions: Numerous echo/Doppler measurements correlate with elevated LV filling pressure. However, both the ASE/EAE model and our experimental model had poor test performance that did not permit confident identification of patients with elevated LVEDP. Assessment using echo/Doppler is not adequate to either reliably include or exclude patients with elevated LVEDP as a cause of severe PH.
Phase I/II study of the investigational aurora A kinase (AAK) inhibitor MLN8237 (alisertib) in patients (pts) with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), breast cancer (BrC), head/neck cancer (H&amp;N), and gastroesophageal (GE) adenocarcinoma: Preliminary phase II results.
Authors: Peter Lee, Ricardo H. Alvarez, Bohuslav Melichar, Antoine Adenis, Jaafar Bennouna, Claudia Schusterbauer, Bin Zhang, Ely Benaim, Peter J. Rosen
Journal: Journal of Clinical Oncology (2012)

3010 Background: AAK is a key mitotic regulator that is amplified or overexpressed in multiple tumor types. MLN8237 is an investigational oral, selective AAK inhibitor being studied in both hematologic (phase III) and nonhematologic malignancies. In the phase 1 part of this study, MLN8237 was generally well tolerated in pts with solid tumors. The maximum tolerated dose was 50 mg BID for 7d + 2 wks rest in 21-d cycles; this dose was recommended for phase II evaluation. Here we report preliminary data from the 5-arm phase 2 part (NCT01045421). Methods: 20 pts each with one of 5 tumor types in the relapsed/refractory setting were enrolled in phase II for efficacy evaluation: NSCLC (inc. 8–10 pts with mainly squamous-cell histology), SCLC (inc. 8–12 chemotherapy refractory pts), BrC (inc. 8–10 pts with a basal-like intrinsic subtype, and 8–10 HER2+ pts), H&amp;N (inc. 8–12 pts with tonsillar or base-of-tongue disease), or GE adenocarcinoma. Pts were aged ≥18 y, and had ECOG PS 0–1, measurable disease by RECIST, and ≤2 prior cytotoxic chemotherapy regimens (≤4 in BrC). Oral MLN8237 was administered as an enteric-coated tablet at 50 mg BID for 7d + 2 wks rest in 21-d cycles. The primary endpoint was overall response rate. Response was determined by RECIST v1.1. Each arm with ≥2 partial responses (PR) is being expanded with 25 additional pts. Results: In 100 efficacy-evaluable pts, median age was 59 y (range 33–88) and 89% were caucasian. Pts received a median of 3 cycles (range 1–9). PRs were observed in 11 pts: H&amp;N, SCLC (each n=3), BrC, GE adenocarcinoma (each n=2), and NSCLC (n=1). 45 pts had a best response of stable disease. In the safety population (n=196), most frequent grade ≥3 drug-related AEs were neutropenia (37%), leukopenia (12%), fatigue, anemia, stomatitis, and thrombocytopenia (each 6%). Updated data will be presented. Conclusions: Preliminary phase II data suggest that oral MLN8237 is tolerable and has antineoplastic activity in a range of solid tumors studied. This study is currently ongoing to further evaluate MLN8237 in the expansion cohorts.
Incidence of Long-term Opioid Use Among Opioid-Naive Patients With Hidradenitis Suppurativa in the United States
Authors: Sarah Reddy, Lauren A.V. Orenstein, Andrew Strunk, Amit Garg
Journal: JAMA Dermatology (2019)

Risk of long-term opioid use among patients with hidradenitis suppurativa (HS), who experience pain that substantially impairs quality of life, is unknown to date.
Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP
Authors: Shawn H. Reginauld, Valentina Cannone, Seethalakshmi Iyer, Christopher Scott, Kent Bailey, Jacob Schaefer, Yang Chen, S. Jeson Sangaralingham, John C. Burnett
Journal: JACC Heart Failure (2019)
The social character of moral reasoning
Authors: Nick Chater, Hossam Zeitoun, Tigran Melkonyan
Journal: Behavioral and Brain Sciences (2019)

May provides a compelling case that reasoning is central to moral psychology. In practice, many morally significant decisions involve several moral agents whose actions are interdependent - and agents embedded in society. We suggest that social life and the rich patterns of reasoning that underpin it are ethical through and through.
Paradoxical Rules of Spike Train Decoding Revealed at the Sensitivity Limit of Vision
Authors: Lina Smeds, Daisuke Takeshita, Tuomas Turunen, Jussi Tiihonen, Johan Westö, Nataliia Martyniuk, Aarni Seppänen, Petri Ala-Laurila
Journal: Neuron (2019)
Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial
Authors: Andreas Stahl, Domenico Lepore, Alistair Fielder, Brian Fleck, James D Reynolds, Michael F Chiang, Jun Li, Melissa Liew, Rainer Maier, Qi Zhu, Neil Marlow
Journal: The Lancet (2019)
Opioid lawsuits: Sackler family and Purdue reach tentative settlement with 27 US states
Authors: Owen Dyer
Journal: BMJ (2019)

Purdue Pharma, the maker of OxyContin accused of promoting excessive opioid use by US doctors, sparking the US opioid epidemic, has reached a tentative settlement with lawyers representing 27 states and thousands of counties, municipalities, and native tribes.

Negotiations have been under way for months as the company sought to avoid trial in a consolidated civil case set to begin on 21 October in a federal court in Cleveland, Ohio. The case pits Purdue and six other drug companies against public authorities that are seeking compensation for burdens imposed by the opioid epidemic.

The settlement deal, which could lead to a final payout worth up to $12bn, will see Purdue’s owners, the Sackler family, relinquish control and possession of the company. …