tbuckley/cabot-search huggingface dataset:
The impact of changes in servicedelivery in patients with colorectalcancer during the first peak of theCOVID-19 pandemic
Authors: K. Kamposioras, K. H. J. Lim, M. P. Saunders, K. Marti, D. Anderson, M. Cutting, D. McCool, J. Connell, L. Simpson, J. Hasan, M. Braun, V. Lavin, S. Mullamitha, J. Barriuso
Journal: Journal of Clinical Oncology (2021)

Background: Increased levels of anxiety and distress in both patients and physicians have been reported in response to the significant impact COVID-19 has on cancer service delivery globally  We aimed to investigate how these changes have been perceived by patients diagnosed with colorectal cancer and identify determinants of increased anxiety  Methods: Survey (32-item) of consecutive patients diagnosed with colorectal cancer attending a large tertiary comprehensive cancer centre in the United Kingdom (18 May to 1 July 2020)  Self-reported GAD-7 (both paper/electronic forms) was used as a screening tool for anxiety  Statistical analyses of associations:Chi-square, Fisher's exact, and uni- and multi-variable analyses were performed using SPSS v19 and R  Results: A total of 143 patients (response rate 67%), 82% male, and median age of 61-70 years were included  Majority of patients had telephone consultation (78%), including 40% who had scan results discussed over the phone;with favourable feedback received with both respectively  Twenty-three patients (18%) were considered to have anxiety, with 7 (6%) scoring for moderate or severe anxiety  Three items asked patients if they had concerns about getting COVID-19, were worried that COVID-19 would have effect on mental health, and affect their experience of cancer care  Patients answering positively to any of these items were most likely to have anxiety;multivariate analysis - OR 2 361 (95% CI 1 187-4 694, p=0 014), 3 219 (95% CI 1 401-7 395, p=0 006) and 3 206 (95% CI 1 036-9 920, p=0 043), respectively  Majority of the patients did not feel that they needed support during the pandemic period and hence the available well-being services were not used  Patients felt that friends and family had been very supportive but less so the primary care services (p<0 05)  However, they felt they were supported by the clinical team  Conclusions: At our centre, during the first-peak of COVID-19 pandemic in the UK, patients with colorectal cancer did not display increased rates of significant anxiety  The findings of this survey suggests that some service changes implemented, including increased telephone follow-up, may have already improved the overall experience of cancer care  Importantly, patients were much more concerned about their cancer treatment than COVID-19, emphasising the need to continue to provide comprehensive cancer care even if we get a ?2nd wave? of COVID-19
External Stimuli Modulate EZH2 Expression in Chronic Lymphocytic Leukemia. Rationale and Evidence for Synergistic Anti-Tumor Effects of B Cell Signaling and EZH2 Inhibitors
Authors: Elisavet Chartomatsidou, Stavroula Ntoufa, Konstantia Kotta, Marianna Akritidou, Theoni Trangas, Niki Stavroyianni, Achilles Anagnostopoulos, Richard Rosenquist, Paolo Ghia, Nikos Papakonstantinou, Kostas Stamatopoulos
Journal: Blood (2017)
Why Defend Harm Reduction for Severe and Enduring Eating Disorders? Who Wouldn’t Want to Reduce Harms?
Authors: Joel Yager
Journal: The American Journal of Bioethics (2021)

In “The Ethical Defensibility of Harm Reduction and Eating Disorders,” Andria Bianchi et al. (2021) defend the use of harm reduction strategies to treat patients with severe and enduring anorexia n...
Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules
Authors: Georgina V. Long, Caroline Robert, Marcus O. Butler, Felix Couture, Matteo S. Carlino, Steven O'Day, Victoria Atkinson, Jonathan S. Cebon, Michael P. Brown, Stéphane Dalle, Andrew G. Hill, Geoffrey T. Gibney, Steven McCune, Alexander M. Menzies, Cuizhen Niu, Nageatte Ibrahim, Blanca Homet Moreno, Adi Diab
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) were tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens. Patients and Methods: Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for ≤24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100). Primary end points were incidence of grade 3–5 treatment-related adverse events (TRAE) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3–5 TRAE incidence ≤26% indicated meaningful toxicity reduction and ORR ≥48% indicated no decrease in efficacy versus data reported for other PD-1 inhibitor/ipilimumab combinations. Results: Median follow-up on February 18, 2019, was 16.3 months in PEM200+IPI50 (N = 51) and 16.4 months in PEM200+IPI100 (N = 51). Grade 3–5 TRAEs occurred in 12 (24%) patients in PEM200+IPI50 and 20 (39%) in PEM200+IPI100. One patient in PEM200+IPI50 died from treatment-related autoimmune myocarditis. Immune-mediated AEs or infusion reactions occurred in 21 (42%) patients in PEM200+IPI50 and 28 (55%) in PEM200+IPI100. ORR was 55% in PEM200+IPI50; 61% in PEM200+IPI100. Conclusions: Pembrolizumab 200 mg Q3W plus ipilimumab 50 mg Q6W or 100 mg Q12W demonstrated antitumor activity above the predefined threshold; pembrolizumab plus ipilimumab 50 mg Q6W had lower incidence of grade 3–5 TRAEs than the predefined threshold, suggesting a reduction in toxicity. See related commentary by Jameson-Lee and Luke, p. 5153
Lay Stakeholders in Science and Research Initiative: A Science Advisory From the American Heart Association
Authors: William H. Roach, James M. Bischoff, Bernie Dennis, Marvis Donalson, Sandra B. Dunbar, Debbie Hill, Jacqueline Ng-Osorio, Sally Powers, Loren E. Wold
Journal: Circulation (2021)

The American Heart Association (AHA) is the largest not-for-profit funder of cardiovascular and cerebrovascular disease research in the United States. It has supported research of independent scientists for 7 decades with the goal of finding novel discoveries that will reduce death and disability from these diseases and ultimately improve overall health. In 2014, the AHA approved a pilot initiative to include lay stakeholders (patients, caregivers, and passionate advocates) in its research and science operations. The initiative was based on the premise that lay stakeholders would add a unique and necessary perspective that would improve decisions concerning research funding, research direction, and scientific guidelines. The AHA developed a framework for the initiative that defined lay stakeholder, created a volunteer recruitment and training program, established policies for incorporating lay stakeholders into science operations, and set metrics for evaluating the initiative over time. It has instituted creative ways to engage lay volunteers and to foster lay and scientist cooperation. Program assessments have been consistently positive and have identified needed future improvements. The benefits of lay/scientist collaboration have far exceeded the AHA's expectations. The AHA will continue to strengthen lay volunteer engagement throughout its science and research operations; to focus on developing a larger, diverse group of qualified lay stakeholders; to educate scientists on how to communicate research effectively to the public and donors; and to retain the respect of donors for the rigors of its research funding, scientific statements, and clinical guidelines.
Ideation and Assessment of a Novel Nitric Oxide Delivery System for Spontaneously Breathing Subjects S. Gianni1
Authors: C. C. Araujo Morais, G. Larson, R. Pinciroli, R. W. Carroll, B. Yu, W. M. Zapol, L. Berra
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale High dose nitric oxide (NO) produces broad antimicrobial activity and several clinical trials are now testing the efficacy of NO inhalation on patients infected by SARS CoV-2. Nitrogen dioxide (NO2) is formed by the reaction between NO and oxygen, and when combined with water in the airways, NO2, forms nitric acid, leading to a caustic burn of the airways. In this study, we designed and developed a breathing system capable of safely delivering high concentrations of NO. Methods We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide (Ca(OH)2) (Fig. 1). The system was tested using a bench testing lung and a mechanical ventilator. The NO concentration was measured by a NO analyzer connected to the inspiratory limb via a sampling line. NO2 levels were simultaneously evaluated by the Cavity Attenuated Phase Shift (CAPS) NO2 monitor using the same sampling port. To assess the efficacy of the Ca(OH)2 scavenger in reducing the inspiratory levels of NO2, we used a range of target NO concentrations (50, 150, and 250 ppm), two different levels of FiO2 (0.21 and 0.40) and measured NO2 levels with and without the scavenger. We administered high-dose NO with our system to healthy adult volunteers as part of a trial conducted at MGH. Each administration lasted for 15 minutes. Peripheral oxygen saturation (SpO2) and methemoglobin (MetHb) were continuously monitored with a pulse co-oximeter. Results Using our delivery system, we were able to reach NO concentration up 250 ppm with an Inspired oxygen fraction (FiO2) between 0.21 and 0.4. The scavenger reduced the inhaled NO2 concentration to an average of 0.9 ppm (CI -1.58, -0.22;p=0.01). At 150 ppm of inhaled NO, the NO2 concentration was maintained below 1.2 ppm with FiO2 from 0.21 to 0.40. Our data suggest that the scavenger can efficiently reduce NO2 in the circuit for NO delivery. We administered NO to 4 adult volunteers. The total number of NO administrations was 30. The average concentration of inspired NO was 163.9±10.1 ppm with NO2 levels of 0.75±0.08 ppm. During the administration methemoglobin levels increased from a baseline value of 0.97±0.6% to 2.17±0.43%. The subjects did not experience any adverse events. Conclusions We built a NO delivery system that provides a safe alternative to a ventilator-based system to give high dose NO to spontaneously breathing patients.
Enhanced delivery efficiency and sustained release of biopharmaceuticals by complexation-based gel encapsulated coated microneedles: rhIFNα-1b example
Authors: Zequan Zhou, Suohui Zhang, Guozhong Yang, Yunhua Gao
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Coated microneedles (MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs (GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate (SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs (72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs (88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFNα-1b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFNα-1b in GEC-MNs showed a linearly dose-dependent relationship. The AUC of rhIFNα-1b in GEC-MNs (4.51 ng/ml·h) was bioequivalent to the intradermal (ID) injection (5.36 ng/ml·h) and significantly higher than water-soluble coated MNs (3.12 ng/ml·h). The rhIFNα-1b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GEC-MNs have proved to be more efficient, stable, and achieve the sustained-release of water-soluble drug in coating MNs, constituting a high value to biopharmaceutical.
Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis
Authors: Shinichi Kako, Shin-ichiro Fujiwara, Miki Sato, Shun-ichi Kimura, Hideki Nakasone, Kazuteru Ohashi, Michihiro Hidaka, Tetsuo Maeda, Morishita Takanobu, Ritsuro Suzuki, Takahiro Fukuda, Tatsuo Ichinohe, Mio Kurata, Yoshiko Atsuta, Yoshinobu Kanda
Journal: Blood (2017)
Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021
Authors: Alberto Mateo-Urdiales, Stefania Spila Alegiani, Massimo Fabiani, Patrizio Pezzotti, Antonietta Filia, Marco Massari, Flavia Riccardo, Marco Tallon, Valeria Proietti, Martina Del Manso, Maria Puopolo, Matteo Spuri, Cristina Morciano, Fortunato (Paolo) D’Ancona, Roberto Da Cas, Serena Battilomo, Antonino Bella, Francesca Menniti-Ippolito
Journal: Eurosurveillance (2021)

To assess the real-world impact of vaccines on COVID-19 related outcomes, we analysed data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy. Taking 0–14 days post-first dose as reference, the SARS-CoV-2 infection risk subsequently decreased, reaching a reduction by 78% (incidence rate ratios (IRR): 0.22; 95% CI: 0.21–0.24) 43–49 days post-first dose. Similarly, hospitalisation and death risks decreased, with 89% (IRR: 0.11; 95% CI: 0.09–0.15) and 93% (IRR: 0.07; 95% CI: 0.04–0.11) reductions 36–42 days post-first dose. Our results support ongoing vaccination campaigns.
Novel treatments for autism spectrum disorder based on genomics and systems biology
Authors: Danielle Baribeau, Evdokia Anagnostou
Journal: Pharmacology & Therapeutics (2021)

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic architecture. There are currently no known pharmacologic treatments for the core ASD symptoms of social deficits and restricted/ repetitive behavior. However, there are dozens of clinical trials currently underway that are testing the impact of novel and existing agents on core and associated symptoms in ASD.We present a narrative synthesis of the historical and contemporary challenges to drug discovery in ASD. We then provide an overview of novel treatments currently under investigation from a genomics and systems biology perspective.Data driven network and cluster analyses suggest alterations in transcriptional regulation, chromatin remodelling, synaptic transmission, neuropeptide signalling, and/or immunological mechanisms may contribute to or underlie the development of ASD. Agents and upcoming trials targeting each of the above listed systems are reviewed.Identifying effective pharmacologic treatments for the core and associated symptom domains in ASD will require further collaboration and innovation in the areas of outcome measurement, biomarker research, and genomics, as well as systematic efforts to identify and treat subgroups of individuals with ASD who may be differentially responsive to specific treatments.
Abstract 430: Spectral Changes Caused by Radiofrequency Ablation of Cardiac Tissue
Authors: Mohammed Aljishi, Huda Asfour, Tigran Chahbazian, Narine Muselimyan, Luther Swift, Marco Mercader, Narine Sarvazyan
Journal: Circulation Research (2016)

Persistent atrial fibrillation is commonly treated using an endoscopic catheter to eliminate anomalous sources of cardiac activity via thermal ablation. However, the procedure lacks real-time feedback. Newly developed radiofrequency ablation (RFA) catheters include a fiberoptic bundle through which visual information of tissue conditions may be collected offering an opportunity to reveal subtle differences in tissue physiology. Currently little is known about the spectral changes caused by RFA. We hypothesized that by comparing spectral changes in various areas in the heart before and after RFA, optical signatures can be used to distinguish healthy cardiac tissue from thermally ablated tissue. Excitation emission matrices (EEM) were acquired from excised porcine hearts (300-600nm). Distinct EEMs were collected from the endocardium of the left atria, ventricle, and aorta. Additionally, the fluorescence and reflectance profiles of each tissue were altered by thermal ablation. In the ventricular muscle, a reduction in the NADH fluorescence peak (360/460nm excitation/emission maxima) was most prominent. While in the aorta, collagen and elastin fluorescence peaks fused and broadened upon ablation. Changes in atrial tissue included a drop in NADH fluorescence and an overall increase in reflectance. The latter is likely caused by thermal coagulation of heme-containing proteins such as myoglobin and a weaker absorption within the Soret band. We concluded that optical signals revealed by EEMs offer quantitative information that can be used to develop diagnostic catheters, including hyperspectral imaging protocols to discern spectral changes elicited by RFA treatment.
Antimicrobial properties of dental cements modified with zein-coated magnesium oxide nanoparticles
Authors: Ghada H. Naguib, Hani M. Nassar, Mohamed T. Hamed
Journal: Bioactive Materials (2021)

The aim of this study was to test the antimicrobial properties of dental cements modified with magnesium oxide (MgO) nanoparticles. Zein-modified MgO nanoparticles (zMgO) in concentrations (0.0, 0.3, 0.5, and 1.0%) were mixed with dental cements (Fuji II, Rely X Temp E, Ionoglass Cem, Es Temp NE, and System P link). Eight discs were fabricated from each zMgO-cement pair for a total of 32 specimens for each cement. Characterization of the dental cements incorporating zMgO was done by X-ray Diffraction (XRD) and Field Emission Scanning Electron Microscopy (FESEM). The antimicrobial properties of the mixtures were tested using direct contact and agar diffusion assays against Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Candida albicans. Data was analyzed using two-way analysis of variance and LSD post hoc test at 0.05 significance level. XRD spectra showed sharp peaks of zMgO indicating its high crystalline nature, while the amorphous dental cements with zMgO had broad peaks. FESEM analysis showed a uniform distribution of the zMgO nanoparticles in the cement. There were significant inhibition zone values associated with all concentrations of zMgO-cement mixtures tested compared to controls (p < 0.001) with a dose-response recorded only with Fuji II. Optical density values were significantly lower in zMgO groups compared to controls for all microorganisms. The effect was most prominent with Rely X against C. albicans and S. aureus. Dental cements containing zMgO showed significant antimicrobial properties that were dependent on the specific initial cement substrate.
Abstract 411: In Utero Exposure to PM2.5 Causes Adult Cardiovascular Dysfunction and Reduced Exercise Capacity
Authors: Vineeta Tanwar, Kristin I Stanford, Loren E Wold
Journal: Circulation Research (2016)

Objective: Exposure to particulate matter 2.5 μm (PM2.5) during intrauterine development is associated with adverse cardiovascular outcomes at adulthood. Deteriorations in cardiac function are observed with increased myocardial demand in PM2.5-exposed individuals. The goal of this study was to determine the effects of in utero PM2.5exposure on exercise training capacity and cardiac function in adult mice. Methods: Female FVB mice were exposed either to filtered air (FA) or PM2.5at an average concentration of 73.61μg/m 3 for 6h/day, 7days/wk throughout pregnancy. 12wk old male offspring from exposed dams were assigned to in utero FA (n=5) or PM2.5 (n=5) exposed groups which underwent exercise training for 3 weeks (housed with running wheels for 3 weeks). We measured total distance travelled and performed echocardiography at baseline, 1, 2 and 3 weeks. Results: There was a progressive decrease in total distance travelled each week in the in utero PM2.5 exposed mice (Week 1: 12.2±3.46 Km FA, 5.32±2.06 Km PM2.5; Week 2: 41.4±9.62 Km FA, 17.28±6.60 Km PM2.5; Week 3: 61.8±16.59 Km FA, 25.92.±8.62 Km PM2.5) compared to the in utero FA exposed mice. When comparing to their respective sedentary counterparts, the FA exercise group showed increased fractional shortening (%FS), left ventricular end systolic (LVESd) and diastolic (LVEDd) diameters, suggesting eccentric hypertrophy. There was a modest decrease in %FS and marked increase in posterior wall thickness during diastole (PWTd) in the PM2.5 exercise group suggesting concentric hypertrophy. Comparison of in utero FA vs PM2.5 exercise groups after 3 weeks of exercise training showed reduced %FS and marked decrease in LVEDd in the PM2.5 exercise group compared to the FA exercise group. Furthermore, a decrease in PWTs and increased PWTd was also observed in the PM2.5 group compared to FA controls. Conclusions: In utero PM2.5exposure reduced exercise capacity at adulthood and the development of both systolic and diastolic dysfunction. Thus, our study showed that individuals residing in high pollution areas are predisposed to develop cardiac dysfunction under conditions of increased myocardial demand.
Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer’s disease: the Altoida large cohort study
Authors: Irene B. Meier, Max Buegler, Robbert Harms, Azizi Seixas, Arzu Çöltekin, Ioannis Tarnanas
Journal: npj Digital Medicine (2021)

Abstract Conventional neuropsychological assessments for Alzheimer’s disease are burdensome and inaccurate at detecting mild cognitive impairment and predicting Alzheimer’s disease risk. Altoida’s Digital Neuro Signature (DNS), a longitudinal cognitive test consisting of two active digital biomarker metrics, alleviates these limitations. By comparison to conventional neuropsychological assessments, DNS results in faster evaluations (10 min vs 45–120 min), and generates higher test-retest in intraindividual assessment, as well as higher accuracy at detecting abnormal cognition. This study comparatively evaluates the performance of Altoida’s DNS and conventional neuropsychological assessments in intraindividual assessments of cognition and function by means of two semi-naturalistic observational experiments with 525 participants in laboratory and clinical settings. The results show that DNS is consistently more sensitive than conventional neuropsychological assessments at capturing longitudinal individual-level change, both with respect to intraindividual variability and dispersion (intraindividual variability across multiple tests), across three participant groups: healthy controls, mild cognitive impairment, and Alzheimer’s disease. Dispersion differences between DNS and conventional neuropsychological assessments were more pronounced with more advanced disease stages, and DNS-intraindividual variability was able to predict conversion from mild cognitive impairment to Alzheimer’s disease. These findings are instrumental for patient monitoring and management, remote clinical trial assessment, and timely interventions, and will hopefully contribute to a better understanding of Alzheimer’s disease.