tbuckley/cabot-search huggingface dataset:
Professional and psychological impact of COVID-19 pandemic on medical and radiation oncology residents: Results of a national survey
Authors: Marc Hilmi, Alice Boileve, Anabelle Ducousso, Morgan Michalet, Anthony Turpin, Cindy Neuzillet, Natacha Naoun
Journal: Clinical Cancer Research (2020)

Background: The COVID-19 pandemic deeply impacted clinical practices in oncology leading to organizational, ethical, and medical issues  It has raised challenges in a context of competing care priorities between COVID-19and cancer treatment  Residents and fellows were in the front line and had to face difficulties related to increasingcare needs and urgent reorganization of the health care system while managing stress and uncertainty  Methods: We conducted a national survey (39 questions) in France among all oncology and radiation therapyresidents to describe psychological impact and difficulties encountered by residents (i e , reassignment, training/research time, supervision, teleworking, management of patients) during the COVID-19 pandemic  Results: Overall, 222 residents (oncologists: 61% and radiation therapists: 39%) participated in our survey(representing around one third of all residents and fellows in France)  Reassignment in COVID-19 wards involved32% of respondents  Training and research activity were decreased for 89% and 41% of respondents, respectively 70% have been confronted with ethical issues, 35% felt worried about their health, and 23% experiencedpsychological distress  According to the Hospital Anxiety and Depression Scale, 32% were anxious and 17%depressive  Consumption of tobacco, psychostimulants, and alcohol was increased in 45%, 40%, and 24%, respectively  Conclusion: French oncology residents were highly impacted by the COVID-19 pandemic in terms of training andemotions  This national survey can be used as a basis for improved management, medical reorganization, andtraining of residents during the COVID-19 pandemic, especially when further waves are not excluded
Patients With Severely Reduced Ejection Fraction Undergoing Revascularization—Is Something Missing?—Reply
Authors: Louise Y. Sun, Mario Gaudino, Marc Ruel
Journal: JAMA Cardiology (2020)

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Sensory Discrimination of Blood and Floral Nectar by Aedes aegypti Mosquitoes
Authors: Veronica Jové, Zhongyan Gong, Felix J.H. Hol, Zhilei Zhao, Trevor R. Sorrells, Thomas S. Carroll, Manu Prakash, Carolyn S. McBride, Leslie B. Vosshall
Journal: Neuron (2020)
Removing barriers and disparities in health: lessons from the COVID-19 pandemic
Authors: Emily Sirotich, Jonathan S. Hausmann
Journal: Nature Reviews Rheumatology (2020)

The COVID-19 pandemic has compelled the global community to work together to understand SARS-CoV-2 and mitigate its effects, but it has also highlighted health disparities faced by people from minority racial or ethnic groups and other marginalized populations. International collaboration needs to be leveraged to address these disparities and inequities.
Nanoemulsion adjuvantation strategy of tumor-associated antigen therapy rephrases mucosal and immunotherapeutic signatures following intranasal vaccination
Authors: Chung-Hsiung Huang, Chiung-Yi Huang, Hui-Min Ho, Ching-Hung Lee, Pang-Ti Lai, Suh-Chin Wu, Shih-Jen Liu, Ming-Hsi Huang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Emulsion adjuvants are a potent tool for effective vaccination; however, the size matters on mucosal signatures and the mechanism of action following intranasal vaccination remains unclear. Here, we launch a mechanistic study to address how mucosal membrane interacts with nanoemulsion of a well-defined size at cellular level and to elucidate the impact of size on tumor-associated antigen therapy. Methods The squalene-based emulsified particles at the submicron/nanoscale could be elaborated by homogenization/extrusion. The mucosal signatures following intranasal delivery in mice were evaluated by combining whole-mouse genome microarray and immunohistochemical analysis. The immunological signatures were tested by assessing their ability to influence the transportation of a model antigen ovalbumin (OVA) across nasal mucosal membranes and drive cellular immunity in vivo. Finally, the cancer immunotherapeutic efficacy is monitored by assessing tumor-associated antigen models consisting of OVA protein and tumor cells expressing OVA epitope. Results Uniform structures with ~200 nm in size induce the emergence of membranous epithelial cells and natural killer cells in nasal mucosal tissues, facilitate the delivery of protein antigen across the nasal mucosal membrane and drive broad-spectrum antigen-specific T-cell immunity in nasal mucosal tissues as well as in the spleen. Further, intranasal vaccination of the nanoemulsion could assist the antigen to generate potent antigen-specific CD8+ cytotoxic T-lymphocyte response. When combined with immunotherapeutic models, such an effective antigen-specific cytotoxic activity allowed the tumor-bearing mice to reach up to 50% survival 40 days after tumor inoculation; moreover, the optimal formulation significantly attenuated lung metastasis. Conclusions In the absence of any immunostimulator, only 0.1% content of squalene-based nanoemulsion could rephrase the mucosal signatures following intranasal vaccination and induce broad-spectrum antigen-specific cellular immunity, thereby improving the efficacy of tumor-associated antigen therapy against in situ and metastatic tumors. These results provide critical mechanistic insights into the adjuvant activity of nanoemulsion and give directions for the design and optimization of mucosal delivery for vaccine and immunotherapy.
Alzheimer’s disease beyond amyloid: strategies for future therapeutic interventions
Authors: Jiong Shi, Marwan N Sabbagh, Bruno Vellas
Journal: BMJ (2020)

Neurodegenerative diseases encompass a variety of medical conditions that affect the survival and function of neurons in the brain.Neuronal loss often results in a decline of cognitive function and advances to dementia.Dementia is the common denominator of neurodegenerative diseases.The World Health Organization estimated that the number of people living with dementia worldwide in 2015 was 47.47 million.As the population ages, this number is expected to reach 75.63 million in 2030 and 135.46 million in 2050.Alzheimer's disease is the most common cause of dementia in older people.The natural course of dementia, particularly Alzheimer's disease, results in significant disability and dependence.The effect on care givers and the public health system is staggering.The total estimated costs of dementia were $604bn (£471bn; €519bn) in 2010, roughly 1% of the world's gross domestic product (www.who.int).No disease modifying treatment exists for dementia.
Endoscopic band ligation for weight loss
Authors: Mohamed Abeid, Tarek Kaddah
Journal: Endoscopy (2020)

To the best of our knowledge, this is the first study to use endoscopic band ligation for weight loss in a 30-year-old woman, who had an initial weight of 85 kg (height 155 cm; body mass index [BMI] 35.4 kg/m2). Endoscopy was performed with the patient sedated using propofol. All ligatures were applied in the gastric body, starting at the distal body; five parallel rows were created, with the last one in the proximal body, using 33 bands ([Fig. 1]). The entire procedure was completed in 30 minutes. Oxygen was used for endoscopic air insufflation. Notably, no immediate complications occurred during endoscopy ([Video 1]).
Efficacy and Safety of Guselkumab, an Interleukin‐23p19–Specific Monoclonal Antibody, Through One Year in Biologic‐Naive Patients With Psoriatic Arthritis
Authors: Iain B. McInnes, Proton Rahman, Alice B. Gottlieb, Elizabeth C. Hsia, Alexa P. Kollmeier, Soumya D. Chakravarty, Xie L. Xu, Ramanand A. Subramanian, Prasheen Agarwal, Shihong Sheng, Yusang Jiang, Bei Zhou, Yanli Zhuang, Désirée van der Heijde, Philip J. Mease
Journal: Arthritis & Rheumatology (2020)

Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings.Adults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized.Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumab-randomized patients. No patient developed an opportunistic infection or died.In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.
Intravital molecular imaging reveals the restrained capacity of CTLs in the killing of tumor cells in the liver
Authors: Lei Liu, Bolei Dai, Ruixue Li, Zheng Liu, Zhihong Zhang
Journal: Theranostics (2020)

Cytotoxic T lymphocytes (CTLs) and their gene-engineered cells display great application prospects in tumor immunotherapy.The timing of CTL-induced molecular events in tumor cells is unclear, and we also unknow whether the killing efficiency of CTLs is restrained in the liver, an immunotolerant organ with a high tumor incidence.Methods: We used intravital imaging to dynamically monitor the fluorescence resonance energy transfer (FRET) signals of caspase-3 and calcium sensor in tumor cells after transferring CTLs into tumor-bearing mice.Results: Our data show that several CTLs attacked on one tumor cell, and on average each CTL killed 1.24 ± 0.11 tumor cells per day in the liver, which was much less efficient than that in the spleen (3.18 ± 0.26 tumor cells/CTL/day).The killing efficiency of CTLs is restrained in the liver and can be reversed by blocking immunosuppressive cytokine.Tumor cells exposed to CTLs appeared to have prolonged calcium influx, which occurred dozens of minutes before caspase-3 activity. Conclusion:The quantitative characterization of these molecular and cellular events provides accurate information to evaluate the efficiency of cellular immunotherapy against tumors and understand the impact of an organ's immune status.
Home-based oral self-testing for absent and declining individuals during a door-to-door HIV testing campaign in rural Lesotho (HOSENG): a cluster-randomised trial
Authors: Alain Amstutz, Thabo Ishmael Lejone, Lefu Khesa, Josephine Muhairwe, Moniek Bresser, Fiona Vanobberghen, Mathebe Kopo, Mpho Kao, Bienvenu Lengo Nsakala, Katleho Tlali, Thomas Klimkait, Manuel Battegay, Niklaus Daniel Labhardt, Tracy Renée Glass
Journal: The Lancet HIV (2020)
Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance
Authors: Dominik Aschenbrenner, Maria Quaranta, Soumya Banerjee, Nicholas Ilott, Joanneke Jansen, Boyd Steere, Yin-Huai Chen, Stephen Ho, Karen Cox, Carolina V Arancibia-Cárcamo, Mark Coles, Eamonn Gaffney, Simon PL Travis, Lee Denson, Subra Kugathasan, Jochen Schmitz, Fiona Powrie, Stephen N Sansom, Holm H Uhlig
Journal: Gut (2020)

Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.
Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference
Authors: Joongyu D. Song, Tiago C. Alves, Douglas E. Befroy, Rachel J. Perry, Graeme F. Mason, Xian-Man Zhang, Alexander Munk, Ye Zhang, Dongyan Zhang, Gary W. Cline, Douglas L. Rothman, Kitt Falk Petersen, Gerald I. Shulman
Journal: Cell Metabolism (2020)
Obstructive jaundice with a biliary clot post-endoscopic sphincterotomy treated with clipping and endoscopic biliary stenting
Authors: Takashi Abe, Takehiko Nariyasu, Takayuki Nagai, Marina Hamamoto, Masato Hanzawa, Yasuhisa Hiroshima, Kazunari Murakami
Journal: Endoscopy (2020)

A 62-year-old man was admitted with epigastralgia. He had a history of laparoscopic cholecystectomy for cholecystolithiasis. He had no coagulopathy and was not taking anticoagulants. Abdominal computed tomography (CT) showed a common bile duct (CBD) stone ([Fig. 1 a]). Endoscopic retrograde cholangiography (ERC) and intraductal ultrasonography (IDUS) also showed a 2.8-mm CBD stone ([Fig. 1 b, ] [Fig. 2 a, b]). Endoscopic sphincterotomy (EST) was performed ([Fig. 2 c]) and the CBD stone was removed using a wire basket ([Fig. 2 d]).
Pre-COVID-19 food insecurity prevalence and risk factors in caregivers of pediatric cancer patients at a children’s cancer hospital.
Authors: Stephanie J. Wells, Brandon Douglas Brown, Kris Michael Mahadeo, Keri L. Schadler, Joya Chandra, Michael D. Swartz, Maria Chang Swartz
Journal: Journal of Clinical Oncology (2020)

205 Background: Food insecurity (FI) affects 1 in 5 US households with children and is associated with malnutrition and poor diet quality in children. Malnutrition negatively impacts clinical trial outcomes, chemotherapy tolerance, and survival rate in cancer patients, who may be at higher FI risk given the financial toxicity of treatment. Thus, we aimed to assess FI prevalence and sociodemographics of pediatric patient caregivers at MD Anderson Cancer Center Children’s Cancer Hospital (MDACC-CCH) and to identify healthcare provider sociodemographics and FI practice considerations. Methods: We surveyed caregivers and providers at MDACC-CCH anonymously from December 2019 to January 2020. Caregiver surveys included sociodemographics and The Hunger Vital Sign FI screening tool. Oncologists and other providers were surveyed on FI-related practice considerations. Univariate relationships between known covariates and FI were explored using purposeful covariate selection and multivariable logistic regression to model variables associated with FI risk factors. Results: Baseline characteristics are listed in Table. Of 67 caregiver responses, 36% were positive for FI. Univariate analyses revealed that race, education level, spousal/child support, marital status, and household income were associated with FI status. Final logistic regression model indicated that race other than Non-Hispanic White and lower education level were positively associated with FI. Of 38 provider responses, 58% reported being knowledgeable about FI to some extent. No providers referred patients to community food access resources. Conclusions: In a small pilot study, FI is prevalent in families of pediatric cancer patients at MDACC-CCH and may be associated with race and education level. Further research is needed to assess the impact of the COVID-19 pandemic on FI in this population and to determine appropriate interventions and clinical pathways to improve FI status. [Table: see text]
New era of personalised epilepsy management
Authors: Zhibin Chen, Ben Rollo, Ana Antonic-Baker, Alison Anderson, Yuanlin Ma, Terence J O’Brien, Zongyuan Ge, Xuefeng Wang, Patrick Kwan
Journal: BMJ (2020)

The trial and error approach to epilepsy treatment has not changed for over a century but machine learning and patient derived stem cells promise a personalised and more effective strategy, argue <b>Patrick Kwan and colleagues</b>
Associations of care experiences with survival among people with cancer in SEER-CAHPS, 2006 to 2017.
Authors: Lisa Dimartino, Justin Kirschner, Amy Huebeler, George L. Jackson, Michelle Mollica, Lisa M Lines
Journal: Journal of Clinical Oncology (2020)

177 Background: A growing body of literature indicates associations between cancer care experiences and survival. Several studies suggest people with cancer who report worse care experiences have greater mortality. However, studies in general patient populations have found worse care experiences are associated with lower mortality. To our knowledge, no study has evaluated the relationship between care experiences and survival using a large, nationally representative sample of cancer patients. Methods: We used linked SEER cancer registry-Consumer Assessment of Healthcare Providers and Systems (CAHPS) data to identify people diagnosed 8/2006-12/2013 with one of the top ten solid tumor cancer sites with the highest mortality rates among those over age 65 (lung, colon, prostate, pancreas, breast, bladder, ovary, esophagus, kidney, or liver cancers). We included people who completed a survey between 6-24 months post-diagnosis and were continuously enrolled in Medicare A &amp; B from ≤6 months pre-diagnosis through survey completion. CAHPS outcomes were ratings of Overall Care, Specialist Physician, Health Plan, and Prescription Drug Plan (PDP) and composite scores of Getting Needed Care. We used survey-weighted Cox proportional hazard models to compare those who gave lower (0-8) vs higher ratings (9-10), and lower (0-89) vs higher (90-100) scores. Results: We identified 2,403 eligible people. Mean survival was 46 months and 26% died by 5 years after diagnosis. In unadjusted models, lower Overall Care ratings were significantly associated with higher mortality (HR=1.25, p=.04), but this did not persist in the adjusted model. In contrast, lower ratings of PDP were significantly associated with lower mortality after covariate adjustment (HR=.63, p=.02). Conclusions: Except for PDP, survival was similar among those with worse vs better care experiences. People with better cancer prognoses may perceive worse services from their PDP compared to those with poorer prognoses. Future research examining mechanisms underlying this association may be warranted. [Table: see text]