tbuckley/cabot-search huggingface dataset:
Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption
Authors: Yanjuan Huang, Zhanghong Xiao, Zilin Guan, Zishan Zeng, Yifeng Shen, Xiaoyu Xu, Chunshun Zhao
Journal: Acta Pharmaceutica Sinica B (2020)

The "vicious cycle" established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the "vicious cycle", innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn2+ crosslinking for combination therapy was reported. The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo. Additionally, DZ@ALN could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro. Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo, eventually leading to the breakdown of "vicious cycle" without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis.
Circulating MicroRNAs and Extracellular Vesicle–Containing MicroRNAs as Response Biomarkers of Anti–programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Therapy in NSCLC
Authors: Takehito Shukuya, Vikas Ghai, Joseph M. Amann, Tamio Okimoto, Konstantin Shilo, Taek-Kyun Kim, Kai Wang, David P. Carbone
Journal: Journal of Thoracic Oncology (2020)
Chronic immune checkpoint inhibitor pneumonitis
Authors: Jarushka Naidoo, Tricia R Cottrell, Evan J Lipson, Patrick M Forde, Peter B Illei, Lonny B Yarmus, K Ranh Voong, David Feller-Kopman, Hans Lee, Joanne Riemer, Daphne Wang, Janis M Taube, Julie R Brahmer, Cheng Ting Lin, Sonye K Danoff, Franco R D'Alessio, Karthik Suresh
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4–6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ≥12 weeks of immunosuppression. Methods Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ≥12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&amp;E staining and multiplex immunofluorescence (mIF), where available. Results Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0–50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3–12 weeks), with all patients requiring steroid reintroduction when tapered to ≤10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16–43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper. Conclusions A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ≥12 weeks, and has distinct clinicopathological features.
Association of Air Pollution and Heat Exposure With Preterm Birth, Low Birth Weight, and Stillbirth in the US
Authors: Bruce Bekkar, Susan Pacheco, Rupa Basu, Nathaniel DeNicola
Journal: JAMA Network Open (2020)

Knowledge of whether serious adverse pregnancy outcomes are associated with increasingly widespread effects of climate change in the US would be crucial for the obstetrical medical community and for women and families across the country.To investigate prenatal exposure to fine particulate matter (PM2.5), ozone, and heat, and the association of these factors with preterm birth, low birth weight, and stillbirth.This systematic review involved a comprehensive search for primary literature in Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, PubMed, ClinicalTrials.gov website, and MEDLINE. Qualifying primary research studies included human participants in US populations that were published in English between January 1, 2007, and April 30, 2019. Included articles analyzed the associations between air pollutants or heat and obstetrical outcomes. Comparative observational cohort studies and cross-sectional studies with comparators were included, without minimum sample size. Additional articles found through reference review were also considered. Articles analyzing other obstetrical outcomes, non-US populations, and reviews were excluded. Two reviewers independently determined study eligibility. The Arskey and O'Malley scoping review framework was used. Data extraction was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Of the 1851 articles identified, 68 met the inclusion criteria. Overall, 32 798 152 births were analyzed, with a mean (SD) of 565 485 (783 278) births per study. A total of 57 studies (48 of 58 [84%] on air pollutants; 9 of 10 [90%] on heat) showed a significant association of air pollutant and heat exposure with birth outcomes. Positive associations were found across all US geographic regions. Exposure to PM2.5 or ozone was associated with increased risk of preterm birth in 19 of 24 studies (79%) and low birth weight in 25 of 29 studies (86%). The subpopulations at highest risk were persons with asthma and minority groups, especially black mothers. Accurate comparisons of risk were limited by differences in study design, exposure measurement, population demographics, and seasonality.This review suggests that increasingly common environmental exposures exacerbated by climate change are significantly associated with serious adverse pregnancy outcomes across the US.
Covid-19: Doctors “face difficulties” getting life insurance after exposure to disease
Authors: Abi Rimmer
Journal: BMJ (2020)

Covid-19: Doctors "face difficulties" getting life insurance after exposure to disease Abi RimmerDoctors have encountered difficulties in applying for life insurance because of their exposure to covid-19, the BMA has found.The association and the financial adviser Chase de Vere worked to establish how insurers assessed the risks from covid-19 for doctors applying for life insurance policies.
SAT0584 SPECIFIC ACPA REACTIVITIES AND INFLAMMATORY BIOMARKERS ALONG WITH ULTRASOUND TENOSYNOVITIS ARE ASSOCIATED WITH ARTHRITIS ONSET IN A POPULATION AT RISK FOR RHEUMATOID ARTHRITIS
Authors: A. Circiumaru, Y. Kisten, M. Hansson, V. Joshua, M. Sun, H. Rezaei, E. Af Klint, A. Antovic, A. Catrina, A. Hensvold
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anti-citrullinated protein antibodies (ACPA) are characteristic markers for rheumatoid arthritis (RA), developing years before disease onset. Early clinical and biological biomarkers could provide useful information on the onset of RA in predisposed individuals. Objectives: The aim of the study was to investigate whether ACPA along with inflammatory markers and musculoskeletal ultrasound changes could predict arthritis development in individuals at risk for RA. Methods: ACPA-positive individuals with musculoskeletal complaints were referred from primary care to a rheumatology clinic, recruited in the Risk-RA research program and followed-up for up to 3 years, between April 2014 and October 2019. All individuals lacked arthritis both at clinical examination by a trained rheumatologist and ultrasound assessment of hands and feet and any other symptomatic joints (according to EULAR-OMERACT definition). Blood samples were collected at inclusion and were analyzed for 15 ACPA fine specificities (by custom made peptide array), 92 inflammation-associated protein biomarkers (by multiplex immunoassay with Olink extension technology) and HLA-SE (DR low resolution kit). Statistical analysis used univariate and multivariate models with backwards selection and cox regression. Results: 268 individuals with a median age of 48 (36-58) were recruited, out of which 212 (79%) were females. 75 (28%) developed arthritis within 11 months of follow-up while the median follow-up for those not developing arthritis was 21 months (14-28). Increased ACPA levels, shorter symptom duration and RF positivity were the main differences between individuals developing arthritis and those who did not. In univariate models, the presence of HLA-SE, specific ACPA reactivities, certain inflammatory markers and ultrasound-detected tenosynovitis were associated with arthritis development. In multivariate analysis the presence of anti-cit-fillagrin (HR 2.1 (95% CI 1.2-3.7, p 0.01), IL6 levels (HR 1.4 (95% CI 1.2-1.7, p 0.0001) and tenosynovitis (HR 2.9 (95% CI 1.7-5.0, p 0.0001) remained significant predictors for arthritis onset. Conclusion: Certain ACPA reactivities together with inflammatory markers and ultrasound-detected tenosynovitis predict arthritis development in predisposed individuals for developing RA. Disclosure of Interests: None declared
SARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases
Authors: I. Colmenero, C. Santonja, M. Alonso‐Riaño, L. Noguera‐Morel, A. Hernández‐Martín, D. Andina, T. Wiesner, J.L. Rodríguez‐Peralto, L. Requena, A. Torrelo
Journal: British Journal of Dermatology (2020)

Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established.To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue.We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one.Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage. What is already known about this topic? Despite the high number of cases of chilblains seen during the COVID-19 pandemic, a definite causative role for SARS-CoV-2 has not yet been proven. Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors. What does this study add? The demonstration of SARS-CoV-2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID-19. Virus-induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID-19 chilblains. Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a pathogenetic role in the severe forms of COVID-19. Linked Comment: Wetter. Br J Dermatol 2020; 183:611.
Shared reality and abstraction: The social nature of predictive models
Authors: Maya Rossignac-Milon, Federica Pinelli, E. Tory Higgins
Journal: Behavioral and Brain Sciences (2020)

Abstract We propose that abstraction is an interpersonal process and serves a social function. Research on shared reality shows that in communication, people raise their level of abstraction in order to create a common understanding with their communication partner, which can subsequently distort their mental representation of the object of communication. This work demonstrates that, beyond building accurate models, abstraction also functions to build socially shared models – to create a shared reality.
OP0007-PARE CAMPAIGN TO PROMOTE PHYSICAL ACTIVITY &amp; EXERCISE TO RMD PATIENTS THROUGH EDUCATION AND PRACTICE
Authors: A. Iacovou
Journal: Annals of the Rheumatic Diseases (2020)

Background: Eular give’ s a lot of attention to outline the need of a change in RMD patients life style that is very well outlined into the 2018 Eular recommendations for Physical Activity (PA). Objectives: Driven by those recommendations that says that “PA should be an integral part of standard care throughout the course of disease”, CypLAR decided to create a campaign to promote PA through educating RMD patients on the PA benefits, make them to change their life style and enroll them to PA programs. More over we want to inform Rheumatologist and HPR’s on that effort and enroll them to that campaign.The CypLAR’ s goal through that campaign is to manage and enroll as much as possible patients to PA Programs for a continual period of about 10 months. Methods: To achieve all the above we decided to move to the following steps: Offer PA Programs organized by CypLAR or HPR associates Increase awareness regarding the benefits of the PA (Land based &amp; Aquatic) programs to Rheumatologists, HPR’s and RMD patients Integrate PA into National Health System and procedures Offer incentives Results: We managed to increase the PA programs that we used to offer from 1 to 3 in every major cities with also some more opportunities ahead. That also increases the number of participants attracting around 100 participants instead of 20 that we uses to before. Towards awareness, we presented Exercise rehabilitation in conferences around Europe (Agora 2017,2018,2019, Eular 2018, Cyprus – Crete Conference 2017, 2019, Enfa 2019, Pain Conference, Athens 2019) and also published related articles on CypLAR’s magazine that is published twice a year that is distributed to more than 5000 members. We managed to include the Aquatic Exercise Rehabilitation to the new National Strategic plan for Rheumatic Diseases. As incentives, we created a fund that is addressed to partially support low income patients. Furthermore we acquire special discount membership fees to our members on PA programs that are offered by associates. We organize our own sport related fund events and also participate in others sport funding events. Especially the Charity Swimming Event “Swim for my fellow” which is co-organized by the Iacovou Swimming Centre and Cyplar for the last 5 years is also under the Limassol Municipality Annual Sport Events called “Lemesia” which this year will have an International promotion due Limassol’s Award as the “European City of Sports” for 2020. We are in the process and in contact with big companies in order to become our campaign Sponsors We attracted a fund of €2000 from Cyprus Sport Organization that offered a partial financial support to 30 patients for their participation in PA programs for 3 months. Conclusion: We all believe that the success on that campaign is based on Education (articles, presentations), the available options (programs/positions to participate) and Incentives (financial) that all of them needs further development. Disclosure of Interests: None declared
A Clarion Warning About Pregnancy Outcomes and the Climate Crisis
Authors: Linda C. Giudice
Journal: JAMA Network Open (2020)

Without mitigating efforts, the climate crisis is anticipated to result in increasingly warmer global temperatures, more frequent and extreme weather events, changes in precipitation patterns, and rising sea levels.These adverse events are predicted to have devastating effects on global water and food supplies, economic sustainability, forced population and wildlife migrations, civil conflict, and physical and mental health-related illnesses. 1,2Human populations most affected include disadvantaged communities, indigenous peoples, persons with disabilities and preexisting or chronic medical conditions, older adults, pregnant women, the developing fetus, and children. 3Pregnant
Trends in Readmission and Mortality Rates Following Heart Failure Hospitalization in the Veterans Affairs Health Care System From 2007 to 2017
Authors: Justin T. Parizo, Shun Kohsaka, Alexander T. Sandhu, Jay Patel, Paul A. Heidenreich
Journal: JAMA Cardiology (2020)

The Centers for Medicare & Medicaid Services and the Veterans Affairs Health Care System provide incentives for hospitals to reduce 30-day readmission and mortality rates. In contrast with the large body of evidence describing readmission and mortality in the Medicare system, it is unclear how heart failure readmission and mortality rates have changed during this period in the Veterans Affairs Health Care System.To evaluate trends in readmission and mortality after heart failure admission in the Veterans Affairs Health Care System, which had no financial penalties, in a decade involving focus on heart failure readmission reduction (2007-2017).This cohort study used data from all Veterans Affairs-paid heart failure admissions from January 2007 to September 2017. All Veterans Affairs-paid hospital admissions to Veterans Affairs and non-Veterans Affairs facilities for a primary diagnosis of heart failure were included, when the admission was paid for by the Veterans Affairs. Data analyses were conducted from October 2018 to March 2020.Admission for a primary diagnosis of heart failure at discharge.Thirty-day all-cause readmission and mortality rates.A total of 164 566 patients with 304 374 hospital admissions were included. Among the 304 374 hospital admissions between 2007 and 2017, 298 260 (98.0%) were for male patients, and 195 205 (64.4%) were for white patients. The mean (SD) age was 70.8 (11.5) years. The adjusted odds ratio of 30-day readmission declined throughout the study period to 0.85 (95% CI, 0.83-0.88) in 2015 to 2017 compared with 2007 to 2008. The adjusted odds ratio of 30-day mortality remained stable, with an adjusted odds ratio of 1.01 (95% CI, 0.96-1.06) in 2015 to 2017 compared with 2007 to 2008. Stratification by left ventricular ejection fraction showed similar readmission reduction trends and no significant change in mortality, regardless of strata.In this analysis of an integrated health care system that provided guidance and nonfinancial incentives for reducing readmissions, such as public reporting of readmission rates, risk-adjusted 30-day readmission declined despite inclusion of clinical variables in risk adjustment, but mortality did not decline. Future investigations should focus on evaluating the effectiveness of specific approaches to readmission reduction to inform efficient and effective application in individual health systems, hospitals, and practices.
The role of sleep in the formation and updating of abstract mental representations
Authors: Antonino Visalli, Nicola Cellini
Journal: Behavioral and Brain Sciences (2020)

Abstract According to Gilead and colleagues, to be efficient abstraction requires a hierarchical organization of information into long-term memory. But, how and when are abstract representations consolidated into long-term memory and how are they integrated with pre-existing abstracta are questions not discussed by Gilead and colleagues. Here, we propose that these processes occur preferentially during offline periods such as sleep.
Inverse Association Between Fatty Liver at Baseline Ultrasonography and Remission of Type 2 Diabetes Over a 2-Year Follow-up Period
Authors: Hajime Yamazaki, Jui Wang, Shinichi Tauchi, Mitsuru Dohke, Nagisa Hanawa, Akio Katanuma, Yoshifumi Saisho, Tsukasa Kamitani, Shunichi Fukuhara, Yosuke Yamamoto
Journal: Clinical Gastroenterology and Hepatology (2020)
Two-dimensional silicene composite nanosheets enable exogenous/endogenous-responsive and synergistic hyperthermia-augmented catalytic tumor theranostics
Authors: Huican Duan, Haiyan Guo, Ruifang Zhang, Fangfang Wang, Zhuang Liu, Min Ge, Luodan Yu, Han Lin, Yu Chen
Journal: Biomaterials (2020)