tbuckley/cabot-search huggingface dataset:
PTU-053 Development of an alcohol liaison service: clinical outcomes
Authors: C Kelly, M Pericleous, A Gartland, S Davies, M Gallagher
Journal: Gut (2017)

Introduction  The annual cost of alcohol related harm in the UK is 2.7 billion, 78% of which is for acute care (20% and 40% for hospital and A and E admissions respectively)1. Alcohol harm cost NHS Surrey £73m annually with a higher spend per adult than national and regional levels1. Admissions to hospital for alcohol related conditions in Surrey was 12 079 per 1 00 000 (2014/15)2. To address local issues, an alcohol liaison service (ALS) was introduced in 2014. ALS has a prominent role in the education of fellow health care practitioners and in the clinical care of patients with alcohol issues. Here we describe our experience and outcomes  Method  The introduction of the ALS prompted a shift in practice in our hospital from fixed dose chlordiazepoxide reducing regimen for all patients at risk of alcohol withdrawal lasting at least 5 days to introduce the CIWA scoring regimen. This was followed by a tailored reducing course calculated on initial dose required to control symptoms. A program of education, training and regular team debriefs allowed a successful transition. Patients with alcohol related presentation are referred to ALS at admission with all requiring CIWA scoring reviewed. There are close links with community teams to foster a seamless transition for those requiring urgent support. Both prospective and retrospective data on all inpatient detoxes and referrals to this service was collected through each clinical encounter and medical records respectively  Results  The number of referrals received has increased in the 2 years of this service (Fig 1). Data on need for full detox after initial CIWA and length of stay (LOS) [Table 1] reflects the growing presence of the ALS in acute services. We have shown that those admitted with primarily medical problems require, on average, a shorter detox.  Conclusion  The ALS has been successful in changing trust policy and facilitating early discharge without detox where appropriate and reducing length of stay for those with primary alcohol presentations. These patients can now be seen in the ALS dedicated out patient clinic for ongoing support. Interestingly, our results show that patients admitted for non alcohol related problems receive less intense detox compared to their counterparts. This observation merits further study to explore the contributing factors to this. Our future work will also focus on developing care plans for frequent attenders to minimise number of admissions.  References  . National Health Intelligence Service (NHiS) Ltd2014: Alcohol Impact Model  . Local Alcohol Profile - Surrey2017, Public Health England  Disclosure of Interest  None Declared
Detection of Usutu virus infection in wild birds in the United Kingdom, 2020
Authors: Arran J Folly, Becki Lawson, Fabian ZX Lean, Fiona McCracken, Simon Spiro, Shinto K John, Joseph P Heaver, Katharina Seilern-Moy, Nic Masters, Luis M Hernández-Triana, L Paul Phipps, Alejandro Nuñez, Anthony R Fooks, Andrew A Cunningham, Nicholas Johnson, Lorraine M McElhinney
Journal: Eurosurveillance (2020)

In August 2020, as part of a long-term disease surveillance programme, Usutu virus was detected in five Eurasian blackbirds ( Turdus merula ) and one house sparrow ( Passer domesticus ) from Greater London, England. This was initially detected by reverse transcription-PCR and was confirmed by virus isolation and by immunohistochemical detection of flavivirus in tissues. Phylogenetic analysis identified Usutu virus African 3.2 lineage, which is prevalent in the Netherlands and Belgium, suggesting a potential incursion from mainland Europe.
OP0069 Microchimerism and sjÖgren? s syndrome: a preliminary study on salivary glands
Authors: F Carlucci, A Stoppacciaro, R Priori, F Barone, C Alessandri, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Recent researches suggested a role of microchimerism in the pathogenesis of systemic sclerosis and Graft Versus Host Disease. <h3>Objectives</h3> Aim of the present study was to evaluate whether fetal microchimerism plays a role in the pathogenesis of Sjögren's syndrome (SS). <h3>Methods</h3> We looked for male microchimerism in minor salivary glands tissue from 6 women with SS and at least one male pregnancy or miscarriage. SS diagnosis was made according to EEC criteria. As control we used DNA from minor salivary biopsy of 3 women with SS and female pregnancies only, 1 woman with SS without previous pregnancies and 2 healthy women, one with a male pregnancy and one with a female pregnancy. We assayed by PCR for a specific Y chromosome sequence, SRY, and for the homologous gene of Amelogenin. <h3>Results</h3> We didn't find male DNA neither in the tissue from women with SS and male pregnancy nor in the controls. <h3>Conclusion</h3> This preliminary study doesn't support the hypothesis of a role of microchimerism in the pathogenesis of Sjögren's syndrome, however further analysis should be performed to better clarify the hypothetical association between microchimerism and SS.
Upper Airway Stimulation/Hypoglossal Nerve Stimulator
Authors: Shalini Manchanda, Pritam Neupane, Ninotchka L. Sigua
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Upper Airway Stimulation/Hypoglossal Nerve Stimulator." American Journal of Respiratory and Critical Care Medicine, 202(8), pp. P23–P24
SAT0582 THE LATIN AMERICAN RHEUMATOLOGIST SURVEY: LARS STUDY
Authors: Genessis Maldonado, Enrique Soriano, Letty Moreno, Carlos Rios
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Currently, Latin America does not have detailed information of rheumatologists in the region based on: education, working conditions, productivity, distribution of time between work activities and job satisfaction. <h3>Objectives:</h3> The purpose of this survey was to provide more information on the rheumatology community in Latin America <h3>Methods:</h3> A digital survey was created using the Google Forms platform, it was approved and endorsed by the scientific committee of PANLAR and later sent to the different rheumatology associations of the region. The data was analyzed in the statistical programSPSS v.23: <h3>Results:</h3> 456 surveys of rheumatologists from 23 countries were received. The majority were females (54%). The mean age was 47.18 ± 11.79 [25-78] years, with a majority of mixed race 58%. 63% are married, 23% are single, 8% are divorced, 5% in free union and 2% are widowed. The mean number of children was 2 [0-7]. Birthplaces included Argentina (27%), Brazil (18%). The setting of the professional practice after obtaining the title of specialists was: public hospital (35%), private (25%), private/teaching in a university hospital (12%), public/teaching in a university hospital (14%), and industry (1%). The main place of work was in public/government hospitals by 30% followed by private practice 31%, private hospital 23%, university hospital 15% and nonprofit organizations 1%. The average of weekly working hours was 39.12 ± 27.53. 89% of the sample practices adult rheumatology, 17% pediatric rheumatology, 2% immunology and 3% another specialty. 30% had an early arthritis care center at their workplace, 71% had an infusion unit, 17% had ultrasound, 23% had a densitometer, 17% had a resonator and 9% had X-rays, however, most work in collaboration. 30% have training in ultrasound and 9% are in training period, 75% have training in reading densitometry and 2% in training period, 54% have training in resonance reading and 11% in training period. The average satisfaction with practice as a rheumatologist was 5/7, career options/professional growth 4/7, geographic location 5/7, income 4/7, job security 4/7, colleagues and co-workers 5/7. 33% had an annual compensation of &lt;19,000 US dollars. Only 58% have malpractice insurance and 87% have medical insurance. 40% present at least one clinical comorbidity. <h3>Conclusion:</h3> The majority of rheumatologists in the region who responded were female and feel satisfied with their clinical practice. This survey shows a low level of income for the region, however, more data should be obtained. This is the first study of its kind in Latin America, being an initiative for similar projects. <h3>Disclosure of Interests:</h3> None declared
Pulmonary Arterial Hypertension Caused by AhR Signal Activation Protecting against Colitis
Authors: Takahiro Hiraide, Toshiaki Teratani, Shizuka Uemura, Yusuke Yoshimatsu, Makoto Naganuma, Yoshiki Shinya, Mizuki Momoi, Eiji Kobayashi, Yoji Hakamata, Keiichi Fukuda, Takanori Kanai, Masaharu Kataoka
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Differential Responses to Targeting Matrix Metalloproteinase 9 in Idiopathic Pulmonary Fibrosis
Authors: Milena S. Espindola, David M. Habiel, Ana Lucia Coelho, Barry Stripp, William C. Parks, Justin Oldham, Fernando J. Martinez, Imre Noth, David Lopez, Amanda Mikels-Vigdal, Victoria Smith, Cory M. Hogaboam
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Aberrant lung remodeling in idiopathic pulmonary fibrosis (IPF) is characterized by elevated MMP9 (matrix metalloproteinase 9) expression, but the precise role of this matrix metalloproteinase in this disease has yet to be fully elucidated.Objectives: To evaluate antifibrotic effects of MMP9 inhibition on IPF.Methods: Quantitative genomic, proteomic, and functional analyses both in vitro and in vivo were used to determine MMP9 expression in IPF cells and the effects of MMP9 inhibition on profibrotic mechanisms.Measurements and Main Results: In the present study, we demonstrate that MMP9 expression was increased in airway basal cell (ABC)-like cells from IPF lungs compared with ABC cells from normal lungs. The inhibition of MMP9 activity with an anti-MMP9 antibody, andecaliximab, blocked TGF-β1 (transforming growth factor β1)-induced Smad2 phosphorylation. However, in a subset of cells from patients with IPF, TGF-β1 activation in their ABC-like cells was unaffected or enhanced by MMP9 blockade (i.e., nonresponders). Further analysis of nonresponder ABC-like cells treated with andecaliximab revealed an association with type 1 IFN expression, and the addition of IFNα to these cells modulated both MMP9 expression and TGF-β1 activation. Finally, the inhibition of MMP9 ameliorated pulmonary fibrosis induced by responder lung cells but not a nonresponder in a humanized immunodeficient mouse model of IPF.Conclusions: Together, these data demonstrate that MMP9 regulates the activation of ABC-like cells in IPF and that targeting this MMP might be beneficial to a subset of patients with IPF who show sufficient expression of type 1 IFNs.
Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration
Authors: Hui Li, Jingjing Sun, Hefeng Yang, Xue Han, Xiangyou Luo, LiJun Liao, Bo Yang, Tian Zhu, Fangjun Huo, Weihua Guo, Weidong Tian
Journal: Bioactive Materials (2020)

Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation, fibrosis, and remodeling process. Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues. This study fabricated PPARγ-primed CD68+CD206+ M2 phenotype (M2γ), and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration. Our results showed that Th1-type CD3+CD8+ T cell response to xenogeneic-dentin matrix-based bioengineered root complex (xeno-complex) was significantly inhibited by M2γ macrophage in vitro. PPARγ activation also timely recruited CD68+CD206+ tissue macrophage polarization to xeno-complex in vivo. These subsets alleviated proinflammatory cytokines (TNF-α, IFN-γ) at the inflammation site and decreased CD3+CD8+ T lymphocytes in the periphery system. When translated to an orthotopic nonhuman primate model, PPARγ-primed M2 macrophages immunosuppressed IL-1β, IL-6, TNF-α, MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity. These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression. Finally, the regenerated root showed structure-biomechanical and functional equivalency to the native tooth. The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis, fibrogenesis, and osteogenesis, which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.
Abstract 12730: Marked Impairment of Endothelium-dependent Digital Vasodilatations in Patients With Microvascular Angina -possible Manifestation of Systemic Small Artery Disease
Authors: Shoko Kajitani, Takashi Shiroto, Shigeo Godo, Akiyo Ito, Yosuke Ikumi, Koichi Sato, Jun Sugisawa, Satoshi Tsuchiya, Akira Suda, Tomohiko Shindo, Shohei Ikeda, Kiyotaka Hao, Yoku Kikuchi, Kotaro Nochioka, Yasuharu Matsumoto, Jun Takahashi, Hiroaki Shimokawa
Journal: Circulation (2019)

Introduction: The roles of endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) remain unclear in the pathogenesis of vasospastic angina (VSA) or microvascular an...
Contrast-FEL—A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches
Authors: Sergei L Kosakovsky Pond, Sadie R Wisotsky, Ananias Escalante, Brittany Rife Magalis, Steven Weaver
Journal: Molecular Biology and Evolution (2020)

Abstract A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.
Important Concerns Over SARS-CoV-2 Infection in Children With Cancer
Authors: Lipeng Zhang, Danni He, Wenquan Niu
Journal: JAMA Oncology (2020)

targeting agents because of potential false responses owing to their effect on contrast uptake. 2 Therefore, further value is added if the response is maintained for a meaningful duration.Longer DOR has been consistently noted following antiprogrammed cell death 1 (PD-1) therapy across tumor types, explained by generation of polyclonal and memory-adaptive tumor immunity. 3Therefore, DOR is an increasingly important end point, in addition to ORR, for evaluating the efficacy and long-term clinical benefit of immunotherapy.Given the above rationale, we presented a descriptive summary of DOR. 4 We agree with McCaw et al that the differing response rates between arms and the small number of responders may cause a potential bias in case of imbalance in baseline disease burden in responding patients.Although our study 4 did not collect overall baseline disease burden, we conducted a post hoc evaluation of tumor location and the number of sites with lesions at baseline (data not presented).While there was no difference in the tumor location distribution between the arms, all responders in the nivolumab arm (n = 12) had only 1 site involved, while 78% (n = 28) of responders in the bevacizumab arm had 1 site involved and 22% (n = 8) had 2 sites involved.However, the median DOR in the bevacizumab arm was similar between patients with 1 and 2 sites involved. 4Additionally, the median DOR for responders to nivolumab in CA209-143 is longer than that typically observed with salvage agents, such as lomustine 5,6 or temozolomide rechallenge (NCT00392171), and surpassed that achieved by bevacizumab, suggesting that PD-1 inhibition may offer longer-term clinical benefit among glioblastoma responders.We also acknowledge the concerns of dependent censoring.However, in the current study, 4 because of the length of follow-up, there were very few censored participants remaining.Thus, dependent censoring may have minimal influence on this descriptive analysis.We also evaluated the median DOR while including both responders and nonresponders. 4However, given the high numbers of nonresponders, this method only yields the value of zero for both treatment arms, which may be less informative to clinicians.Given the totality of the clinical, mechanistic, and statistical rationales presented above, we conclude that there is value to reporting median DOR in a descriptive manner, while acknowledging the caveats discussed here and by McCaw et al.Additional research in a larger patient population may be needed to further evaluate the value of the DOR benefit in patients with glioblastoma treated with immunotherapy.Better understanding of patient and treatment characteristics among those who achieve a durable DOR may help guide improvement of the efficacy of immunotherapy in a patient population with an urgent need for better treatments.
Alpha-dystroglycan binding peptide A2G80-modified stealth liposomes as a muscle-targeting carrier for Duchenne muscular dystrophy
Authors: Eri Sasaki, Yoshihiro Hayashi, Yuka Kimura, Sanae Sashida, Nobuhito Hamano, Kei Nirasawa, Keisuke Hamada, Fumihiko Katagiri, Yamato Kikkawa, Takaaki Sakai, Akihiro Yoshida, Masahiro Kawada, Shin-ichi Hirashima, Tsuyoshi Miura, Yoko Endo-Takahashi, Motoyoshi Nomizu, Yoichi Negishi
Journal: Journal of Controlled Release (2020)
Guidelines for Care of Adults With Down Syndrome
Authors: Jason F. Woodward, Sophia Jan, Mary R. Ciccarelli
Journal: JAMA (2020)

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Biological and prognostic impact of apobec-induced mutations in the spectrum of plasma cell dyscrasias
Authors: Francesco Maura, Mia Petljak, Marta Lionetti, Ingrid Cifola, Winnie Liang, Eva Pinatel, Ludmil Alexadrov, Anthony Fullam, Inigo Martincorena, Kevin J. Dawson, Nicos Angelopoulos, Raphael Szalat, Paolo Corradini, Kenneth C. Anderson, Stephane Minvielle, Mehmet K. Samur, Antonino Neri, Herve Avet-Loiseau, Jonathan Keats, Peter J. Campbell, Nikhil Munshi, Niccolo Bolli
Journal: Blood (2017)
Lost in translation: true clinical impact of reflectance confocal microscopy overlooked in ‘Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial’: reply from authors
Authors: W. Woliner‐van der Weg, M. Peppelman, P.E.J. Erp, S.F.K. Lubeek
Journal: British Journal of Dermatology (2020)

Linked Articles: Gill et al. Br J Dermatol 2021; 184:775–776. Woliner‐van der Weg et al. Br J Dermatol 2021; 184:663–671.
Asymptomatic and Presymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Rates in a Multistate Sample of Skilled Nursing Facilities
Authors: Elizabeth M. White, Christopher M. Santostefano, Richard A. Feifer, Cyrus M. Kosar, Carolyn Blackman, Stefan Gravenstein, Vincent Mor
Journal: JAMA Internal Medicine (2020)

Limitations.Limitations of this study are that it is a singlecenter analysis from a large community hospital that has the capability to adequately supply PPE to all health care workers.The present results may therefore not be applicable to all health care settings.Testing for COVID-19 was offered on a voluntary basis, with most employees complying.While no differences were observed between those tested and those not tested, a potential selection bias cannot be completely excluded.
Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice
Authors: Pierre Montay-Gruel, Munjal M. Acharya, Patrik Gonçalves Jorge, Benoît Petit, Ioannis G. Petridis, Philippe Fuchs, Ron Leavitt, Kristoffer Petersson, Maude Gondré, Jonathan Ollivier, Raphael Moeckli, François Bochud, Claude Bailat, Jean Bourhis, Jean-François Germond, Charles L. Limoli, Marie-Catherine Vozenin
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. Experimental Design: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT. Results: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens. Conclusions: The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT. See related commentary by Huang and Mendonca, p. 662