tbuckley/cabot-search huggingface dataset:
AB0834 CLINICAL CHARACTERISTICS OF PSORIATIC ARTHRITIS IN CHINESE PATIENTS: A CROSS‑SECTIONAL OBSERVATIONAL STUDY
Authors: Z. Song, B. Li, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: The clnical features of psoriatic arthritis(PsA)greatly varied in reports fomr different countries.There was no exact data in China. Objectives: To disclose the characteristics of PsA in China, we initiated an investigation it in our cohort of PsA patients. Methods: A cross-sectional observational study was conducted in our PsA cohort of Peking University First Hospital. All the clinical and imaging data at the patient’s first visit were collected, including the age, gender, disease course, skin lesion, arthritis, dactylitis, enthesis, laboratory tests, concomitant diseases and so on. Results: Two hundred and seventy-nine patients with PsA were enrolled in this study. Their mean age was 41 year-old with 132 (47.3%) female. Median disease duration was 3 years. Among these patients, 196(73.4%)patients had the skin lesion first, 47 (17.6%)patients had the arthritis first, and the other 24(9.0%) patients had the psoriasis and the arthritis at the same time. Arthritis was the most common manifestation. Polyarthritis was the most common arthritic manifestation with proximal interphalangeal (PIP) joint as the most frequently involved joint. Dactylitis was observed in 89 (31.9%) patients, mostly at the second, third and fourth toe. Enthesis was found in 18 (6.5%) patients by physical examination, however, in 158 (56.5%) patients with the aid of ultrasound and MRI. Conclusion: Polyarthritis was the most common arthritis type in Chinese PsA patients, and PIP joint was the most involved joint, and the second, the middle and the fourth toe were the most frequently digits. The imaging techniques, especially ultrasound dramatically increased the identification of enthesis. References: [1]Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med 2017;376: 957–70. [2]Qing Yu Zeng, Ren Chen, John Darmawan et al. Rheumatic Diseases in China. Arthritis Research &amp; Therapy Vol 10 No 1. Disclosure of Interests: None declared
Possible Reasons US Adults Are Not Having Sex as Much as They Used To
Authors: Jean M. Twenge
Journal: JAMA Network Open (2020)

In their recent analysis, Ueda et al 1 found decreases in sexual activity among US individuals aged 18-44 years between 2000 and 2018.The percentage of 18-to 24-year-old men who were sexually inactive in the past year increased from 18.9% in 2000-2002 to 30.9% in 2016-2018.Similar trends in sexual inactivity appeared among individuals aged 25-34 years but not among individuals aged 35-44 years.Ueda et al 1 built on several previous studies 2-4 that found decreases in sexual frequency and increases in sexual inactivity among US adults. 2 The percentage of British residents sexually inactive
Versatile Nanoplatforms with enhanced Photodynamic Therapy: Designs and Applications
Authors: Kai Yan, Yabin Zhang, Chenglong Mu, Qunna Xu, Xunan Jing, Daquan Wang, Dongfeng Dang, Lingjie Meng, Jianzhong Ma
Journal: Theranostics (2020)

As an emerging antitumor strategy, photodynamic therapy (PDT) has attracted intensive attention for the treatment of various malignant tumors owing to its noninvasive nature and high spatial selectivity in recent years.However, the therapeutic effect is unsatisfactory on some occasions due to the presence of some unfavorable factors including nonspecific accumulation of PS towards malignant tissues, the lack of endogenous oxygen in tumors, as well as the limited light penetration depth, further hampering practical application.To circumvent these limitations and improve real utilization efficiency, various enhanced strategies have been developed and explored during the past years.In this review, we give an overview of the state-of-the-art advances progress on versatile nanoplatforms for enhanced PDT considering the enhancement from targeting or responsive, chemical and physical effect.Specifically, these effects mainly include organelle-targeting function, tumor microenvironment responsive release photosensitizers (PS), self-sufficient O2 (affinity oxygen and generating oxygen), photocatalytic water splitting, X-rays light stimulate, surface plasmon resonance enhancement, and the improvement by resonance energy transfer.When utilizing these strategies to improve the therapeutic effect, the advantages and limitations are addressed.Finally, the challenges and prospective will be discussed and demonstrated for the future development of advanced PDT with enhanced efficacy.
Managing fragility fractures during the COVID-19 pandemic
Authors: Nicola Napoli, Ann L. Elderkin, Douglas P. Kiel, Sundeep Khosla
Journal: Nature Reviews Endocrinology (2020)

The COVID-19 pandemic has broad implications for the care of patients with bone fragility. A dramatic surge in fractures and related mortality is expected in the next few months. We pledge to intensify the current efforts to improve the management of bone health, and to prioritize fragility fracture care and prevention.
Corrigendum to: Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a/p38/ZEB1 axis
Authors: Eun-Jung Lim, Seungmo Kim, Yoonjee Oh, Yongjoon Suh, Neha Kaushik, Ji-Hyun Lee, Hae-June Lee, Min-Jung Kim, Myung-Jin Park, Rae-Kwon Kim, Junghwa Cha, Se Hoon Kim, Jin-Kyoung Shim, Junjeong Choi, Jong Hee Chang, Yong Kil Hong, Yong Min Huh, Pilnam Kim, Seok-Gu Kang, Su-Jae Lee
Journal: Neuro-Oncology (2020)
Enteroendocrine Dynamics – New Tools Reveal Hormonal Plasticity in the Gut
Authors: Joep Beumer, Helmuth Gehart, Hans Clevers
Journal: Endocrine Reviews (2020)

Abstract The recent intersection of enteroendocrine cell biology with single-cell technologies and novel in vitro model systems has generated a tremendous amount of new data. Here we highlight these recent developments and explore how these findings contribute to the understanding of endocrine lineages in the gut. In particular, the concept of hormonal plasticity, the ability of endocrine cells to produce different hormones over the course of their lifetime, challenges the classic notion of cell types. Enteroendocrine cells travel in the course of their life through different signaling environments that directly influence their hormonal repertoire. In this context, we examine how enteroendocrine cell fate is determined and modulated by signaling molecules such as bone morphogenetic proteins (BMPs) or location along the gastrointestinal tract. We analyze advantages and disadvantages of novel in vitro tools, adult stem cell or iPS-derived intestinal organoids, that have been crucial for recent findings on enteroendocrine development and plasticity. Finally, we illuminate the future perspectives of the field and discuss how understanding enteroendocrine plasticity can lead to new therapeutic approaches.
Blocking integrin α4β7-mediated CD4 T cell recruitment to the intestine and liver protects mice from western diet-induced non-alcoholic steatohepatitis
Authors: Ravi P. Rai, Yunshan Liu, Smita S. Iyer, Silvia Liu, Biki Gupta, Chirayu Desai, Pradeep Kumar, Tekla Smith, Aatur D. Singhi, Asma Nusrat, Charles A. Parkos, Satdarshan P. Monga, Mark J. Czaja, Frank A. Anania, Reben Raeman
Journal: Journal of Hepatology (2020)
Response to: ‘Beware of wolves in sheep's clothing: immune cell plasticity and instability in health and disease’ by Alunno<i>et al</i>
Authors: Abdulla Watad, Hannah Rowe, Darren Newton, Charlie Bridgewood, Dennis G McGonagle
Journal: Annals of the Rheumatic Diseases (2020)

We thank Alunno et al 1 for their comments on our paper reporting on the isolation and preliminary characterisation of normal human enthesis CD4+ and CD8+ conventional T-cells.2 Our work showed that up to 2% of CD4+ T cells were Th17 in nature as demonstrated by intracellular flow cytometry. We were unable to identify FOXP3+ Tregs at the enthesis, but these were readily demonstrable in peripheral blood from the same patients. Alunno and colleagues1 point towards the transdifferentiation between Th17s and Tregs that may occur in vivo and which can be modulated by pivotal spondyloarthritis (SpA) associated cytokines including TNF. Our results were generated in an artificial ‘in vitro enthesitis’ model, and we agree with the comments by Alunno et al 1 in regard to the role …
Author Correction: Complement as a target in COVID-19?
Authors: Antonio M. Risitano, Dimitrios C. Mastellos, Markus Huber-Lang, Despina Yancopoulou, Cecilia Garlanda, Fabio Ciceri, John D. Lambris
Journal: Nature reviews. Immunology (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Exploratory study of the subcutaneous fat gene expression profile in patients with metastatic pancreatic carcinoma treated with standard gemcitabine chemotherapy regimen
Authors: D. E. Castellano, C. Gomez-Martin, R. Cubedo Cervera, J. Garcia Lopez, R. Gomez-Sanz, C. Gravalos, J. Nuñez Sobrino, H. Cortes-Funes
Journal: Journal of Clinical Oncology (2009)

e22220 Background: Most clinical trials are designed to assess the antitumor effect of the chemoterapeutic intervention. There are few examples where the endpoint is to assess the biology of the host response to the treatment of the tumor. A large number of patients with pancreatic cancer present features of the cachexia syndrome and specially a marked weight loss. It has been postulated that a “cytokine storm” is the cause of the profound effect that this cancer has on distant tissues. This trial analyzed changes in the subcutaneous fat gene expression profile in relation with the clinical benefit variable with standard gemcitabine (G) treatment. Methods: Patients with histology confirmed advanced pancreatic cancer, adequate organ function and written informed consent. Eligible pts were intended for a subcutaneous fat biopsy pretreatment and after 7 weeks of gemcitabine 1000 mg/m 2 together with response assessment. Clinical benefit (CB) (pain, analgesic consumption, Karnofsky and weight), QLQ-C30, serum cytokines and tumor markers were evaluated pretreatment, at 4 and 8 weeks. Fat gene expression profile was analyzed using Affimetrix U133Plus2.0 with the corresponding bioinformatic software. Serum cytokines where analyzed with xMAP technology with the Luminex 200 platform. Results: 16 pts [8 m, 8 f, median age 62 yrs (range 47–72)]. Median weight change -0.75 kg (range -4.5 to 2). Nine pts had pre and post treatment biopsies and 7 only pretreatment. Three pts achieved CB at 8 weeks. Objective responses: 0 CR, 0 PR, 31% SD and 68%PD. Toxicity was similar to the one reported in gemcitabine's label. It was possible to extract quality RNA for microarray from subcutaneous fat use from all samples but 1. The limited number of samples precluded to obtain genes clearly involved in cachexia, however the IL-8 expression (p0.03) was significantly correlated with CB response either to gene and serum profile. Conclusions: It is feasible to study prospectively the impact of cancer treatment on different tissue biomarkers and correlated with standard antitumor evaluation system. The reduced number of samples in this exploratory trial precludes producing significant biological conclusions. No significant financial relationships to disclose.
Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Ralf Gutzmer, Daniil Stroyakovskiy, Helen Gogas, Caroline Robert, Karl Lewis, Svetlana Protsenko, Rodrigo P Pereira, Thomas Eigentler, Piotr Rutkowski, Lev Demidov, Georgy Moiseevich Manikhas, Yibing Yan, Kuan-Chieh Huang, Anne Uyei, Virginia McNally, Grant A McArthur, Paolo A Ascierto
Journal: The Lancet (2020)
Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans
Authors: Johana Norona, Petya Apostolova, Dominik Schmidt, Rebekka Ihlemann, Nadine Reischmann, Gregory Taylor, Natalie Köhler, Jocelyn de Heer, Steffen Heeg, Geoffroy Andrieux, Benjamin A. Siranosian, Annette Schmitt-Graeff, Dietmar Pfeifer, Antonella Catalano, Ian J. Frew, Michele Proietti, Bodo Grimbacher, Alla Bulashevska, Ami S. Bhatt, Tilman Brummer, Till Clauditz, Tatjana Zabelina, Nicolaus Kroeger, Bruce R. Blazar, Melanie Boerries, Francis Ayuk, Robert Zeiser
Journal: Blood (2020)
Controlling the Release of Neurotrophin‐3 and Chondroitinase ABC Enhances the Efficacy of Nerve Guidance Conduits
Authors: Anthony Donsante, Jiajia Xue, Kelly M. Poth, Nathan S. Hardcastle, Bruna Diniz, Deirdre M. O'Connor, Younan Xia, Nicholas M. Boulis
Journal: Advanced Healthcare Materials (2020)

Abstract Nerve guidance conduits (NGCs) have the potential to replace autografts in repairing peripheral nerve injuries, but their efficacy still needs to be improved. The efficacy of NGCs is augmented by neurotrophic factors that promote axon growth and by enzymes capable of degrading molecules that inhibit axon growth. In the current study, two types of NGCs loaded with factors (both neurotrophin‐3 and chondroitinase ABC) are constructed and their abilities to repair an 8 mm gap in the rat sciatic nerve are examined. The factors are encapsulated in microparticles made of a phase‐change material (PCM) or collagen and then sandwiched between two layers of electrospun fibers. The use of PCM allows to achieve pulsed release of the factors upon irradiation with a near‐infrared laser. The use of collagen enables slow, continuous release via diffusion. The efficacy is evaluated by measuring compound muscle action potentials (CMAP) in the gastrocnemius muscle and analyzing the nerve histology. Continuous release of the factors from collagen results in enhanced CMAP amplitude and increased axon counts in the distal nerve relative to the plain conduit. In contrast, pulsed release of the same factors from PCM shows a markedly adverse impact on the efficacy, possibly by inhibiting axon growth.
Analysis of Normal High-Frequency Intracranial Pressure Values and Treatment Threshold in Neurocritical Care Patients
Authors: Gregory W. J. Hawryluk, Jessica L. Nielson, J. Russell Huie, Lara Zimmermann, Rajiv Saigal, Quan Ding, Ryan Hirschi, Frederick A. Zeiler, Adam R. Ferguson, Geoffrey T. Manley
Journal: JAMA Neurology (2020)

Intracranial pressure (ICP) elevation is a compartment syndrome that impairs blood flow to the brain. Despite the importance of ICP values in neurocritical care, normal ICP values and the precise ICP threshold at which treatment should be initiated remain uncertain.To refine our understanding of normal ICP values and determine the ICP threshold most strongly associated with outcome.Prospective observational study (2004-2010), with outcomes determined at hospital discharge. The study included neurocritical care patients from a single level I trauma center, San Francisco General Hospital. Three hundred eighty-three patients had a traumatic brain injury with or without craniectomy; 140 patients had another indication for ICP monitoring. Consecutive patients were studied. Data analyses were completed between March 2015 and December 2019.Five hundred twenty-three ICP-monitored patients.A computer system prospectively and automatically collected 1-minute physiologic data from patients in the intensive care unit during a 6-year period. Mean ICP was calculated, as was the proportion of ICP values greater than thresholds from 1 to 80 mm Hg in 1-mm Hg increments. The association between these measures and outcome was explored for various epochs up to 30 days from the time of injury. A principal component analysis was used to explore physiologic changes at various ICP thresholds, and elastic net regression was used to identify ICP thresholds most strongly associated with Glasgow Outcome Scale score at discharge.Of the 523 studied patients, 70.7% of studied patients were men (n = 370) and 72.1% had a traumatic brain injury (n = 377). A total of 4 090 964 1-minute ICP measurements were recorded for the included patients (7.78 years of recordings). Intracranial pressure values of 8 to 9 mm Hg were most commonly recorded and could possibly reflect normal values. The principal component analysis suggested state shifts in the physiome occurred at ICPs greater than 19 mm Hg and 24 mm Hg. Elastic net regression identified an ICP threshold of 19 mm Hg as most robustly associated with outcome when considering all neurocritical care patients, patients with TBI, and patients with TBI who underwent craniectomy. Intracranial pressure values greater than 19 mm Hg were associated with mortality, while lower values were associated with outcome in surviving patients.This study provides insight into what normal ICP values could be. An ICP threshold of 19 mm Hg was robustly associated with outcome in studied patients, although lower ICP values were associated with outcome in surviving patients.
The Impact of the COVID-19 Pandemic on Cardiovascular Fellows-in-Training
Authors: Prashant Rao, Jamie Diamond, Serge Korjian, Lila Martin, Merilyn Varghese, John D. Serfas, Ran Lee, Ariane Fraiche, Joseph Kannam, Nosheen Reza
Journal: Journal of the American College of Cardiology (2020)
Gadofullerene nanoparticles for robust treatment of aplastic anemia induced by chemotherapy drugs
Authors: Wang Jia, Mingming Zhen, Lei Li, Chen Zhou, Zihao Sun, Shuai Liu, Zhongpu Zhao, Jie Li, Chunru Wang, Chunli Bai
Journal: Theranostics (2020)

Aplastic anemia (AA) is characterized as hypoplasia of bone marrow hematopoietic cells and hematopenia of peripheral blood cells.Though the supplement of exogenous erythropoietin (EPO) has been clinically approved for AA treatment, the side-effects hinder its further application.Here a robust treatment for AA induced by chemotherapy drugs is explored using gadofullerene nanoparticles (GFNPs).Methods: The gadofullerene were modified with hydrogen peroxide under alkaline conditions to become the water-soluble nanoparticles (GFNPs).The physicochemical properties, in vitro chemical construction, stability, hydroxyl radical scavenging ability, in vitro cytotoxicity, antioxidant activity, in vivo treatment efficacy, therapeutic mechanism and biological distribution, metabolism, toxicity of GFNPs were examined.Results: GFNPs with great stability and high-efficiency antioxidant activity could observably increase the number of red blood cells (RBC) in the peripheral blood of AA mice and relieve the abnormal pathological state of bone marrow.The erythropoiesis mainly includes hemopoietic stem cells (HSCs) differentiation, erythrocyte development in bone marrow and erythrocyte maturation in peripheral blood.The positive control-EPO promotes erythropoiesis by regulating HSCs differentiation and erythrocyte development in bone marrow.Different from the anti-AA mechanism of EPO, GFNPs have little impact on both the differentiation of HSCs and the myeloid erythrocyte development, but notably improve the erythrocyte maturation.Besides, GFNPs can notably decrease the excessive reactive oxygen species (ROS) and inhibit apoptosis of hemocytes in blood.In addition, GFNPs are mostly excreted from the living body and cause no serious toxicity.Conclusion: Our work provides an insight into the advanced nanoparticles to powerfully treat AA through ameliorating the erythrocyte maturation during erythropoiesis.
Abstract 11442: Outcomes After Switching Anticoagulation From Warfarin to DOACs in Patients With Non-valvular Atrial Fibrillation
Authors: Shinichiro Ueda, Takeshi Morimoto
Journal: Circulation (2019)

Study objectives: The primary objective of this study is to comparatively evaluate safety of switching from warfarin to direct oral anticoagulants (DOACs) and continuous warfarin in retrospectively...
Covid-19: Lack of confidentiality affects healthcare staff too
Authors: Vedamurthy Adhiyaman
Journal: BMJ (2020)

<h3>ABSTRACT</h3> A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.
Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice
Authors: Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose Angel Lorente, Duncan J Stewart, Philip Marsden, W Conrad Liles, Pingzhao Hu, Claudia C dos Santos
Journal: Thorax (2020)

Introduction Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. Objectives To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. Methods and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a statistical estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3′UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. Conclusions Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.