tbuckley/cabot-search huggingface dataset:
Unusual cause of bloody stool with earache and saddle-nose deformity
Authors: Zhenzhen Liu, Xiaolei Liu, Jie Liang, Yongquan Shi, Min Chen
Journal: Gut (2020)

A 41-year-old female patient was admitted to hospital with bloody stool and diarrhoea for 2 months, accompanied with fever, left earache, obvious saddle-nose deformity and red eyes for 2 weeks. She had history of repeated multiple sore joints for 6 months and hearing impairment in the left ear for 4 months. Laboratory tests showed elevated white cell count (WBC) of 15.57×10ˆ9/L, neutrophil of 76.8% and C reactive protein (CRP) of 95.4 mg/L. Haemoglobin was decreased at 94 g/L. Antineutrophil cytoplasmic antibody was negative. Colonoscopy showed diffuse inflammation and ulcers in the left-sided colon (figure 1). Histological findings from sigmoid colon showed chronic inflammation without vasculitis appearance. CT enterography revealed left-sided colon inflammation (figure 2). MRI of …
Response to: ‘Short duration antibiotic therapy for native joint arthritis cause by<i>Neisseria</i>infection?’ by Durcours<i>et al</i>
Authors: Ilker Uçkay, Konstantinos Vakalopoulos, Ergys Gjika
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the contribution of Ducours et al 1 to our article,2 which randomised adult patients with native joint septic arthritis to either 2 or 4 weeks of systemic targeted antibiotic therapy after surgical drainage.2 Ducours et al reveal a similar experience with a short duration of targeted systemic antibiotic therapy for adult native joint bacterial arthritis due to gonococci and meningococci.1 There are substantial differences between our both studies: (1) Our arthritis episodes (majority hand arthritis) included all pyogenic bacteria, but not gonococci. In contrast, the …
The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial
Authors: Ian J. Neeland, Bjorn Eliasson, Takatoshi Kasai, Nikolaus Marx, Bernard Zinman, Silvio E. Inzucchi, Christoph Wanner, Isabella Zwiener, Brian S. Wojeck, Henry K. Yaggi, Odd Erik Johansen
Journal: Diabetes Care (2020)

To explore the effects of empagliflozin on the incidence of obstructive sleep apnea (OSA) and its effects on metabolic, cardiovascular (CV), and renal outcomes among participants with or without OSA in the EMPA-REG OUTCOME trial.Participants with diabetes and CV disease were randomized to empagliflozin (10 and 25 mg) or placebo daily in addition to standard of care. OSA was assessed by investigator report using Medical Dictionary for Regulatory Activities version 18.0, and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models.OSA was reported in 391 of 7,020 (5.6%) participants at baseline. Those with OSA were more likely to be male (83% vs. 71%) and to have moderate to severe obesity (BMI ≥35 kg/m2; 55% vs. 18%). Over a median of 3.1 years, empagliflozin had similar placebo-adjusted reductions in HbA1c, waist circumference, and systolic blood pressure, regardless of OSA status, but a larger effect on weight (adjusted mean ± SE difference at week 52: OSA vs. no OSA -2.9 ± 0.5 vs. -1.9 ± 0.1 kg). Incidence of 3-point major adverse CV events, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo group was 1.2- to 2.0-fold higher for those with baseline OSA compared with those without. Empagliflozin significantly reduced the risk for outcomes regardless of OSA status (P-interaction all >0.05). Fifty patients reported a new diagnosis of OSA through 7 days after medication discontinuation, and this occurred less often with empagliflozin treatment (hazard ratio 0.48 [95% CI 0.27, 0.83]).In EMPA-REG OUTCOME, participants with OSA had greater comorbidity and higher frequency of CV and renal events. Empagliflozin had favorable effects on risk factors and CV and renal outcomes regardless of preexisting OSA and may also reduce the risk for new-onset OSA.
Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging
Authors: Nicholas E. Propson, Ethan R. Roy, Alexandra Litvinchuk, Jörg Köhl, Hui Zheng
Journal: Journal of Clinical Investigation (2020)

Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood. The complement pathway is a well-established regulator of innate immunity in the brain. Here, we report robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability. These phenotypes were subdued by global inactivation and by endothelial cell–specific ablation of C3ar1. Using an in vitro model of the BBB, we identified intracellular Ca2+ as a downstream effector of C3a/C3aR signaling and a functional mediator of vascular endothelial cadherin junction and barrier integrity. Endothelial C3ar1 inactivation also dampened microglia reactivity and improved hippocampal and cortical volumes in the aging brain, demonstrating a crosstalk between brain vasculature dysfunction and immune cell activation and neurodegeneration. Further, prominent C3aR-dependent vascular inflammation was also observed in a tau-transgenic mouse model. Our studies suggest that heightened C3a/C3aR signaling through endothelial cells promotes vascular inflammation and BBB dysfunction and contributes to overall neuroinflammation in aging and neurodegenerative disease.
Regarding “Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer : observational study of mortality outcomes”, BMJ. 2014 Feb 26;348
Authors: A. Widmark, A. Gunnlaugsson, A. Bossi, D. Dearnaley, P. Nilsson, B. Zackrisson, R. Blom, I. Franck Lissbrant, A. Lawrence Zietman, H. Sandler, R.H. Bloom, H. Jonsson
Journal: BMJ (2014)

Regarding “Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer : observational study of mortality outcomes”, BMJ. 2014 Feb 26;348
Invasive group B Streptococcus infections in non-pregnant adults: a retrospective study, France, 2007–2019
Authors: Xavier Vuillemin, Constantin Hays, Céline Plainvert, Nicolas Dmytruk, Mathilde Louis, Gérald Touak, Benjamin Saint-Pierre, Lucie Adoux, Franck Letourneur, Amandine Frigo, Claire Poyart, Asmaa Tazi
Journal: Clinical Microbiology and Infection (2020)
Immunosurveillance and Regression in the Context of Squamous Pulmonary Premalignancy
Authors: Kostyantyn Krysan, Linh M. Tran, Steven M. Dubinett
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue of Cancer Discovery, Pennycuick and colleagues comprehensively evaluate the immune contexture of progressive and regressive lesions in squamous pulmonary premalignancy. The authors dissect the molecular features of these lesions and the potential pathways of immune escape operative in progression to invasive cancer. See related article by Pennycuick et al., p. 1489.
Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma
Authors: Yunzhen Qian, Yitao Gong, Zhiyao Fan, Guopei Luo, Qiuyi Huang, Shengming Deng, He Cheng, Kaizhou Jin, Quanxing Ni, Xianjun Yu, Chen Liu
Journal: Journal of Hematology & Oncology (2020)

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. The realization of targeted therapies in patients with PDAC may be summarized by three approaches. First, because oncogenes play a pivotal role in tumorigenesis, inhibition of dysregulated oncogenes is a promising method (Table 3). Numerous researchers are developing strategies to target oncogenes, such as KRAS, NRG1, and NTRK and related molecules, although most of the results are unsatisfactory. Accordingly, emerging strategies are being developed to target these oncogenes, including simultaneously inhibiting multiple molecules or pathways, modification of mutant residues by small molecules, and RNA interference. Second, researchers have attempted to reactivate inactivated tumour suppressors or modulate related molecules. TP53, CDKN2A and SMAD4 are three major tumour suppressors involved in PDAC. Advances have been achieved in clinical and preclinical trials of therapies targeting these three genes, and further investigations are warranted. The TGF-β-SMAD4 signalling pathway plays a dual role in PDAC tumorigenesis and participates in mediating tumour-stroma crosstalk and modulating the tumour microenvironment (TME); thus, molecular subtyping of pancreatic cancer according to the SMAD4 mutation status may be a promising precision oncology technique. Finally, genes such as KDM6A and BRCA have vital roles in maintaining the structural stability and physiological functions of normal chromosomes and are deficient in some patients with PDAC, thus serving as potential targets for correcting these deficiencies and precisely killing these aberrant tumour cells. Recent clinical trials, such as the POLO (Pancreas Cancer Olaparib Ongoing) trial, have reported encouraging outcomes. In addition to genetic event-guided treatment, immunotherapies such as chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates, and immune checkpoint inhibitors also exhibit the potential to target tumours precisely, although the clinical value of immunotherapies as treatments for PDAC is still limited. In this review, we focus on recent preclinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for PDAC.
Ocular prodrugs: Attributes and challenges
Authors: Jagpreet kour, Neha Kumari, Bharti Sapra
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems. From a drug delivery point of view, eye is an intricate organ to investigate and explore. In spite of many limitations, advancements have been made with the intention of improving the residence time or permeation of the drug in the ocular region. Poor bioavailability of topically administered drugs is the major issue pertaining to ocular drug delivery. Several efforts have been made towards improving precorneal residence time and corneal penetration, e.g. iontophoresis, prodrugs and ion-pairing, etc. Prodrug approach (chemical approach) has been explored by the formulation scientists to optimize the physicochemical and biochemical properties of drug molecules for improving ocular bioavailability. Formulation of ocular prodrugs is a challenging task as they should exhibit optimum chemical stability as well as enzymatic liability so that they are converted into parent drug after administration at the desired pace. This review will encompass the concept of derivatization and recent academic and industrial advancements in the field of ocular prodrugs. The progression in prodrug designing holds a potential future for ophthalmic drug delivery.
Highly interconnected enhancer communities control lineage-determining genes in human mesenchymal stem cells
Authors: Jesper G. S. Madsen, Maria S. Madsen, Alexander Rauch, Sofie Traynor, Elvira L. Van Hauwaert, Anders K. Haakonsson, Biola M. Javierre, Mette Hyldahl, Peter Fraser, Susanne Mandrup
Journal: Nature Genetics (2020)
Delaying Pregnancy during a Public Health Crisis — Examining Public Health Recommendations for Covid-19 and Beyond
Authors: Sonja A. Rasmussen, Anne Drapkin Lyerly, Denise J. Jamieson
Journal: New England Journal of Medicine (2020)

Delaying Pregnancy during a Public Health Crisis Whether public health agencies should recommend that women avoid becoming pregnant during public health crises like Covid-19 because of potential ri...
Follow-up of adults with noncritical COVID-19 two months after symptom onset
Authors: Claudia Carvalho-Schneider, Emeline Laurent, Adrien Lemaignen, Emilie Beaufils, Céline Bourbao-Tournois, Saïd Laribi, Thomas Flament, Nicole Ferreira-Maldent, Franck Bruyère, Karl Stefic, Catherine Gaudy-Graffin, Leslie Grammatico-Guillon, Louis Bernard
Journal: Clinical Microbiology and Infection (2020)
Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD
Authors: Monika A. Sarkar, Ayako Suzuki, Manal F. Abdelmalek, Katherine P. Yates, Laura A. Wilson, Nathan M. Bass, Ryan Gill, Marcelle Cedars, Norah Terrault
Journal: Clinical Gastroenterology and Hepatology (2020)
Covid-19: Government promises an “uninterrupted supply” of PPE this winter
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Covid-19: Government promises an "uninterrupted supply" of PPE this winter Gareth IacobucciNHS leaders have welcomed a commitment by the government to guarantee an "uninterrupted supply" of personal protective equipment (PPE) this winter as the service braces itself for an increase in covid-19 cases.
Randomized controlled trial of topical corticosteroid and home‐based narrowband ultraviolet B for active and limited vitiligo: results of the HI‐Light Vitiligo Trial*
Authors: K.S. Thomas, J.M. Batchelor, P. Akram, J.R. Chalmers, R.H. Haines, G.D. Meakin, L. Duley, J.C. Ravenscroft, A. Rogers, T.H. Sach, M. Santer, W. Tan, J. White, M.E. Whitton, H.C. Williams, S.T. Cheung, H. Hamad, A. Wright, J.R. Ingram, N.J. Levell, J.M.R. Goulding, A. Makrygeorgou, A. Bewley, M. Ogboli, J. Stainforth, A. Ferguson, B. Laguda, S. Wahie, R. Ellis, J. Azad, A. Rajasekaran, V. Eleftheriadou, A.A. Montgomery
Journal: British Journal of Dermatology (2020)

Evidence for the effectiveness of vitiligo treatments is limited. To determine the effectiveness of (i) handheld narrowband UVB (NB‐UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB‐UVB, compared with TCS alone, for localized vitiligo. A pragmatic, three‐arm, placebo‐controlled randomized controlled trial (9‐month treatment, 12‐month follow‐up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB‐UVB), NB‐UVB (NB‐UVB + placebo TCS) or a combination (TCS + NB‐UVB). TCS was applied once daily on alternating weeks; NB‐UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant‐reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. In total 517 participants were randomized to TCS (n = 173), NB‐UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB‐UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between‐group difference 10·9% (95% confidence interval 1·0%–20·9%; P = 0·032; number needed to treat = 10). NB‐UVB alone was not superior to TCS: adjusted between‐group difference 5·2% (95% CI − 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). Combination treatment with home‐based handheld NB‐UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one‐quarter of participants.
Pulmonary edema in COVID-19: Explained by bradykinin?
Authors: Suzanne Zwaveling, Roy Gerth van Wijk, Faiz Karim
Journal: Journal of Allergy and Clinical Immunology (2020)

tied values in Mann-Whitney-Wilcoxon test and a P value indicating statistical significance (P 5 .0475)was obtained.The P value proposed by Li and Liu 1 is derived from chi-square test.Chi-square test is more appropriate when the response (CT improvement) is a nominal variable and it is designed to test whether 2 distributions are from the same population, and hence may not be appropriate for checking whether a distribution shifts to higher values compared with another distribution.Therefore, Mann-Whitney-Wilcoxon test is more suitable here and our conclusion was valid.In conclusion, the comments made by the readers further underline the great importance of randomized controlled trials for evaluating the efficacy and safety of novel treatments for COVID-19.
Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death
Authors: Stephen Sakuma, Marcela Raices, Joana Borlido, Valeria Guglielmi, Ethan Y.S. Zhu, Maximiliano A. D'Angelo
Journal: Cancer Discovery (2020)

Nuclear pore complexes (NPC) are the central mediators of nucleocytoplasmic transport. Increasing evidence shows that many cancer cells have increased numbers of NPCs and become addicted to the nuclear transport machinery. How reducing NPC numbers affects the physiology of normal and cancer cells and whether it could be exploited for cancer therapies has not been investigated. We report that inhibition of NPC formation, a process mostly restricted to proliferating cells, causes selective cancer cell death, prevents tumor growth, and induces tumor regression. Although cancer cells die in response to NPC assembly inhibition, normal cells undergo a reversible cell-cycle arrest that allows them to survive. Mechanistically, reducing NPC numbers results in multiple alterations contributing to cancer cell death, including abnormalities in nuclear transport, catastrophic alterations in gene expression, and the selective accumulation of DNA damage. Our findings uncover the NPC formation process as a novel targetable pathway in cancer cells. SIGNIFICANCE: Reducing NPC numbers in cancer cells induces death, prevents tumor growth, and results in tumor regression. Conversely, normal cells undergo a reversible cell-cycle arrest in response to inhibition of NPC assembly. These findings expose the potential of targeting NPC formation in cancer.This article is highlighted in the In This Issue feature, p. 1.
Abstract IA13: Opportunities and challenges in melanoma early detection
Authors: David Polsky
Journal: Cancer Research (2020)

Abstract It is well established that survival outcomes for melanoma are highest when these tumors are diagnosed and surgically removed at their earliest stages, prior to the escape of tumor cells to regional and distant anatomic sites. Screening efforts in other malignancies such as colorectal and cervical cancers have yielded benefits in reducing the incidence of invasive cancers and their respective mortalities. Therefore, early detection through broad-based skin cancer screening appears to be a logical step to reduce melanoma mortality. To date, this strategy has not been endorsed by the United States Preventative Services Task Force (USPSTF) due to a lack of conclusive evidence. For example, the initially promising reductions in melanoma mortality observed during a skin cancer screening program in Schleswig-Holstein, Germany, were not replicated in subsequent years in Schleswig-Holstein itself or throughout Germany when the screening program was extended countrywide. The lack of solid evidence demonstrating the benefits of skin screening on melanoma mortality, coupled with the potential harms of screening, and the phenotypic heterogeneity of melanoma raise important concerns regarding the utility of broad-based skin cancer screening programs. Nevertheless, melanoma’s visibility on the skin compared to internal malignancies, and the development of new diagnostic technologies, may help balance the benefits and harms of melanoma screening when considering the varied patient populations in which screening could be deployed. In this presentation we will review current data in the context of developing early-detection strategies to reduce melanoma mortality and/or the cost of care while minimizing potential harms. Citation Format: David Polsky. Opportunities and challenges in melanoma early detection [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA13.
Urethral-sparing Robot-assisted Simple Prostatectomy: An Innovative Technique to Preserve Ejaculatory Function Overcoming the Limitation of the Standard Millin Approach
Authors: Francesco Porpiglia, Enrico Checcucci, Daniele Amparore, Gabriel Niculescu, Gabriele Volpi, Federico Piramide, Sabrina De Cillis, Matteo Manfredi, Riccardo Autorino, Cristian Fiori
Journal: European Urology (2020)
Taking a wellbeing years approach to policy choice
Authors: Jan-Emmanuel De Neve, Andrew E Clark, Christian Krekel, Richard Layard, Gus O’Donnell
Journal: BMJ (2020)

Every day, policy makers must decide whether a policy is desirable. They do so by examining its impact on a range of outcomes. But the problem is how to aggregate these disparate outcomes. For example, as covid-19 cases rise again, some lockdown measures are gradually being reintroduced across the UK. These policy choices will lead to outcomes that are good (such as fewer deaths from covid-19, less commuting, better air quality) and some that are bad (unemployment, income losses, loneliness, domestic abuse). How can policy makers aggregate these disparate effects in order to arrive at an overall assessment? To do so requires a “common currency” with which to measure all the effects. The currency we propose is the change in years of human wellbeing resulting from the policy.
Tackling osteoarthritis during COVID-19 pandemic
Authors: Francisco Airton Castro da Rocha, Lucas da Ponte Melo, Francis Berenbaum
Journal: Annals of the Rheumatic Diseases (2020)

In this opinion article, we would like to draw attention to the fact that COVID-19 has a significant impact not only on immune-mediated arthritis but also on osteoarthritis (OA), the most common rheumatic disease. We suggest herein strategies for pain relief and symptom prevention in patients with OA during COVID-19 pandemic.
Local Targeting of NAD+ Salvage Pathway Alters the Immune Tumor Microenvironment and Enhances Checkpoint Immunotherapy in Glioblastoma
Authors: Ming Li, Ameya R. Kirtane, Juri Kiyokawa, Hiroaki Nagashima, Aaron Lopes, Zain A. Tirmizi, Christine K. Lee, Giovanni Traverso, Daniel P. Cahill, Hiroaki Wakimoto
Journal: Cancer Research (2021)

In the original version of this article (1), the original version of Fig. 4C used two different exposures of the same field of cells to represent two different treatment conditions. The authors provided a corrected version of Fig. 4C and the error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.