tbuckley/cabot-search huggingface dataset:
Effect of obstructive sleep apnea in severity and short-term prognosis of acute coronary syndrome
Authors: Marina Florés, Manuel Sánchez-de-la-Torre, Cristina Esquinas, Jorge Abad, Joaquín Durán-Cantolla, Olga Mediano, José Amilibia, María José Masdeu, Monica de la Peña, Albina Aldomà, Fernando Worner, Alicia Sánchez-de-la-Torre, Núria Roure, Ferran Barbé
Journal: European Respiratory Journal (2014)

Background: The role of obstructive sleep apnea (OSA) on the prognosis of acute coronary syndrome (ACS) is under debate. Our objective was to evaluate the influence of OSA in severity and short-term prognosis in patients admitted for ACS.

Methods: We included nonsleepy patients admitted for ACS. All patients underwent a polygraphy (Embletta; ResMed, Spain) in the first 72 h after admission.The echocardiographic evaluation and Killip classification was performed during patient admission. Severity and short-term prognosis of ACS were evaluated during the hospitalization period.

Results: Of the 431 patients included in the study, 213 suffered OSA ((mean±SD) apnea-hipopnea index (AHI); 32±15 h-1) and 218 presented an AHI < 15 h-1.Gender distribution and age were similar between OSA patients and controls (82% male in both groups, and 60.5±11 vs. 58.5±12 years old, respectively). Compared to controls, patients with OSA had higher prevalence of arterial hypertension (54 vs. 40 %, p=0.006), and body mass index (28.6±6 vs. 25.5±7 Kg·m-2, p<0.001). The number of affected vessels was independently associated with the presence of OSA. There were no differences between groups for other variables related to ACS severity (ejection fraction, Killip scale, number of stents implanted, peak plasma troponin, or CPK-MB plasma levels). Short-term prognosis (days of stay in the coronary unit, days of hospitalization, complications and mortality during hospitalization) was similar between groups.

Conclusion: Obstructive sleep apnea does not influence severity of ACS and short-term prognosis.
Why Scotland’s slow and steady approach to covid-19 is working
Authors: Devi Sridhar, Adriel Chen
Journal: BMJ (2020)

Deaths and new infections from covid-19 are falling to low levels in Scotland. Devi Sridhar and Adriel Chen look at how the country is on course to eliminate the virus In April 2020, the Scottish government published a framework for decision making on covid-19 which notably included that there
ITK deficiency presenting as autoimmune lymphoproliferative syndrome
Authors: Jacqueline G. Wallace, Mohammed F. Alosaimi, Claudia Djambas Khayat, Faris Jaber, Abduarahman Almutairi, Sarah Beaussant-Cohen, Geraldine Pinkus, Mark Fleming, Cybel Mehawej, Janet Chou, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2020)
Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index
Authors: Christine Desmedt, Marco Fornili, Florian Clatot, Romano Demicheli, Davide De Bortoli, Angelo Di Leo, Giuseppe Viale, Evandro de Azambuja, John Crown, Prudence A. Francis, Christos Sotiriou, Martine Piccart, Elia Biganzoli
Journal: Journal of Clinical Oncology (2020)

Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI).We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status.There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04).This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.
Traditional Diagnostics versus Disruptive Technology: The Role of the Pathologist in the Era of Liquid Biopsy
Authors: Lynette M. Sholl, Geoffrey R. Oxnard, Cloud P. Paweletz
Journal: Cancer Research (2020)

Precision medicine in cancer care is predicated on access to several fundamental pieces of data: (i) a precise tumor diagnosis, (ii) accurate stage classification, and (iii) protein or molecular biomarkers that predict efficacy of targeted therapies. For all patients with cancer, these data points are generated by obtaining a tumor sample and subjecting it to analysis by a pathologist and, when appropriate, a molecular pathologist. While tumor diagnosis and pathologic staging (gross and microscopic examination of the primary tumor and draining lymph nodes) require the infrastructure and expertise of an anatomic pathology program, the advent of "liquid biopsy" has driven a shift in molecular biomarker testing away from local pathology laboratories and into high-throughput, centralized (and often for-profit) laboratories. What does this mean for patient care? How is the role of the pathologist affected? What are the implications for integration of diagnostic information and ultimately for appropriate therapy selection? This article will consider the current testing landscape, address current challenges in the use of liquid biopsy in clinical practice, and consider ways the pathologist should be involved in interpreting liquid biopsy data in the context of the patient's cancer diagnosis and stage.
Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: retrospective long-term follow-up of the LIR!C trial
Authors: Toer W Stevens, Maria L Haasnoot, Geert R D'Haens, Christianne J Buskens, E Joline de Groof, Emma J Eshuis, Tjibbe J Gardenbroek, Bregje Mol, Pieter C F Stokkers, Willem A Bemelman, Cyriel Y Ponsioen, Ailsa Hart, Janindra Warusavitarne, Ad A. Van Bodegraven, Menno A. Brink, Esther C.J. Consten, Bart A. Van Wagensveld, Marno C.M. Rijk, Rogier M.P.H. Crolla, Casper G. Noomen, Alexander P.J. Houdijk, Rosalie C. Mallant, Maarten Boom, Willem A. Marsman, Hein B. Stockmann, A. Jeroen De Groof, Karlien Bruin, John Maring, Theo van Ditzhuijsen, Hubert Prins, Jan van den Brande, Paul Kingma, Anna van Geloven, Nanne de Boer, Donald van der Peet, Jeroen Jansen, Michael Gerhards, Janneke van der Woude, Ruud Schouten, Bas Oldenburg, Richard van Hillegersberg, Rachel West, Guido Mannaerts, Marcel Spanier, Ernst Jan Spillenaar Bilgen, Rob Lieverse, Edwin van der Zaag, Annekatrien Depla, Arnold van de Laar, Clemens Bolwerk, Hans Brouwer, Nofel Mahmmod, Eric Hazebroek, Juda Vecht, Robert Pierik, Gerard Dijkstra, Sijbrand Hofker, Tessa Uiterwaal, Quirijn Eijsbouts, Liekele Oostenbrug, Meindert Sosef, Djuna Cahen, Sjoerd van der Werff, Andreas Marinelli, Job Peters, Huib Cense, Nynke Talstra, Pritesh Morar
Journal: The Lancet. Gastroenterology & hepatology (2020)
BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity
Authors: Charles R. Schmidt, Nicholas J. Achille, Aravinda Kuntimaddi, Adam M. Boulton, Benjamin I. Leach, Shubin Zhang, Nancy J. Zeleznik-Le, John H. Bushweller
Journal: Blood Cancer Discovery (2020)

Abstract MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population. Significance: Direct recruitment of BCOR to MLL-AF9 is essential for leukemia via EYA1 phosphatase regulation, altering MYC and SIX gene expression programs. Specific partner binding (AF4, DOT1L, and BCOR) contributes in distinct ways to MLL leukemia. This may provide a rationale for combination DOT1L and EYA1 inhibition for MLL fusion leukemia treatment. This article is highlighted in the In This Issue feature, p. 127
Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries
Authors: Ju-Sheng Zheng, Stephen J Sharp, Fumiaki Imamura, Rajiv Chowdhury, Thomas E Gundersen, Marinka Steur, Ivonne Sluijs, Yvonne T van der Schouw, Antonio Agudo, Dagfinn Aune, Aurelio Barricarte, Heiner Boeing, María-Dolores Chirlaque, Miren Dorronsoro, Heinz Freisling, Douae El-Fatouhi, Paul W Franks, Guy Fagherazzi, Sara Grioni, Marc J Gunter, Cecilie Kyrø, Verena Katzke, Tilman Kühn, Kay-Tee Khaw, Nasser Laouali, Giovanna Masala, Peter M Nilsson, Kim Overvad, Salvatore Panico, Keren Papier, J Ramón Quirós, Olov Rolandsson, Daniel Redondo-Sánchez, Fulvio Ricceri, Matthias B Schulze, Annemieke M W Spijkerman, Anne Tjønneland, Tammy Y N Tong, Rosario Tumino, Elisabete Weiderpass, John Danesh, Adam S Butterworth, Elio Riboli, Nita G Forouhi, Nicholas J Wareham
Journal: BMJ (2020)

Abstract Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design Prospective case-cohort study. Setting Populations from eight European countries. Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure Incident type 2 diabetes. Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
Mast cells in asthma: Here I am, stuck in the middle with you
Authors: Raymond B. Penn
Journal: European Respiratory Journal (2020)

<b>Bonvini and co-workers employ a creative combination of cell, tissue and <i>in vivo</i> models to delineate a complex intercellular communication between mast cells and airway smooth muscle by which TRPV4 activation causes bronchoconstriction</b>https://bit.ly/35U4Mqg
COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?
Authors: Eddy Fan, Jeremy R Beitler, Laurent Brochard, Carolyn S Calfee, Niall D Ferguson, Arthur S Slutsky, Daniel Brodie
Journal: The Lancet Respiratory Medicine (2020)

The COVID-19 pandemic has seen a surge of patients with acute respiratory distress syndrome (ARDS) in intensive care units across the globe. As experience of managing patients with COVID-19-associated ARDS has grown, so too have efforts to classify patients according to respiratory system mechanics, with a view to optimising ventilatory management. Personalised lung-protective mechanical ventilation reduces mortality and has become the mainstay of treatment in ARDS. In this Viewpoint, we address ventilatory strategies in the context of recent discussions on phenotypic heterogeneity in patients with COVID-19-associated ARDS. Although early reports suggested that COVID-19-associated ARDS has distinctive features that set it apart from historical ARDS, emerging evidence indicates that the respiratory system mechanics of patients with ARDS, with or without COVID-19, are broadly similar. In the absence of evidence to support a shift away from the current paradigm of ventilatory management, we strongly recommend adherence to evidence-based management, informed by bedside physiology, as resources permit.
Utility of Human-Derived Models for Glioblastoma
Authors: Xujun Luo, William A. Weiss
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue, Pine and colleagues compared single-cell RNA-sequencing data across four distinct types of glioblastoma stem cell–derived tumor models, reinforcing the importance of a three-dimensional microenvironment for accurate recapitulation of cellular states. See related article by Pine et al., p. 964.
Abstract P379: The Association of Sex Hormones with Carotid Artery Distensibility in Men and Women: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Nowreen Haq, Dhananjay Vaidya, Susan R Heckbert, Kiang Liu, Pamela Ouyang
Journal: Circulation (2013)

Authors: Nowreen Haq MD, MPH, Dhananjay Vaidya MBBS, PHD, Susan R. Heckbert MD, PhD, Kiang Liu PhD, Pamela Ouyang MBBS Introduction: We have previously shown that the association of aging with carotid artery distensibility coefficient (DC) differs between men and postmenopausal women. We therefore examined the association between endogenous sex hormones (SH) and DC in men and postmenopausal women in MESA. Methods: B-mode ultrasound-measured carotid diameters and brachial pressures were obtained from 5761 participants (48% female, 38% white, 12% Chinese, 27% black, 23% Hispanic, 45-85 years) of the MESA baseline examination. We examined differences in DC by sex-specific quartiles of SH (bioavailable Testosterone [BioT, estradiol [E2] and Sex Hormone Binding Globulin [SHBG]) separately in men and women, adjusted for demographic and cardiovacular risk factors, using mixed models to adjust for blood pressures that are included in the calculation of DC. Results: The table shows that higher BioT quartiles are s...
Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology
Authors: Adrienne L. Romer, Maxwell L. Elliott, Annchen R. Knodt, Maria L. Sison, David Ireland, Renate Houts, Sandhya Ramrakha, Richie Poulton, Ross Keenan, Tracy R. Melzer, Terrie E. Moffitt, Avshalom Caspi, Ahmad R. Hariri
Journal: American Journal of Psychiatry (2020)

Objective: Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the structural brain correlates of mental disorders mirrors already well-documented phenotypic comorbidity of psychiatric symptoms and diagnoses, which can be indexed by a general psychopathology or p factor. The authors hypothesized that if general psychopathology drives the convergence of structural alterations common across disorders, then 1) there should be few associations unique to any one diagnostic family of disorders, and 2) associations with the p factor should overlap with those for the broader diagnostic families. Methods: Analyses were conducted on structural MRI and psychopathology data collected from 861 members of the population-representative Dunedin Multidisciplinary Health and Development Study at age 45. Results: Study members with high scores across three broad diagnostic families of disorders (externalizing, internalizing, thought disorder) exhibited highly overlapping patterns of reduced global and widely distributed parcel-wise neocortical thickness. Study members with high p factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families. Conclusions: A pattern of pervasively reduced neocortical thickness appears to be common across all forms of mental disorders and may represent a transdiagnostic feature of general psychopathology. As has been documented with regard to symptoms and diagnoses, the underlying brain structural correlates of mental disorders may not exhibit specificity, and the continued pursuit of such specific correlates may limit progress toward more effective strategies for etiological understanding, prevention, and intervention.
Surgical planning with patient-specific three-dimensional printed pancreaticobiliary disease models – Cross-sectional study
Authors: Ayse Hilal Bati, Ezgi Guler, Mehmet Asim Ozer, Figen Govsa, Kamil Erozkan, Safa Vatansever, Muhtar Sinan Ersin, Zehra Nevra Elmas, Mustafa Harman
Journal: International Journal of Surgery (2020)
Positive effects of covid-19 and social determinants of health: all in it together?
Authors: Sarah E Hill, Sharon Friel, Jeff Collin
Journal: BMJ (2020)

We welcome Nelson's analysis of the potentially positive effects of covid-19, 1 particularly in providing an opportunity to reassess priorities.Nelson points out the unanticipated benefits of recent behaviour changes.We think that the real revolution is a re-discovery of the health potential of state intervention.
COVID-19: a multifaceted threat to refugee camps
Authors: Talha Burki
Journal: The Lancet Microbe (2020)

There are approximately 26 million refugees in the world. Roughly a third live in camps. The remainder are mainly scattered across urban areas. A further 51 million or so people are internally displaced, largely as a result of conflict. Whether they are in camps or the community, those who have fled their homes tend to live in overcrowded conditions with limited access to water, soap, and sanitation. Their lives are precarious at the best of times. Even if they manage to avoid a destructive outbreak of COVID-19, the pandemic is likely to take a tremendous toll.
Customer is always right: optimising inhaler design to fit patient preferences in obstructive lung disease
Authors: Andrew Gangemi, Victor Kim, Gerard Criner
Journal: Thorax (2020)

Patient confidence in their inhaler regimen is essential in the management of asthma and COPD. Inhaler misuse is associated with poorer symptom control, more frequent use of oral corticosteroids and antibiotics for rescue, and more frequent hospitalisations in both COPD and asthma.1 Device designs have expanded to allow for ease of use; each device has its benefits and drawbacks. Metered dose inhalers (MDIs) are pressurised and therefore less reliant on inspiratory effort. Breath-actuated MDIs, while more expensive and limited in range of agents, help to minimise timing errors. Dry powder inhalers also require less coordination but may be less effective with higher degrees of airflow obstruction. Soft mist inhalers offer extremely low resistance, improved delivery to the deeper respiratory tract, and less deposition in the oropharynx and upper trachea. There is currently only one soft mist device approved by the FDA, which limits the number of available agents through this delivery method.2 Education during initiation and follow-up is key for ensuring effective drug delivery, as technical errors are as frequent as 30% during each …
TOX is expressed by exhausted and polyfunctional human effector memory CD8 <sup>+</sup> T cells
Authors: Takuya Sekine, André Perez-Potti, Son Nguyen, Jean-Baptiste Gorin, Vincent H. Wu, Emma Gostick, Sian Llewellyn-Lacey, Quirin Hammer, Sara Falck-Jones, Sindhu Vangeti, Meng Yu, Anna Smed-Sörensen, Ahmed Gaballa, Michael Uhlin, Johan K. Sandberg, Christian Brander, Piotr Nowak, Paul A. Goepfert, David A. Price, Michael R. Betts, Marcus Buggert
Journal: Science Immunology (2020)

The transcription factor TOX is not exclusively linked to T cell exhaustion (see related Focus by Utzschneider and Kallies).