tbuckley/cabot-search huggingface dataset:
Limited diagnostic accuracy and clinical impact of single-operator peroral cholangioscopy for indeterminate biliary strictures
Authors: Adriaan B. de Vries, Frans van der Heide, Rinze W. F. ter Steege, Jan Jacob Koornstra, Karel T. Buddingh, Annette S. H. Gouw, Rinse K. Weersma
Journal: Endoscopy (2019)

Abstract Background Single-operator peroral cholangioscopy (sPOCS) is considered a valuable diagnostic modality for indeterminate biliary strictures. Nevertheless, studies show large variation in its characteristics and measures of diagnostic accuracy. Our aim was to estimate the diagnostic accuracy of sPOCS visual assessment and targeted biopsies for indeterminate biliary strictures. Additional aims were: estimation of the clinical impact of sPOCS and comparison of diagnostic accuracy with brush cytology. Methods A retrospective single-center study of adult patients who underwent sPOCS for indeterminate biliary strictures was performed. Diagnostic accuracy was defined as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The clinical impact of sPOCS was assessed by review of medical records, and classified according to its influence on patient management. Results 80 patients were included, with 40 % having primary sclerosing cholangitis (PSC). Prior ERCP was performed in 88 %, with removal of a biliary stent prior to sPOCS in 55 %. The sensitivity, specificity, PPV, and NPV for sPOCS visual impression and targeted biopsies were 64 %, 62 %, 41 %, and 84 %, and 15 %, 65 %, 75 %, and 69 %, respectively. The clinical impact of sPOCS was limited; outcome changed management in 17 % of patients. Sequential brush cytology sensitivity, specificity, PPV, and NPV were 47 %, 95 %, 80 %, and 83 %. Conclusions The diagnostic accuracy of sPOCS for indeterminate biliary strictures was found to be inferior to brush cytology, with a low impact on patient management. These findings are obtained from a select patient population with a high prevalence of PSC and plastic stents in situ prior to sPOCS.
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
Authors: Lucie Abeler-Dörner, Adam G. Laing, Anna Lorenc, Dmitry S. Ushakov, Simon Clare, Anneliese O. Speak, Maria A. Duque-Correa, Jacqueline K. White, Ramiro Ramirez-Solis, Namita Saran, Katherine R. Bull, Belén Morón, Jua Iwasaki, Philippa R. Barton, Susana Caetano, Keng I. Hng, Emma Cambridge, Simon Forman, Tanya L. Crockford, Mark Griffiths, Leanne Kane, Katherine Harcourt, Cordelia Brandt, George Notley, Kolawole O. Babalola, Jonathan Warren, Jeremy C. Mason, Amrutha Meeniga, Natasha A. Karp, David Melvin, Eleanor Cawthorne, Brian Weinrick, Albina Rahim, Sibyl Drissler, Justin Meskas, Alice Yue, Markus Lux, George X. Song-Zhao, Anna Chan, Carmen Ballesteros Reviriego, Johannes Abeler, Heather Wilson, Agnieszka Przemska-Kosicka, Matthew Edmans, Natasha Strevens, Markus Pasztorek, Terrence F. Meehan, Fiona Powrie, Ryan Brinkman, Gordon Dougan, William Jacobs, Clare M. Lloyd, Richard J. Cornall, Kevin J. Maloy, Richard K. Grencis, Gillian M. Griffiths, David J. Adams, Adrian C. Hayday
Journal: Nature Immunology (2019)
Abstract 12926: Using Natural Language Processing to Accurately Identify Aortic Stenosis in a Large, Integrated Healthcare Delivery System
Authors: Matthew D Solomon, Grace Tabada, Amanda Allen, Sue Hee Sung, Alan S Go
Journal: Circulation (2019)

Introduction: Administrative claims data are often used for population management and quality reporting, but diagnosis codes for conditions such as valvular heart disease can be inaccurate and vary...
Suicide Risk Assessment in Youth and Young Adults With Type 1 Diabetes
Authors: Shideh Majidi, Holly K. O’Donnell, Kelly Stanek, Erin Youngkin, Tara Gomer, Kimberly A. Driscoll
Journal: Diabetes Care (2019)

OBJECTIVE To describe sociodemographic and clinical characteristics of youth and young adults with type 1 diabetes who endorsed suicidal ideations as part of routine depression screening and the results of their suicide risk assessments. RESEARCH DESIGN AND METHODS The Patient Health Questionnaire–9 was used to assess depressive symptoms and suicide/death ideation in 550 youth and young adults with type 1 diabetes ages 10–24 years. Only individuals who endorsed suicidal/death ideations (n = 49) completed a standardized suicide risk assessment protocol and safety planning. RESULTS Nine percent of individuals endorsed suicidal/death ideation and of those, 83.4% reported clinically elevated depressive symptoms; 16% made a previous suicide attempt. No youth (n = 39) or young adults (n = 11) disclosed current plans or preparations for suicide, but five who expressed suicidal ideation acknowledged the lethality of insulin for an attempt. Three previously used insulin to attempt suicide. The overwhelming majority of individuals were classified as being low risk for future suicide attempt/completion. None were hospitalized as a part of the suicide risk assessment, and no suicide completions have occurred. CONCLUSIONS The findings of this study provide initial insight into the behaviors and cognitions of youth and young adults with type 1 diabetes who experience suicidal and death ideations. Comprehensive suicide risk assessment and safety planning are feasible during routine type 1 diabetes clinic appointments.
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer
Authors: Chenxi Zhao, Chenming Zeng, Song Ye, Xiaoyang Dai, Qiaojun He, Bo Yang, Hong Zhu
Journal: Acta Pharmaceutica Sinica B (2019)

Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis, and highlight questions that might have a potential impact in the future.
NAMPT Inhibition Suppresses Cancer Stem-like Cells Associated with Therapy-Induced Senescence in Ovarian Cancer
Authors: Timothy Nacarelli, Takeshi Fukumoto, Joseph A. Zundell, Nail Fatkhutdinov, Stephanie Jean, Mark G. Cadungog, Mark E. Borowsky, Rugang Zhang
Journal: Cancer Research (2019)

Epithelial ovarian cancer (EOC) is the most lethal of gynecologic malignancies. The standard-of-care treatment for EOC is platinum-based chemotherapy such as cisplatin. Platinum-based chemotherapy induces cellular senescence. Notably, therapy-induced senescence contributes to chemoresistance by inducing cancer stem-like cells (CSC). However, therapeutic approaches targeting senescence-associated CSCs remain to be explored. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT) inhibition suppresses senescence-associated CSCs induced by platinum-based chemotherapy in EOC. Clinically applicable NAMPT inhibitors suppressed the outgrowth of cisplatin-treated EOC cells both in vitro and in vivo. Moreover, a combination of the NAMPT inhibitor FK866 and cisplatin improved the survival of EOC-bearing mice. These phenotypes correlated with inhibition of the CSCs signature, which consists of elevated expression of ALDH1A1 and stem-related genes, high aldehyde dehydrogenase activity, and CD133 positivity. Mechanistically, NAMPT regulates EOC CSCs in a paracrine manner through the senescence-associated secretory phenotype. Our results suggest that targeting NAMPT using clinically applicable NAMPT inhibitors, such as FK866, in conjunction with platinum-based chemotherapy represents a promising therapeutic strategy by suppressing therapy-induced senescence-associated CSCs. SIGNIFICANCE: This study highlights the importance of NAMPT-mediated NAD+ biosynthesis in the production of cisplatin-induced senescence-associated cancer stem cells, as well as tumor relapse after cisplatin treatment.
A Magnetic Drug Delivery System with “OFF–ON” State via Specific Molecular Recognition and Conformational Changes for Precise Tumor Therapy
Authors: Junjie Liu, Wei Liu, Kaixiang Zhang, Jinjin Shi, Zhenzhong Zhang
Journal: Advanced Healthcare Materials (2019)

To enhance the tumor-targeting and tumor cell-specific drug-release capacity of nano drug delivery systems, a magnetic resonance imaging-traceable, magnetic-targeted nanoplatform is developed, and the nanoplatform is prepared by capping mesoporous silica (MSN)-coated iron oxide nanoparticles (IONPs) with programmable DNA hairpin sensor "gates." In normal cells (HL-7702, human liver cells), the nanoplatform is able to entrap the loaded drugs, showing an "OFF" state; the nanoplatform is activated by endogenous miRNA-21 overexpressed in tumor cells (HepG2, human liver tumor cells), which serve as an exclusive key to unlock the nanoplatform through hybridization with programmable DNA hairpin, leading to a rapid drug release, showing an "ON" state. The nanoplatform exhibits high antitumor efficacy and low toxicity in in vitro and in vivo studies owing to its magnetic targeting and tumor cell-activated properties, paving the way for targeted and personalized tumor treatment and showing potential for clinical applications.
Facilitating access to new therapeutic options through clinical trials: the vision of a regulator to reconcile innovation and safety
Authors: S Vignot, M Martin, N Albin, C Schurtz, E Chapel
Journal: Annals of Oncology (2019)

In the field of onco-hematology, targeted molecular therapies, immunotherapies and personalized treatments are undoubtedly a source of hope not only for patients and their relatives, but also for caregivers, in whom this hope is also combined with ever-increasing scientific interest. Expectations are high for all stakeholders, and questions on the best way to access these innovations can quickly arise, potentially leading to frustration and even irritation. Many national and European initiatives have been implemented to accelerate market access for new therapies (new drugs, new combinations and new strategies).
Ассоциация синдрома избыточного бактериального роста и неалкогольной жировой болезни печени у детей
Authors: Yu.M. Stepanov, N.Yu. Zavhorodnia, O.Yu. Lukianenko, E.V. Zygalo, V.B. Yagmur
Journal: GASTROENTEROLOGY (2019)

Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) занимает лидирующие позиции среди хронических заболеваний печени у детей в промышленно развитых странах. Известно, что для пациентов с НАЖБП характерна высокая распространенность синдрома избыточного бактериального роста (СИБР). Цель работы — изучить влияние СИБР на структурно-функциональные показатели печени у детей с избыточным весом и ожирением. Материалы и методы. Обследовано 73 ребенка в возрасте от 6 до 17 лет, средний возраст пациентов составил (11,41 ± 2,68) года. В зависимости от наличия избыточного веса/ожирения и результатов водородного дыхательного теста (ВДТ) с глюкозой пациенты были разделены на 2 группы: 1 группа — 30 детей с избыточным весом/ожирением и наличием СИБР, 2 группа — 28 детей с избыточным весом/ожирением без СИБР. Контрольную группу составили 15 практически здоровых детей с нормальным весом и без СИБР по результатам ВДТ с глюкозой. Наличие стеатоза печени устанавливали при помощи транзиентной эластографии с функцией САР. Дополнительно проводили ВДТ с лактозой и биохимический анализ крови с определением показателей биохимической гепатограммы, липидного и углеводного спектров. Результаты. Установлено, что 70 % детей 1 группы имели сопутствующую НАЖБП по сравнению с 32 % во 2 группе. В 1 группе скорость оседания эритроцитов была выше, чем во 2 и 3 группах (p &lt; 0,05). Также у детей 1 группы уровни триглицеридов и липопротеинов очень низкой плотности были в 1,5 раза выше. Отмечена тенденция к более высоким значениям инсулина и индекса НОМА в 1 группе по сравнению со второй. Мальабсорбция лактозы диагностирована у 17 (56,7 %) детей с НАЖБП, лактозозависимый СИБР — у 15 (50,0 %). При ожирении без НАЖБП мальабсорбция лактозы выявлена у 10 (35,7 %) пациентов, а лактозозависимый СИБР — у 9 (32,1 %). Таким образом, у детей с НАЖБП мальабсорбция лактозы встречалась в 1,6 раза чаще, чем у детей без НАЖБП. Выводы. Установлено, что НАЖБП является фактором риска формирования СИБР. СИБР ассоциирован с низкоуровневым воспалением, дети с СИБР на фоне ожирения характеризовались более неблагоприятным метаболическим профилем в виде изменений параметров липидного и углеводного обмена, что может приводить к прогрессированию НАЖБП. Продемонстрирована высокая частота мальабсорбции лактозы и лактозозависимого СИБР у детей с НАЖБП.
Syndromic Surveillance for E-Cigarette, or Vaping, Product Use–Associated Lung Injury
Authors: Kathleen P. Hartnett, Aaron Kite-Powell, Megan T. Patel, Brittani L. Haag, Michael J. Sheppard, Taylor P. Dias, Brian A. King, Paul C. Melstrom, Matthew D. Ritchey, Zachary Stein, Nimi Idaikkadar, Alana M. Vivolo-Kantor, Dale A. Rose, Peter A. Briss, Jennifer E. Layden, Loren Rodgers, Jennifer Adjemian
Journal: New England Journal of Medicine (2019)

Vaping Syndromic Surveillance Increases in EVALI were identified in 2019. Using the National Syndromic Surveillance Program, which includes about 70% of U.S. EDs, researchers found a gradual increa...
Getting Better at Measuring Hospital Mortality
Authors: Mark R. Chassin
Journal: JAMA Internal Medicine (2019)

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Adolescents and young adults versus adults’ patients with large B-cell lymphoma: A matched-control analysis on 55 patients.
Authors: Reda Bouabdallah, Diane Coso, Benjamin Esterni, Norbert Vey, Bruno Chetaille, Didier Blaise
Journal: Journal of Clinical Oncology (2012)

e18526 Background: Among non-Hodgkin’s lymphomas, large B-cell lymphoma (LBCL) accounts for 60% in adolescents and young adults (AYA). There are no so many reports in the literature on LBCL in AYA patients. Moreover, there are no data available to suggest whether AYA patients with LBCL would benefit more from pediatric-chemotherapy regimen or from adult rituximab-chemotherapy treatment. In order to clarify this point, we conducted a matched-control analysis comparing AYA patients and adult’s patients with LBCL. Methods: We performed a clinical and pathological review of LBCL cases referred to our institution over a 15-year period from 1996 to 2010. Fifty-five AYA (16-30 years) were fully matched to 165 adult’s patients aged between 31 years and 65 years (ratio 1/3) for each of the following factors: international prognostic index (IPI), chemotherapy regimen, and rituximab delivery. Results: When compared to LBCL adults’ patients, pathological features in AYA showed a high incidence of primary mediastinal thymic LBCL subtype (33% vs. 5%, P= 0, 0001), while histological transformation was rare (2% vs. 14%, P= 0, 01). LBCL in AYA also presented with a bulky mediastinal mass (51% vs. 21%, P= 0, 0001), gastrointestinal tract involvement was less frequent (2% vs. 13%, P=0, 03), and LDH value was significantly higher (73% vs. 54%, P= 0, 01). The complete response rate to chemotherapy combination regimen was at 82% in AYA, with no difference with that observed in adult patients (82%, P=0, 8). With a median follow-up of 80 months, the 5-year overall survival (OS) and event-free survival (EFS) of AYA patients were at 73% ± 12% and 68% ± 12%, respectively. The matched-control analysis showed no difference either for OS (P = 0.8) or EFS (P = 0.9). Conclusions: LBCL in AYA should be considered as a true clinical and pathological entity. However, age does not confer a prognostic value different from that observed in LBCL in patients older than 30 years.
The Secretome of Hypoxia Conditioned hMSC Loaded in a Central Depot Induces Chemotaxis and Angiogenesis in a Biomimetic Mineralized Collagen Bone Replacement Material
Authors: Mandy Quade, Pina Münch, Anja Lode, Sarah Duin, Corina Vater, Anastasia Gabrielyan, Angela Rösen‐Wolff, Michael Gelinsky
Journal: Advanced Healthcare Materials (2019)

Abstract The development of biomaterials with intrinsic potential to stimulate endogenous tissue regeneration at the site of injury is a main demand on future implants in regenerative medicine. For critical‐sized bone defects, an in situ tissue engineering concept is devised based on biomimetic mineralized collagen scaffolds. These scaffolds are functionalized with a central depot loaded with a signaling factor cocktail, obtained from secretome of hypoxia‐conditioned human mesenchymal stem cells (MSC). Therefore, hypoxia‐conditioned medium (HCM)‐production is standardized and adapted to achieve high signaling factor‐yields; a concentration protocol based on dialysis and freeze‐drying is established to enable the integration of sufficient and defined amounts into the depot. In humid milieu—as after implantation—signaling factors are released by forming a chemotactic gradient, inducing a directed migration of human bone marrow stroma cells (hBMSC) into the scaffold. Angiogenic potential, determined by coculturing human umbilical vein endothelial cells (HUVEC) with osteogenically induced hBMSC shows prevascular structures, which sprout throughout the interconnected pores in a HCM‐concentration‐dependent manner. Retarded release by alginate‐based (1 vol%) depots, significantly improves sprouting‐depth and morphology of tubular structures. With the intrinsic potential to supply attracted cells with oxygen and nutrients, this bioactive material system has great potential for clinical translation.
Hypertension in Cancer Patients and Survivors
Authors: Jordana B. Cohen, Abdallah S. Geara, Jonathan J. Hogan, Raymond R. Townsend
Journal: JACC CardioOncology (2019)

Cancer patients and survivors of cancer have a greater burden of cardiovascular disease compared to the general population. Much of the elevated cardiovascular risk in these individuals is likely attributable to hypertension, as individuals with cancer have a particularly high incidence of hypertension following cancer diagnosis. Treatment with chemotherapy is an independent risk factor for hypertension due to direct effects of many agents on endothelial function, sympathetic activity, and renin-angiotensin system activity as well as nephrotoxicity. Diagnosis and management of hypertension in cancer patients requires accurate blood pressure measurement and consideration of potential confounding factors, such as adjuvant treatments and acute pain, that can temporarily elevate blood pressure readings. Home blood pressure monitoring can be a useful tool to facilitate longitudinal blood pressure monitoring for titration of antihypertensive medications. Selection of antihypertensive agents in cancer patients should account for treatment-specific morbidities and target organ injury.
A career in rehabilitation medicine
Authors: Morag Sime
Journal: BMJ (2019)

Have you ever wondered what happens after the initial “life saving” aspect of medicine? What happens to those who lose limbs from sepsis, have a spinal cord injury from trauma, or have a neurodegenerative condition? How do those people get out of hospital and back to living a good life? That’s where the specialty of rehabilitation medicine comes in.

Rehabilitation medicine does not focus on one organ or body system—but involves individuals with cognitive or physical impairments, or both. Those impairments may be secondary to a variety of congenital or acquired conditions, including spinal cord injury, limb loss, brain injury, neurological and musculoskeletal conditions. Health professionals working in rehabilitation medicine deal with a patient’s physical, psychological, and social needs to ensure the best recovery and improvement in quality of life. They support patients and their families through life changing, and sometimes life limiting times. Rehabilitation medicine offers care in outpatient clinics, inpatient neurorehabilitation wards, intensive care, and the community. Doctors who work in rehabilitation medicine coordinate care, work with therapy teams, use technologies, and perform procedures such as botulinum toxin injections for spasticity.

The miracle recovery story everyone likes to hear about is not always the case. Rehabilitation medicine can be challenging emotionally and ethically—for example, caring for people with prolonged disorders of consciousness, such as vegetative and minimally conscious states.

Ludwig Guttman, a doctor who worked …