tbuckley/cabot-search huggingface dataset:
Increasing Mortality in Adults With Diabetes and Low Estimated Glomerular Filtration Rate in the Absence of Albuminuria
Authors: Holly Kramer, Robert E. Boucher, David Leehey, Linda Fried, Guo Wei, Tom Greene, Sylvia E. Rosas, Richard Cooper, Guichan Cao, Srinivasan Beddhu
Journal: Diabetes Care (2018)

OBJECTIVE Improved blood pressure control and use of renin-angiotensin-aldosterone system blockers have altered the clinical presentation or phenotype of chronic kidney disease (CKD) in U.S. adults with diabetes. These changes may influence mortality. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Surveys (NHANES) 1988–2006 were used to examine mortality trends in adults with diabetes, defined as physician diagnosis, fasting glucose ≥126 mg/dL, HbA1c &amp;gt;6.5% (48 mmol/mol), or use of glucose-lowering medications. Mortality trends by CKD phenotype (estimated glomerular filtration rate [eGFR] and urine albumin-to-creatinine ratio [ACR] level) were obtained via linkage with the National Death Index through 31 December 2011 while accounting for the complex survey design. RESULTS From 1988 to 2006, adults with an eGFR &amp;lt;60 mL/min/1.73 m2 and an ACR &amp;lt;30 mg/g increased from ∼0.9 million (95% CI 0.7, 1.1) or 6.6% of the total population with diabetes during years 1988–1994 to 2.4 million (95% CI 1.9, 2.9) or 10.1% of the total population with diabetes during years 2007–2010. Mortality rates generally trended downward for adults with diabetes and an ACR ≥30 mg/g but increased in those with eGFR &amp;lt;60 mL/min/1.73 m2 and an ACR &amp;lt;30 mg/g from 35 deaths per 1,000 person-years (95% CI 22, 55) during years 1988–1994 to 51 deaths per 1,000 person-years (95% CI 33, 83) during years 2003–2006. CONCLUSIONS ACR values are decreasing in U.S. adults with diabetes, but optimal management strategies are needed to reduce mortality in those with a low eGFR and an ACR &amp;lt;30 mg/g.
Inherited pulmonary cylindromas: extending the phenotype of <i>CYLD</i> mutation carriers
Authors: S.M. Brown, M. Arefi, R. Stones, P.S. Loo, S. Barnard, C. Bloxham, N. Stefanos, J.A.A. Langtry, S. Worthy, E. Calonje, A. Husain, N. Rajan
Journal: British Journal of Dermatology (2018)

Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas.To search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations.A retrospective case-note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In-depth investigation was carried out for patients with pulmonary tumours.Four patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre-emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse.Pulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.
EXOSOMAL MIR-106A-363 CLUSTER FROM THE HYPOXIC HUMAN IPSC-DERIVED CARDIOMYOCYTES RESTORE THE ISCHEMIC MYOCARDIUM
Authors: Ji Hye Jung, Yuko Tada, Daniel Bornstaedt, Christine Wahlquist, Mark Mercola, Y. Woo, Phillip Yang
Journal: Journal of the American College of Cardiology (2018)
Abstract P6-05-03: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Authors: X Zhang, H-C Chiang, Y Wang, VX Jin, Y Hu, R Li
Journal: Cancer Research (2018)

Abstract Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development. Citation Format: Zhang X, Chiang H-C, Wang Y, Jin VX, Hu Y, Li R. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-03.
RET fusions in a small subset of advanced colorectal cancers at risk of being neglected
Authors: F. Pietrantonio, F. Di Nicolantonio, A.B. Schrock, J. Lee, F. Morano, G. Fucà, P. Nikolinakos, A. Drilon, J.F. Hechtman, J. Christiansen, K. Gowen, G.M. Frampton, P. Gasparini, D. Rossini, C. Gigliotti, S.T. Kim, M. Prisciandaro, J. Hodgson, A. Zaniboni, V.K. Chiu, M. Milione, R. Patel, V. Miller, A. Bardelli, L. Novara, L. Wang, S.M. Pupa, G. Sozzi, J. Ross, M. Di Bartolomeo, A. Bertotti, S. Ali, L. Trusolino, A. Falcone, F. de Braud, C. Cremolini
Journal: Annals of Oncology (2018)

BackgroundRecognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC).Patients and methodsIn this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors. RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: (i) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811), (ii) cohorts screened at two Italian and one South Korean Institutions and (iii) Foundation Medicine Inc. database. Next-generation sequencing data were analyzed for RET rearranged cases.ResultsRET fusions were more frequent in older patients (median age of 66 versus 60 years, P = 0.052), with ECOG PS 1–2 (90% versus 50%, P = 0.02), right-sided (55% versus 32%, P = 0.013), previously unresected primary tumors (58% versus 21%, P < 0.001), RAS and BRAF wild-type (100% versus 40%, P < 0.001) and MSI-high (48% versus 7%, P < 0.001). Notably, 11 (26%) out of 43 patients with right-sided, RAS and BRAF wild-type tumors harbored a RET rearrangement. At a median follow-up of 45.8 months, patients with RET fusion-positive tumors showed a significantly worse OS when compared with RET-negative ones (median OS 14.0 versus 38.0 months, HR: 4.59; 95% CI, 3.64–32.66; P < 0.001). In the multivariable model, RET rearrangements were still associated with shorter OS (HR: 2.97; 95% CI, 1.25–7.07; P = 0.014), while primary tumor location, RAS and BRAF mutations and MSI status were not.ConclusionsThough very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management.
Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases
Authors: Chun Gwon Park, Christina A. Hartl, Daniela Schmid, Ellese M. Carmona, Hye-Jung Kim, Michael S. Goldberg
Journal: Science Translational Medicine (2018)

Prolonged perioperative delivery of immunotherapy prevents local tumor recurrence and eliminates established spontaneous metastases.
Results of phase I plus expansion cohorts of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus ipilimumab (Ipi) in patients (pts) with with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies.
Authors: Rosa Maria Nadal, Amir Mortazavi, Mark Stein, Sumanta K. Pal, Nicole N. Davarpanah, Howard L. Parnes, Yang-Min Ning, Lisa M. Cordes, Mohammadhadi H. Bagheri, Liza Lindenberg, Ryan Thompson, Seth M. Steinberg, Tina Moore, Tiffany Lancaster, Milisyaris Velez, Esther Mena, Rene Costello, Donald Bottaro, William L. Dahut, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2018)

515 Background: Tolerability and efficacy of CaboNivo and CaboNivoIpi were demonstrated in the initial phase I cohort, prompting longer follow-up and the addition of expansion cohorts to further evaluate both combinations Methods: Phase I cohort had 7 dose levels (DL). Recommended phase 2 doses for CaboNivo=Cabo 40mg/Nivo 3mg/kg (DL2) &amp; CaboNivoIpi=Cabo 40mg/Nivo 3mg/kg/Ipi 1mg/kg (DL6) (Nadal ESMO 2017).In expansion cohorts, pts were treated: [1] DL8: Cabo 40mg/Nivo 1mg/kg/Ipi 3mg/kg; [2]DL2: mUC, metastatic renal cell carcinoma (mRCC), adenocarcinoma bladder (AcB): post-PD-1-PDL1 inhibitor mUC (p-mUC), and [3] DL6 mRCC. Objectives: safety, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) &amp; overall survival (OS). Results: 75 pts enrolled. Median age 59 yo. 83% male, 17% female. 47 treated with CaboNivo (mUC n=24; AcB n= 9; germ cell tumor (GCT) n= 5; castrate-resistant prostate cancer (CRPC) n= 4; bladder squamous cell carcinoma (SCC) n= 2; penile n=1; mRCC n= 7). 28 treated with CaboNivoIpi: (mUC n=8; penile n=3; CRPC n=7; Sertoli n=1; mRCC n=6; bladder small cell carcinoma n=1; renal medullary carcinoma (RMC) n=2). Any grade (G) adverse events (AEs) (CaboNivo 96% &amp; CaboNivoIpi 96%)/G3–4 AEs (CaboNivo 62% &amp; CaboNivoIpi 71%). Most common any G, CaboNivo: fatigue 70%, diarrhea 60%, AST/ALT 60%, hypophosphatemia (hypoP) 45% &amp; CaboNivoIpi: fatigue 71%, diarrhea 68%, hypoP 50%, AST/ALT 43%. Most common G3-4, CaboNivo: lipase 17%, hypoP 15%, fatigue 6% &amp; CaboNivoIpi: hypoP 21%, AST/ALT 14%, lipase 14%. Selected irAs: colitis (2.6%), hepatitis (2.6%), pneumonitis (2.6%), aseptic meningitis (1.3%). ORR: 36%; 3CR (2mUC, 1SCC) &amp; 20PR (5mUC, 2SCC, 7mRCC, 2Penile, 2AcB, 1CRPC, 1RMC). mDOR: 24.1 mo [95% CI: 14.7-NR], mPFS: 7.2 mo [95%CI: 5.1-18.4], mOS:18.8 mo [95%CI: 10.6-NR]. OS 6/12 mo: 83%/61%. Cohort of p-mUC pts(n=5):1PR/3SD/1PD Conclusions: Updated results from phase I and expanded cohorts confirm initial safety findings and promising antitumor activity for both combinations in mUC, mRCC, and rare GU malignancies Clinical trial information: NCT02496208.
Severe asthma in obese patients: Improvement of lung function after treatment with omalizumab
Authors: M.J. Oliveira, M. Vieira, D. Coutinho, I. Ladeira, I. Pascoal, J. Ferreira, J.M. da Silva, A. Carvalho, R. Lima
Journal: Pulmonology (2018)

Asthma and obesity have a considerable impact on public health and their prevalence is increasing. Obesity is a known risk factor for asthma and can make it more difficult to control. Omalizumab is recommended in patients with severe allergic persistent asthma. The aim of this study was to assess the impact of omalizumab treatment in obese asthmatic patients with poorly controlled severe persistent asthma.A non-interventional, prospective study was conducted, in an outpatient asthma clinic. All patients with severe asthma who started treatment with omalizumab were included and followed over 12 months. The study population was divided into two groups (obese and non-obese) for statistical analysis (descriptive and comparative analysis).Thirty-two patients (19 obese) were followed. After 12 months of omalizumab treatment, there was a statistically significant improvement in body mass index, number of exacerbations in the previous year, rescue medication, disease control and lung function, in the whole population. At the end of the study obese patients had a significantly better lung function (FEV1) than non-obese.As described in the literature, there was a significant reduction in the number of exacerbations in the previous year, rescue medication and better disease control, in the whole population. In relation to lung function, about which published data are inconsistent, treatment with omalizumab significantly improved it in obese patients.Our study showed that omalizumab significantly improved asthma control, reduced rescue medication and asthma exacerbations in all the population; and for the first time showed that obese patients achieved significantly improved lung function.
Exam bias could be tackled by tailored training, royal colleges believe
Authors: Abi Rimmer
Journal: BMJ (2015)

Medical royal colleges and other training organisations are looking at how medical training that is tailored to individual trainees’ needs could help make medical exams fairer, the chair of the BMA’s equality and inclusion committee has said.

Medical training organisations, including the medical royal colleges, who are taking part in work to improve fairness in exams are beginning to talk about personalising doctors’ training, said Krishna Kasaraneni. The work was prompted by a desire to improve the performance in royal college entrance exams of ethnic minority candidates and medical graduates from overseas.

“For the first time this year, discussions about personalised training and tailoring training to individual trainees are …
Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics, and Therapeutic Applications
Authors: Chava Angell, Mingxuan Kai, Sibai Xie, Xiangyi Dong, Yi Chen
Journal: Advanced Healthcare Materials (2018)

Abstract Beside its genomic properties, DNA is also recognized as a novel material in the field of nanoengineering. The specific bonding of base pairs can be used to direct the assembly of highly structured materials with specific nanoscale features such as periodic 2D arrays, 3D nanostructures, assembly of nanomaterials, and DNA nanomachines. In recent years, a variety of DNA nanomachines are developed because of their many potential applications in biosensing, diagnostics, and therapeutic applications. In this review, the fuel‐powered motors and secondary structure motors, whose working mechanisms are inspired or derived from natural phenomena and nanomachines, are discussed. The combination of DNA motors with other platforms is then discussed. In each section of these motors, their mechanisms and their usage in the biomedical field are described. Finally, it is believed that these DNA‐based nanomachines and hybrid motifs will become an integral point‐of‐care diagnostics and smart, site‐specific therapeutic delivery.
Assessing Health-Related Quality of Life in Patients With Diabetic Foot Disease: Why Is It Important and How Can We Improve? The 2017 Roger E. Pecoraro Award Lecture
Authors: Dane K. Wukich, Katherine M. Raspovic
Journal: Diabetes Care (2018)

Patient-reported outcomes (PROs) have become an important subject in the area of diabetes-related foot complications. Self-reported health-related quality of life (HRQOL) surveys can provide a generic measure of overall health (global) and can be disease specific (i.e., diabetes) or even region specific (i.e., lower-extremity function). Analysis of PRO measures utilizing validated instruments allows health care providers to determine whether medical and surgical treatments are providing patients with the highest level of outcome possible and are actually improving HRQOL. The 36-item Short Form (SF-36), EuroQol five-dimension questionnaire (EQ-5D-5L), and Foot and Ankle Ability Measure (FAAM) are examples of commonly used HRQOL surveys. Low HRQOL has been associated with higher rates of hospital admission and mortality in patients with diabetes. Previous studies have demonstrated that patients with diabetes-related foot disease have low self-reported physical quality of life but do not typically report low mental quality of life. The impact of mental quality of life may be underestimated in these patients using the SF-36. In this article, we will discuss several widely used outcome instruments used to measure patient HRQOL and the impact of diabetic foot disease on HRQOL. As health care providers, we must continue to adjust and modify our treatments to achieve the best patient outcomes and associated high quality of life. Assessing PROs will become increasingly important as health care systems transition from a volume-based reimbursement model to a value-based model.
CONE-BEAM CT PROVIDES A LOWER RADIATION OPTION FOR EVALUATION OF CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION COMPARED TO BI-PLANE PULMONARY ANGIOGRAPHY
Authors: Akanksha Thakkar, Ponraj Chinnadurai, Monteiro Gary, Alan Lumsden, C. Huie Lin
Journal: Journal of the American College of Cardiology (2018)
Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound
Authors: Yang Cao, Yuli Chen, Tao Yu, Yuan Guo, Fengqiu Liu, Yuanzhi Yao, Pan Li, Dong Wang, Zhigang Wang, Yu Chen, Haitao Ran
Journal: Theranostics (2018)

Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release.
Preparation and characterization of multimodal hybrid organic and inorganic nanocrystals of camptothecin and gold
Authors: Christin P. Hollis, Alan K. Dozier, Barbara L. Knutson, Tonglei Li
Journal: Acta Pharmaceutica Sinica B (2018)

We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography (CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope (TEM) and further quantified by energy dispersive X-ray spectrometry (EDS) and inductively coupled plasma-optical emission spectrometers (ICP-OES). Due to gold's high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded gold atoms and clusters are expected to share the same biological fate as the camptothecin nanocrystals, reaching and accumulating in tumor site due to the enhanced permeation and retention (EPR) effect.
Evaluation of the immunogenicity in humans of a new adjuvanted anti-allergic therapeutic vaccine
Authors: Wendy Ramirez Gonzalez, Maytee Mateo Morejon, Mary C. Reyes Zamora, Miriam Lastre, Elisabet González, Damaris Torralba Averoff, Oliver Perez, Alexis Labrada Rosado
Journal: Journal of Allergy and Clinical Immunology (2018)
Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?
Authors: Sabrina Giammarco, Régis Peffault de Latour, Simona Sica, Carlo Dufour, Gerard Socie, Jakob Passweg, Nicolaus Kröger, Eefke Petersen, Maria Teresa Van Lint, Rosi Oneto, Alessio Signori, Andrea Bacigalupo
Journal: Blood (2018)
Martha returns to work
Authors: Nicola Sharp
Journal: BMJ (2004)

⇓



“You can't stop me now,” Martha announced to the lump under the bedclothes. The lump under the bedclothes did not move.

Martha did 30 star jumps. “It's all right for you to lie in,” she continued. “I've got to get to work.” The lump did not stir.

Martha did 40 sit ups. “I'm a very busy woman,” she said. “I've got patients to see and lives to save.” Still no movement.

Martha did 50 press ups. “Really David, enough is enough. Even psychiatrists have to get up and go to work sometimes.” Martha went over to the bed and pulled off the bed-clothes to reveal a tartan dressing gown, a pillow and several copies of the British Journal of Psychiatry .

“Stop playing tricks, David.” Martha looked under the bed and pulled out three odd socks and half a bottle of Glenfiddich.

“People don't disappear,” said Martha to herself.

\* * *|

“Is your mother always this noisy?” Janet sat up in bed.

“You get used to it.” Douglas's voice sounded muffled from under the duvet.

“I don't want to get used to it,” said Janet. “I don't want to live with your parents.”

“We could move back to the residence,” said Douglas.

“And …
RELATIONSHIP OF ARTERIAL INFLAMMATION WITH INSULIN RESISTANCE IN FAMILIAL DYSLIPIDEMIAS
Authors: Georgios Benetos, Konstantinos Toutouzas, Iosif Koutagiar, Ioannis Skoumas, Nikoletta Pianou, Alexandros Georgakopoulos, Spyros Galanakos, Alexios Antonopoulos, Evangelos Oikonomou, Pavlos Kafouris, Emmanouil Athanasiadis, Marinos Metaxas, George Spyrou, Zoi Pallantza, Constantina Aggeli, Charalambos Antoniades, Georgia Keramida, Adrien Peters, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)