tbuckley/cabot-search huggingface dataset:
The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance
Authors: Shang Yao, Lavender Yuen-Nam Fan, Eric Wing-Fai Lam
Journal: Seminars in Cancer Biology (2017)

The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial for cell proliferation, differentiation, cell survival, senescence, DNA damage repair and cell cycle control. The development of resistance to both conventional and newly emerged molecularly targeted therapies is a major challenge confronting current cancer treatment in the clinic. Intriguingly, the mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to molecularly targeted therapies are invariably linked to deregulated signalling through the FOXO3 and FOXM1 transcription factors. This is owing to the involvement of FOXO3 and FOXM1 in the regulation of genes linked to crucial drug action-related cellular processes, including stem cell renewal, DNA repair, cell survival, drug efflux, and deregulated mitosis. A better understanding of the mechanisms regulating the FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and functions, may render these proteins reliable and early diagnostic/prognostic factors as well as crucial therapeutic targets for cancer treatment and importantly, for overcoming chemotherapeutic drug resistance.
Determining Health Effects of Hazardous Materials Released During Hurricane Harvey
Authors: M.J. Friedrich
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Functional Impairment and Decline in Middle Age
Authors: Rebecca T. Brown, L. Grisell Diaz-Ramirez, W. John Boscardin, Sei J. Lee, Michael A. Steinman
Journal: Annals of Internal Medicine (2017)

Background: Difficulties with daily functioning are common in middle-aged adults. However, little is known about the epidemiology or clinical course of these problems, including the extent to which they share common features with functional impairment in older adults. Objective: To determine the epidemiology and clinical course of functional impairment and decline in middle age. Design: Cohort study. Setting: The Health and Retirement Study. Participants: 6874 community-dwelling adults aged 50 to 56 years who did not have functional impairment at enrollment. Measurements: Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, assessed every 2 years for a maximum follow-up of 20 years, and impairment in instrumental ADLs (IADLs), defined similarly. Data were analyzed by using multistate models that estimate probabilities of different outcomes. Results: Impairment in ADLs developed in 22% of participants aged 50 to 64 years, in whom further functional transitions were common. Two years after the initial impairment, 4% (95% CI, 3% to 5%) of participants had died, 9% (CI, 8% to 11%) had further ADL decline, 50% (CI, 48% to 52%) had persistent impairment, and 37% (CI, 35% to 39%) had recovered independence. In the 10 years after the initial impairment, 16% (CI, 14% to 18%) had 1 or more episodes of functional decline and 28% (CI, 26% to 30%) recovered from their initial impairment and remained independent throughout this period. The pattern of findings was similar for IADLs. Limitation: Functional status was self-reported. Conclusion: Functional impairment and decline are common in middle age, as are transitions from impairment to independence and back again. Because functional decline in older adults has similar features, current interventions used for prevention in older adults may hold promise for those in middle age. Primary Funding Source: National Institute on Aging and National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Sciences Institute.
Optical coherence tomography of basal cell carcinoma: influence of location, subtype, observer variability and image quality on diagnostic performance
Authors: J. Holmes, T. von Braunmühl, C. Berking, E. Sattler, M. Ulrich, U. Reinhold, H. Kurzen, T. Dirschka, C. Kellner, S. Schuh, J. Welzel
Journal: British Journal of Dermatology (2017)

We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here.To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes.A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion.Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required.OCT is useful in the diagnosis of BCC.
Serious incidents after death: content analysis of incidents reported to a national database
Authors: Iain E Yardley, Andrew Carson-Stevens, Liam J Donaldson
Journal: Journal of the Royal Society of Medicine (2017)

Objectives To describe serious incidents occurring in the management of patient remains after their death. Design Incidents occurring after patient deaths were analysed using content analysis to determine what happened, why it happened and the outcome. Setting The Strategic Executive Information System database of serious incidents requiring investigation occurring in the National Health Service in England. Participants All cases describing an incident that occurred following death, regardless of the age of the patient. Main outcome measures The nature of the incident, the underlying cause or causes of the incident and the outcome of the incident. Results One hundred and thirty-two incidents were analysed; these related to the storage, management or disposal of deceased patient remains. Fifty-four incidents concerned problems with the storage of bodies or body parts. Forty-three incidents concerned problems with the management of bodies, including 25 errors in postmortem examination, or postmortems on the wrong body. Thirty-one incidents related to the disposal of bodies, 25 bodies were released from the mortuary to undertakers in error; of these, nine were buried or cremated by the wrong family. The reported underlying causes were similar to those known to be associated with safety incidents occurring before death and included weaknesses in or failures to follow protocol and procedure, poor communication and informal working practices. Conclusions Serious incidents in the management of deceased patient remains have significant implications for families, hospitals and the health service more broadly. Safe mortuary care may be improved by applying lessons learned from existing patient safety work.
P3.02b-099 Pharmacokinetics of Osimertinib (AZD9291) in Chinese Patients with Advanced NSCLC: A Phase I Study
Authors: Junning Cao, Jianhua Chang, Clara Zhang, Shiang Jiin Leaw, Jia Wang, Mireille Cantarini, Li Zhang
Journal: Journal of Thoracic Oncology (2017)
Engineered Microenvironments for Maturation of Stem Cell Derived Cardiac Myocytes
Authors: Rachel R. Besser, Matthew Ishahak, Vera Mayo, Daniel Carbonero, Isabella Claure, Ashutosh Agarwal
Journal: Theranostics (2017)

Through the use of stem cell-derived cardiac myocytes, tissue-engineered human myocardial constructs are poised for modeling normal and diseased physiology of the heart, as well as discovery of novel drugs and therapeutic targets in a human relevant manner.This review highlights the recent bioengineering efforts to recapitulate microenvironmental cues to further the maturation state of newly differentiated cardiac myocytes.These techniques include long-term culture, co-culture, exposure to mechanical stimuli, 3D culture, cell-matrix interactions, and electrical stimulation.Each of these methods has produced various degrees of maturation; however, a standardized measure for cardiomyocyte maturation is not yet widely accepted by the scientific community.
Arginine reverses growth hormone resistance through the inhibition of toll-like receptor 4-mediated inflammatory pathway
Authors: Jingren Xu, Canjun Zhu, Mengyuan Zhang, Qingchun Tong, Xiaojuan Wan, Zhengrui Liao, Xingcai Cai, Yaqiong Xu, Yexian Yuan, Lina Wang, Xiaotong Zhu, Songbo Wang, Ping Gao, Qianyun Xi, Yong Xu, Qingyan Jiang, Gang Shu
Journal: Metabolism (2017)
Targets set reference points for clinic comparisons
Authors: H. Bergrem, K. S. Johansen
Journal: BMJ (1995)

additionally breast fed by a lactating relative or the child's natural mother.In my experience in Papua New Guinea this method worked well in all cases in which the adoptive mother was motivated and received the necessary support from her family.Side effects of the drugs used were rarely complained of, and only once was it necessary to add methyldopa in the sequence as described above.Clearly, in industrialised countries, where induction of lactation is not considered to be essential for the survival of the infant, the relative importance of side effects and concerns regarding excretion of the drugs into the milk are greater.Nevertheless, at least some of the aspects of the above method could well be adopted in in- dustrialised countries.
Defining the molecular basis of oncogenic cooperation between TAL1 expression and Pten deletion in T-ALL using a novel pro-T-cell model system
Authors: S Bornschein, S Demeyer, R Stirparo, O Gielen, C Vicente, E Geerdens, B Ghesquière, S Aerts, J Cools, C E de Bock
Journal: Leukemia (2017)

T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple mutations combined with the ectopic expression of transcription factors in developing T cells. However, the molecular basis underlying cooperation between transcription factor expression and additional oncogenic mutations in driving T-ALL has been difficult to assess due to limited robust T-cell model systems. Here we utilize a new ex vivo pro-T-cell model to study oncogenic cooperation. Using a systems biological approach we first dissect the pro-T-cell signaling network driven by interleukin-7, stem cell factor and Notch1 and identify key downstream Akt, Stat, E2f and Myc genetic signaling networks. Next, this pro-T-cell system was used to demonstrate that ectopic expression of the TAL1 transcription factor and Pten deletion are bona-fide cooperating events resulting in an increased stem cell signature, upregulation of a specific E2f signaling network and metabolic reprogramming with higher influx of glucose carbons into the tricarboxylic acid cycle. This ex vivo pro-T-cell system thereby provides a powerful new model system to investigate how normal T-cell signaling networks are perturbed and/or hijacked by different oncogenic events found in T-ALL.
Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings
Authors: Annapoorna Mohandas, S. Deepthi, Raja Biswas, R. Jayakumar
Journal: Bioactive Materials (2017)

Chitosan based nanocomposite scaffolds have attracted wider applications in medicine, in the area of drug delivery, tissue engineering and wound healing. Chitosan matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial properties. This review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg, Chitosan/nAu, Chitosan/nCu, Chitosan/nZnO and Chitosan/nTiO2 towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.
Interdisciplinary palliative care services for cancer patients: Assessing quality of care and outcomes measures of successful intervention.
Authors: Yun Rose Li, Eric Anderson, Beverly Ingelson, Kiarash Noorizadeh
Journal: Journal of Clinical Oncology (2017)

127 Background: Interdisciplinary palliative care (IPC) services play a critical role in improving patient care by establishing goals of care and expectations, reducing unnecessary readmissions, and limiting the resource and economic costs associated with end-of-life care. Identifying factors that impact the likelihood of readmissions and measures that help facilitate the transition of patients to hospice care may reduce these costs. Methods: We retrospectively reviewed the demographics, clinical parameters, and outcomes of nearly 500 patient consultations performed by the IPC service at our institution between 2014-2016. Focusing on patients with cancer as the primary diagnosis, we evaluated factors that increased the risk of 6-month readmission, likelihood of transitioning to hospice, and documentation of code-status at time of discharge using Fisher’s exact test and student’s t-tests. Results: Among all patients evaluated by IPC, the median age at consultation was 79.2+/-14.7, and 56.3% are male. Advanced cancer was the most common primary diagnosis (45.5%), with median age 70.9+/-16.0, and 62.1% are male. The 6-month readmission rate among oncology patients (6.5%) was not significantly greater than observed in non-oncology patients (5.9%), P = 0.95, although it was significantly lower than in Medicare patients (~20% in 30 days). Shortness of breath (SOB) was the most common chief complaint (53.9%) on admission. Compared to other chief complaints, such as failure to thrive and frailty, SOB was not associated with increased readmission rates. Reduced readmission rates were strongly reduced with transition to hospice (p &lt; 2.1x10-4) and Do-Not-Resuscitate code status (p &lt; 0.04). Disposition to home at discharge (p &lt; 8.01e-05) was significantly associated with 6-month readmission, as compared to discharge to hospice (0.8%) or SNF (15.0%). Female patients (9/74) were more likely to be readmitted as compared to males (4/132), p &lt; 0.035. Conclusions: We identified multiple predictors of 6-month readmission in our retrospective cohort, which may help stakeholders to identify opportunities to reduce readmission rates for terminal cancer patients.
Un caso humano de rabia asociada a viajes en Austria, Septiembre de 2004
Authors: R Strauss, A Gränz, M Wassermann-Neuhold, R Krause, Z Bago, S Revilla-Fernández, F Simón-Soria, J E Echevarria, T Popow-Kraupp, F Allerberger, M Schönbauer, H Hrabcik
Journal: Eurosurveillance (2005)

Un joven turista austriaco de 23 anos, que no estaba vacunado contra la rabia, fue mordido por un perro en Marruecos en Julio de 2004. Un mes despues fue hospitalizado en Ceuta con sintomas compatibles con rabia. Murio el 23 de Septiembre en un hospital en Austria. Se confirmo el diagnostico de rabia por FAT, IHC y RT-PCR (con determinacion de la secuencia) en una muestra de piel del cuello y por RT-PCR (con determinacion de la secuencia) de un frotis faringeo. Este caso austriaco de rabia biologicamente confirmada subraya la necesidad urgente de reforzar las recomendaciones internacionales para las vacunaciones asociadas a los viajes.
Abstract 51: A Unique Combination of SMarTR Bioinformatics and Cardiomyocyte Screening Technology Allows for Development of Novel Cardio-protective Drugs
Authors: Nirupama Pike, Kevin Kim, Eunhye Park, Chris Armstrong, Lisa Pham, Eithon Cadag
Journal: Circulation Research (2016)

Anthracyclines are a class of highly effective chemotherapy drugs used in the treatment of many cancers, including leukemias, lymphomas, breast, uterine, ovarian, bladder and lung cancers. Approximately 50% of childhood cancer treatment regimens include anthracyclines. Dose dependent cardiotoxicity is a major side effect of anthracyclines. Cancer survivors receiving anthracycline therapy are 15 times more likely to develop heart failure and 8 times more likely to die of cardiovascular disease. Dexrazoxane is the only clinically approved cardio-protectant that has been shown to reduce the risk of cardiotoxicity. However, it is only indicated for metastatic breast cancer and has been linked to secondary malignancies. It is, therefore, critical to develop safer and more effective cardio-protectant drugs to address this major unmet medical need. The recent advancement in generation of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CMs) enables a biologically relevant setting for compound screening because hiPSC-CMs possess many similar functional characteristics as primary human cardiomyocytes and can be generated in significant quantities. We have established a platform to screen small compounds and natural product for efficacy and safety across multiple donor lines using hiPSC-CMs. Compounds to be screened were selected in collaboration with Capella Biosciences who used their SMarTR computational analysis platform to identify potential candidates for further screening in hiPSC-CMs. Using this novel drug discovery engine that combines bioinformatics-driven in-silico screening and hiPSC-CM-based compound screening platforms, we discovered four drugs that protect hiPSC-CMs from doxorubicin-induced cardiotoxicity. We used two cancer cell lines to confirm that these candidates do not interfere with doxorubicin’s anti-cancer activity. We also demonstrated that these candidates do not show acute cardiotoxicity mediated through ion channels. Thus, a unique platform combining SMarTR computational approaches and hiPSC-CMs screening technology allows for rapid identification of highly effective cardio-protective drugs.
Using natural language processing to assess palliative care processes in cancer patients receiving venting gastrostomy tube.
Authors: Charlotta Lindvall, Elizabeth J. Lilley, Zara Cooper, Alexander W. Forsyth, Regina Barzilay, Karl A. Lorenz, Anne Margaret Walling, James A. Tulsky
Journal: Journal of Clinical Oncology (2017)

7 Background: Natural Language Processing (NLP) presents a novel method of extracting text-embedded information from the electronic health record (EHR) to improve routine assessment of palliative quality metrics such as timely advance care planning (ACP), palliative care provision (PC), and hospice referral. Methods: We identified cancer patients (ICD-9-CM codes 140-209) who received a gastrostomy tube (ICD-9-CM 43.11, 43.19, 44.32; CPT code 49440) from Jan 1, 2012, to Mar 31, 2016 at an academic medical center. We used NLP to identify palliative indication for gastrostomy tube placement by labeling clinical notes from the EHR containing the key word “venting” near the time of the procedure. Documentation of ACP, PC, and hospice referral was identified by NLP using a validated key term library. The sensitivity and specificity of the NLP method was determined by comparing outcome identification to manual chart abstraction performed by two clinicians. All NLP code was written in the open-source programming language Python. Results: NLP was performed for 75,626 documents. Among 305 cancer patients who underwent gastrostomy, 75 (24.6%) were classified by NLP as having a palliative indication for the procedure compared to 72 patients (23.6%) classified by human coders. Manual chart abstraction took &gt; 2,600 times longer than NLP (28 hrs vs. 38 seconds). NLP identified the correct patients with high precision (0.92) and recall (0.96). ACP was documented during the index admission for 89.3% of patients. PC was documented for 85.7% and hospice referral was documented for 64.3% of these patients with advanced cancer during the index hospitalization. NLP identified ACP, PC and hospice referral with high precision (0.88-1.0) and recall (0.92-1.0) compared to human coders. Median survival was 37 days following gastrostomy tube procedure. Conclusions: NLP can greatly speed the assessment of established palliative quality metrics with an accuracy approaching that of human coders. These methods offer opportunities for facilitate quality improvement in palliative care for patients with advanced cancer.
Colleagues are best source of support for doctors facing complaints, researchers find
Authors: Abi Rimmer
Journal: BMJ (2017)

Doctors facing a complaint have lower levels of depression and anxiety if they seek support from their colleagues, research published in BMJ Open has shown.1

UK and Belgian researchers concluded that denying doctors the chance to speak to colleagues, as may happen in serious cases, is “unreasonable,” as having the support of colleagues as well as management “was associated with less avoidance and psychological morbidity.” “Avoidance” can include avoiding some procedures, not accepting high risk patients, and abandoning procedures early.

The researchers sent …