tbuckley/cabot-search huggingface dataset:
Adverse Events in Long-term Care Residents Transitioning From Hospital Back to Nursing Home
Authors: Alok Kapoor, Terry Field, Steven Handler, Kimberly Fisher, Cassandra Saphirak, Sybil Crawford, Hassan Fouayzi, Florence Johnson, Ann Spenard, Ning Zhang, Jerry H. Gurwitz
Journal: JAMA Internal Medicine (2019)

Transition from hospital to nursing home is a high-risk period for adverse events in long-term care (LTC) residents. Adverse events include harms from medical care, including failure to provide appropriate care.To report the incidence, type, severity, and preventability of adverse events in LTC residents transitioning from hospital back to the same LTC facility.Prospective cohort study of LTC residents discharged from hospital back to LTC from March 1, 2016, to December 31, 2017, and followed up for 45 days. In a random sample of 32 nursing homes located in 6 New England states, 555 LTC residents were selected, contributing 762 transitions from hospital back to the same LTC facility.The main outcome was an adverse event within the 45-day period after transition from hospital back to nursing home. Trained nurse abstractors reviewed nursing home records for the period, and then 2 physicians independently reviewed each potential adverse event to determine whether harm occurred and to characterize the type, severity, and preventability of each event. When reviewers disagreed, they met to reach consensus.Of the 555 individual residents, 365 (65.6%) were female, and the mean (SD) age at the time of discharge was 82.2 (11.5) years. Five hundred twenty (93.7%) were non-Hispanic white, 21 (3.8%) were non-Hispanic black, 9 (1.6%) were Hispanic, and 5 (0.9%) were of other non-Hispanic race/ethnicity. In the cohort, there were 379 adverse events among 762 discharges. One hundred ninety-seven events (52.0%) related to resident care, with pressure ulcers, skin tears, and falls with injury representing the most common types of events in this category. Health care-acquired infections (108 [28.5%]) and adverse drug events (64 [16.9%]) were the next most common. One hundred ninety-eight (52.2%) adverse events were characterized as less serious. However, 145 (38.3%) events were deemed serious, 28 (7.4%) life-threatening, and 8 (2.1%) fatal. In terms of preventability, 267 (70.4%) adverse events were found to be preventable or ameliorable, with less serious events more often considered preventable or ameliorable (146 [73.7%]) compared with more severe events (121 [66.9%]). In addition, resident care-related adverse events such as fall with injury, skin tear, and pressure ulcer were more commonly deemed preventable (173 of 197 [87.8%]) compared with adverse drug events (39 of 64 [60.9%]) or health care-acquired infections (49 of 108 [45.4%]).Adverse events developed in nearly 4 of 10 of discharges from hospital back to LTC. Most were preventable or ameliorable. Standardized reporting of events and better coordination and information transfer across settings are potential ways to prevent adverse events in LTC residents.
Targeting radiation resistance in p53 mutant tumors with AKT inhibitors.
Authors: Aswin George Abraham, Garth Hamilton, Eric O'Neill
Journal: Journal of Clinical Oncology (2013)

11115 Background: Increasing our understanding of how resistance to radiation occurs, helps us develop more efficient and personalised radiotherapy treatments for cancer patients. Through molecular dissection of events that drive tumour initiation and progression, we have uncovered a functional connection between the most frequent oncogenic mutations that are likely to contribute to therapeutic resistance in 30% of all human tumours. Mutations activating the "AKT" signalling pathway and inactivation of the “TP53” tumour suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. We find that in combination these events lead to therapeutic resistance that is reversible by the AKT clinical candidate, MK-2206 and the PI3K inhibitor PI-103. Methods: Using a combination of in vivo and in vitro techniques we have tracked the molecular mechanism for AKT mediated resistance to treatment in solid tumours. This has helped us to simultaneously derive potential biomarkers that could highlight where the greatest efficacy may be achieved in clinical practise. Results: Tumours employ many strategies to inactivate p53; however sequence mutations that result in mutant p53 protein (p53mut) are most often observed. p53mut tumours not only fail to respond to DNA damaging therapy, but are also described to promote therapeutic resistance by dominant negative suppression of p53 dependent promoter activity. We demonstrate that AKT inhibitors- and as proof of concept, the clinical candidate AKT inhibitor, MK-2206, and PI3K inhibitor, PI-103, are effective in treatment of mice with therapeutically resistant tumours with elevated AKT and carrying p53mut. AKT inhibition promotes reduced cellular levels of p53mut via a novel mechanism and promoted re-engagement of cell cycle arrest, senescence and increased sensitivity to ionising radiation in both in vivo and in vitro systems. Conclusions: We show that AKT inhibitors sensitise xenografts carrying p53 mutations to DNA damaging therapy. We have also been identifying potential molecular markers to select the cohort of patient most likely to benefit from this treatment.
A functionalized TiO2/Mg2TiO4 nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection
Authors: Zhengjie Lin, Ying Zhao, Paul K. Chu, Luning Wang, Haobo Pan, Yufeng Zheng, Shuilin Wu, Xuanyong Liu, Kenneth M.C. Cheung, Takman Wong, Kelvin W.K. Yeung
Journal: Biomaterials (2019)
Treatment outcomes of primary mediastinal and intrathoracic great vessels sarcoma: Royal Marsden Hospital experience.
Authors: Shir Kiong Lu, Charlotte Benson, Sushila Ganguli, Michelle R. Scurr, Cyril Fisher, Komel Khabra, Omar Al-Muhaderis, Alison Dunlop, Frank Saran, Gillian Ross, Aisha Miah, Ian Robert Judson
Journal: Journal of Clinical Oncology (2012)

10060 Background: Sarcoma of the mediastinum and great vessels remain a rare subgroup of soft tissue sarcoma and prognosis remains poor with patients (pts) often presenting with advanced disease. There is no standard treatment due to paucity of data hence its management relies on case series. To date this is the largest series of pts reported. Methods: Retrospective analysis of pts identified anonymously from a prospectively maintained database of the sarcoma unit. Results: 46 pts were included in the analysis. The median age at diagnosis was 45.9 with a male: female ratio of 1.2: 1. 60% of pts presented with localised disease. The most common histological subtype was spindle cell sarcoma followed by angiosarcoma. The heart (n=21), majority in the atria, was the commonest primary site. 28 pts presented with localised disease of which 21 had surgery and 16 received chemotherapy (CT). 4 pts received multi-modality treatment. 83% of pts with metastases had CT. 6 of them attained stable disease, 1 had partial response and 4 (Ewing’s, rhabdomyosarcoma and angiosarcoma) had complete response. 31 pts developed disease recurrence of which 58% had initial localised disease. 6 pts had metastectomy, 19 received palliative CT and 11 had palliative radiotherapy (RT). RT of 50-60Gy to the heart or mediastinum was delivered to 61% of pts with initial localized disease and 33% of pts with metastases. 2 pts had documented post-treatment cardiac complication. After a median follow up of 2.16 years, the median event-free survival was 0.97 years (95%CI 0.65-1.30), median overall survival (OS) was 1.7 years (95% CI 0.70-2.71) and 5 year OS was 17.9%. Conclusions: The optimal management in this disease is unclear. In this study, surgery was frequently implemented in both localised and metastatic settings but challenges remain in achieving clear margins. Chemotherapy has a role and it is key to identify chemosensitive subtypes. RT is offered as an adjunct following suboptimal resection. Despite aggressive treatments, this group of young pts had high recurrence rate and poor prognosis. Multi-modality treatment may have a role in selected pts but its efficacy and long-term cardiac sequelae need to be evaluated prospectively.
Compensation in autism is not consistent with social motivation theory
Authors: Lucy Anne Livingston, Punit Shah, Francesca Happé
Journal: Behavioral and Brain Sciences (2019)

Abstract Growing evidence, as presented by Jaswal &amp; Akhtar, indicates that social motivation is not universally reduced in autism. Here, we evaluate and extend this argument in light of recent evidence of “compensation” in autism. We thereby argue that autistic “compensators” – exhibiting neurotypical behaviour despite persistent difficulties in social cognition – indicate intact or potentially heightened social motivation in autism.
A Novel Single Next-Generation Sequencing (NGS) Approach for the Molecular Karyotyping and Genotyping of Patients with Myelodysplastic Syndromes
Authors: Alessandro Liquori, Esperanza Such, Laura Palomo, Ivan Lesende, Alexander Neef, Mariam Ibañez, Gayane Avetisyan, Sarah Moreau, Laia Pedrola, Jorge Selles, Ana Saus, Javi Ayala, Pamela Acha, Alejandra Sanjuan, Mireia Boluda, Beatrice De Matteo, Elisa Gonzalez, Miguel A. Sanz, Francesc Sole, Guillermo Sanz, José Cervera
Journal: Blood (2017)
Implantation of Patient-Derived Acute Leukemia Cells into the Hematopoietic Niche of Immunocompromised Mice Favors Faithful Recapitulation of the Disseminated Growth of Human Leukemia
Authors: Julia Schueler, Gabriele Greve, Dorothee Lenhard, Kerstin Klingner, Milena Pantic, Eva Oswald, Michael Lubbert
Journal: Blood (2017)
Implementation of a genomic medicine multi-disciplinary team approach for rare disease in the clinical setting: a prospective exome sequencing case series
Authors: John Taylor, Jude Craft, Edward Blair, Sarah Wordsworth, David Beeson, Saleel Chandratre, Judith Cossins, Tracy Lester, Andrea H. Németh, Elizabeth Ormondroyd, Smita Y. Patel, Alistair T. Pagnamenta, Jenny C. Taylor, Kate L. Thomson, Hugh Watkins, Andrew O. M. Wilkie, Julian C. Knight
Journal: Genome Medicine (2019)

A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. Here we describe the results of establishing a genomic medicine multi-disciplinary team (GM-MDT) for case selection, processing, interpretation and return of results. We report a consecutive case series of 132 patients (involving 10 medical specialties with 43.2% cases having a neurological disorder) undergoing exome sequencing over a 10-month period following the establishment of the GM-MDT in a UK NHS tertiary referral hospital. The costs of running the MDT are also reported. In total 76 cases underwent exome sequencing following triage by the GM-MDT with a clinically reportable molecular diagnosis in 24 (31.6%). GM-MDT composition, operation and rationale for whether to proceed to sequencing are described, together with the health economics (cost per case for the GM-MDT was £399.61), the utility and informativeness of exome sequencing for molecular diagnosis in a range of traits, the impact of choice of sequencing strategy on molecular diagnostic rates and challenge of defining pathogenic variants. In 5 cases (6.6%), an alternative clinical diagnosis was indicated by sequencing results. Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization. This consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians.
Preferences for cancer prevention strategies (CPS) in women with hereditary nonpolyposis colectal cancer (HNPCC)
Authors: C. C. Sun, S. K. Peterson, K. G. White, B. G. Watts, M. S. Daniels, S. G. Boyd-Rogers, K. M. Schmeler, D. C. Bodurka, K. H. Lu
Journal: Journal of Clinical Oncology (2006)

1018 Background: Women with HNPCC have 40–60% lifetime risk of endometrial and colon cancer (CA) and 10–12% risk of ovarian CA. Because CPS have significant QOL implications, understanding how women evaluate CPS and personal risks of CA may facilitate physician and pt communication for medical decision making in this group of pts. Methods: Using the visual analog scale (VAS) and standard gamble (SG), women with HNPCC or with a family history (FHx) that fulfilled Amsterdam II criteria were asked to: 1) score CPS from 0.0=worst to 1.0=best; and 2) state the % personal risk of CA they would need to have in order to undergo each CPS. CPS included oral contraceptives ± COX-2 inhibitors (OC ± COX2); endometrial biopsy/transvaginal ultrasound/CA125 ± colonoscopy (Bx/US ± CSPY); pre- and post-menopausal total abdominal hysterectomy/oophorectomy ± subtotal colectomy (TAH/BSO ± COL). Results: To date, 32 women have enrolled (median age=38.4 yrs). Bx/US + CSPY was rated most favorably (0.95) followed by OC, Bx/US, and CSPY(.90). Pre-menopausal TAH/BSO, COL, and TAH/BSO+ COL had the least favorable ratings (0.50, 0.30, and 0.25, respectively). Women accepted non-surgical CPS if their personal risk of CA was at least 30%; pre- and post-menopausal TAH/BSO if the personal risk of CA was at least 73% and 50%, respectively. Women accepted COL and TAH/BSO + COL if their risks of CA were at least 78% and 80%, respectively. Women without FHx of HNPCC-gynecologic (GYN) CA would participate in all CPS more readily than women with FHx of HNPCC-GYN CA. Specifically, to accept COX2, women without FHx of HNPCC-GYN CA would do to if their personal CA risk was at least 10% compared to a 30% risk for women in the 2nd group (p=.04). For the 2 groups, risks for Bx/US, pre-menopausal TAH/BSO, post-menopausal TAH/BSO, TAH/BSO + COL and COL were 20% vs 30% (p=.06), 40% vs 80% (p=.03), 30% vs 55% (p=.02), 65% vs 80% (p=.06), and 80% vs 100% (p=.01), respectively. Conclusions: Our data indicate that women without FHx of HNPCC-GYN CA are more willing to undergo chemoprevention, screening and prophylactic surgery for HNPCC CA compared to women with a FHx of HNPCC-GYN CA. This may be due to the perception of a more favorable clinical outcome associated with endometrial CA, the more common of the HNPCC-GYN CA. No significant financial relationships to disclose.
A radiomics approach based on support vector machine using MR images for preoperative lymph node status evaluation in intrahepatic cholangiocarcinoma
Authors: Lei Xu, Pengfei Yang, Wenjie Liang, Weihai Liu, Weigen Wang, Chen Luo, Jing Wang, Zhiyi Peng, Lei Xing, Mi Huang, Shusen Zheng, Tianye Niu
Journal: Theranostics (2019)

Purpose: Accurate lymph node (LN) status evaluation for intrahepatic cholangiocarcinoma (ICC) patients is essential for surgical planning.This study aimed to develop and validate a prediction model for preoperative LN status evaluation in ICC patients.Methods and Materials: A group of 106 ICC patients, who were diagnosed between April 2011 and February 2016, was used for prediction model training.Image features were extracted from T1-weighted contrast-enhanced MR images.A support vector machine (SVM) model was built by using the most LN status-related features, which were selected using the maximum relevance minimum redundancy (mRMR) algorithm.The mRMR method ranked each feature according to its relevance to the LN status and redundancy with other features.An SVM score was calculated for each patient to reflect the LN metastasis (LNM) probability from the SVM model.Finally, a combination nomogram was constructed by incorporating the SVM score and clinical features.An independent group of 42 patients who were diagnosed from March 2016 to November 2017 was used to validate the prediction models.The model performances were evaluated on discrimination, calibration, and clinical utility.Results: The SVM model was constructed based on five selected image features.Significant differences were found between patients with LNM and non-LNM in SVM scores in both groups (the training group: 0.5466 (interquartile range (IQR), 0.4059-0.6985)vs. 0.3226 (IQR, 0.0527-0.4659),P<0.0001; the validation group: 0.5831 (IQR, 0.3641-0.8162)vs. 0.3101 (IQR, 0.1029-0.4661),P=0.0015).The combination nomogram based on the SVM score, the CA 19-9 level, and the MR-reported LNM factor showed better discrimination in separating patients with LNM and non-LNM, comparing to the SVM model alone (AUC: the training group: 0.842 vs. 0.788; the validation group: 0.870 vs. 0.787).Favorable clinical utility was observed using the decision curve analysis for the nomogram. Conclusion:The nomogram, incorporating the SVM score, CA 19-9 level and the MR-reported LNM factor, provided an individualized LN status evaluation and helped clinicians guide the surgical decisions.
Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study
Authors: Rob W van der Pluijm, Mallika Imwong, Nguyen Hoang Chau, Nhu Thi Hoa, Nguyen Thanh Thuy-Nhien, Ngo Viet Thanh, Podjanee Jittamala, Borimas Hanboonkunupakarn, Kitipumi Chutasmit, Chalermpon Saelow, Ratchadaporn Runjarern, Weerayuth Kaewmok, Rupam Tripura, Thomas J Peto, Sovann Yok, Seila Suon, Sokunthea Sreng, Sivanna Mao, Savuth Oun, Sovannary Yen, Chanaki Amaratunga, Dysoley Lek, Rekol Huy, Mehul Dhorda, Kesinee Chotivanich, Elizabeth A Ashley, Mavuto Mukaka, Naomi Waithira, Phaik Yeong Cheah, Richard J Maude, Roberto Amato, Richard D Pearson, Sónia Gonçalves, Christopher G Jacob, William L Hamilton, Rick M Fairhurst, Joel Tarning, Markus Winterberg, Dominic P Kwiatkowski, Sasithon Pukrittayakamee, Tran Tinh Hien, Nicholas PJ Day, Olivo Miotto, Nicholas J White, Arjen M Dondorp
Journal: The Lancet Infectious Diseases (2019)

The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015-18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year.
Cancer and heart disease: associations and relations
Authors: Rudolf A. de Boer, Wouter C. Meijers, Peter van der Meer, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2019)

Emerging evidence supports that cancer incidence is increased in patients with cardiovascular (CV) disease and heart failure (HF), and patients with HF frequently die from cancer. Recently, data have been generated showing that circulating factors in relation to HF promote tumour growth and development in murine models, providing proof that a causal relationship exists between both diseases. Several common pathophysiological mechanisms linking HF to cancer exist, and include inflammation, neuro‐hormonal activation, oxidative stress and a dysfunctional immune system. These shared mechanisms, in combination with risk factors, in concert may explain why patients with HF are prone to develop cancer. Investigating the new insights linking HF with cancer is rapidly becoming an exciting new field of research, and we herein review the most recent data. Besides insights in mechanisms, we call for clinical awareness, that is essential to optimize treatment strategies of patients having developed cancer with a history of HF. Finally, ongoing and future trials should strive for comprehensive phenotyping of both CV and cancer end points, to allow optimal usefulness of data, and to better describe and understand common characteristics of these two lethal diseases.
Abstract 5167: Rab27a promotes melanoma cell invasion and metastasis via the regulation of exosome secretion
Authors: DAJIANG GUO, Goldie Y. Lui, Danae M. Sharp, Siew Li Lai, Shweta Tikoo, Rain Kwan, Michelle van Geldermalsen, Jeff Holst, Nikolas K. Haass, Wolfgang Weninger, Kimberley A. Beaumont
Journal: Cancer Research (2018)

Abstract Introduction: The Rab GTPase family has been increasingly related to carcinogenesis and cancer biology during the past decade. In melanoma, Rab27a has been identified as a tumor dependency gene. Rab27a is thought to regulate exosome secretion in several cell types, however the exact role of Rab27a in melanoma biology and the underlying mechanisms are not well investigated. Experimental Procedures: To investigate the influence of Rab27a on melanoma biology and exosome secretion, Rab27a shRNA knockdown (KD) or CRISPR knockout (KO) was performed in human and murine melanoma cell lines. The effect of Rab27a loss on melanoma cell invasion and motility was analyzed by in vitro 3D spheroid invasion and live cell imaging. Rab27a function on melanoma metastasis was investigated using a mouse melanoma spontaneous metastasis model. Exosomes secreted by melanoma cell lines with/without Rab27a KD/KO were purified and characterized by electron microscopy, NanoSight analysis, BCA assay, western blotting and mass spectrometry. Results: Our results indicate that Rab27a loss in Rab27a high metastatic melanoma cell lines reduced 3D spheroid invasion and cell motility and Rab27a loss also reduced spontaneous melanoma metastasis in vivo. Rab27a KD invasion phenotype can be partially rescued by addition of exosomes from Rab27a replete cell conditioned media, but not exosomes derived from Rab27a KD cells. Loss of Rab27a does not alter the number of exosomes secreted from melanoma cells, but does alter exosome protein composition and morphology. Mass spectrometry analysis has shown that Rab27a replete cell secreted exosomes are more involved in regulating cell invasion and motility than the exosomes from Rab27a KD cells. Conclusion: In summary, Rab27a promotes the invasion and metastasis of a subset of melanoma cells via the regulation of pro-invasive exosomes, which indicates Rab27a as a potential therapeutic target for preventing melanoma progression. Citation Format: DAJIANG GUO, Goldie Y. Lui, Danae M. Sharp, Siew Li Lai, Shweta Tikoo, Rain Kwan, Michelle van Geldermalsen, Jeff Holst, Nikolas K. Haass, Wolfgang Weninger, Kimberley A. Beaumont. Rab27a promotes melanoma cell invasion and metastasis via the regulation of exosome secretion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5167.