tbuckley/cabot-search huggingface dataset:
Breathing Rate Estimation From the Electrocardiogram and Photoplethysmogram: A Review
Authors: Peter H. Charlton, Drew A. Birrenkott, Timothy Bonnici, Marco A. F. Pimentel, Alistair E. W. Johnson, Jordi Alastruey, Lionel Tarassenko, Peter J. Watkinson, Richard Beale, David A. Clifton
Journal: IEEE Reviews in Biomedical Engineering (2017)

Breathing rate (BR) is a key physiological parameter used in a range of clinical settings. Despite its diagnostic and prognostic value, it is still widely measured by counting breaths manually. A plethora of algorithms have been proposed to estimate BR from the electrocardiogram (ECG) and pulse oximetry (photoplethysmogram, PPG) signals. These BR algorithms provide opportunity for automated, electronic, and unobtrusive measurement of BR in both healthcare and fitness monitoring. This paper presents a review of the literature on BR estimation from the ECG and PPG. First, the structure of BR algorithms and the mathematical techniques used at each stage are described. Second, the experimental methodologies that have been used to assess the performance of BR algorithms are reviewed, and a methodological framework for the assessment of BR algorithms is presented. Third, we outline the most pressing directions for future research, including the steps required to use BR algorithms in wearable sensors, remote video monitoring, and clinical practice.
Meis2 as a critical player in MN1-induced leukemia
Authors: C K Lai, G L Norddahl, T Maetzig, P Rosten, T Lohr, L Sanchez Milde, N von Krosigk, T R Docking, M Heuser, A Karsan, R K Humphries
Journal: Blood Cancer Journal (2017)

Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets. Using gene expression profiling of these subsets combined with previously published comparisons of full-length MN1 and mutants with varying leukemogenic activity, we identified candidate genes critical to leukemia. Functional analysis identified Hlf and Hoxa9 as critical to MN1 in vitro proliferation, self-renewal and impaired myeloid differentiation. Although critical to transformation, Meis1 knockdown had little impact on these properties in vitro. However, we identified Meis2 as critical to MN1-induced leukemia, with essential roles in proliferation, self-renewal, impairment of differentiation and disease progression in vitro and in vivo. Here, we provide evidence of phenotypic and functional hierarchy in MN1-induced leukemic cells, characterise contributions of Hlf, Hoxa9 and Meis1 to in vitro leukemic properties, and reveal Meis2 as a novel player in MN1-induced leukemogenesis.
In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering
Authors: Shengjie Huang, Chunfen Wang, Jingwei Xu, Lie Ma, Changyou Gao
Journal: Bioactive Materials (2017)

Hyaluronic acid (HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA) in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A) to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G') were higher than the loss moduli (G″) over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.
Tumor Heterogeneity Predicts Metastatic Potential in Colorectal Cancer
Authors: Je-Gun Joung, Bo Young Oh, Hye Kyung Hong, Hisham Al-Khalidi, Faisal Al-Alem, Hae-Ock Lee, Joon Seol Bae, Jinho Kim, Hong-Ui Cha, Maram Alotaibi, Yong Beom Cho, Mazen Hassanain, Woong-Yang Park, Woo Yong Lee
Journal: Clinical Cancer Research (2017)

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis.Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated.Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors.Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209-16. ©2017 AACR.
Experimental Observations on Achlorhydria of Gastric Cancer&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Alexander Brunschwig, Robert L. Schmitz, Richard Rasmussen
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Experimental Observations on Achlorhydria of Gastric Cancer Get access Alexander Brunschwig, Alexander Brunschwig professor of surgery Department of Surgery and Medicine, University of Chicago Clinics Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert L. Schmitz, Robert L. Schmitz Department of Surgery and Medicine, University of Chicago Clinics Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Rasmussen Richard Rasmussen research assistants Department of Surgery and Medicine, University of Chicago Clinics Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 4, February 1941, Pages 481–488, https://doi.org/10.1093/jnci/1.4.481 Published: 01 February 1941
Concurrent bariatric operations and association with perioperative outcomes: registry based cohort study
Authors: Jason B Liu, Kristen A Ban, Julia R Berian, Matthew M Hutter, Kristopher M Huffman, Yaoming Liu, David B Hoyt, Bruce L Hall, Clifford Y Ko
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To determine whether perioperative outcomes differ between patients undergoing concurrent compared with non-concurrent bariatric operations in the USA. <b>Design</b>&nbsp;Retrospective, propensity score matched cohort study. <b>Setting</b>&nbsp;Hospitals in the US accredited by the American College of Surgeons' metabolic and bariatric surgery accreditation and quality improvement program. <b>Participants</b>&nbsp;513 167 patients undergoing bariatric operations between 1 January 2014 and 31 December 2016. <b>Main outcome measures</b>&nbsp;The primary outcome measure was a composite of 30 day death, morbidity, readmission, reoperation, anastomotic or staple line leak, and bleeding events. Operative duration and lengths of stay were also assessed. Operations were defined as concurrent if they overlapped by 60 or more minutes or in their entirety. <b>Results</b>&nbsp;In this study of 513 167 operations, 739 (29.5%) surgeons at 483 (57.8%) hospitals performed 6087 (1.2%) concurrent operations. The most frequently performed concurrent bariatric operations were sleeve gastrectomy (n=3250, 53.4%) and Roux-en-Y gastric bypass (n=1601, 26.3%). Concurrent operations were more often performed at large academic medical centers with higher operative volumes and numbers of trainees and by higher volume surgeons. Compared with non-concurrent operations, concurrent operations lasted a median of 34 minutes longer (P&lt;0.001) and resulted in 0.3 days longer average length of stay (P&lt;0.001). Perioperative adverse events were not observed to more likely occur in concurrent compared with non-concurrent operations (7.5% <i>v</i> 7.4%; relative risk 1.02, 95% confidence interval 0.90 to 1.15; P=0.84). <b>Conclusions</b>&nbsp;Concurrent bariatric operations occurred infrequently, but when they did, there was no observable increased risk for adverse perioperative outcomes compared with non-concurrent operations. These results, however, do not argue against improved and more meaningful disclosure of concurrent surgery practices.
Contribution of Opioid-Involved Poisoning to the Change in Life Expectancy in the United States, 2000-2015
Authors: Deborah Dowell, Elizabeth Arias, Kenneth Kochanek, Robert Anderson, Gery P. Guy, Jan L. Losby, Grant Baldwin
Journal: JAMA (2017)

This study uses US National Vital Statistics mortality data to assess change in US life expectancy from 2000 to 2015 attributable to opioid-involved poisonings.
The effects of major burn related pathophysiological changes on the pharmacokinetics and pharmacodynamics of drug use: An appraisal utilizing antibiotics
Authors: Andrew A. Udy, Jason A. Roberts, Jeffrey Lipman, Stijn Blot
Journal: Advanced Drug Delivery Reviews (2017)

Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.
Introduction to Dr. Castle
Authors: C. C. Little
Journal: JNCI Journal of the National Cancer Institute (1954)

Introduction to Dr. Castle Get access C. C. Little C. C. Little Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 593–594, https://doi.org/10.1093/jnci/15.3.593 Published: 01 December 1954
Overall survival (OS) in METEOR, a randomized phase 3 trial of cabozantinib (Cabo) versus everolimus (Eve) in patients (pts) with advanced renal cell carcinoma (RCC).
Authors: Toni K. Choueiri, Thomas Powles, Bernard J. Escudier, Nizar M. Tannir, Paul Mainwaring, Brian I. Rini, Hans J. Hammers, Frede Donskov, Bruce J. Roth, Katriina Peltola, Jae-Lyun Lee, Daniel Yick Chin Heng, Manuela Schmidinger, Dana T. Aftab, Colin Hessel, Christian Scheffold, Gisela Schwab, Sumanta K. Pal, Thomas E. Hutson, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

4506 Background: Cabo is an inhibitor of tyrosine kinases including MET, VEGF receptors, and AXL, which are oncogenic drivers in RCC. In the METEOR trial (NCT01865747), Cabo showed a statistically significant improvement in progression-free survival (PFS, the primary endpoint) compared with Eve in pts with previously treated RCC (median of 7.4 vs 3.8 mo; HR=0.58, 95% CI 0.45–0.75; P <0.001) and improved the objective response rate (Choueiri NEJM 2015). The safety profile of Cabo was acceptable and similar to other VEGFR TKIs in this population. Interim analysis of the secondary endpoint of OS with a minimum follow-up of 6 mo revealed a favorable trend for Cabo vs Eve (HR=0.67, 95% CI 0.51–0.89; P=0.005). Here we present the final OS results, arising from a second interim analysis. Methods: Pts with measurable clear cell RCC, KPS ≥70, and ≥1 prior VEGFR TKI were randomized 1:1 to Cabo (60 mg qd) or Eve (10 mg qd) stratified by MSKCC risk group and number of prior VEGFR TKIs (1 or ≥2). The study was designed to detect a HR for OS of 0.75 (80% power, 2-sided α=0.04). Results: From Aug 2013–Nov 2014, 658 pts were randomized. As of 31 Dec 2015, with a minimum follow-up of 13 mo, 320 deaths were recorded (140 for Cabo and 180 for Eve). 74 (22%) pts remained on therapy in the Cabo arm vs 25 (8%) pts in the Eve arm. The secondary endpoint of improved OS for Cabo-treated pts was met. The median OS was 21.4 mo for Cabo vs 16.5 mo for Eve, with a 33% reduction in the rate of death (HR 0.67, 95% CI 0.53 to 0.83, P=0.0003). Landmark estimates of survival at 18 mo were 58% in the Cabo arm vs 47% of the Eve arm. OS benefit with Cabo was consistently observed across all prespecified subgroups including MSKCC risk group, number and type of prior VEGFR TKIs, prior anti-PD-1/PD-L1 treatment, location and extent of tumor metastases, and tumor MET expression level. SAEs were consistent with the safety profile previously reported. Conclusions: Cabo is the only agent to demonstrate a significant benefit in OS, PFS, and ORR in a Phase 3 trial in previously treated pts with advanced RCC. Cabo is an important new treatment option for these patients. Clinical trial information: NCT01865747.
Pneumothorax management: time to improve the evidence base
Authors: Nick A Maskell
Journal: Thorax (2017)

Pneumothorax remains a common reason for medical admission to hospital with a UK annual incidence of 16.7 cases per 100 000 for men and 5.8 cases per 100 000 for women.1 This equates to around 8000 admissions a year for pneumothorax accounting for 50 000 bed days given an average length of stay of just under 1 week.2 Despite its frequency and the existence of established guidelines,3 4 there is still wide variation in pneumothorax management, which is likely to be driven by the paucity of good quality evidence in this field.

Pneumothorax has traditionally been divided into primary spontaneous pneumothorax (PSP), with no known underlying lung disease and secondary spontaneous pneumothorax (SSP), with existing lung disease. This is likely to be too simplistic an approach. Smoking cessation has been shown to significantly reduce the risk of recurrence in PSP and this together with the presence of decreased lung density/early emphysematous change seen on CT imaging in the lung apexes of current smokers presenting with PSP suggests many cases of PSP having underlying lung abnormalities.5 6 As current guidelines triage treatment according to whether they are primary or secondary pneumothorax, a better definition may lead to better algorithms and patient treatments.3 

So why is the existing evidence so poor? Perhaps because it is so difficult to recruit to good quality randomised controlled trials (RCTs) in this area. The reasons for …
Phase I study of weekly treatment with paclitaxel injection concentrate for nanodispersion (PICN), a novel solvent and protein-free formulation of paclitaxel.
Authors: Minish Mahendra Jain, Chetan Dilip Deshmukh, Shailesh Arjun Bondarde, Niraj Bhatt, Vijay Shinde, Shravanti Bhowmik, Ganesh Divekar
Journal: Journal of Clinical Oncology (2013)

3039 Background: PICN is a novel solvent and protein-free 100-110 nm particle formulation of paclitaxel stabilized with polymer and lipid using Nanotecton Technology. Paclitaxel has shown superior safety and efficacy profile when administered on a weekly schedule. We studied safety, tolerability, and pharmacokinetics (PK) of PICN using a weekly schedule in patients with advanced solid malignancies. Methods: Patients aged18-65 years with advanced solid malignancies, ECOG performance status ≤ 2, estimated survival ≥ 12 weeks, and adequate organ function were enrolled. A standard phase I, 3+3 dose escalation design to determine the maximum tolerated dose (MTD) of PICN administered on a weekly schedule (three consecutive weeks, one week recovery) was employed. PICN dose was escalated at pre-determined fixed dose levels of 80, 100, 125, 150, 175, and 200 mg/m 2 . PICN was administered as a 30 min infusion without any premedication for hypersensitivity. Results: Twenty-one patients treated with PICN had a mean age of 52.1 yrs (range 35-67); 20 were female and entered with metastatic breast cancer (MBC; n=15), cervical cancer (n=3), skin cancer (n=2). One male had oral cancer. Doses studied were 80 (n=3), 100 (n=3), 125 (n=3), 150 (n=3), 175 (n=6), and 200 (n=3) mg/m 2 . Despite the lack of dexamethasone premedication, no patient receiving PICN reported hypersensitivity reaction. Two DLTs (neutropenia and febrile neutropenia; both grade 3) were reported at PICN 200 mg/m 2 . PICN PK (AUC 0-24, AUC 0-∞, and C max ) increased in a dose proportionate manner from 80 to 200 mg/m 2 . Grade 3 or worse related AEs were: neutropenia, leucopenia, peripheral neuropathy, febrile neutropenia, anemia, thrombocytopenia, fatigue, syncope, hypotension and maculopapular rash. Partial responses were observed in MBC (100, 125, 150, 175, and 200 mg/m 2 ) and cervical cancer (80 mg/m 2 ). Conclusions: PICN on thrice monthly schedule was tolerable in the dose range evaluated. Two DTLs were reported: neutropenia and febrile neutropenia (both grade 3). Anti-tumor activity was observed in MBC and cervical cancer. Final trial data for PICN PK, safety, and efficacy will be presented at the conference. Clinical trial information: CTRI/2011/11/002124.
Mutation-Driven Parallel Evolution during Viral Adaptation
Authors: Andrew M Sackman, Lindsey W McGee, Anneliese J Morrison, Jessica Pierce, Jeremy Anisman, Hunter Hamilton, Stephanie Sanderbeck, Cayla Newman, Darin R Rokyta
Journal: Molecular Biology and Evolution (2017)

Convergent evolution has been demonstrated across all levels of biological organization, from parallel nucleotide substitutions to convergent evolution of complex phenotypes, but whether instances of convergence are the result of selection repeatedly finding the same optimal solution to a recurring problem or are the product of mutational biases remains unsettled. We generated 20 replicate lineages allowed to fix a single mutation from each of four bacteriophage genotypes under identical selective regimes to test for parallel changes within and across genotypes at the levels of mutational effect distributions and gene, protein, amino acid, and nucleotide changes. All four genotypes shared a distribution of beneficial mutational effects best approximated by a distribution with a finite upper bound. Parallel adaptation was high at the protein, gene, amino acid, and nucleotide levels, both within and among phage genotypes, with the most common first-step mutation in each background fixing on an average in 7 of 20 replicates and half of the substitutions in two of the four genotypes occurring at shared sites. Remarkably, the mutation of largest beneficial effect that fixed for each genotype was never the most common, as would be expected if parallelism were driven by selection. In fact, the mutation of smallest benefit for each genotype fixed in a total of 7 of 80 lineages, equally as often as the mutation of largest benefit, leading us to conclude that adaptation was largely mutation-driven, such that mutational biases led to frequent parallel fixation of mutations of suboptimal effect.
Propranolol for Off-label Treatment of Patients With Melanoma
Authors: Vincenzo De Giorgi, Marta Grazzini, Silvia Benemei, Niccolò Marchionni, Edoardo Botteri, Elisabetta Pennacchioli, Pierangelo Geppetti, Sara Gandini
Journal: JAMA Oncology (2017)

Preclinical and retrospective studies showed that β-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenaline-dependent responses.To study the clinical effectiveness of β-blocker therapy in patients with melanoma and to determine whether propranolol improves progression-free survival in patients with melanoma.We conducted a prospective study in patients treated for melanoma in our center with propranolol for off-label use. Patients with histologically confirmed stage IB to IIIA cutaneous melanoma and no evidence of metastasis were eligible for the study. At the time of diagnosis, they were asked to take propranolol (80 mg daily) as an off-label adjuvant treatment. If they accepted the treatment, they were considered part of the propranolol cohort (PROP). If they refused treatment but agreed to participate in the study control group, they were considered part of the nonpropranolol cohort (No-PROP).The primary outcome was progression-free survival. Disease progression was assessed by evaluating the presence of lymphatic, in-transit, or visceral metastases, and the cause of death was recorded.Among the 53 patients (median [interquartile range] age 63 [48-75] years; 33 men) included in the study, 19 were eligible for the PROP cohort. Thirty-four patients otherwise eligible but unwilling to take propranolol were enrolled in the No-PROP cohort. The 2 cohorts were comparable in terms of demographic characteristics and primary prognostic factors at baseline. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users (hazard ratio, 0.18; 95% CI, 0.04-0.89; P = .03).In the absence of randomized, double-blind, placebo-controlled clinical trials, this study is the first off-label study of which we are aware of propranolol for melanoma treatment. These results confirm recent observation that β-blockers protect patients with thick cutaneous melanoma from disease recurrence. This study is in accordance with the present policy of "drug repurposing" in oncology. Repurposing the vast arsenal of approved drugs with a nononcology primary purpose may prove an attractive and inexpensive strategy for offering more effective treatment options to patients with cancer.