bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure
Authors: Dinglas Victor D , Chessare Caroline M , Davis Wesley E , Parker Ann , Friedman Lisa Aronson , Colantuoni Elizabeth , Bingham Clifton O , Turnbull Alison E , Needham Dale M 
Published: July 2017

BackgroundThere is heterogeneity among the outcomes evaluated in studies of survivors of acute respiratory failure (ARF).AimTo evaluate the importance of specific outcome domains to acute respiratory distress syndrome (ARDS) survivors, their family members and clinical researchers.MethodsNineteen outcome domains were identified from the National Institutes of Health’s Patient Reported Outcomes Measurement Information System; WHO’s International Classification of Functioning, Disability, and Health; Society of Critical Care Medicine’s Post-Intensive Care Syndrome (PICS); as well as patient, clinician and researcher input. We surveyed ARDS survivors, family members and critical care researchers, 279 respondents in total, using a 5-point scale (strongly disagree, disagree, neutral, agree and strongly agree) to rate the importance of measuring each domain in studies of ARF survivors’ postdischarge outcomes.Measurements and main resultsAt least 80% of patients and family members supported (ie, rated ‘agree’ or ‘strongly agree’) that 15 of the 19 domains should be measured in all future studies. Among researchers, 6 of 19 domains were supported, with researchers less supportive for all domains, except survival (95% vs 72% support). Overall, four domains were supported by all groups: physical function, cognitive function, return to work or prior activities and mental health.ConclusionPatient, family and researcher groups supported inclusion of outcome domains that fit within the PICS framework. Patients and family members also supported many additional domains, emphasising the importance of including patients/family, along with researchers, in consensus processes to select core outcome domains for future research studies.
Assessment of short reports using a human rights-based approach to tobacco control to the Commitee on Economics, Cultural and Social Rights
Authors: Dresler Carolyn , Henry Kirsten , Loftus John , Lando Harry 
Published: July 2017

BackgroundThe health impact of tobacco use remains a major global public health concern and a human rights issue. The Human Rights and Tobacco Control Network (HRTCN) was established to increase the visibility of tobacco as a human rights issue. HRTCN submitted short reports to the UN Committee on Economic Social and Cultural Rights evaluating individual nations' tobacco control policies and offering recommendations.MethodsHRTCN reviewed Concluding Observations documents for nations for which the HRTCN submitted reports. If tobacco was mentioned in the Concluding Observations through acknowledging the Framework Convention on Tobacco Control ratification, policy changes or discussing tobacco in the recommendations, this was scored as a positive finding. HRTCN also reviewed Concluding Observations for nations for which HRTCN did not submit reports as a comparison.ResultsThirty-eight HRTCN reports were submitted and tobacco was mentioned in Concluding Observations for 11 nations for a rate of 28.9%. In a comparison set of Concluding Observations (n=59), 7% had comments or recommendations relative to tobacco.ConclusionsThis was not a controlled study and the 28.9% ’success rate' for impacting the Concluding Observations, although encouraging, is less than optimal—and leaves room for improvement. The higher rate of tobacco mentions for the cases where the HRTCN short reports were submitted provides preliminary indications that the short reports may have potential to increase the state focus on tobacco control. Future work will seek to improve the design and scope of the reports, and the specificity of the background information and recommendations offered.
Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation of Lats1
Authors: Si Yuan , Ji Xinyan , Cao Xiaolei , Dai Xiaoming , Xu Lingyi , Zhao Hongxia , Guo Xiaocan , Yan Huan , Zhang Haitao , Zhu Chu , Zhou Qi , Tang Mei , Xia Zongping , Li Li , Cong Yu-Sheng , Ye Sheng , Liang Tingbo , Feng Xin-Hua , Zhao Bin 
Published: July 2017

Abstract
The Hippo pathway regulates cell proliferation, apoptosis, and stem cell self-renewal, and its inactivation in animal models causes organ enlargement followed by tumorigenesis. Hippo pathway deregulation occurs in many human cancers, but the underlying mechanisms are not fully understood. Here, we report tyrosine phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism underlying its regulation by cell adhesion. A tyrosine kinase library screen identified Src as the kinase to directly phosphorylate LATS1 on multiple residues, causing attenuated Mob kinase activator binding and structural alteration of the substrate-binding pocket in the kinase domain. Cell matrix adhesion activated the Hippo pathway effector transcription coactivator YAP partially through Src-mediated phosphorylation and inhibition of LATS1. Aberrant Src activation abolished the tumor suppressor activity of LATS1 and induced tumorigenesis in a YAP-dependent manner. Protein levels of Src in human breast cancer tissues correlated with accumulation of active YAP dephosphorylated on the LATS1 target site. These findings reveal tyrosine phosphorylation of LATS1 by Src as a novel mechanism of Hippo pathway regulation by cell adhesion and suggest Src activation as an underlying reason for YAP deregulation in tumorigenesis. Cancer Res; 77(18); 4868–80. ©2017 AACR.
Underreporting of Research Biopsies from Clinical Trials in Oncology
Authors: Parseghian Christine M. , Raghav Kanwal , Wolff Robert A. , Ensor Joe , Yao James , Ellis Lee M. , Tam Alda L. , Overman Michael J. 
Published: July 2017

Abstract
Purpose: Research biopsies are frequently incorporated within clinical trials in oncology and are often a mandatory requirement for trial enrollment. However, limited information is available regarding the extent and completeness of research biopsy reporting.
Experimental Design: We identified a cohort of therapeutic clinical trials where research biopsies were performed between January 2005 and October 2010 from an IR database at our institution. Clinical trial protocols were compared with the highest level of corresponding publication as a manuscript or registry report.
Results: A total of 866 research biopsies were performed across 46 clinical trials, with a median of 8 patients biopsied/trial and 19 biopsies collected/trial. After a median follow-up time of 4.3 years from trial completion, 36 of 46 trials (78%) reported trial results: published manuscripts (n = 35), or registry report (n = 1). A total of 635 conducted biopsies were reported in 18 of the 46 trials (39%). Six (33%) of these 18 trials underreported the number of biopsies performed. Of 33 trials with mandatory research biopsies, 13 (39%) trials reported on these biopsies. Biopsy complications occurred in 8 trials [n = 39 patients, 6 grade 3/4 adverse events (AE)] but only 1 trial reported these. Factors associated with biopsy reporting included a larger number of biopsies (P ≤ 0.001) and serial biopsies (P &lt; 0.001). Twelve of 16 (75%) trials with &gt;12 biopsies performed reported on these biopsies compared with only 20% (6/30) that performed ≤12 biopsies.
Conclusions: Despite ethical obligations to report research biopsies, the majority (61%) of trials do not report results from research biopsies. Complications are rarely reported in these studies. Improved reporting of results and AEs from research biopsies is needed. Clin Cancer Res; 23(21); 6450–7. ©2017 AACR.
Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties
Authors: Pagano Paul C. , Tran Linh M. , Bendris Nawal , O'Byrne Sean , Tse Henry T. , Sharma Shivani , Hoech Jonathan W. , Park Stacy J. , Liclican Elvira L. , Jing Zhe , Li Rui , Krysan Kostyantyn , Paul Manash K. , Fontebasso Yari , Larsen Jill E. , Hakimi Shaina , Seki Atsuko , Fishbein Michael C. , Gimzewski James K. , Carlo Dino Di , Minna John D. , Walser Tonya C. , Dubinett Steven M. 
Published: July 2017

Abstract
Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8 weeks after selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short-term assays and enhanced outgrowth of premalignant lesions in longer-term assays, thus overcoming important aspects of “metastatic inefficiency.” Overall, our findings indicate that among immortalized premalignant airway epithelial cell lines, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior. Cancer Prev Res; 10(9); 514–24. ©2017 AACR.
See related editorial by Hynds and Janes, p. 491
DARC extracellular domain remodeling in maturating reticulocytes explains Plasmodium vivax tropism
Authors: Ovchynnikova Elina , Aglialoro Francesca , Bentlage Arthur E. H. , Vidarsson Gestur , Salinas Nichole D. , von Lindern Marieke , Tolia Niraj H. , van den Akker Emile 
Published: July 2017

Key PointsP vivax Duffy binding protein associates exclusively with a small population of immature reticulocytes. Increased DARC-DBP binding site accessibility in immature reticulocytes compared with erythrocytes is a key to infection by P vivax.
Frontline Science: Tim-3-mediated dysfunctional engulfment of apoptotic cells in SLE
Authors: Zhao Di , Guo Min , Liu Bing , Lin Qinghai , Xie Tingting , Zhang Qianqian , Jia Xiaoxia , Shu Qiang , Liang Xiaohong , Gao Lifen , Ma Chunhong 
Published: July 2017

Abstract
T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction. Alanine at 111, locating around the FG-CC′ loop of hTim-3, was necessary for its engulfment of apoptotic cells. In accordance, Tim-3 on CD14+ cells negatively correlated with the percentage of peripheral apoptotic cells in control subjects. However, although Tim-3 was significantly increased on CD14+ cells in SLE patients, peripheral apoptotic cells remained much higher than those in control subjects. Tim-3 on CD14+ cells showed positive correlation with percentage of apoptotic cells and level of dsDNA, indicating the involvement of Tim-3 in SLE. Accordingly, soluble Tim-3 (sTim-3) was significantly increased in plasma of SLE patients, which might contribute to higher expression of a disintegrin and metalloproteinase (ADAM)-10. Pretreatment with both plasma from SLE patients and recombinant sTim-3 greatly inhibited hTim-3-initiated phagocytosis of apoptotic cells. Furthermore, anti-tim-3 antibody depletion of plasma from SLE patients reversed the decreased phagocytosis of apoptotic cells. Collectively, our data suggest that sTim-3 might play inhibitory roles in impaired Tim-3-mediated clearance of apoptotic cells in SLE.
Elastase inhibitors as potential therapies for ELANE-associated neutropenia
Authors: Makaryan Vahagn , Kelley Merideth L , Fletcher Breanna , Bolyard Audrey Anna , Aprikyan A Andrew , Dale David C 
Published: July 2017

Abstract
Mutations in ELANE, the gene for neutrophil elastase (NE), a protease expressed early in neutrophil development, are the most frequent cause of cyclic (CyN) and severe congenital neutropenia (SCN). We hypothesized that inhibitors of NE, acting either by directly inhibiting enzymatic activity or as chaperones for the mutant protein, might be effective as therapy for CyN and SCN. We investigated β-lactam–based inhibitors of human NE (Merck Research Laboratories, Kenilworth, NJ, USA), focusing on 1 inhibitor called MK0339, a potent, orally absorbed agent that had been tested in clinical trials and shown to have a favorable safety profile. Because fresh, primary bone marrow cells are rarely available in sufficient quantities for research studies, we used 3 cellular models: patient-derived, induced pluripotent stem cells (iPSCs); HL60 cells transiently expressing mutant NE; and HL60 cells with regulated expression of the mutant enzyme. In all 3 models, the cells expressing the mutant enzyme had reduced survival as measured with annexin V and FACS. Coincubation with the inhibitors, particularly MK0339, promoted cell survival and increased formation of mature neutrophils. These studies suggest that cell-permeable inhibitors of neutrophil elastase show promise as novel therapies for ELANE-associated neutropenia.
The Evaluation of a Noninvasive Respiratory Volume Monitor in Pediatric Patients Undergoing General Anesthesia
Authors: Gomez-Morad Andrea D. , Cravero Joseph P. , Harvey Brian C. , Bernier Rachel , Halpin Erin , Walsh Brian , Nasr Viviane G. 
Published: July 2017

BACKGROUND:Pediatric patients following surgery are at risk for respiratory compromise such as hypoventilation and hypoxemia depending on their age, comorbidities, and type of surgery. Quantitative measurement of ventilation in nonintubated infants/children is a difficult and inexact undertaking. Current respiratory assessment in nonintubated patients relies on oximetry data, respiratory rate (RR) monitors, and subjective clinical assessment, but there is no objective measure of respiratory parameters that could be utilized to predict early respiratory compromise. New advances in technology and digital signal processing have led to the development of an impedance-based respiratory volume monitor (RVM, ExSpiron, Respiratory Motion, Inc, Waltham, MA). The RVM has been shown to provide accurate real-time, continuous, noninvasive measurements of tidal volume (TV), minute ventilation (MV), and RR in adult patients.In this prospective observational study, our primary aim was to determine whether the RVM accurately measures TV, RR, and MV in pediatric patients.METHODS:A total of 72 pediatric patients (27 females, 45 males), ASA I to III, undergoing general anesthesia with endotracheal intubation were enrolled. After endotracheal intubation, continuous data of MV, TV, and RR were recorded from the RVM and an in-line monitoring spirometer (NM3 monitor, Phillips Healthcare). RVM and NM3 measurements of MV, TV, and RR were compared during a 10-minute period prior to the incision (“Presurgery”) and a 10-minute period after the end of surgery (“Postsurgery”). Relative errors were calculated over 1-minute segment within each 10-minute period. Bias, precision, and accuracy were calculated using Bland-Altman analyses and paired-difference equivalence tests were performed.RESULTS:Combined across the Presurgery and Postsurgery periods, the RVM’s mean measurement bias (RVM − NM3 measurement) for MV was −3.8% (95% limits of agreement) (±1.96 SD): (−19.9% to 12.2%), for TV it was −4.9 (−21.0% to 11.3%), and for RR it was 1.1% (−4.1% to 6.2%). The mean measurement accuracies for MV, TV, and RR were 11.9%, 12.0%, and 4.2% (0.6 breaths/min), respectively. Note that lower accuracy numbers correspond to more accurate RVM measurements. The equivalence tests rejected the null hypothesis that the RVM and NM3 have different mean values and conclude with 90% power that the measurements of MV, TV, and RR from the RVM and NM3 are equivalent within ±10%.CONCLUSIONS:Our data indicate acceptable agreement between RVM and NM3 measurements in pediatric mechanically-ventilated patients. Future studies assessing the capability of the RVM to detect respiratory compromise in other clinical settings are needed.
Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter Perioperative Outcomes Group
Authors: Berman Mitchell F. , Iyer Nikhil , Freudzon Leon , Wang Shuang , Freundlich Robert E. , Housey Michelle , Kheterpal Sachin 
Published: July 2017

BACKGROUND:
Continuous medication infusions are commonly used during surgical procedures. Alarm settings for infusion pumps are considered important for patient safety, but limits are not created in a standardized manner from actual usage data. We estimated 90th and 95th percentile infusion rates from a national database for potential use as upper limit alarm settings.

METHODS:
We extracted infusion rate data from 17 major hospitals using intraoperative records provided by Multicenter Perioperative Outcomes Group for adult surgery between 2008 and 2014. Seven infusions were selected for study: propofol, remifentanil, dexmedetomidine, norepinephrine, phenylephrine, nitroglycerin, and esmolol. Each dosage entry for an infusion during a procedure was included. We estimated the 50th, 90th, and 95th percentile levels for each infusion across institutions, and performed quantile regression to examine factors that might affect the percentiles rates, such as use in general anesthesia versus sedation.

RESULTS:
The median 90th and 95th percentile infusion rates (with interquartile range) for propofol were 150 (140–150) and 170 (150–200) μg/kg/min. Quantile regression demonstrated higher 90th and 95th percentile rates during sedation for gastrointestinal endoscopy than for all surgical procedures performed under general anesthesia. For selected vasoactive medications, the corresponding median 90th and 95th percentile rates (with interquartile range) were norepinephrine 14.0 (9.8–18.1) and 18.3 (12.6–23.9) μg/min, and phenylephrine 60 (55–80) and 80 (75–100) μg/min.

CONCLUSIONS:
Alarm settings based on infusion rate percentile limits would be triggered at predictable rates; ie, the 95th percentile would be exceeded and an alarm sounded during 1 in 20 infusion rate entries. As a result, institutions could establish pump alarm settings consistent with desired alarm frequency using their own or externally validated usage data. Further study will be needed to determine the optimal percentile for infusion alarm settings.
Addition of Nasal Cannula Can Either Impair or Enhance Preoxygenation With a Bag Valve Mask: A Randomized Crossover Design Study Comparing Oxygen Flow Rates
Authors: McQuade David , Miller Matthew R. , Hayes-Bradley Clare 
Published: July 2017

BACKGROUND:
A critical safety component of emergency anesthesia is the avoidance of hypoxemia during the apneic phase of a rapid sequence intubation. Preoxygenation with a bag valve mask (BVM) or anesthetic circuit may be improved with supplemental oxygen by nasal cannula (NC) if there is a mask leak. In addition, NC is recommended for apneic oxygenation after induction and may be placed before preoxygenation. However, the optimum NC flow rate for preoxygenation or whether the presence of NC alone creates a mask leak remains unclear.

METHODS:
We performed a randomized crossover study on healthy volunteers comparing BVM alone and BVM with NC flow rates of 0 (NC-0), 5 (NC-5), 10 (NC-10), and 15 (NC-15) liters per minute (lpm). Our primary outcome was end-tidal oxygen (ETo
2) after 3-minute preoxygenation.

RESULTS:
There was no difference in ETo
2 between NC-15, NC-10, or BVM-only at 3 minutes. NC-0 and NC-5 recorded significantly lower ETo
2 at all times compared with NC-15, NC-10, or BVM-only (least difference NC-5, −7% [95% confidence interval {CI}, −4% to −10%), NC-0, 16% [95% CI, 13%–19%]). There was a difference in ETo
2 between NC-15 and BVM-only at 1 minute (7%; 95% CI, 5%–9%), but not at 2 or 3 minutes. There was no difference in ETo
2 between NC-10 and NC-15.

CONCLUSIONS:
Our study found that NC at 0 and 5 lpm with a BVM is deleterious to preoxygenation and should be avoided. In addition, a lack of difference between NC-10 and BVM-only demonstrates that NC at flows of at least 10 lpm should not impair the preoxygenation process. While NC-15 may offer a benefit by reaching maximal ETo
2 at 1 minute, this would need to be balanced against patient comfort.