bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Tailored Feedback Improves Accuracy of Delirium Documentation in the Burn ICU: Results of a Performance Improvement Initiative
Authors: Gloger Amy N , Nakonezny Paul A , Phelan Herb A
Published: August 2019

One of the most widely used tools for delirium assessment in burn intensive care units is the Confusion Assessment Method for the Intensive Care Unit delirium assessment tool. However, some nurses struggle with inaccurate delirium documentation. This performance improvement project was undertaken to assess the impact that routine chart audits with tailored feedback would have on documentation accuracy. An a priori goal of at least 90% documentation accuracy was set by burn leadership at our academic, American Burn Association-verified burn center. For the precorrectional feedback time period, nursing delirium documentation was reviewed for accuracy by the nurse educator. In the postcorrectional feedback time period, an intervention was started, in which the educator sent tailored feedback to nurses with inaccurate delirium documentation. A Poisson regression with robust standard errors was used to compare the proportions of correct delirium documentation for the precorrectional feedback and postcorrectional feedback time periods. The overall rates of correct delirium documentation in the precorrectional feedback time period were 49.15% (SD = 31.86), 95% CI: 36.43 to 66.31. A significant increase was seen in the rates of correct delirium documentation for the postcorrectional feedback time period (91.47% [SD = 8.28], 95% CI: 87.45 to 95.67), P = .0001. In the 4 months prior to starting corrective feedback, zero out of five (0%) audits reached the 90% goal of accurate delirium documentation. In the 8 months in which corrective feedback was being given, 9 out of 15 (60%) audits reached the compliance goal set by leadership. Using corrective feedback improves the accuracy of nursing delirium documentation.
Bad Mothers and Dirty Lousers: Representing Abortionists in Postindependence Ireland
Authors: Delay Cara , Liger Annika
Published: August 2019

This article investigates how the criminal courts and popular press depicted abortionists across key decades of political, economic, and cultural transformations in postindependence Ireland (1922–1950). It demonstrates how and why the legal system and the media highlighted those abortion-related crimes in which bad mothers, ambitious parvenus, and ethnic “others” subverted society, religion, motherhood, and, in Ireland’s case, national values. At stake in depictions of abortionists was not only morality and criminality but also Irishness itself. Courts and newspapers presented abortion defendants as “others” in terms of gender, sexuality, class, race, and religion. Doing so branded abortionists as dangerous outsiders in, and even traitors to, a fragile Irish nation still working to define itself.
Kinematics with Gaia DR2: the force of a dwarf
Authors: Carrillo I , Minchev I , Steinmetz M , Monari G , Laporte C F P , Anders F , Queiroz A B A , Chiappini C , Khalatyan A , Martig M , McMillan P J , Santiago B X , Youakim K
Published: August 2019

We use Gaia DR2 astrometric and line-of-sight velocity information combined with two sets of distances obtained with a Bayesian inference method to study the 3D velocity distribution in the Milky Way disc. We search for variations in all Galactocentric cylindrical velocity components (Vϕ, VR, and Vz) with Galactic radius, azimuth, and distance from the disc mid-plane. We confirm recent work showing that bulk vertical motions in the R–z plane are consistent with a combination of breathing and bending modes. In the x–y plane, we show that, although the amplitudes change, the structure produced by these modes is mostly invariant as a function of distance from the plane. Comparing to two different Galactic disc models, we demonstrate that the observed patterns can drastically change in short time intervals, showing the complexity of understanding the origin of vertical perturbations. A strong radial VR gradient was identified in the inner disc, transitioning smoothly from 16 km s−1 kpc−1 at an azimuth of 30° < ϕ < 45° ahead of the Sun-Galactic centre line to −16 km s−1 kpc−1 at an azimuth of −45° < ϕ < −30° lagging the solar azimuth. We use a simulation with no significant recent mergers to show that exactly the opposite trend is expected from a barred potential, but overestimated distances can flip this trend to match the data. Alternatively, using an N-body simulation of the Sagittarius dwarf–Milky Way interaction, we demonstrate that a major recent perturbation is necessary to reproduce the observations. Such an impact may have strongly perturbed the existing bar or even triggered its formation in the last 1–2 Gyr.
The Impact of Gradual and Immediate Nicotine Reduction on Subjective Cigarette Ratings
Authors: Smith Tracy T , Donny Eric C , Luo Xianghua , Allen Alicia M , Carroll Dana M , Denlinger-Apte Rachel L , Dermody Sarah S , Koopmeiners Joseph S , McClernon F Joseph , Pacek Lauren R , Vandrey Ryan , Hatsukami Dorothy K
Published: August 2019

Background

A recent clinical trial showed that an immediate transition to very low nicotine content (VLNC) cigarettes, compared with a gradual transition, produced greater reductions in smoking behavior, smoke exposure, and dependence. However, there was less compliance with the instruction to smoke only VLNC cigarettes in the immediate versus gradual reduction condition. The goal of this study was to test whether nicotine reduction method alters subjective ratings of VLNC cigarettes, and whether subjective ratings mediate effects of nicotine reduction method on smoking behavior, smoke exposure, dependence, and compliance.

Methods

This is a secondary analysis of a randomized trial conducted across 10 sites in the United States. Smokers (n = 1250) were randomized to either a control condition, or to have the nicotine content of their cigarettes reduced immediately or gradually to 0.04 mg nicotine/g of tobacco during a 20-week study period. Participants completed the modified Cigarette Evaluation Questionnaire (mCEQ).

Results

After Week 20, the immediate reduction group scored significantly lower than the gradual reduction group on multiple subscales of the mCEQ (ps < .001). The Satisfaction subscale of the mCEQ mediated the impact of nicotine reduction method on smoke exposure, smoking behavior, dependence, compliance, and abstinence. Other subscales also mediated a subset of these outcomes.

Conclusions

An immediate reduction in nicotine content resulted in lower product satisfaction than a gradual reduction, suggesting that immediate reduction further reduces cigarette reward value. This study will provide the Food and Drug Administration with information about the impact of nicotine reduction method on cigarette reward value.

Implications

These data suggest that an immediate reduction in nicotine content will result in greater reductions in cigarette satisfaction than a gradual reduction, and this reduction in satisfaction is related to changes in smoking behavior and dependence.
Workplace Violence Prevention for Nurses
Authors: Hartley Daniel , Ridenour Marilyn , Wassell James T.
Published: August 2019

An online NIOSH course raises awareness of workplace violence and offers preventive strategies.
More Steps, Lower Mortality Among Older Women
Authors: Rosenberg Karen
Published: August 2019

According to this study:

Older women who walk more steps per day (up to approximately 7,500 steps) have lower mortality rates than less active women.

The number of steps is more important than stepping intensity.
Quantifiable Bleeding in Children Supported by Extracorporeal Membrane Oxygenation and Outcome
Authors: Nellis Marianne E. , Dalton Heidi , Karam Oliver
Published: August 2019

Objectives:

To evaluate the association between bleeding from chest tubes and clinical outcomes in children supported by extracorporeal membrane oxygenation.

Design:

Secondary analysis of a large observational cohort study.

Setting:

Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Collaborative Pediatric Critical Care Research Network.

Patients:

Critically ill children supported by extracorporeal membrane oxygenation.

Interventions:

None.

Measurements and Main Results:

Daily chest tube bleeding, results from hemostatic assays, transfusion volumes, 90-day PICU-free days, and mortality were collected prospectively by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Extracorporeal membrane oxygenation was employed in the care of 514 consecutive patients. Sixty percent of patients had at least one episode of chest tube bleeding (median chest tube blood volume over the entire extracorporeal membrane oxygenation course was 123 mL/kg [interquartile range, 47–319 mL/kg]). Twenty-six percent had at least 1 day of bleeding from the chest tube greater than 100 mL/kg/d. The number of days with chest tube bleeding greater than 60 mL/kg/d was independently associated with increased in-hospital mortality (adjusted odds ratio, 1.43; 95% CI, 1.05–1.97; p = 0.02) and decreased PICU-free days (beta coefficient, –4.2; 95% CI, –7.7 to –0.6; p = 0.02). The total amount of bleeding from chest tube were independently associated with increased mortality (per mL/kg/extracorporeal membrane oxygenation run; adjusted odds ratio, 1.002; 95% CI, 1.000–1.003; p = 0.04). Fibrinogen, weight, indication for extracorporeal membrane oxygenation, and need for hemodialysis were independently associated with chest tube bleeding, whereas platelet count, coagulation tests, heparin dose, and thrombotic events were not.

Conclusions:

In children supported by extracorporeal membrane oxygenation, chest tube bleeding above 60 mL/kg/d was independently associated with worse clinical outcome. Low fibrinogen was independently associated with chest tube bleeding, whereas platelet count and hemostatic tests were not. Further research is needed to evaluate if interventions to prevent or stop chest tube bleeding influence the clinical outcome.
Extracorporeal Membrane Oxygenation in ARDS
Authors: Naddour Mouhib , Kalani Mehboob , Ashraf Obaid , Patel Kaushal , Bajwa Omer , Cheema Tariq
Published: August 2019

Extracorporeal membrane oxygenation (ECMO) has become a key tool in the management of cardiac and/or respiratory failure refractory to conventional management. Although ECMO has multiple indications, it has been widely studied for the management of acute respiratory distress syndrome in adults. ECMO provides rest and support while the damaged lungs heal. It is an invasive modality with risks of serious complications; therefore, clinicians should be vigilant during patient selection. Furthermore, users should be familiar with different components of the ECMO machinery and the management of different organ systems while patients are on the circuit. ECMO is a relatively new modality that has shown good results when used in certain circumstance, and its use is becoming more popular across the United States.
State Variability in Diagnosed Conditions for IDEA Part C Eligibility
Authors: Barger Brian , Squires Jane , Greer Maureen , Noyes-Grosser Donna , Martin Eile Julia , Rice Catherine , Shaw Evelyn , Surprenant Kala Shah , Twombly Elizabeth , London Sarah , Zubler Jennifer , Wolf Rebecca B.
Published: August 2019

An infant or toddler can begin the process of receiving Part C early intervention services by having a diagnosed condition with a high probability of developmental delay (Individuals with Disabilities Education Improvement Act, 2004). How states define those diagnosed conditions that begin the initiation process varies widely. Lists of diagnosed conditions were collected from state Part C websites and Part C coordinators for a descriptive analysis. Across 49 states, the District of Columbia, and 4 territories, a final list of 620 unique conditions was compiled. No single condition was listed by all jurisdictions. Hearing impairment was the condition listed by the most states (n = 38), followed by fetal alcohol syndrome (n = 34). Of the 620 conditions, 168 (27%) were listed by only 1 state, 554 (89%) were listed by fewer than 10 states, and 66 (11%) were listed by 10 or more states. Of these 66 conditions, 47 (71%) were listed by fewer than 20 states. Most of these 66 conditions (n = 48; 72.7%) had a prevalence of “very rare or rare,” 8 (12%) were “common,” 6 (9%) were “very common,” and 4 (6.1%) were “unknown.” The wide heterogeneity in the number and type of diagnostic conditions listed across states should be further investigated as it may represent imbalances in children with diagnosed conditions gaining access to Part C evaluations and individualized family service plans and potentially the services themselves across states. In addition, providing ready access to lists of diagnosed conditions is a simple step that could help states and Part C programs facilitate access to services.
Patient Dissatisfaction With Primary Care and Nonurgent Emergency Department Use
Authors: Xin Haichang
Published: August 2019

A well-functioning primary care system will have the capacity to provide timely, adequate, and effective care for patients to avoid nonurgent emergency department (ED) use. This study advances academic discussion by examining whether patient negative experiences during their encounter with a primary care physician (PCP) are associated with nonurgent ED use nationwide in the United States. This retrospective cohort study used data from the 2010-2011 Medical Expenditure Panel Survey. The independent measures were patient perceptions of PCPs' communication and care quality in 2010. The multivariate logit model was employed to analyze the nonurgent ED use as opposed to no ED use in 2011, after controlling for age, gender, race and ethnicity, rural/urban location, marital status, and education levels in 2010. All predictors were treated as dummy variables. We employed the lagged time effect and controlled health status to account for the endogeneity between outcomes and the main independent variables. The weights and variance were adjusted using the survey procedures to yield nationally representative results. The study sample consisted of 5242 adults, which represented 131 317 908 weighted people in the total population. While the measure of patient satisfaction with providers' communication was not associated with nonurgent ED use (P = .750), patient perceived poor and intermediary levels of primary care quality had higher odds of a nonurgent ED visit (OR = 1.75, P = .049, and OR = 1.48, P = .050, respectively) compared with high levels of care quality. For PCPs, endeavors may be considered in improving health care quality to reduce nonurgent ED use. Whenever possible, PCPs' efforts may want to be devoted to both communication and care quality to improve patients' health outcomes and satisfaction and to reduce nonurgent ED use.
The Common Attributes of Successful Care Manager Programs for High-Need, High-Cost Persons
Authors: Thurber Emilia G. , Boyd Cynthia , Leff Bruce , Wolff Jennifer , Anderson Gerard
Published: August 2019

Many programs use care managers to improve care coordination for high-need, high-cost patient populations. However, little is known about how programs integrate care managers into care delivery or the attributes shared by successful programs. We used a case study approach to examine the common attributes of 10 programs for high-need, high-cost individuals utilizing a longitudinal care manager that had achieved success in reducing cost, improving quality, or increasing patient satisfaction. Through interviews with program leaders and document review, we identified 10 common attributes of successful care manager programs, offering insights for providers aiming to better serve the high-need, high-cost population.
Measurement of Patients' Perceptions of the Quality of Acute Stroke Services: Development and Validation of the STROKE Perception Report
Authors: Alexandrov Anne W. , Brewer Barbara B. , Moore Kari , Grau Charlene , Beenstock Dana J. , Cudlip Fern , Murphy Deborah A. , Klassman Lynn , Korsnack Andrea M. , Johnson Brenda , Parliament Connie F. , Lane Patricia C. , Walsh Tina , Gottbrath Deidra , Wojner Alexis J. , DiBiase Stephen E. , Alexandrov Andrei V.
Published: August 2019

INTRODUCTION

Patients' perceptions of healthcare quality have become an important part of quality measurement. We explored patients' and family's lived experiences during acute stroke hospitalization to develop a quantitative instrument.

METHODS

Focus groups were conducted using open-ended scripted questions. Interview data were coded and analyzed using an inductive approach to thematic analysis. Symmetric patient and family instruments were developed based on qualitative domains and serially refined to a set of 30 survey items, 12 stroke knowledge test items, and 5 subject demographic fields. Scales were evaluated for internal consistency reliability using Cronbach α; construct validity with exploratory factor analysis using principal components with varimax rotation was performed to determine the extent to which items in a scale measure the same underlying factor. Feasibility of an electronic cloud-based survey was also tested.

RESULTS

Three main themes emerged: fast action to diagnose and treat stroke, genuine caring, and education to prevent and respond to stroke. A total of 1029 subjects completed the final instrument with no differences in perception found by race, ethnicity, or length of stay. Scales showed satisfactory internal consistency reliability (Cronbach α scores, .89–.94); factor loadings across each scale ranged from 0.55 to 0.87. Data entry by electronic pad was perceived by 77% to be more confidential than paper surveys; median score for difficulty was 4 (“easy to use”).

CONCLUSION

The STROKE Perception Report enables understanding of patients' and family's beliefs about the quality of acute stroke care in essential new domains never explored before.
Through Thick and Thin
Authors: Koo Jenny K. , Narvasa Averyl , Bode Lars , Kim Jae H.
Published: August 2019

Background:

Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies.

Methods:

We thickened donor human milk (DHM) and formula using various thickeners: starch‐based thickeners (SBT; Thick It, rice cereal), and gum‐based thickeners (GBT; xanthan gum: Simply Thick, Thicken Up Clear; carob gum: GelMix). We also assessed formula with added starches marketed for reflux, including Similac Spit Up (SSU) and Enfamil AR (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested.

Results:

Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan‐gum thickened DHM resulted in phase separation and formation of solid precipitant.

Conclusions:

Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum‐based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.
Relationships Between Early Neonatal Nutrition and Neurodevelopment at School Age in Children Born Very Preterm
Authors: Tottman Anna C. , Alsweiler Jane M. , Bloomfield Frank H. , Gamble Greg D. , Jiang Yannan , Leung Myra , Poppe Tanya , Thompson Benjamin , Wouldes Trecia A. , Harding Jane E. ,   PIANO study group
Published: August 2019

Objectives:

The aim of this study was to determine whether a new nutrition protocol designed to increase early protein intakes while reducing fluid volume in infants born very preterm was associated with altered neurodevelopment and growth in childhood.

Methods:

A retrospective, observational cohort study of children born <30 weeks’ gestation or <1500 g and admitted to the neonatal unit, National Women's Hospital, Auckland, New Zealand, before and after a change in nutrition protocol. The primary outcome was neurodevelopmental impairment at 7 years (any of Wechsler Intelligence Scale for Children full scale IQ < 85, Movement Assessment Battery for Children‐2 total score ⩽5th centile, cerebral palsy, blind, or deaf requiring aids). Outcomes were compared between groups and for the overall cohort using generalized linear regression, adjusted for sex and birth weight z score.

Results:

Of 201 eligible children, 128 (64%) were assessed (55/89 [62%] exposed to the old nutrition protocol, 73 of 112 [65%] to the new protocol). Children who experienced the new protocol received more protein, less energy, and less carbohydrate in postnatal days 1 to 7. Neurodevelopmental impairment was similar at 7 years (30/73 [41%] vs 25/55 [45%], adjusted odds ratio [AOR] [95% confidence interval] 0.78 [0.35–1.70], P = 0.55), as was the incidence of cerebral palsy (AOR 7.36 [0.88–61.40], P = 0.07). Growth and body composition were also similar between groups. An extra 1 g/kg parenteral protein intake in postnatal days 1 to 7 was associated with a 27% increased odds of cerebral palsy (AOR 1.27 [1.03–1.57], P = 0.006).

Conclusions:

Higher early protein intakes do not change overall rates of neurodevelopmental impairment or growth at 7 years. Further research is needed to determine the effects of higher early parenteral protein intake on motor development.
Resurgence of Vaccine-Preventable Disease
Authors: Dreisinger Naomi , Lim Czer Anthoney
Published: August 2019

After a decades-long reduction in vaccine-preventable illnesses worldwide, there has been a reappearance of childhood illnesses once thought to be eradicated. This resurgence in illnesses such as polio and measles is a consequence of multifactorial events leading to decreased vaccination rates. A lack of resources in poor and war-torn countries, coupled with increasing global travel, and decisions to delay or defer vaccinations because of inaccurate studies further emphasized by media have combined to result in current state of frequent local and widespread epidemics, specifically the current outbreak of measles. As providers in the pediatric emergency department, we are often the first to encounter children manifesting these diseases. It is imperative that we understand the circumstances leading to these encounters, so that we can have engaged conversations with families, gain an understanding of their motivations, dispel any misinformed beliefs, and encourage positive health behaviors for their children.
A Comparison of the Aesthetics Outcomes and Respiratory Side Effects of the Use of Spreader Flap and Spreader Graft Techniques in Open Rhinoplasty
Authors: Shafaeei Yousef , Zare Narges Jafari
Published: August 2019

Background:

Considering the fact that both spreader flap and spreader graft techniques cause respiratory complications and yield different aesthetics results in patients undergoing open rhinoplasty, this study was aimed at comparing these 2 techniques in terms of aesthetics and respiratory side effects.

Methods:

The study was conducted on patients undergoing open rhinoplasty in Ardabil, Iran, during 2016 to 2017. During the Study, a questionnaire containing 7 items related to respiratory complications and 7 items related to aesthetics side effects was completed for each of the patients. After that, the patients were photographed from 6 standard views by the researchers and then the aesthetics side effects were assessed. Finally, the obtained data were all fed into SPSS Software Version 16 and the needed statistical analyses were conducted.

Results:

One hundred thirty patients were investigated in this study the majority of whom were female. Rhinoplasty in 69 of them was done with spreader graft technique and in 61 of them with spreader flap technique. The analysis of the side effects in these 2 groups of patients indicated that the use of spreader graft technique increases the incidence of nasal hump while the use of spreader flap technique results in an increase in the incidence of obstructive sleep apnea. As regards the other respiratory and aesthetics side effects, the 2 techniques did not yield significantly different results.

Conclusion:

The findings of the present research indicated that there is no significant difference between the use of spreader graft and spreader flap techniques. Therefore, considering the clinical conditions of patients, either of the 2 techniques can be used effectively in rhinoplasties.
Semi-Automated Three-Dimensional Condylar Reconstruction
Authors: Méndez-Manjón Irene , Haas Orion Luiz , Guijarro-Martínez Raquel , Belle de Oliveira Rogério , Valls-Ontañón Adaia , Hernández-Alfaro Federico
Published: August 2019

The objective was to validate a semi-automated segmentation method for 3-dimensional (3D) reconstruction of the mandibular condyle from cone beam computed tomography (CBCT) data and illustrate its application in volumetric analysis of the condyle.

Ten CBCT datasets were used to validate the proposed semi-automatic method for 3D rendering of mandibular condyles. First, a standardized orientation protocol of the skull was applied. After defining the volume of interest, a grey-scale cut-off value was selected to allow an automatic reconstruction of the condyle's surface. Subsequently, condylar contour was optimized manually. The whole process was repeated twice by 2 independent investigators. Volumetric measurements of the condyle were used as a measure of conformity between both investigators. The reproducibility of condylar volume reconstruction was excellent for intra-examiner measurements (CV = 3.65%, intraclass correlation coefficient = 0.97) and good for inter-examiner measurements (CV = 7.15%, ICC = 0.89). The overall mean time required for the segmentation process was 6.31 + 2.78 minutes. The proposed protocol provides an accurate and reproducible tool for 3D reconstruction of the mandibular condyle using CBCT data. Its implementation will enable adequate follow-up of morphological changes in bone tissue with a Hounsfield unit-based imaging segmentation method.
Senescence: Still an Unsolved Problem of Biology
Authors: Roper Mark , Capdevila Pol , Salguero-Gómez Roberto
Published: August 2019

Peter Medawar’s ‘An Unsolved Problem of Biology’1was one of several formal attempts to provide an explanation for the evolution of senescence, the increasing risk of mortality and decline in reproduction with age after achieving maturity. Despiteca.seven decades of theoretical elaboration aiming to explain the problem since Medawar first outlined it, we argue that this fundamental problem of biology remains unsolved. Here, we utilise demographic information2, 3for 308 multicellular species to derive age-based trajectories of mortality and reproduction that provide evidence against the predictions of the classical, still prevailing, theories of ageing1, 4, 5, 6. These theories predict the inescapability of senescence1, 4, or its universality at least among species with a clear germ-soma barrier5, 6. The patterns of senescence in animals and plants that we report contradict both of these predictions. With the largest ageing comparative dataset of these characteristics to date, we build on recent evidence7, 8to show that senescence is not the rule, and highlight the discrepancy between existing evidence and theory7, 8, 9. We also show that species’ age patterns of mortality and reproduction often follow divergent patterns, suggesting that organisms may display senescence for one component but not the other. We propose that ageing research will benefit from widening its classical theories beyond merely individual chronological age; key life history traits such as size, the ecology of the organism, and kin selection, may together play a hidden, yet integral role in shaping senescence outcomes.
The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research
Authors: Painter Corrie A. , Jain Esha , Tomson Brett N. , Dunphy Michael , Stoddard Rachel E. , Thomas Beena S. , Damon Alyssa L. , Shah Shahrayz , Kim Dewey , Zañudo Jorge Gómez Tejeda , Hornick Jason L. , Chen Yen-Lin , Merriam Priscilla , Raut Chandrajit P. , Demetri George D. , Van Tine Brian A. , Lander Eric S. , Golub Todd R. , Wagle Nikhil
Published: August 2019

Despite collectively accounting for 25% of tumors in U.S. adults, rare cancers have significant unmet clinical needs as they are difficult to study due to low incidence and geographically dispersed patient populations. We sought to assess whether a patient-partnered research approach using online engagement can overcome these challenges and accelerate scientific discovery in rare cancers, focusing on angiosarcoma (AS), an exceedingly rare sarcoma with a dismal prognosis and an annual U.S. incidence of 300 cases. Here, we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling patients across the U.S. and Canada to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 AS patients registered for the ASCproject, comprising a significant fraction of all patients. Whole exome sequencing of 47 AS tumors revealed several recurrently mutated genes, including KDR, TP53, and PIK3CA. Activating mutations in PIK3CA were observed nearly exclusively in primary breast AS, suggesting a therapeutic rationale in these patients. AS of the head, neck, face, and scalp (HNFS) was associated with high tumor mutation burden and a dominant mutational signature of UV light exposure, suggesting that UV damage may be a causative factor in HNFS AS and that this AS subset might be amenable to immune checkpoint inhibitor therapy. Medical record review revealed two patients with HNFS AS received off-label treatment with anti-PD-1 therapy and experienced exceptional responses, highlighting immune checkpoint inhibition as a therapeutic avenue for HNFS AS. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for AS patients. Collectively, this proof of concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and enable biological and clinical discoveries.
Topography and Land Use Modulate Hydrological and Nutrient Export Dynamics in two Andean Streams
Authors: Sosnovsky Alejandro , Lallement Mailén Elizabeth , Rechencq Magalí , Zattara Eduardo Enrique , Fernández María Valeria , Leiva Sergio , Suárez María José , Daga Romina , Cantet Rodolfo Juan Carlos
Published: August 2019

Fluvial dynamics are driven by multiple environmental factors and scales. Studies coupling hydrological and nutrient dynamics of Andean streams are almost nonexistent. We characterized two adjacent streams with contrasting drainage basins: Casa de Piedra, originating in a small mountain lake and running through a pristine landscape, and Gutiérrez, originating in a large piedmont lake and running through an anthropized landscape. Despite both drainage basins sharing geology and climate, we found that the streams presented contrasting hydrological and nutrient dynamics. Casa de Piedra had higher discharge flashiness with shorter response delays to precipitation. Interestingly, Gutiérrez’s hydrology was buffered by the upstream lake, but its nutrient exports were not. Differences observed in quality and timing of coarse particulate organic matter export and basal export levels of phosphorus and nitrogen could be explained by human activities affecting Gutiérrez but not Casa de Piedra. Moreover, nitrogen:phosphorus ratio indicates a possible future shift to phosphorus as the limiting nutrient as Andean basins become more densely populated. In summary, our annual basis study shows that even under a common geology and climate, stream dynamics of adjacent basins can be starkly different due to differences in topography and land use.
Breast tumor-associated metalloproteases restrict reovirus oncolysis by cleaving the σ1 cell-attachment protein, and can be overcome by mutation of σ1
Authors: Fernandes Jason , Cristi Francisca , Eaton Heather , Chen Patricia , Haeflinger Sarah , Bernard Isabelle , Hitt Mary , Shmulevitz Maya
Published: August 2019

Reovirus is undergoing clinical testing as an oncolytic therapy for breast cancer. Given that reovirus naturally evolved to thrive inentericenvironments, we sought to better understand howbreast tumormicroenvironments impinge on reovirus infection. Reovirus was treated with extracellular extracts generated from polyoma virus middle T-antigen-derived mouse breast tumors. Unexpectedly, these breast tumor extracellular extracts inactivated reovirus, reducing infectivity of reovirus particles by 100-fold. Mechanistically, inactivation was attributed to proteolytic cleavage of the viral cell attachment protein σ1, which diminished virus binding to sialic acid-low tumor cells. Among various specific protease class inhibitors and metal ions, EDTA and ZnCl2effectively modulated σ1 cleavage, indicating that breast tumor-associated zinc-dependent metalloproteases are responsible for reovirus inactivation. Moreover, media from MCF7, MB468, MD-MB-231 and HS578T breast cancer cell lines recapitulated σ1 cleavage and reovirus inactivation, suggesting that inactivation of reovirus is shared among mouse and human breast cancers, and that breast cancer cells in by themselves can be a source of reovirus-inactivating proteases. Binding assays and quantification of sialic acid (SA) levels on a panel of cancer cells showed that truncated σ1 reduced virus binding to cells with low surface SA. To overcome this restriction, we generated a reovirus mutant with a mutation (T249I) in σ1 that prevents σ1 cleavage and inactivation by breast tumor-associated proteases. The mutant reovirus showed similar replication kinetics in tumorigenic cells, equivalent toxicity as wild-type reovirus in a severely compromised mouse model, and increased tumor titers. Overall, the data shows that tumor microenvironments have the potential to reduce infectivity of reovirus.

SIGNIFICANCE

We demonstrate that metalloproteases in breast tumor microenvironments can inactivate reovirus. Our findings expose that tumor microenvironment proteases could have negative impact on proteinaceous cancer therapies such as reovirus, and that modification of such therapies to circumvent inactivation by tumor metalloproteases merits consideration.
Compressed sensing for imaging transcriptomics
Authors: Cleary Brian , Simonton Brooke , Bezney Jon , Murray Evan , Alam Shahul , Sinha Anubhav , Habibi Ehsan , Marshall Jamie , Lander Eric S. , Chen Fei , Regev Aviv
Published: August 2019

Tissue and organ function rely on the organization of cells and molecules in specific spatial structures. In order to understand these structures and how they relate to tissue function in health and disease, we would ideally be able to rapidly profile gene expression over large tissue volumes. To this end, in recent years multiple molecular assays have been developed that can image from a dozen to ~100 individual proteins1–3 or RNAs4–10 in a sample at single-cell resolution, with barcodes to allow multiplexing across genes. These approaches have serious limitations with respect to (i) the number of genes that can be studied; and (ii) imaging time, due to the need for high-resolution to resolve individual signals. Here, we show that both challenges can be overcome by introducing an approach that leverages the biological fact that gene expression is often structured across both cells and tissue organization. We develop Composite In Situ Imaging (CISI), that combines this biological insight with algorithmic advances in compressed sensing to achieve greater efficiency. We demonstrate that CISI accurately recovers the spatial abundance of each of 37 individual genes from 11 composite measurements in 12 bisected mouse brain coronal sections covering 180mm2 and 476,276 cells without the need for spot-level resolution. CISI achieves the current scale of multiplexing with two orders of magnitude greater efficiency, and can be leveraged in combination with existing methods to multiplex far beyond current scales.
TheSetaria viridisgenome and diversity panel enables discovery of a novel domestication gene
Authors: Mamidi Sujan , Healey Adam , Huang Pu , Grimwood Jane , Jenkins Jerry , Barry Kerrie , Sreedasyam Avinash , Shu Shengqiang , Lovell John T. , Feldman Maximilian , Wu Jinxia , Yu Yunqing , Chen Cindy , Johnson Jenifer , Sakakibara Hitoshi , Kiba Takatoshi , Sakurai Tetsuya , Tavares Rachel , Nusinow Dmitri A. , Baxter Ivan , Schmutz Jeremy , Brutnell Thomas P. , Kellogg Elizabeth A.
Published: August 2019

Diverse wild and weedy crop relatives hold genetic variants underlying key evolutionary innovations of crops under domestication. Here, we provide genome resources and probe the genetic basis of domestication traits in green millet (Setaria viridis), a close wild relative of foxtail millet (S. italica). Specifically, we develop and exploit a platinum-quality genome assembly andde novoassemblies for 598 wild accessions to identify loci underlying a) response to climate, b) a key ‘loss of shattering’ trait that permits mechanical harvest, and c) leaf angle, a major predictor of yield in many grass crops. With CRISPR-Cas9 genome editing, we validatedLess Shattering1(SvLES1) as a novel gene for seed shattering, which is rendered non-functional via a retrotransposon insertion inSiLes1, the domesticated loss-of-shattering allele ofS. italica. Together these results and resources projectS. viridisas a key model species for complex trait dissection and biotechnological improvement of panicoid crops.
Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis
Authors: Wang Ke , Wang Yixuan , Hu Zebing , Zhang Lijun , Li Gaozhi , Dang Lei , Tan Yingjun , Cao Xinsheng , Shi Fei , Zhang Shu , Zhang Ge
Published: August 2019

Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS)6-liposome delivery to the bone formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU can function as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of the OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.
Duodenal diverticulitis masquerading as acute cholecystitis: A lesson learnt
Authors: Khan Amena , Karanth Veena , Khan Afroz , Rodrigues Gabriel
Published: August 2019

Acute cholecystitis is one of the common surgical emergencies encountered in daily practice. Clinical examination coupled with an ultrasound scan of the abdomen will usually confirm the diagnosis. The rare presence and inflammation of a duodenal diverticula can mimic acute cholecystitis and lead to a diagnostic dilemma that can result in a surgical catastrophe. We present a case of a 62‐year‐old lady with a provisional diagnosis of acute cholecystitis, which turned out to be duodenal diverticulitis, who did not respond to conservative management and was successfully managed surgically.
Jejunogastric intussusception after distal gastrectomy with Billroth II reconstruction
Authors: Ng Shiu‐Yan , Yiu Chun‐Wang , Wong Ka‐Fai , Leung Siu‐Kee
Published: August 2019

Intussusception in adults is uncommon. We present a rare case of intussusception of efferent jejunum through gastrojejunostomy in a patient who underwent distal gastrectomy with Billroth II reconstruction. Revision total gastrectomy was performed successfully. High index of suspicion and early diagnosis is crucial as delayed intervention can lead to a mortality rate of 50%.
Bronchogenic cyst of the stomach treated by surgical resection
Authors: Wong Ching‐Yiu , Chan Man‐Pan , Cheung Chung‐Yeung , Lau Chun‐Fai , Leung Chi‐Keung , Wong Kwok‐Wa , Gao Yang , Yuen Wah‐Fun
Published: August 2019

Bronchogenic cysts are congenital cystic lesions caused by abnormal budding of the primitive tracheobronchial tube. Most bronchogenic cysts are found in the mediastinum, whereas abdominal bronchogenic cysts are rare with only 39 cases reported in the literature to date. The indication of surgical intervention is still controversial in previous studies. In the present study, we report a case of a bronchogenic cyst of the stomach in an adult who was treated by wedge excision.
Board gender composition, board independence and sustainable supply chain responsibility
Authors: Benjamin Samuel , Mansi Mansi , Pandey Rakesh
Published: August 2019

The consideration of social and environmental factors in companies’ supply chain is a prevalent research topic because stakeholders are now inquisitive about the social and environmental impacts of companies’ suppliers. Using a sample of S&P 500 firms, we find that board gender composition and board independence are positively associated with sustainable supply chain responsibility (SSCR). We also identify three channels (CEO duality, sustainability committee and sensitive industries) through which board gender composition and board independence affect SSCR, where board gender composition consistently explains SSCR, but the effect of board independence is less pronounced in firms with CEO duality and firms with a sustainability committee. Finally, we explore the reason for the less‐pronounced findings for board independence in our subsample analyses and find that, compared with independent female directors who continue to display significant associations with SSCR, independent male directors do not engender SSCR across the three subsample tests.
Long‐term significance of an anastomotic leak in patients undergoing an ultra‐low anterior resection for rectal cancer
Authors: Vu Linda , Penter Cheryl , Platell Cameron
Published: August 2019

Background

Australia has one of the highest rates of colorectal cancer worldwide. Despite technological advances in colorectal surgery, anastomotic leaks (ALs) continue to cause significant morbidity and mortality. Ultra‐low anterior resections (ULARs) carry the highest prevalence of AL. The aim of the study is to evaluate the incidence, treatment and consequences of AL following ULAR for colorectal cancer from a single colorectal unit.

Methods

This is a retrospective evaluation of prospectively collected data on patients undergoing ULAR following rectal cancer. The main end points include the prevalence and management of AL following initial operation and the morbidity, re‐operation and mortality rates associated with AL. A stepwise logistic regression analysis and a multivariate analysis were performed to identify independent risk factors.

Results

A total of 467 patients underwent an ULAR. There were 32 (6.8%) ALs. Average follow‐up time was 79 months. There were five subclinical leaks and only one (20%) required intervention. The overall survival rate at 5 years was 80% (95% confidence interval 58–91). On univariate analysis male sex was a risk factor for AL (P = 0.03). On multivariate analysis patients who had a complete response to radiotherapy were more likely to have a leak than the patients who had no radiotherapy (grade 4, odds ratio 4.0, 95% confidence interval 1.4–10.9, P = 0.01).

Conclusion

This study has highlighted the relevance of subclinical leaks and their associated morbidity. It identified that radiotherapy a risk factor for AL, but the response to radiotherapy is an even better predictor of leakage.
BAG3 expression correlates with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix
Authors: Raffone Antonio , Travaglino Antonio , D'Antonio Antonio , De Marco Margot , Caccese Miriam , Mascolo Massimo , Insabato Luigi , Zeppa Pio , Rosati Alessandra , Mollo Antonio , Zullo Fulvio , Guida Maurizio
Published: August 2019

Introduction

Bcl‐2‐associated athanogene 3 (BAG3) is a protein involved in apoptosis and stress response, which is overexpressed in invasive cervical cancer. However, nothing is known about BAG3 expression in precancerous lesions of the uterine cervix. We aimed to evaluate the expression of BAG3 in cervical intraepithelial neoplasia/squamous intraepithelial lesions (CIN/SIL).

Material and methods

Forty patients (16 CIN1/L‐SIL, 11 CIN2/H‐SIL and 13 CIN3/H‐SIL) were assessed by immunohistochemistry for BAG3. The intensity of BAG3 expression was categorized as null, minimal, weak, moderate or strong. The association of BAG2 intensity of expression with the grade of dysplasia was assessed using Chi‐square test (significant P value <0.05).

Results

In all normal controls, BAG3 expression was negative. In L‐SIL specimens, BAG3 expression was confined to the basal third of the epithelium, with an intensity minimal in nine cases (56.3%), weak in six (37.5%) and strong in one (6.3%). In H‐SIL specimens, BAG3 expression involved also the two upper thirds of the epithelium, with an intensity moderate in 13 cases (54.2%; 8 CIN2 and 5 CIN3) and strong in 11 cases (45.8%; 3 CIN2 and 8 CIN3). The distribution of BAG3 expression correlated perfectly with the grade of dysplasia (P = 0.0); a moderate/strong expression of BAG3 was significantly associated with H‐SIL (P < 0.0001), with no significant difference between CIN2 and CIN3 (P = 0.1228).

Conclusions

In CIN/SIL, both distribution and intensity of BAG3 expression correlate directly with the grade of dysplasia, supporting the involvement of BAG3 in all phases of cervical carcinogenesis and its possible diagnostic and prognostic role in cervical premalignant lesions.