bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Excretion Profile of 11-Nor-9-Carboxy-Δ9-Tetrahydrocannabinol (THCCOOH) Following Smoked and Vaporized Cannabis Administration in Infrequent Cannabis Users
Authors: Spindle Tory R , Cone Edward J , Schlienz Nicolas J , Mitchell John M , Bigelow George E , Flegel Ronald , Hayes Eugene , Vandrey Ryan
Published: April 2019

As cannabis has become more accessible, use of alternative methods for cannabis administration such as vaporizers has become more prevalent. Most prior controlled pharmacokinetic evaluations have examined smoked cannabis in frequent (often daily) cannabis users. This study characterized the urinary excretion profile of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), the primary analytical outcome for detection of cannabis use, among infrequent cannabis users following controlled administration of both smoked and vaporized cannabis. Healthy adults (N = 17), with a mean of 398 (range 30–1,825) days since last cannabis use, smoked and vaporized cannabis containing 0, 10, and 25 mg of Δ9-tetrahydrocannabinol (THC) across six outpatient sessions. Urinary concentrations of THCCOOH were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity, and agreement between three immunoassays (IA) for THCCOOH (with cutoffs of 20, 50, and 100 ng/mL) and gas chromatography-mass spectrometry (GC/MS) results (confirmatory concentration of 15 ng/mL) were assessed. THCCOOH concentrations peaked 4–6 h after cannabis administration. Median maximum concentrations (Cmax) for THCCOOH were qualitatively higher after administration of vaporized cannabis compared to equal doses of smoked cannabis. Urine THCCOOH concentrations were substantially lower in this study relative to prior examinations of experienced cannabis users. The highest agreement between IA and GC/MS was observed at the 50 ng/mL IA cutoff while sensitivity and specificity were highest at the 20 and 100 ng/mL IA cutoffs, respectively. Using federal workplace drug-testing criteria (IA cutoff of 50 ng/mL and GC/MS concentration ≥15 ng/mL) urine specimens tested positive in 47% of vaporized sessions and 21% of smoked sessions with active THC doses (N = 68). Urinary concentrations of THCCOOH are dissimilar after administration of smoked and vaporized cannabis, with qualitatively higher concentrations observed after vaporization. Infrequent users of cannabis may excrete relatively low concentrations of THCCOOH following acute inhalation of smoked or vaporized cannabis.
Burrow use by juvenile platypuses (Ornithorhynchus anatinus) in their natal home range
Authors: Thomas Jessica L , Parrott Marissa L , Handasyde Kathrine A , Temple-Smith Peter
Published: April 2019

We determined patterns of burrow use by juvenile platypuses (Ornithorhynchus anatinus) in their natal home range, and evaluated associations between burrows and vegetation. Between March 2015 and March 2017, we captured seven juvenile platypuses along a 3-km stretch of Badger Creek, Victoria and fitted them with radiotransmitters. We recorded the locations of animals in their burrows daily while transmitters were attached (range: 14–132 days). Juveniles used 74 different burrows, with each using 11 ± 2 burrows. Overall, 65% of burrows (48) were used once, 22% (16) were used between 2 and 9 times (moderate-use), and 13% (10) were used frequently (> 10 times). No juveniles dispersed during the monitoring period (14–132 days). Although some association was observed between burrow use and particular vegetation communities, vegetation was not a strong factor driving site selection of burrows. Use of multiple burrows may allow juveniles to avoid competition with conspecifics, reduce exposure to ectoparasites, and develop shelter-seeking behavior. Juvenile platypuses remained in their natal home range, where conditions are likely to be good because they supported recent breeding, while completing their growth and development prior to dispersal.
To clean or not to clean phenotypic datasets for outlier plants in genetic analyses?
Authors: Alvarez Prado Santiago , Sanchez Isabelle , Cabrera-Bosquet Llorenç , Grau Antonin , Welcker Claude , Tardieu François , Hilgert Nadine
Published: April 2019

Excluding outlier plants (biological replicates deviating from the expected distribution on a multi-criteria basis) from phenotypic datasets is necessary to avoid false-positive associations between genome markers and traits.
Determination of Epstein-Barr Virus–Infected Lymphocyte Cell Types in Peripheral Blood Mononuclear Cells as a Valuable Diagnostic Tool in Hematological Diseases
Authors: Zhang Peiling , Zeng Chen , Cheng Jiali , Zhou Jing , Gu Jia , Mao Xia , Zhang Wei , Cao Yang , Luo Hui , Xu Bin , Li Qinlu , Xiao Min , Zhou Jianfeng
Published: April 2019

Background

High loads of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells (PBMCs) can be indicative of a broad spectrum of diseases, ranging from asymptomatic infection to fatal cancers.

Methods

We retrospectively investigated the EBV-infected cell types in PBMCs among 291 patients. Based on EBV-infected cell types, the clinical features and prognoses of 93 patients with EBV-associated (EBV+) T/natural killer (NK)–cell lymphoproliferative diseases (LPDs) T/NK-LPDs) were investigated over a 5-year period.

Results

Although B-cell-type infection was found in immunocompromised patients and patients with asymptomatic high EBV carriage, infectious mononucleosis, EBV+ B-cell LPDs and B-cell lymphomas, T-cell, NK-cell or multiple-cell-type infection in immunocompetent hosts were highly suggestive of EBV+ T/NK-LPDs, EBV+ T/NK-cell lymphomas, and aggressive NK-cell leukemia. Patients with non–B-cell infection had a poorer prognosis than those with B-cell-type infection. In our cohort, 79.6% of patients with EBV+ T/NK-LPDs were >18 years old, and NK cells were identified as EBV-infected cell type in 54.8%. Nearly half of patients with EBV+ T/NK-LPDs had genetic defects associated with immunodeficiency. However, hemophagocytic lymphohistiocytosis, and not genetic defects, was the only parameter correlated with poor prognosis of EBV+ T/NK-LPDs.

Conclusions

Determination of EBV-infected cell types among PBMCs is a valuable tool for the differential diagnosis of EBV+ hematological diseases.

In this study, determination of Epstein-Barr virus-infected cell types in peripheral blood mononuclear cells of 291 patients with high Epstein-Barr virus loads were retrospectively investigated, which indicate it is a valuable tool for Epstein-Barr virus-associated hematological diseases.
The CpnClassiPhyR Is a Resource for cpn60 Universal Target-Based Classification of Phytoplasmas
Authors: Muirhead Kevin , Pérez-López Edel , Bahder Brian W. , Hill Janet E. , Dumonceaux Tim
Published: April 2019

Phytoplasmas are plant-pathogenic bacteria that are associated with yield losses in many crop plants worldwide. Phytoplasma strain differentiation is accomplished using in silico restriction fragment length polymorphism (RFLP) analysis of 16S ribosomal RNA-encoding gene sequences, which has resulted in the definition of ribosomal groups and subgroups of phytoplasmas. Due to limitations associated with this approach, a complementary classification scheme was recently developed based on RFLP analysis of the single-copy, protein-encoding gene chaperonin-60 (cpn60). We present the CpnClassiPhyR, software that facilitates phytoplasma strain classification using both RFLP and automated phylogenetic analysis of cpn60 sequences. This software is available through a web interface at http://cpnclassiphyr.ca .
Molecular Mapping of Stripe Rust Resistance Gene Yr81 in a Common Wheat Landrace Aus27430
Authors: Gessese Mesfin , Bariana Harbans , Wong Debbie , Hayden Matthew , Bansal Urmil
Published: April 2019

The deployment of diverse sources of resistance in new cultivars underpins durable control of rust diseases. Aus27430 exhibited a moderate level of stripe rust resistance against Puccinia striiformis f. sp. tritici (Pst) pathotypes currently prevalent in Australia. Aus27430 was crossed with the susceptible parent Avocet S (AvS) and subsequent filial generations were raised. Monogenic segregation observed among Aus27430/AvS F3 families was confirmed through stripe rust screening of an F6 recombinant inbred line (RIL) population, and the resistance locus was temporarily named YrAW5. Selective genotyping using an Illumina iSelect 90K wheat SNP bead chip array located YrAW5 in chromosome 6A. Genetic mapping of the RIL population with linked 90K SNPs that were converted into PCR-based marker assays, as well as SSR markers previously mapped to chromosome 6A, confirmed the chromosomal assignment for YrAW5. Comparative analysis of other stripe rust resistance genes located in chromosome 6A led to the formal designation of YrAW5 as Yr81. Tests with a marker linked with Yr18 also demonstrated the presence of this gene in Aus27430. Yr18 interacted with Yr81 to produce stripe rust responses lower than those produced by RILs carrying these genes individually. Although gwm459 showed higher recombination with Yr81 compared with the other flanking marker KASP_3077, it amplified the AvS allele in 80 cultivars, whereas KASP_3077 amplified AvS allele in 67 cultivars. Both markers can be used in marker-assisted selection after confirming parental polymorphism.
Psyche Meets the Gatekeepers: Creating a More Humane Culture for Women in Medicine
Authors: Flaherty Susan M. , Misra Madhusmita , Scott-Vernaglia Shannon E. , Taveras Elsie M. , Israel Esther J.
Published: April 2019

In the Greek myth of Psyche and Eros, Psyche must fulfill four seemingly impossible tasks to achieve full consciousness before she can be reunited with her bridegroom, Eros. From early childhood, girls and women can encounter gender stereotyping, sexual harassment and assault, and other gender-related challenges. Although both men and women can face mistreatment in medical school, female students experience sexual harassment and sexual assault at higher rates than male students. In medical training and career advancement, women often face additional obstacles unrelated to the formal education of physicians, such as salary and promotional disparities, and lack of mentorship, sponsorship, or role models. The suicide rate for male physicians is nearly 1.5 times higher than the general population; for female physicians, it is more than twice as high. Parenthood can pose additional challenges for mothers and fathers early in their academic careers, and women are vastly underrepresented as they try to move past the “gatekeepers” into leadership roles. Using the framework of the Psyche and Eros myth to examine the trajectory of a female physician’s career, this article provides insights into these challenges, as well as strategies to address some of these inequities, such as programs to support female promotion and leadership, expanded mentorship and mentor models, sponsorship opportunities, leadership accountability, implicit bias training, and others. The authors call for the participation of both men and women as essential in ventures to create a more humane environment for the training and practice of medicine.
Using the Shapes of Clinical Data Trajectories to Predict Mortality in ICUs
Authors: Ma Junchao , Lee Donald K. K. , Perkins Michael E. , Pisani Margaret A. , Pinker Edieal
Published: April 2019

Objectives:

1) To show how to exploit the information contained in the trajectories of time-varying patient clinical data for dynamic predictions of mortality in the ICU; and 2) to demonstrate the additional predictive value that can be achieved by incorporating this trajectory information.

Design:

Observational, retrospective study of patient medical records for training and testing of statistical learning models using different sets of predictor variables.

Setting:

Medical ICU at the Yale-New Haven Hospital.

Subjects:

Electronic health records of 3,763 patients admitted to the medical ICU between January 2013 and January 2015.

Interventions:

None.

Measurements and Main Results:

Six-hour mortality predictions for ICU patients were generated and updated every 6 hours by applying the random forest classifier to patient time series data from the prior 24 hours. The time series were processed in different ways to create two main models: 1) manual extraction of the summary statistics used in the literature (min/max/median/first/last/number of measurements) and 2) automated extraction of trajectory features using machine learning. Out-of-sample area under the receiver operating characteristics curve and area under the precision-recall curve (“precision” refers to positive predictive value and “recall” to sensitivity) were used to evaluate the predictive performance of the two models. For 6-hour prediction and updating, the second model achieved area under the receiver operating characteristics curve and area under the precision-recall curve of 0.905 (95% CI, 0.900–0.910) and 0.381 (95% CI, 0.368–0.394), respectively, which are statistically significantly higher than those achieved by the first model, with area under the receiver operating characteristics curve and area under the precision-recall curve of 0.896 (95% CI, 0.892–0.900) and 0.905 (95% CI, 0.353–0.379). The superiority of the second model held true for 12-hour prediction/updating as well as for 24-hour prediction/updating.

Conclusions:

We show that statistical learning techniques can be used to automatically extract all relevant shape features for use in predictive modeling. The approach requires no additional data and can potentially be used to improve any risk model that uses some form of trajectory information. In this single-center study, the shapes of the clinical data trajectories convey information about ICU mortality risk beyond what is already captured by the summary statistics currently used in the literature.
Dermatological Implications of Galectin-3 in Circulation: An Evaluation From the Perspective of Patients With Differential Manifestations of Post–Kala-Azar Dermal Leishmaniasis
Authors: Datta Souvik , Ghosh Manab , Dewan Koushik , Banerjee Nilotpal , Saha Bibhuti , Mukhopadhyay Sumi
Published: April 2019

Galectin-3, a β-galactoside–binding lectin, has been implicated in vast repertoire of inflammatory and immunomodulatory processes including skin diseases. However, galectin-3 has not been comprehensively studied in infectious diseases. This study emphasizes on fascinating aspects of galectin-3 expression in dermal infection by studying post–kala-azar dermal leishmaniasis (PKDL), an intracellular infection caused by Leishmania donovani. Indian PKDL is a well-recognized parasitic dermatosis, with a high risk of anthroponotic transmission of L. donovani in causing leishmaniasis. This study aims to investigate the levels of galectin-3 and galectin-3–binding site expression in circulation of different forms of Indian patients with PKDL. Thirty-seven confirmed untreated PKDL patients, comprising 20 polymorphic and 17 macular PKDL manifestations, were evaluated for the levels of sera galectin-3 with respect to 28 age- and sex-matched healthy controls from endemic areas. Result shows a significant increment (P < 0.001) in circulatory galectin-3 levels in PKDL variants as compared to healthy controls. In addition, there were heightened levels of galectin-3 and galectin-3–binding sites on cellular infiltrates on lesional sites. Furthermore, there was a positive correlation between frequencies of mononuclear cells and galectin-3 during microcirculation in lesions. Data were well corroborated with positive correlation of IL-10 and IFN-γ with sera galectin-3 levels. Moreover, flow cytometry demonstrated the enhanced expression levels of the galectin-3–binding site in circulation in patients with PKDL as compared to healthy controls. Taken together, elevated levels of galectin-3 reflect its involvement in PKDL pathogenesis.
Microbial Keratitis in Stevens–Johnson Syndrome: A Prospective Study
Authors: Sharma Namrata , Venugopal Renu , Singhal Deepali , Maharana Prafulla Kumar , Sangwan Sushil , Satpathy Gita
Published: April 2019

Purpose:

To evaluate the microbiological profile and outcome in cases with infective keratitis in Stevens–Johnson syndrome (SJS).

Methods:

Eighty-three eyes of 68 patients with SJS presenting with microbial keratitis were recruited and managed with standard antimicrobial therapy.

Results:

Microbial keratitis developed in 34% of patients with SJS (83 eyes, 68 patients) over a period of 5 years. Four eyes (4.8%) had a history of concurrent topical steroid use at the onset of keratitis. Mean baseline best-corrected visual acuity was 1.8 ± 0.9 logMAR units. The site of corneal ulceration was central in 52 eyes (62.6%), paracentral in 17 eyes (20.5%), and peripheral in 14 eyes (16.8%). The mean ulcer area was 3.9 ± 2.7 mm2. Approximately 15 of 24 (62.5%) culture-positive eyes had bacterial infection, most of which (80%) were caused by Gram-positive bacteria. Polymicrobial infection was noted in 7 of 24 eyes (29.1%). Although 57 of 83 (68.6%) eyes healed with medical therapy, 26 of 83 (31.3%) eyes had corneal perforation and were managed with cyanoacrylate glue application (30.7%) or therapeutic keratoplasty (69.3%). Systemic infection as an inciting factor of SJS and an early presentation for keratitis were the major risk factors associated with corneal perforation. Large mean ulcer size, paracentral ulcers, and punctal involvement were associated with a good visual outcome.

Conclusions:

Infective keratitis in SJS is common, and unlike routine cases, surgical intervention is often required. However, the antibiotic sensitivity pattern suggests that resistance is not that high.
Shifting Priorities for the Survival of My Child
Authors: Tsimicalis Argerie , Stevens Bonnie , Ungar Wendy J. , Castro Aimee , Greenberg Mark , Barr Ronald
Published: April 2019

Background

Parents are confronted with a range of direct costs and intense caregiving demands following their child’s cancer diagnosis, which may potentially threaten the financial stability of the family.

Objective

The aims of this study were to explore the financial impact of a new childhood cancer diagnosis on families and understand the strategies families use to manage these financial impacts.

Methods

As part of the mixed-methods Childhood Cancer Cost Study, a descriptive qualitative design was conducted. Parents discussed costs and their impact in a semistructured, audio-taped interview. A qualitative content analysis was used to analyze the transcribed data.

Results

Seventy-eight parents participated. Parents used several strategies to maintain financial stability. These strategies consisted of managing expenses, which entailed reducing living expenses and cutting unexpected cancer costs. Efforts to absorb these expenses required families to increase their debt while seeking ways to tap into available resources, including relying on their savings and leveraging their benefits and assets, increasing their paid work hours, relying on their support networks, and seeking help from philanthropy and government agencies for financial help.

Conclusion

Parents used several strategies to manage the increased out-of-pocket expenses and reduced household income.

Implications for Practice

Our findings of the financial impact of cancer costs on families provide insight into needed practice and policy changes aimed at lessening the economic impact of a childhood cancer diagnosis on the family and allow healthcare professionals and researchers to pursue more in-depth cost assessments in the future.
Influence of Age, Sex, and Body Mass Index on the Thickness of the Gluteal Subcutaneous Fat: Implications for Safe Buttock Augmentation Procedures
Authors: Frank Konstantin , Casabona Gabriela , Gotkin Robert H. , Kaye Kai O. , Lorenc Paul Z. , Schenck Thilo L. , Lachman Nirusha , Green Jeremy B. , Duran-Vega Héctor , Cotofana Sebastian
Published: April 2019

Background:

The deep intramuscular approach during buttock augmentation with fat grafting has been associated with a significantly increased risk for pulmonary fat embolism. This study was designed to provide guidance for injection into the subcutaneous fat.

Methods:

The authors investigated 150 Caucasian individuals with an equal distribution of men and women (n = 75 each) and a balanced distribution of age (n = 30 per decade: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 to 69 years) and body mass index (n = 50 per group: ≤24.9 kg/m2, between 25.0 and 29.9kg/m2, and ≥30 kg/m2). Ultrasound-based measurements were conducted of the thickness of the total, superficial, and deep gluteal fatty layers.

Results:

An increase in body mass index of 1.0 kg/m2 corresponded to an increase of 3 mm of the total gluteal subcutaneous fat of men and a 4-mm increase of the total gluteal subcutaneous fat in women. With increasing age, the thickness of the deep fatty layer increased, whereas with increasing body mass index the thickness of the superficial layer primarily increased. Formulas were generated to estimate the total thickness of the gluteal subcutaneous fatty layer for men [total thickness (in millimeters) = −33.56 + (age × 0.078) + (body mass index × 3.042)] and women [total thickness (in millimeters) = −56.997 + (age × 0.1) + (body mass index × 3.86)].

Conclusions:

Knowing the total thickness of the gluteal subcutaneous fat (i.e., the safe space) allows surgeons to estimate their operating range for cannula motion even if no ultrasound machine is available during buttock augmentation with fat grafting. This can increase safety, potentially reducing the number of adverse events.
Sumatriptan Increases Skin Flap Survival through Activation of 5-Hydroxytryptamine 1b/1d Receptors in Rats: The Mediating Role of the Nitric Oxide Pathway
Authors: Dehdashtian Amir , Afshari Khashayar , Zarifeh Jazaeri Seyedeh , Haddadi Nazgol-Sadat , Sheikhi Mehdi , Abbaszadeh-Kasbi Ali , Tavangar Seyed Mohammad , Jazaeri Farahnaz , Amirlak Bardia , Dehpour Ahmad Reza
Published: April 2019

Background:

Random pattern skin flaps are applicable for reconstructing any defect in plastic surgery. However, they are difficult to apply because of necrosis. Sumatriptan, a selective 5-hydroxytryptamine 1b/1d agonist, is routinely used to offset acute migraine attacks. Recent studies have suggested that sumatriptan may induce vasodilation at lower concentrations. The authors’ aim is to investigate the effect of sumatriptan on skin flap survival and the role of nitric oxide in this phenomenon.

Methods:

Seventy-two male Sprague-Dawley rats were divided into eight groups. Increasing doses of sumatriptan (0.1, 0.3, and 1 mg/kg) were given intraperitoneally to three different groups after dorsal random pattern skin flaps were performed. To assess the exact role of 5-hydroxytryptamine 1b/1d receptors, GR-127935 was administered solely and with sumatriptan. N-ω-nitro-
l
-arginine methyl ester (l-NAME, a nonselective nitric oxide synthase inhibitor) was used to evaluate any possible involvement of nitric oxide in this study. All rats were examined 7 days later.

Results:

The authors’ results demonstrated that flap survival was increased by lower doses of sumatriptan compared to a control group for both 0.3 mg/kg (p = 0.03, mean difference = 32, SE = 8) and 0.1 mg/kg (p = 0.02, mean difference = 26, SE = 8). This protective effect was eliminated by coadministration of GR-127935 or N-ω-nitro-
l
-arginine methyl ester with sumatriptan. Histopathologic studies revealed a significant increase in capillary count and collagen deposition and a decreased amount of edema, inflammation, and degeneration.

Conclusions:

Sumatriptan in lower concentration increases skin flap survival by means of activation of 5-hydroxytryptamine 1b/1d receptors. This effect is mediated through the nitric oxide synthase pathway.
Complement Deposition on the Surface of RBC After Trauma Serves a Biomarker of Moderate Trauma Severity: A Prospective Study
Authors: Satyam Abhigyan , Andreo Kostas , Lapchak Peter H. , Dalle Lucca Jurandir J. , Davis Roger B. , Tsokos Maria G. , Shapiro Nathan I. , Tsokos George C.
Published: April 2019

Background:

Activation of the complement system and complement deposition on red blood cells (RBCs) contribute to organ damage in trauma. We conducted a prospective study in subjects with traumatic injuries to determine the pattern of complement deposition on RBC and whether they are associated with clinical outcomes.

Method:

A total of 124 trauma patients and 42 healthy controls were enrolled in this prospective study. RBC and sera were collected at 0, 6, 24, and 72 h from trauma patients and healthy controls during a single draw. Presence of C4d, C3d, C5b-9, phosphorylation of band 3 and production of nitric oxide were analyzed by flow cytometry.

Results:

RBC from trauma patients at all time points up to 24 h displayed significantly higher deposition of C4d on their RBC membrane as compared with healthy donors. Incubation of normal RBC with sera from trauma patients resulted in significant increase of C4d deposition (at 0, 6, 24, and 72 h), C5b-9 deposition (at 0 and 6 h), phosphorylation of band 3 (at 0 and 24 h), and nitric oxide production up to 24 h compared with sera from healthy subjects. Deposition of C4d and C5b-9 in patients with an Injury Severity Score (ISS) of 9 and above remained elevated up to 72 h.

Conclusions:

Our study demonstrates that the presence of C4d, C3d, and C5b-9 on the surface of RBC is linked to increased phosphorylation of band 3 and increased production of nitric oxide. Deposition of C4d and C5b-9 decreased faster over course of 3-day study in subjects with ISS less than 9.
Review of Existing Scoring Systems for Massive Blood Transfusion in Trauma Patients: Where Do We Stand?
Authors: El-Menyar Ayman , Mekkodathil Ahammed , Abdelrahman Husham , Latifi Rifat , Galwankar Sagar , Al-Thani Hassan , Rizoli Sandro
Published: April 2019

Background:

Uncontrolled bleeding is the main cause of the potential preventable death in trauma patients. Accordingly, we reviewed all the existing scores for massive transfusion posttraumatic hemorrhage and summarized their characteristics, thus making it easier for the reader to have a global view of these scores—how they were created, their accuracy and to which population they apply.

Methods:

A narrative review with a systematic search method to retrieve the journal articles on the predictive scores or models for massive transfusion was carried out. A literature search using PubMed, SCOPUS, and Google scholar was performed using relevant keywords in different combinations. The keywords used were “massive transfusion,” “score,” “model,” “trauma,” and “hemorrhage” in different combinations. The search was limited for full-text articles published in English language, human species and for the duration from January 1, 1998 to November 30, 2018.

Results:

The database search yielded 295 articles. The search was then restricted to the inclusion criteria which retrieved 241 articles. Duplicates were removed and full-texts were assessed for the eligibility to include in the review which resulted in inclusion of 24 articles. These articles identified 24 scoring systems including modified or revised scores. Different models and scores for identifying patients requiring massive transfusion in military and civilian settings have been described. Many of these scorings were complex with difficult calculation, while some were simple and easy to remember.

Conclusions:

The current prevailing practice that is best described as institutional or provider centered should be supplemented with score-based protocol with auditing and monitoring tools to refine it. This review summarizes the current scoring models in predicting the need for MT in civilian and military trauma. Several questions remain open; i.e., do we need to develop new score, merge scores, modify scores, or adopt existing score for certain trauma setting?
Adverse Outcomes After Bile Spillage in Incidental Gallbladder Cancers
Authors: Horkoff Michael J. , Ahmed Zubir , Xu Yuan , Sutherland Francis R. , Dixon Elijah , Ball Chad G. , Bathe Oliver F.
Published: April 2019

Objective:

To determine the effect of bile spillage during cholecystectomy on oncological outcomes in incidental gallbladder cancers.

Background:

Gallbladder cancer (GBC) is rare, but lethal. Achieving complete resection offers the best chance of survival. About 30% of GBCs are discovered incidentally after cholecystectomy for benign pathology. There is an anecdotal association between peritoneal dissemination and bile spillage during the index cholecystectomy. However, no population-based studies are available that measure the consequences of bile spillage on patient outcomes.

Methods:

We conducted a retrospective cohort comparison of patients with incidental GBC. All cholecystectomies and cases of GBC in Alberta, Canada, from 2001 to 2015, were identified. GBCs discovered incidentally were included. Operative events leading to bile spillage were reviewed. Patient outcomes were compared between cases of bile spillage versus no contamination.

Results:

In all, 115,484 cholecystectomies were performed, and a detailed analysis was possible in 82 incidental GBC cases. In 55 cases (67%), there was bile spillage during the index cholecystectomy. Peritoneal carcinomatosis occurred more frequently in those with bile spillage (24% vs 4%; P = 0.0287). Patients with bile spillage were less likely to undergo a radical re-resection (25% vs 56%; P = 0.0131) and were less likely to achieve an R0 resection margin [odds ratio 0.19, 95% confidence interval (CI) 0.06–0.55]. On Cox regression modeling, bile spillage was an independent predictor of shorter disease-free survival (hazard ratio 1.99, 95% CI 1.07–3.67).

Conclusion:

For incidentally discovered GBC, bile spillage at the time of index cholecystectomy has measureable adverse consequences on patient outcomes. Early involvement of a hepatobiliary specialist is recommended where concerning features for GBC exist.
Microscopic Hematuria as a Screening Tool for Urologic Malignancies in Women
Authors: Jeppson Peter C. , Jakus-Waldman Sharon , Yazdany Tajnoos , Schimpf Megan O. , Ferzandi Tanaz R. , Yurteri-Kaplan Ladin A. , Knoepp Leise , Mamik Mamta , Resnick Helaine E. , Ward Renee M.
Published: April 2019

Introduction

Most causes of microscopic hematuria (MH) are benign but may indicate an underlying malignancy. Current MH evaluation guidelines are reflective of male urologic malignancy risks. The objective of this systematic review was to evaluate whether the finding of MH predicts subsequent urologic malignancy in women.

Methods

MEDLINE was searched between January 1990 and June 8, 2018. The positive predictive value (PPV) of MH as a screening tool for urologic malignancy was calculated for each study individually and collectively. The pooled relative risk of urologic malignancy associated with MH was calculated.

Results

Seventeen studies were included. Eight studies included only women. In total, 300 urinary tract cancers were identified in 110,179 women with MH. The PPV of MH as a screening tool for cancer ranged from approximately 0.6% to 2.8%; confidence intervals (CIs) suggested this is a relatively unstable performance indicator because of small sample sizes. Average PPV across all studies was 2.13%, but the weighted average PPV was 0.24%. The risk of urologic malignancies among women with relative those without MH was 2.01 (95% CI, 1.61–2.51). Based on these limited data, we estimate that 859 (95% CI, 654–1250) women with MH would require complete evaluation to identify 1 urinary tract malignancy.

Conclusions

A very small proportion of women with MH are likely to have a urologic malignancy. Approximately 859 women require full screening to identify 1 malignancy. Current evidence is limited, and further studies, specifically in women, are needed.
The Last Year Before Graft Failure Negatively Impacts Economic Outcomes and is Associated With Greater Healthcare Resource Utilization Compared With Previous Years in the United Kingdom: Results of a Retrospective Observational Study
Authors: Muduma Gorden , Aluvihare Varuna , Clancy Marc , de Nigris Enrico , Whitlock Carolyn , Landeira Margarita , Nazir Jameel
Published: April 2019

Background.

Kidney and liver transplantation is the standard of care for end-stage renal or liver disease. However, long-term survival of kidney and liver grafts remain suboptimal. Our study aimed to understand the healthcare resources utilized and their associated costs in the years before graft failure.

Methods.

Two noninterventional, retrospective, observational studies were conducted in cohorts of kidney or liver transplant patients. Once identified, patients were followed using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics databases from the date of transplantation to the date of the first graft failure. Total healthcare costs in the year before graft failure (primary endpoint) and during years 2–5 before graft failure (secondary endpoint) were collected.

Results.

A total of 269 kidney and 81 liver transplant patients were analyzed. The mean total costs were highest for all resource components in the last year before graft failure, except for mean costs of immunosuppressive therapy per patient, which decreased slightly by index date (ie, graft failure). The mean total healthcare costs in the last year before graft failure were £8115 for kidney and £9988 for liver transplant patients and were significantly (P < 0.05) higher than years 2–5 before graft failure. Mean healthcare costs for years 2, 3, 4, and 5 before graft failure were £5925, £5575, £5469, and £5468, respectively, for kidney, and £6763, £7042, £6020, and £5651, respectively, for liver transplant patients.

Conclusions.

Total healthcare costs in the last year before graft failure are substantial and statistically significantly higher than years 2–5 before graft failure, in both kidney and liver transplant patients. Our findings show the economic burden placed on healthcare services in the years before graft failure.
Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion
Authors: Satpathy Ansuman T. , Granja Jeffrey M. , Yost Kathryn E. , Qi Yanyan , Meschi Francesca , McDermott Geoffrey P. , Olsen Brett N. , Mumbach Maxwell R. , Pierce Sarah E. , Corces M. Ryan , Shah Preyas , Bell Jason C. , Jhutty Darisha , Nemec Corey M. , Wang Jean , Wang Li , Yin Yifeng , Giresi Paul G. , Chang Anne Lynn S. , Zheng Grace X.Y. , Greenleaf William J. , Chang Howard Y.
Published: April 2019

Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here we present a massively parallel droplet-based platform for mapping transposase-accessible chromatin in tens of thousands of single cells per sample (scATAC-seq). We obtain and analyze chromatin profiles of over 200,000 single cells in two primary human systems. In blood, scATAC-seq allows marker-free identification of cell type-specificcis- andtrans-regulatory elements, mapping of disease-associated enhancer activity, and reconstruction of trajectories of differentiation from progenitors to diverse and rare immune cell types. In basal cell carcinoma, scATAC-seq reveals regulatory landscapes of malignant, stromal, and immune cell types in the tumor microenvironment. Moreover, scATAC-seq of serial tumor biopsies before and after PD-1 blockade allows identification of chromatin regulators and differentiation trajectories of therapy-responsive intratumoral T cell subsets, revealing a shared regulatory program driving CD8+T cell exhaustion and CD4+T follicular helper cell development. We anticipate that droplet-based single-cell chromatin accessibility will provide a broadly applicable means of identifying regulatory factors and elements that underlie cell type and function.
Automated Change Detection Methods for Satellite Data that can Improve Conservation Implementation
Authors: Evans Michael J. , Malcom Jacob W.
Published: April 2019

A significant limitation in biodiversity conservation has been the effective implementation of laws and regulations that protect species habitats from degradation. Flexible, efficient, and effective monitoring and enforcement methods are needed to help conservation policies realize their full benefit. As remote sensing data become more numerous and accessible, they can be used to identify and quantify land cover changes and habitat loss. However, these data remain underused for systematic conservation monitoring in part because of a lack of simple tools. We adapted and developed two generalized methods that automatically detect land cover changes in a variety of habitat types using free and publicly available data and tools. We evaluated the performance of these algorithms in two ways. First, we tested the algorithms over 100 sites of known change in the United States, finding these approaches were effective (AUC > 0.90) at distinguishing between areas of land cover change and areas of no change. Second, we evaluated algorithm effectiveness by comparing results to manually identified areas of change in four case studies involving imperiled species habitat: oil and gas development in the range of the Greater Sage Grouse; sand mining operations in the range of the dunes sagebrush lizard; loss of Piping Plover coastal habitat in the wake of hurricane Michael (2018); and residential development in beach mouse habitat. The relative performance of each algorithm differed in each habitat type, but both provided effective means of detecting and delineating habitat loss. Our results show how these algorithms can be used to help close the implementation gap of monitoring and enforcement in biodiversity conservation and we provide a free online tool that can be used to run these analyses.

Article impact statement

Methods for automating the detection of habitat loss in satellite images that can be used to monitor and enforce conservation policy.
Living cell-only bioink and photocurable supporting medium for printing and generation of engineered tissues with complex geometries
Authors: Jeon Oju , Lee Yu Bin , Jeong Hyeon , Lee Sang Jin , Alsberg Eben
Published: April 2019

Scaffold-free engineering of three-dimensional (3D) tissue has focused on building sophisticated structures to achieve functional constructs. Although the development of advanced manufacturing techniques such as 3D printing has brought remarkable capabilities to the field of tissue engineering, technology to create and culture individual cell only-based high-resolution tissues, without an intervening biomaterial scaffold to maintain construct shape and architecture, has been unachievable to date. In this report, we introduce a cell printing platform which addresses the aforementioned challenge and permits 3D printing and long-term culture of a living cell-only bioink lacking a biomaterial carrier for functional tissue formation. A biodegradable and photocrosslinkable microgel supporting bath serves initially as a fluid, allowing free movement of the printing nozzle for high-resolution cell extrusion, while also presenting solid-like properties to sustain the structure of the printed constructs. The printed human stem cells, which are the only component of the bioink, couple together via transmembrane adhesion proteins and differentiate down tissue-specific lineages while being cultured in a further photocrosslinked supporting bath to form bone and cartilage tissue with precisely controlled structure. Collectively, this system, which is applicable to general 3D printing strategies, is paradigm shifting for printing of scaffold-free individual cells, cellular condensations and organoids, and may have far reaching impact in the fields of regenerative medicine, drug screening, and developmental biology.
GIGANTEA recruits deubiquitylases, UBP12 and UBP13, to regulate accumulation of the ZTL photoreceptor complex
Authors: Lee Chin-Mei , Li Man-Wah , Feke Ann , Saffer Adam M. , Liu Wei , Gendron Joshua M.
Published: April 2019

To remain synchronous with the environment, plants constantly survey daily light conditions using an array of photoreceptors and adjust their circadian rhythms accordingly. ZEITLUPE (ZTL), a blue light photoreceptor with E3 ubiquitin ligase activity, communicates end-of-day light conditions to the circadian clock. To function properly, ZTL protein must accumulate but not destabilize target clock transcription factors before dusk, while in the dark ZTL mediates degradation of target proteins. It is not clear how ZTL can accumulate to high levels in the light while its targets remain stable. Two deubiquitylating enzymes, UBIQUITIN-SPECIFIC PROTEASE 12 and UBIQUITIN-SPECIFIC PROTEASE 13 (UBP12 and UBP13), which have opposite genetic and biochemical functions to ZTL, were shown to associate with the ZTL protein complex. Here we demonstrate that the ZTL light-dependent interacting partner, GIGANTEA (GI), recruits UBP12 and UBP13 to the ZTL photoreceptor complex. We show that loss ofUBP12andUBP13reduces ZTL and GI protein levels through a post-transcriptional mechanism. Furthermore, the ZTL target protein TOC1 is unable to accumulate to normal levels inubpmutants, indicating that UBP12 and UBP13 are necessary to stabilize clock transcription factors during the day. Our results demonstrate that the ZTL photoreceptor complex contains both ubiquitin-conjugating and -deconjugating enzymes, and that these two opposing enzyme types are necessary for the complex to properly regulate the circadian clock. This work also shows that deubiquitylating enzymes are a core design element of circadian clocks that is conserved from plants to animals.
Atg8a interacts with transcription factor Sequoia to control the expression of autophagy genes in Drosophila
Authors: Jacomin Anne-Claire , Petridi Stavroula , DiMonaco Marisa , Jain Ashish , Bhujabal Zambarlal , Mulakkal Nitha , Palara Anthimi , Powell Emma L. , Chung Bonita , Zampronio Cleidiane G. , Jones Alexandra , Cameron Alexander , Johansen Terje , Nezis Ioannis P.
Published: April 2019

Autophagy is a fundamental, evolutionarily conserved, process in which cytoplasmic material is degraded through the lysosomal pathway [1–7]. One of the most important and well-studied autophagy-related proteins is LC3 [Microtubule-associated protein 1 light chain 3, (called Atg8 in yeast and Drosophila)], which participates in autophagosome formation and autophagy cargo selection in the cytoplasm, and is one of the most widely utilized markers of autophagy [8, 9]. Despite growing evidence that LC3 is enriched in the nucleus, little is known about the mechanisms involved in targeting LC3 to the nucleus and the nuclear components it interacts with [10–13]. Here we show that Drosophila Atg8a protein, homologous to mammalian LC3 and yeast Atg8, interacts with the transcription factor Sequoia in a LIR-motif dependent manner. We show that Sequoia depletion induces autophagy in nutrient rich conditions through enhanced expression of autophagy genes. We also show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex, and is acetylated at position K46. Additionally, we show that Atg8a interacts with the deacetylase Sir2, which deacetylates Atg8a during starvation in order to activate autophagy. Our results suggest a mechanism of regulation of expression of autophagy genes by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL-1 and Sir2.
A mobile ELF4 delivers circadian temperature information from shoots to roots
Authors: Chen Wei Wei , Takahashi Nozomu , Hirata Yoshito , Nusinow Dmitri A. , Kay Steve A. , Mas Paloma
Published: April 2019

The circadian clock is synchronized by environmental cues, mostly by light and temperature. Elucidating how the plant circadian clock responds to temperature oscillations is crucial to understand plant responsiveness to the environment. Here we found a prevalent temperature-dependent function of the Arabidopsis clock component ELF4 (EARLY FLOWERING 4) in the root clock. Micrografting assays and mathematical analyses show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information but trafficking is essential to control the period of the root clock in a temperature-dependent manner. At low temperatures, ELF4 mobility is favored and results in a slow-paced root clock while high temperatures decrease movement, leading to a fast clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in roots.
Deep learning for cancer type classification
Authors: Zeng Zexian , Mao Chengsheng , Vo Andy , Nugent Janna Ore , Khan Seema A , Clare Susan E , Luo Yuan
Published: April 2019

Genetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic mutations as independent features for classification and are limited by study power. To address these limitations, we propose DeepCues, a deep learning model that utilizes convolutional neural networks to derive features from DNA sequencing data for disease classification and relevant gene discovery. Using whole-exome sequencing, germline variants and somatic mutations, including insertions and deletions, are interactively amalgamated as features. In this study, we applied DeepCues to a dataset from TCGA to classify seven different types of major cancers and obtained an overall accuracy of 77.6%. We compared DeepCues to conventional methods and demonstrated a significant overall improvement (p=8.8E-25). Using DeepCues, we found that the top 20 genes associated with breast cancer have a 40% overlap with the top 20 breast cancer genes in the COSMIC database. These data support DeepCues as a novel method to improve the representational resolution of both germline variants and somatic mutations interactively and their power in predicting cancer types, as well the genes involved in each cancer.
High specificity of widely used phospho-tau antibodies validated using a quantitative whole-cell based assay
Authors: Li Dan , Cho Yong Ku
Published: April 2019

Antibodies raised against defined phosphorylation sites of the microtubule-associated protein tau are widely used in scientific research and being applied in clinical assays. However, recent studies have revealed an alarming degree of non-specific binding found in these antibodies. In order to quantify and compare the specificity phospho-tau antibodies and other post-translational modification site-specific antibodies in general, a measure of specificity is urgently needed. Here we report a robust flow cytometry assay using human embryonic kidney (HEK) cells that enables the determination of a specificity parameter termed Φ, which measures the fraction of non-specific signal in antibody binding. We validate our assay using anti-tau antibodies with known specificity profiles, and apply it to measure the specificity of 7 widely used phospho-tau antibodies (AT270, AT8, AT100, AT180, PHF-6, TG-3, and PHF-1) among others. We successfully determined the Φ values for all antibodies except AT100, which did not show detectable binding in our assay. Our results show that antibodies AT8, AT180, PHF-6, TG-3, and PHF-1 have Φ values near 1, which indicates no detectable non-specific binding. AT270 showed Φ value around 0.8, meaning that approximately 20% of the binding signal originates from non-specific binding. Further analyses using immunocytochemistry and western blotting confirmed the presence of non-specific binding of AT270 to non-tau proteins found in HEK cells and the mouse hippocampus. We anticipate that the quantitative approach and parameter introduced here will be widely adopted as a standard for reporting the specificity for phospho-tau antibodies, and potentially for post-translational modification targeting antibodies in general.