bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservation of Intracellular Pathogenic Strategy among Distantly Related Cryptococcal Species
Authors: Freij Joudeh B. , Fu Man Shun , De Leon Rodriguez Carlos M. , Dziedzic Amanda , Jedlicka Anne E. , Dragotakes Quigly , Rossi Diego C. P. , Jung Eric H. , Coelho Carolina , Casadevall Arturo 
Published: April 2018

ABSTRACT

The genus
Cryptococcus
includes several species pathogenic for humans. Until recently, the two major pathogenic species were recognized to be
Cryptococcus neoformans
and
Cryptococcus gattii
. We compared the interaction of murine macrophages with three
C. gattii
species complex strains (WM179, R265, and WM161, representing molecular types VGI, VGIIa, and VGIII, respectively) and one
C. neoformans
species complex strain (H99, molecular type VNI) to ascertain similarities and differences in the yeast intracellular pathogenic strategy. The parameters analyzed included nonlytic exocytosis frequency, phagolysosomal pH, intracellular capsular growth, phagolysosomal membrane permeabilization, and macrophage transcriptional response, assessed using time-lapse microscopy, fluorescence microscopy, flow cytometry, and gene expression microarray analysis. The most striking result was that the intracellular pathogenic strategies of
C. neoformans
and
C. gattii
species complex strains were qualitatively similar, despite the species having separated an estimated 100 million years ago. Macrophages exhibited a leaky phagolysosomal membrane phenotype and nonlytic exocytosis when infected with either
C. gattii
or
C. neoformans
. Conservation of the intracellular strategy among species that separated long ago suggests that it is ancient and possibly maintained by similar selection pressures through eons.
Comparing standard office-based follow-up with text-based remote monitoring in the management of postpartum hypertension: a randomised clinical trial
Authors: Hirshberg Adi , Downes Katheryne , Srinivas Sindhu 
Published: April 2018

BackgroundMonitoring blood pressure at 72 hours and 7–10 days post partum in women with hypertensive disorders is recommended to decrease morbidity. However, there are no recommendations as to how to achieve this.ObjectiveTo compare the effectiveness of text-based blood pressure monitoring to in-person visits for women with hypertensive disorders of pregnancy in the immediate postpartum period.MethodsRandomised clinical trial among 206 postpartum women with pregnancy-related hypertension diagnosed during the delivery admission between August 2016 and January 2017. Women were randomised to 2 weeks of text-based surveillance using a home blood pressure cuff and previously tested automated platform or usual care blood pressure check at their prenatal clinic 4–6 days following discharge. The primary study outcome was a single recorded blood pressure in the first 10 days post partum. The ability to meet American Congress of Obstetricians and Gynecologists (ACOG) guidelines, defined as having a blood pressure recorded on postpartum days 3–4 and 7–10 was evaluated in the text message group. The study was powered to detect a 1.4-fold increase in a single recorded blood pressure using text messaging. All outcomes were analysed as intention to treat.Results206 women were randomised (103 in each arm). Baseline characteristics were similar. There was a statistically significant increase in a single blood pressure obtained in the texting group in the first 10 days post partum as compared with the office group (92.2% vs 43.7%; adjusted OR 58.2 (16.2–208.1), p<0.001). Eighty-four per cent of patients undergoing text-based surveillance met ACOG criteria for blood pressures at both recommended points.ConclusionsText-based monitoring is more effective in obtaining blood pressures and meeting current clinical guidelines in the immediate postdischarge period in women with pregnancy-related hypertension compared with traditional office-based follow-up.Trial registration numberNCT03185455, Remote Surveillance of Postpartum Hypertension (TextBP), https://clinicaltrials.gov.
Fifty years of preventing and treating childhood behaviour disorders: a systematic review to inform policy and practice
Authors: Waddell Charlotte , Schwartz Christine , Andres Caitlyn , Barican Jenny Lou , Yung Donna 
Published: April 2018

QuestionOppositional defiant and conduct disorders (ODD and CD) start early and persist, incurring high individual and collective costs. To inform policy and practice, we therefore asked: What is the best available research evidence on preventing and treating these disorders?Study selection and analysisWe sought randomised controlled trials (RCTs) evaluating interventions addressing the prevention or treatment of behaviour problems in individuals aged 18 years or younger. Our criteria were tailored to identify higher-quality RCTs that were also relevant to policy and practice. We searched the CINAHL, ERIC, MEDLINE, PsycINFO and Web of Science databases, updating our initial searches in May 2017. Thirty-seven RCTs met inclusion criteria—evaluating 15 prevention programmes, 8 psychosocial treatments and 5 medications. We then conducted narrative synthesis.FindingsFor prevention, 3 notable programmes reduced behavioural diagnoses: Classroom-Centered Intervention; Good Behavior Game; and Fast Track. Five other programmes reduced serious behaviour symptoms such as criminal activity. Prevention benefits were long term, up to 35 years. For psychosocial treatment, Incredible Years reduced behavioural diagnoses. Three other interventions reduced criminal activity. Psychosocial treatment benefits lasted from 1 to 8 years. While 4 medications reduced post-test symptoms, all caused important adverse events.ConclusionsConsiderable RCT evidence favours prevention.Clinical implicationsEffective prevention programmes should therefore be made widely available. Effective psychosocial treatments should also be provided for all children with ODD/CD. But medications should be a last resort given associated adverse events and given only short-term evidence of benefits. Policymakers and practitioners can help children and populations by acting on these findings.
Prehospital neurological deterioration in stroke
Authors: Slavin Sabreena J , Sucharew Heidi , Alwell Kathleen , Moomaw Charles J , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L , Ferioli Simona , McMullan Jason , Mackey Jason , De Los Rios La Rosa Felipe , Martini Sharyl , Kissela Brett M , Kleindorfer Dawn O 
Published: April 2018

Background and purposePatients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND).MethodsAmong the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals’ admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival.ResultsOf 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61–83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND.ConclusionHaemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.
Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis
Authors: Cacoub Patrice , Desbois Anne Claire , Comarmond Cloe , Saadoun David 
Published: April 2018

Background and aimsExtrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-cirrhotic chronically infected individuals.MethodsA systematic review was conducted. Identified studies from targeted database searches on Embase and Medline were screened. The methodological quality of the included publications was evaluated. Random-effect model meta-analyses were performed. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.ResultsData were extracted from a total of 48 identified studies. Achieving sustained virological response (SVR) was associated with reduced extrahepatic mortality (vs no SVR, OR 0.44 (95% CI 0.28 to 0.67)). SVR was associated with higher complete remissions in patients with cryoglobulinemia vasculitis (OR 20.76 (6.73 to 64.05)) and a higher objective response in those with malignant B-cell lymphoproliferative diseases (OR 6.49 (2.02 to 20.85)). Achieving SVR was also associated with reduced insulin resistance at follow-up (OR 0.42 (0.33 to 0.53)) and a significant protective effect on the incidence of diabetes (OR 0.34 (0.21 to 0.56)). Lack of randomised data comparing SVR versus non-SVR patients for the relevant extrahepatic indications attenuated these analyses.ConclusionAntiviral therapy can reduce extrahepatic manifestations related to HCV when SVR is achieved. Higher quality data, and reporting over longer follow-up periods, will be required to thoroughly explore comprehensive HCV treatment strategies.
Telomerase promoter mutations and copy number alterations in solitary fibrous tumours
Authors: Lin Yingbo , Seger Nelly , Tsagkozis Panagiotis , Hesla Asle C , Ghaderi Mehran , Chen Yi , Ehnman Monika , Warsito Dudi , Wejde Johan , Larsson Olle , Haglund Felix 
Published: April 2018

AimsSolitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by theNAB2–STAT6fusion gene. Activating mutations in thetelomerase reverse transcriptase(hTERT) gene promoter has been reported to associate with adverse patient outcome in SFTs.MethodsWe analysed thehTERTgene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions.ResultsActivating −124 C>T (n=12) or −148 C>T (n=2) mutations were found in 33% of the tumours and associated with older age (P=0.006), necrosis (P=0.009), higher mitotic rate (P=0.003), nuclear atypia (P=0.002), malignant histological diagnosis (P=0.04) and worse progression-free survival (P=0.023). We also observed frequent (24%)hTERTpromoter mutations in histologically benign tumours without metastasis (mean follow-up >9 years), and in 14%–18% of low-risk SFTs as determined by three risk-stratification models. Mutations were seen in 2/6 metastatic tumours and metastatic lesions.hTERTcopy number gain was seen in 11/28hTERTpromoter wild-type cases.ConclusionsActivatinghTERTpromoter mutations associate with aggressive histopathological features, indicating a role in tumour progression. Given the comparatively high prevalence ofhTERTpromoter mutations in low-risk and non-metastasising lesions, further studies are required to clarify the prognostic value ofhTERTpromoter analysis before implementing the analysis in clinical diagnostics.
Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment
Authors: Booth Kevin T , Kahrizi Kimia , Najmabadi Hossein , Azaiez Hela , Smith Richard JH 
Published: April 2018

BackgroundHearing loss is a genetically and phenotypically heterogeneous disorder.ObjectivesThe purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families.MethodsWe used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays.ResultsWe identified two homozygous splice-altering variants (c.37G>T and c.662–1G>C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G>T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G>C activates a cryptic splice site inside exon 5 resulting in a shift in the mRNA reading frame.ConclusionsThese results suggest that loss-of-function mutations in CEACAM16 result in postlingual progressive hearing impairment and further support the role of CEACAM16 in auditory function.
Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation
Authors: Echevarria Carlos , Gray Joanne , Hartley Tom , Steer John , Miller Jonathan , Simpson A John , Gibson G John , Bourke Stephen C 
Published: April 2018

BackgroundPrevious models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection. Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable.MethodsIn a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC). The primary outcome was health and social costs at 90 days.ResultsMean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI −2343 to 312). Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1–7), UC=5 (IQR 2–12) (P=0.001). Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected. Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%. There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD.ConclusionHAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients. Compared with earlier models, selection is simpler and approximately twice as many patients are eligible. The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge.Trial registration numberRegistered prospectively ISRCTN29082260.
Genetic parameters of milk cholesterol content in Holstein cattle
Authors: Do Duy N. , Fleming Allison , Schenkel Flavio S. , Miglior Filippo , Zhao Xin , Ibeagha-Awemu Eveline M. 
Published: April 2018

This study aimed to estimate heritability for milk cholesterol (CHL) and genetic correlations between milk CHL and other production traits (test-day milk, fat, and protein yields, fat and protein percentages, and somatic cell score). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). Univariate models were used to estimate variances and heritability, whereas bivariate models were used to compute correlations using data from 1793 cows. The average concentrations (standard deviation) of CHL_fat and CHL_milk were 275.63 (75) mg and 11.16 (3.63) mg, respectively. Milk CHL content was significantly affected by days in milk and herd (P < 0.05), but not by parity, regardless of the scale of expression. Heritability estimates for CHL_fat and CHL_milk were 0.06 ± 0.04 and 0.17 ± 0.06, respectively. Phenotypic and genetic correlations between CHL_fat and CHL_milk were 0.82 and 0.44 ± 0.24, respectively. CHL_fat had nonsignificant genetic correlations with all production traits, whereas CHL_milk had significant (P < 0.05) genetic correlations with milk yield (−0.47), fat yield (0.51), protein percentage (0.56), and fat percentage (0.88). This is the first study to estimate genetic parameters for milk CHL content. Further studies are required to assess the possibility of genetically selecting cows with lower milk CHL content.
MYD88 L265P Mutation in Lymphoid Malignancies
Authors: Yu Xinfang , Li Wei , Deng Qipan , Li Ling , Hsi Eric D. , Young Ken H. , Zhang Mingzhi , Li Yong 
Published: April 2018

Abstract
Next-generation sequencing has revealed cancer genomic landscapes, in which over 100 driver genes that, when altered by intragenic mutations, can promote oncogenesis. MYD88 is a driver gene found in hematologic B-cell malignancies. A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance. Few cancers such as WM have a single amino acid substitution in one gene like MYD88 L265P that occurs in ∼90% of cases, making WM paradigmatic for study of a single causative mutation in oncogenesis. In this review, we summarize the frequency and cancer spectrum of MYD88 L265P and its downstream effects in lymphoid cancers. Malignant B cells with MYD88 L265P are likely transformed from IgM-producing B cells either in response to T-cell–independent antigens or in response to protein antigens before class switching. We also discuss therapeutic strategies that include targeting Bruton tyrosine kinase and other kinases, interfering with the assembly of MYD88 and its interacting partners, and MYD88 L265P-specific peptide-based immunotherapy. Cancer Res; 78(10); 2457–62. ©2018 AACR.
Association of Coffee and Tea Intake with the Oral Microbiome: Results from a Large Cross-Sectional Study
Authors: Peters Brandilyn A. , McCullough Marjorie L. , Purdue Mark P. , Freedman Neal D. , Um Caroline Y. , Gapstur Susan M. , Hayes Richard B. , Ahn Jiyoung 
Published: April 2018

Abstract
Background: The oral microbiota play a central role in oral health, and possibly in carcinogenesis. Research suggests that coffee and tea consumption may have beneficial health effects. We examined the associations of these common beverages with the oral ecosystem in a large cross-sectional study.
Methods: We assessed oral microbiota in mouthwash samples from 938 participants in two U.S. cohorts using 16S rRNA gene sequencing. Coffee and tea intake were assessed from food frequency questionnaires. We examined associations of coffee and tea intake with overall oral microbiota diversity and composition using linear regression and permutational MANOVA, respectively, and with taxon abundance using negative binomial generalized linear models; all models adjusted for age, sex, cohort, body mass index, smoking, ethanol intake, and energy intake.
Results: Higher tea intake was associated with greater oral microbiota richness (P = 0.05) and diversity (P = 0.006), and shifts in overall community composition (P = 0.002); coffee was not associated with these microbiome parameters. Tea intake was associated with altered abundance of several oral taxa; these included Fusobacteriales, Clostridiales, and Shuttleworthia satelles (higher with increasing tea) and Bifidobacteriaceae, Bergeyella, Lactobacillales, and Kingella oralis (lower with increasing tea). Higher coffee intake was only associated with greater abundance of Granulicatella and Synergistetes.
Conclusions: In the largest study to date of tea and coffee consumption in relation to the oral microbiota, the microbiota of tea drinkers differed in several ways from nondrinkers.
Impact: Tea-driven changes to the oral microbiome may contribute to previously observed associations between tea and oral and systemic diseases, including cancers. Cancer Epidemiol Biomarkers Prev; 27(7); 814–21. ©2018 AACR.
The Role of Cold Pools in Tropical Oceanic Convective Systems
Authors: Grant Leah D. , Lane Todd P. , van den Heever Susan C. 
Published: April 2018

Abstract
The processes governing organized tropical convective systems are not completely understood despite their important influences on the tropical atmosphere and global circulation. In particular, cold pools are known to influence the structure and maintenance of midlatitude systems via Rotunno–Klemp–Weisman (RKW) theory, but cold pools may interact differently with tropical convection because of differences in cold pool strength and environmental shear. In this study, the role of cold pools in organized oceanic tropical convective systems is investigated, including their influence on system intensity, mesoscale structure, and propagation. To accomplish this goal, high-resolution idealized simulations are performed for two different systems that are embedded within a weakly sheared cloud population approaching radiative–convective equilibrium. The cold pools are altered by changing evaporation rates below cloud base in a series of sensitivity tests. The simulations demonstrate surprising findings: when cold pools are weakened, the convective systems become more intense. However, their propagation speeds and mesoscale structure are largely unaffected by the cold pool changes. Passive tracers introduced into the cold pools indicate that the convection intensifies when cold pools are weakened because cold pool air is entrained into updrafts, thereby reducing updraft intensity via the cold pools’ initial negative buoyancy. Gravity waves, rather than cold pools, appear to be the important modulators of system propagation and mesoscale structure. These results reconfirm that RKW theory does not fully explain the behavior of tropical oceanic convective systems, even those that otherwise appear consistent with RKW thinking.
A Numerical Water Tracer Model for Understanding Event-Scale Hydrometeorological Phenomena
Authors: Hu Huancui , Dominguez Francina , Kumar Praveen , McDonnell Jeffery , Gochis David 
Published: April 2018

Abstract
We develop and implement a novel numerical water tracer model within the Noah LSM with multiparameterization options (WT-Noah-MP) that is specifically designed to track individual hydrometeorological events. This approach provides a more complete representation of the physical processes beyond the standard land surface model output. Unlike isotope-enabled LSMs, WT-Noah-MP does not simulate the concentration of oxygen or hydrogen isotopes, or require isotope information to drive it. WT-Noah-MP provides stores, fluxes, and transit time estimates of tagged water in the surface–subsurface system. The new tracer tool can account for the horizontal and vertical heterogeneity of tracer transport in the subsurface by allowing partial mixing in each soil layer. We compared model-estimated transit times at the H. J. Andrews Experimental Watershed in Oregon with those derived from isotope observations. Our results show that including partial mixing in the soil results in a more realistic transit time distribution than the basic well-mixed assumption. We then used WT-Noah-MP to investigate the regional response to an extreme precipitation event in the U.S. Pacific Northwest. The model differentiated the flood response due to direct precipitation from indirect thermal effects and showed that a large portion of this event water was retained in the soil after 6 months. The water tracer addition in Noah-MP can help us quantify the long-term memory in the hydrologic system that can impact seasonal hydroclimate variability through evapotranspiration and groundwater recharge.