bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Burst of Genetic Innovation in Drosophila Actin-Related Proteins for Testis-Specific Function
Authors: Schroeder Courtney M , Valenzuela John R , Mejia Natividad Isabel , Hocky Glen M , Malik Harmit S 
Published: November 2019

AbstractMany cytoskeletal proteins perform fundamental biological processes and are evolutionarily ancient. For example, the superfamily of actin-related proteins (Arps) specialized early in eukaryotic evolution for diverse cellular roles in the cytoplasm and the nucleus. Despite its strict conservation across eukaryotes, we find that the Arp superfamily has undergone dramatic lineage-specific diversification in Drosophila. Our phylogenomic analyses reveal four independent Arp gene duplications that occurred in the common ancestor of the obscura group of Drosophila and have been mostly preserved in this lineage. All four obscura-specific Arp paralogs are predominantly expressed in the male germline and have evolved under positive selection. We focus our analyses on the divergent Arp2D paralog, which arose via a retroduplication event from Arp2, a component of the Arp2/3 complex that polymerizes branched actin networks. Computational modeling analyses suggest that Arp2D can replace Arp2 in the Arp2/3 complex and bind actin monomers. Together with the signature of positive selection, our findings suggest that Arp2D may augment Arp2’s functions in the male germline. Indeed, we find that Arp2D is expressed during and following male meiosis, where it localizes to distinct locations such as actin cones—specialized cytoskeletal structures that separate bundled spermatids into individual mature sperm. We hypothesize that this unprecedented burst of genetic innovation in cytoskeletal proteins may have been driven by the evolution of sperm heteromorphism in the obscura group of Drosophila.
Exploring the interactions of short RNAs with the human 40S ribosomal subunit near the mRNA entry site by EPR spectroscopy
Authors: Malygin Alexey A , Krumkacheva Olesya A , Graifer Dmitri M , Timofeev Ivan O , Ochkasova Anastasia S , Meschaninova Maria I , Venyaminova Alya G , Fedin Matvey V , Bowman Michael , Karpova Galina G , Bagryanskaya Elena G 
Published: November 2019

Abstract
The features of previously unexplored labile complexes of human 40S ribosomal subunits with RNAs, whose formation is manifested in the cross-linking of aldehyde derivatives of RNAs to the ribosomal protein uS3 through its peptide 55–64 located outside the mRNA channel, were studied by EPR spectroscopy methods. Analysis of subatomic 40S subunit models showed that a likely site for labile RNA binding is a cluster of positively charged amino acid residues between the mRNA entry site and uS3 peptide 55–64. This is consistent with our finding that the 3′-terminal mRNA fragment hanging outside the 40S subunit prevents the cross-linking of an RNA derivative to this peptide. To detect labile complexes of 40S subunits with RNA by DEER/PELDOR spectroscopy, an undecaribonucleotide derivative with nitroxide spin labels at terminal nucleotides was utilized. We demonstrated that the 40S subunit channel occupancy with mRNA does not affect the RNA derivative binding and that uS3 peptide 55–64 is not involved in binding interactions. Replacing the RNA derivative with a DNA one revealed the importance of ribose 2′-OH groups for the complex formation. Using the single-label RNA derivatives, the distance between the mRNA entry site and the loosely bound RNA site on the 40S subunit was estimated.
Systematic sequencing of chloroplast transcript termini from Arabidopsis thaliana reveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures
Authors: Castandet Benoît , Germain Arnaud , Hotto Amber M , Stern David B 
Published: November 2019

AbstractChloroplast transcription requires numerous quality control steps to generate the complex but selective mixture of accumulating RNAs. To gain insight into how this RNA diversity is achieved and regulated, we systematically mapped transcript ends by developing a protocol called Terminome-seq. Using Arabidopsis thaliana as a model, we catalogued >215 primary 5′ ends corresponding to transcription start sites (TSS), as well as 1628 processed 5′ ends and 1299 3′ ends. While most termini were found in intergenic regions, numerous abundant termini were also found within coding regions and introns, including several major TSS at unexpected locations. A consistent feature was the clustering of both 5′ and 3′ ends, contrasting with the prevailing description of discrete 5′ termini, suggesting an imprecision of the transcription and/or RNA processing machinery. Numerous termini correlated with the extremities of small RNA footprints or predicted stem-loop structures, in agreement with the model of passive RNA protection. Terminome-seq was also implemented for pnp1–1, a mutant lacking the processing enzyme polynucleotide phosphorylase. Nearly 2000 termini were altered in pnp1–1, revealing a dominant role in shaping the transcriptome. In summary, Terminome-seq permits precise delineation of the roles and regulation of the many factors involved in organellar transcriptome quality control.
Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites
Authors: Hammam Elie , Ananda Guruprasad , Sinha Ameya , Scheidig-Benatar Christine , Bohec Mylene , Preiser Peter R , Dedon Peter C , Scherf Artur , Vembar Shruthi S 
Published: November 2019

Abstract
DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2–0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01–0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.
Sex hormone-binding globulin levels are inversely associated with nonalcoholic fatty liver disease in HIV-infected and –uninfected men
Authors: Price Jennifer C , Wang Ruibin , Seaberg Eric C , Brown Todd T , Budoff Matthew J , Kingsley Lawrence A , Palella Frank J , Witt Mallory D , Post Wendy S , Lake Jordan E , Thio Chloe L 
Published: November 2019

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV.

Methods
NAFLD was assessed using non-contrast CT in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank <3 alcoholic drinks/day and were uninfected with chronic hepatitis C or B (340HIV+,190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin and NAFLD.

Results
Median SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD [odds ratio(OR) 0.52 per doubling,95% confidence interval(CI) 0.34-0.80]. In separate multivariable models without SHBG, HIV (OR 0.46,95%CI 0.26-0.79) and higher adiponectin (OR 0.66 per doubling,95%CI 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR 0.74 per doubling,95%CI 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR 0.61,95%CI 0.34-1.08) and adiponectin (OR 0.74,95%CI 0.54-1.02) with NAFLD.

Conclusions
SHBG levels were higher among HIV+ men, independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies.
The differential characteristics between severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome in the endemic regions
Authors: Lu Qing-Bin , Li Hao , Jiang Fa-Chun , Mao Ling-Ling , Liu Xue-Sheng , Wang Ning , Zhou Yong-Yun , Dai Ke , Yang Zhen-Dong , Dong Li-Yan , Cui Ning , Zhang Xiao-Ai , Zhang Shao-Fei , Zhang Pan-He , Fang Li-Qun , Liu Wei 
Published: November 2019

Abstract
The misdiagnosis between severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome were identified in endemic regions for both diseases. A model based on age, mouse/tick contact in recent one month, clinical characteristics including blush, low back pain, diarrhea, enlarged lymph nodes, and white blood cell count, yielded a high area under the curve of 0.985 (95% confidence interval, 0.979-0.992), enabling an effective differentiation between two diseases.
Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial
Authors: May Larissa , Tatro Grant , Poltavskiy Eduard , Mooso Benjamin , Hon Simson , Bang Heejung , Polage Christopher 
Published: November 2019

Abstract

Background
Acute upper respiratory tract infections are a common cause of Emergency Department (ED) visits and often result in unnecessary antibiotic treatment.

Methods
We conducted a randomized clinical trial to evaluate the impact of a rapid, multi-pathogen respiratory panel (RP) test versus usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136).

Results
Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (p=0.0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (-12% [95% CI -25%, 0.4%]; p=0.06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (-19%) versus adults (-9%; post-hoc analysis). There was no difference in antiviral use, length of stay, or disposition.

Conclusions
Rapid RP testing was associated with a trend towards decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.
Mechanisms of allergy and adult asthma
Authors: Chen Xuesong , Corry David B. , Li Evan 
Published: November 2019

Purpose of review
Allergic asthma reflects the interplay between inflammatory mediators and immune, airway epithelial, and other cells. This review summarizes key insights in these areas over the past year.

Recent findings
Key findings over the past year demonstrate that epithelial cells mediate tight junction breakdown to facilitate the development of asthma-like disease in mice. Innate lymph lymphoid cells (ILC), while previously shown to promote allergic airway disease, have now been shown to inhibit the development of severe allergic disease in mice. Fibrinogen cleavage products (previously shown to mediate allergic airway disease and macrophage fungistatic immunity by signaling through Toll-like receptor 4) have now been shown to first bind to the integrin Mac-1 (CD11c/CD18). Therapeutically, recent discoveries include the development of the antiasthma drug PM-43I that inhibits the allergy-related transcription factors STAT5 and STAT6 in mice, and confirmatory evidence of the efficacy of the antifungal agent voriconazole in human asthma.

Summary
Studies over the past year provide critical new insight into the mechanisms by which epithelial cells, ILC, and coagulation factors contribute to the expression of asthma-like disease and further support the development antiasthma drugs that block STAT factors and inhibit fungal growth in the airways.
Anesthetic management of lung transplantation: impact of presenting disease
Authors: Martin Archer Kilbourne , Fritz Ashley V. , Wilkey Barbara J. 
Published: November 2019

Purpose of reviewRecent literature has described the emerging role of anesthesiologists as key members of the lung transplantation team and the impact of anesthetic management on outcomes. This review examines the impact of presenting cause of end-stage lung disease (ESLD) on anesthetic management.Recent findingsThe four primary causes of ESLD are suppurative, obstructive, or restrictive processes, and pulmonary hypertension. Our recent review of perioperative literature revealed new data regarding preoperative risk stratification, intraoperative management, and postoperative use of extracorporeal membrane oxygenation (ECMO) support. Major studies specifically about anesthetic management are lacking; however, the principles studied are readily applicable to the design of a perioperative care plan. The most compelling data have resulted in a revolutionary change in terms of intraoperative support and postoperative planning for pulmonary hypertension patients. Historically treated with cardiopulmonary bypass, significant data have been reported describing the successful use of ECMO both as an intraoperative support with superior outcomes, as well as postoperative support for improved stability during biventricular remodeling post graft implantation.SummaryThe application of these updated findings should assist anesthesiologists as they develop internal protocols and external guidelines to integrate within multidisciplinary teams caring for the lung transplant patient.
Validity of Self-reported Cannabis Use Among Pregnant Females in Northern California
Authors: Young-Wolff Kelly C. , Sarovar Varada , Tucker Lue-Yen , Goler Nancy , Conway Amy , Weisner Constance , Armstrong Mary Anne , Alexeeff Stacey 
Published: November 2019

Background:
Most clinical and epidemiologic estimates of prenatal cannabis use are based on self-report, and the validity of self-reported cannabis use has not been examined in a large, representative population of pregnant women. We determined the validity of self-reported prenatal cannabis use and predictors of nondisclosure using data from Kaiser Permanente Northern California's (KPNC) healthcare system with universal prenatal cannabis screening during prenatal care.

Methods:
Validation study using data from 281,025 pregnancies in KPNC among females aged ≥11 years who completed a self-administered questionnaire on prenatal cannabis use and a cannabis urine toxicology test from 2009 to 2017. We calculated sensitivity, specificity, positive predictive value, and negative predictive value of self-reported prenatal cannabis use using urine toxicology testing as the criterion standard, and sensitivity of urine toxicology testing using self-reported use as the criterion standard. We compared sociodemographics of those who disclosed versus did not disclose prenatal cannabis use.

Results:
Urine toxicology testing identified more instances of prenatal cannabis use than self-report (4.9% vs 2.5%). Sensitivity of self-reported use was low (33.9%). Sensitivity of the toxicology test was higher (65.8%), with greater detection of self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%). Older women, those of Hispanic race/ethnicity, and those with lower median neighborhood incomes were most likely to be misclassified as not using cannabis by self-reported screening.

Conclusions:
Given that many women choose not to disclose prenatal cannabis use, clinicians should educate all prenatal patients about the potential risks and advise them to quit cannabis use during pregnancy.
Local treatment of stage IIIA-N2 nonsmall cell lung cancer: surgery and/or radiotherapy
Authors: Van Meerbeeck Jan P. , De Pooter Christel , Raskin Jo , Janssens Annelies , Van Schil Paul EY 
Published: November 2019

Purpose of review
Controversy exists regarding the optimal treatment of patients with stage IIIA-N2 nonsmall cell lung cancer because of its heterogeneity. Patients are at risk for both local and distant disease relapse after primary local treatment. However, there may be a window of opportunity for surgery, if mediastinal downstaging has been obtained after induction therapy. This manuscript reviews the outcome of patients treated by neo-adjuvant chemotherapy (NA-C) followed by surgery, compared with patients treated with either definitive sequential or concurrent chemoradiotherapy (cCRT), illustrated by a single-centre retrospective case series.

Recent findings
Of 53 eligible patients, 19 received NA-C and underwent surgical resection, whilst 20 and 14 received concurrent or sequential definitive CRT, respectively. A significant difference in progression-free survival favouring NA-C followed by surgery over both CRT modalities was found. However, this translated only in an overall survival benefit in comparison with sequential definitive CRT. A trend for better outcome was observed in selected surgical patients with single-level mediastinal involvement and complete resection.

Summary
Our case series results are consistent with the present standard of care of CRT, which restricts surgical resection to carefully selected patients. Immunotherapy will likely change the treatment paradigm.
Cerebral and peripheral vascular differences between pre- and postmenopausal women
Authors: Brislane Áine , Low David A. , Carter Sophie E. , Holder Sophie M. , Jones Helen , Hopkins Nicola D. 
Published: November 2019

Abstract

Objective:
Menopause is associated with lower peripheral vascular function; however, cerebrovascular responses to this time-period are unclear. We aimed to describe peripheral vascular and cerebrovascular differences between pre- and postmenopausal women.

Methods:
Fifty pre- and postmenopausal women (N = 100) underwent assessments of cerebral blood flow; cerebrovascular reactivity and autoregulation; carotid artery reactivity; brachial and femoral artery flow-mediated dilation; and carotid, brachial, and femoral artery intima-media thickness. Comparisons were made between pre- and postmenopausal women followed by a secondary analysis (N = 20) between late premenopausal women and those within 5 years of menopause using a general linear model.

Results:
Cerebral blood flow (−11 [−17, −4 cm/s]; P = 0.03) and carotid reactivity (−2.3 [−4.3, −0.3%] P = 0.03) were lower postmenopause compared to premenopause, whereas cerebrovascular reactivity and autoregulation did not differ (P > 0.05). Postmenopausal women had a larger carotid (0.16 [0.13, 0.20 mm] P < 0.001), brachial (0.07 [0.03, 0.11 mm] P = 0.004), and femoral artery intima-media thickness (0.09 [0.05, 0.14 mm] P = 0.04), alongside lower brachial (−2.3 [−3.9, −0.7%] P = 0.004) and femoral artery flow-mediated dilation (−3.0 [−4.3, −1.8%] P < 0.001). In the secondary-analysis, early postmenopausal women had a lower femoral artery flow-mediated dilation (−1.9 [−3.9, −0.0%] P = 0.05) and larger carotid intima-media thickness (0.07 [0.00, 0.14 mm] P = 0.03) compared to late premenopausal women.

Conclusions:
Cerebral blood flow, carotid artery reactivity, peripheral vascular function, and structure are negatively affected by age. Preliminary data indicate that femoral artery function and carotid artery structure may be potentially impaired in early postmenopause compared with late premenopause. These findings suggest that conduit arteries susceptible to atherosclerosis may be important targets for lifestyle intervention in early menopause.
Prevalence and Outcomes of Pediatric In-Hospital Cardiac Arrest Associated With Pulmonary Hypertension*
Authors: Morgan Ryan W. , Topjian Alexis A. , Wang Yan , Atkin Natalie J. , Kilbaugh Todd J. , McGowan Francis X. , Berg Robert A. , Mercer-Rosa Laura , Sutton Robert M. , Himebauch Adam S. 
Published: November 2019

Objectives:
In adult in-hospital cardiac arrest, pulmonary hypertension is associated with worse outcomes, but pulmonary hypertension–associated in-hospital cardiac arrest has not been well studied in children. The objective of this study was to determine the prevalence of pulmonary hypertension among children with in-hospital cardiac arrest and its impact on outcomes.

Design:
Retrospective single-center cohort study.

Setting:
PICU of a quaternary care, academic children’s hospital.

Patients:
Children (<18 yr old) receiving greater than or equal to 1 minute of cardiopulmonary resuscitation (cardiopulmonary resuscitation) for an index in-hospital cardiac arrest with an echocardiogram in the 48 hours preceding in-hospital cardiac arrest, excluding those with cyanotic congenital heart disease.

Interventions:
None.

Measurements and Main Results:
Of 284 in-hospital cardiac arrest subjects, 57 (20%) had evaluable echocardiograms, which were analyzed by a cardiologist blinded to patient characteristics. Pulmonary hypertension was present in 20 of 57 (35%); nine of 20 (45%) had no prior pulmonary hypertension history. Children with pulmonary hypertension had worse right ventricular systolic function, measured by fractional area change (p = 0.005) and right ventricular global longitudinal strain (p = 0.046); more right ventricular dilation (p = 0.010); and better left ventricular systolic function (p = 0.001). Children with pulmonary hypertension were more likely to have abnormal baseline functional status and a history of chronic lung disease or acyanotic congenital heart disease and less likely to have sepsis or acute kidney injury. Children with pulmonary hypertension were more likely to have an initial rhythm of pulseless electrical activity or asystole and were more frequently treated with inhaled nitric oxide (80% vs 32%; p < 0.001) at the time of cardiopulmonary resuscitation. On multivariable analysis, pulmonary hypertension was not associated with event survival (14/20 [70%] vs 24/37 [65%]; adjusted odds ratio, 1.30 [CI95, 0.25–6.69]; p = 0.77) or survival to discharge (8/20 [40%] vs 10/37 [27%]; adjusted odds ratio, 1.17 [CI95, 0.22–6.44]; p = 0.85).

Conclusions:
Pulmonary hypertension physiology preceding pediatric in-hospital cardiac arrest may be more common than previously described. Among this cohort with a high frequency of inhaled nitric oxide treatment during cardiopulmonary resuscitation, pulmonary hypertension was not associated with survival outcomes.