bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Suitability of Next-Generation Viral Outgrowth Assays to Measure Human Immunodeficiency Virus 1 Latent Reservoir Size
Authors: Stone Mars , Rosenbloom Daniel I S , Bacchetti Peter , Deng Xutao , Dimapasoc Melanie , Keating Sheila , Bakkour Sonia , Richman Douglas D , Mellors John W , Deeks Steven G , Lai Jun , Beg Subul , Siliciano Janet D , Pagliuzza Amélie , Chomont Nicolas , Lackman-Smith Carol , Ptak Roger G , Busch Michael P
Published: March 2020

Background

Evaluations of human immunodeficiency virus (HIV) curative interventions require reliable and efficient quantification of replication-competent latent reservoirs. The “classic” quantitative viral outgrowth assay (QVOA) has been regarded as the reference standard, although prohibitively resource and labor intensive. We compared 6 “next-generation” viral outgrowth assays, using polymerase chain reaction or ultrasensitive p24 to assess their suitability as scalable proxies for QVOA.

Methods

Next-generation QVOAs were compared with classic QVOA using single leukapheresis-derived samples from 5 antiretroviral therapy–suppressed HIV-infected participants and 1 HIV-uninfected control; each laboratory tested blinded batches of 3 frozen and 1 fresh sample. Markov chain Monte Carlo methods estimated extra-Poisson variation at aliquot, batch, and laboratory levels. Models also estimated the effect of testing frozen versus fresh samples.

Results

Next-generation QVOAs had similar estimates of variation to QVOA. Assays with ultrasensitive readout reported higher infectious units per million values than classic QVOA. Within-batch testing had 2.5-fold extra-Poisson variation (95% credible interval [CI], 2.1–3.5-fold) for next-generation assays. Between-laboratory variation increased extra-Poisson variation to 3.4-fold (95% CI, 2.6–5.4-fold). Frozen storage did not substantially alter infectious units per million values (−18%; 95% CI, −52% to 39%).

Conclusions

The data offer cautious support for use of next-generation QVOAs as proxies for more laborious QVOA, while providing greater sensitivities and dynamic ranges. Measurement of latent reservoirs in eradication strategies would benefit from high throughput and scalable assays.
Frailty Hinders Recovery From Influenza and Acute Respiratory Illness in Older Adults
Authors: Lees Caitlin , Godin Judith , McElhaney Janet E , McNeil Shelly A , Loeb Mark , Hatchette Todd F , LeBlanc Jason , Bowie William , Boivin Guy , McGeer Allison , Poirier André , Powis Jeff , Semret Makeda , Webster Duncan , Andrew Melissa K
Published: March 2020

Background

We examined frailty as a predictor of recovery in older adults hospitalized with influenza and acute respiratory illness.

Methods

A total of 5011 patients aged ≥65 years were admitted to Canadian Serious Outcomes Surveillance Network hospitals during the 2011/2012, 2012/2013, and 2013/2014 influenza seasons. Frailty was measured using a previously validated frailty index (FI). Poor recovery was defined as death by 30 days postdischarge or an increase of more than 0.06 (≥2 persistent new health deficits) on the FI. Multivariable logistic regression controlled for age, sex, season, influenza diagnosis, and influenza vaccination status.

Results

Mean age was 79.4 (standard deviation = 8.4) years; 53.1% were women. At baseline, 15.0% (n = 750) were nonfrail, 39.3% (n = 1971) were prefrail, 39.8% (n = 1995) were frail, and 5.9% (n = 295) were most frail. Poor recovery was experienced by 21.4%, 52.0% of whom had died. Frailty was associated with lower odds of recovery in all 3 seasons: 2011/2012 (odds ratio [OR] = 0.70; 95% confidence interval [CI], 0.59–0.84), 2012/2013 (OR = 0.72; 95% CI, 0.66–0.79), and 2013/2014 (OR = 0.75; 95% CI, 0.69–0.82); results varied by season, influenza status, vaccination status, and age.

Conclusions

Increasing frailty is associated with lower odds of recovery, and persistent worsening frailty is an important adverse outcome of acute illness.
Surveillance Strategies for Tracking Sepsis Incidence and Outcomes
Authors: Shappell Claire N , Klompas Michael , Rhee Chanu
Published: March 2020

Sepsis is a leading cause of death and the target of intense efforts to improve recognition, management and outcomes. Accurate sepsis surveillance is essential to properly interpreting the impact of quality improvement initiatives, making meaningful comparisons across hospitals and geographic regions, and guiding future research and resource investments. However, it is challenging to reliably track sepsis incidence and outcomes because sepsis is a heterogeneous clinical syndrome without a pathologic reference standard, allowing for subjectivity and broad discretion in assigning diagnoses. Most epidemiologic studies of sepsis to date have used hospital discharge codes and have suggested dramatic increases in sepsis incidence and decreases in mortality rates over time. However, diagnosis and coding practices vary widely between hospitals and are changing over time, complicating the interpretation of absolute rates and trends. Other surveillance approaches include death records, prospective clinical registries, retrospective medical record reviews, and analyses of the usual care arms of randomized controlled trials. Each of these strategies, however, has substantial limitations. Recently, the US Centers for Disease Control and Prevention released an “Adult Sepsis Event” definition that uses objective clinical indicators of infection and organ dysfunction that can be extracted from most hospitals’ electronic health record systems. Emerging data suggest that electronic health record–based clinical surveillance, such as surveillance of Adult Sepsis Event, is accurate, can be applied uniformly across diverse hospitals, and generates more credible estimates of sepsis trends than administrative data. In this review, we discuss the advantages and limitations of different sepsis surveillance strategies and consider future directions.
Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms
Authors: Sun Bing , Abadjian Linda , Monto Alexander , Freasier Heather , Pulliam Lynn
Published: March 2020

Background

Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection.

Methods

We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy.

Results

Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation.

Conclusions

Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.

SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.
Female cardiologists in Japan
Authors: Nakayama Atsuko , Morita Hiroyuki , Komuro Issei
Published: March 2020

In Japan, the heavy workload managed by cardiologists might make it difficult for female cardiologists to work comfortably, and some hospital managers hesitate to employ female cardiologists. Are the clinical outcomes of patients with cardiovascular diseases affected by the cardiologist’s gender? In our previous study, the risk of emergency readmission within 30 days after discharge was found to be significantly lower for patients treated by female cardiologists than for those treated by male cardiologists. Compared to male counterparts, female cardiologists were more likely to practice evidence-based and guideline-directed medicine and communicate with other experts, that is, they are better at solving complex problems in the attending doctors’ team. In addition, female cardiologists probably maintain more robust physician–patient communication and successfully provide more fine-tuned and patient-centered preventive care than male cardiologists. In Japan, the rate of female doctors 21.1% is the lowest among the rates for the Organization for Economic Co-operation and Development countries. Under such a situation, in our hospital, a representative teaching hospital where female cardiologists constitute larger than other hospitals in Japan, better clinical outcome was observed in the patients treated by female cardiologists over those treated by male cardiologists. Considering the preference of medical management by female cardiologists, an increase in the number of female cardiovascular medicine practitioners is necessary from the perspective of patients’ clinical outcomes.
Routine laboratory surveillance of antimicrobial resistance in community-acquired urinary tract infections adequately informs prescribing policy in England
Authors: Watts Vicky , Brown Benjamin , Ahmed Maria , Charlett André , Chew-Graham Carolyn , Cleary Paul , Decraene Valerie , Dodgson Kirsty , George Ryan , Hopkins Susan , Esmail Aneez , Welfare William
Published: March 2020

Objectives

To assess whether resistance estimates obtained from sentinel surveillance for antimicrobial resistance (AMR) in community-acquired urinary tract infections (UTIs) differ from routinely collected laboratory community UTI data.

Methods

All patients aged ≥18 years presenting to four sentinel general practices with a suspected UTI, from 13 November 2017 to 12 February 2018, were asked to provide urine specimens for culture and susceptibility. Specimens were processed at the local diagnostic laboratory. Antibiotic susceptibility testing was conducted using automated methods. We calculated the proportion of Escherichia coli isolates that were non-susceptible (according to contemporaneous EUCAST guidelines) to trimethoprim, nitrofurantoin, cefalexin, ciprofloxacin and amoxicillin/clavulanic acid, overall and by age group and sex, and compared this with routine estimates.

Results

Sentinel practices submitted 740 eligible specimens. The specimen submission rate had increased by 28 specimens per 1000 population per year (95% CI 21–35). Uropathogens were isolated from 23% (169/740) of specimens; 67% were E. coli (113/169). Non-susceptibility of E. coli to trimethoprim was 28.2% (95% CI 20.2–37.7) on sentinel surveillance (33.4%; 95% CI 29.5–37.6 on routine data) and to nitrofurantoin was 0.9% (95% CI 0–5.7) (1.5%; 95% CI 0.7–3.0 on routine data).

Conclusions

Routine laboratory data resulted in a small overestimation in resistance (although the difference was not statistically significant) and our findings suggest that it provides an adequate estimate of non-susceptibility to key antimicrobials in community-acquired UTIs in England. This study does not support the need for ongoing local sentinel surveillance.
Low-Density Lipoprotein (LDL)-Triglyceride and Its Ratio to LDL-Cholesterol as Diagnostic Biomarkers for Nonalcoholic Steatohepatitis
Authors: Fujii Yuki , Nouso Kazuhiro , Matsushita Hiroshi , Kariyama Kazuya , Sakurai Toshihiro , Takahashi Yuji , Chiba Hitoshi , Hui Shu-Ping , Ito Yasuki , Ohta Motoko , Okada Hiroyuki
Published: March 2020

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease, but it is difficult to distinguish its pathogenic phenotype, nonalcoholic steatohepatitis (NASH), from nonalcoholic fatty liver (NAFL) without a liver biopsy. We analyzed serum lipids, including low-density lipoprotein triglyceride (LDL-TG), to elucidate their usefulness for diagnosing NASH.

Patients and Methods

Serum samples obtained from 35 NASH and 9 NAFL biopsy-confirmed patients and 6 healthy volunteers (HLT) were studied for 13 lipid-related markers and compared between HLT, NAFL, and NASH groups. The relationship between histological findings and the lipid markers was also analyzed.

Results

There were significant differences in triglyceride, LDL-TG, the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C), small dense LDL-C, and apolipoprotein E between the three groups. Among the 5 lipid components, serum LDL-TG level and the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C) were significantly elevated in NASH. The median concentrations of LDL-TG in HLT, NAFL, and NASH were 9, 15, and 20 mg/dL (P < 0.001), and those of LDL-TG/LDL-C were 0.097, 0.102, and 0.173 (P < 0.001), respectively. Although the degree of steatosis was not correlated with the LDL-TG/LDL-C, the ratio was significantly higher in patients with lobular inflammation (P = 0.071), ballooning (P = 0.031), and fibrosis (P < 0.001). The area under the receiver operating characteristic curve of the ratio for distinguishing NASH from NAFL was 0.857. The rest of studied markers showed no significant utility.

Conclusion

Serum LDL-TG levels and the LDL-TG/LDL-C ratio might serve as simple and noninvasive diagnostic biomarkers for NASH.
First Complete Genome of Lake Sinai Virus Lineage 3 and Genetic Diversity of Lake Sinai Virus Strains From Honey Bees and Bumble Bees
Authors: Šimenc Laura , Kuhar Urška , Jamnikar-Ciglenečki Urška , Toplak Ivan
Published: March 2020

The complete genome of Lake Sinai virus 3 (LSV3) was sequenced by the Ion Torrent next-generation sequencing (NGS) technology from an archive sample of honey bees collected in 2010. This strain M92/2010 is the first complete genome sequence of LSV lineage 3. From October 2016 to December 2017, 56 honey bee samples from 32 different locations and 41 bumble bee samples from five different locations were collected. These samples were tested using a specific reverse transcriptase-polymerase chain reaction (RT-PCR) method; 75.92% of honey bee samples and 17.07% of bumble bee samples were LSV-positive with the RT-PCR method. Phylogenetic comparison of 557-base pair-long RNA-dependent RNA polymerase (RdRp) genome region of selected 23 positive samples of honey bees and three positive bumble bee samples identified three different LSV lineages: LSV1, LSV2, and LSV3. The LSV3 lineage was confirmed for the first time in Slovenia in 2010, and the same strain was later detected in several locations within the country. The LSV strains detected in bumble bees are from 98.6 to 99.4% identical to LSV strains detected among honey bees in the same territory.
Electromagnetic signal characteristics and energy response pattern of briquette hammer fracturing
Authors: Li Jing , Zhao Yuechao , Han Ke , Wang Zhen , Wang Chuan
Published: March 2020

Briquette hammer fracturing experiments were conducted with different impact energies and molding pressures to investigate the characteristics of the electromagnetic signals. The response pattern of the electromagnetic radiation energy as a function of the impact energy and the coal firmness during impact fracturing of a coal mass were analyzed. The characteristics of the electromagnetic radiation signals during the uniaxial compression fracture of a coal mass were also used to analyze their source during fracture. The results show that the generation of electromagnetic radiation during coal mass fracturing can be divided into three stages: compaction, crack propagation and sliding friction. Electromagnetic energy is mainly radiated during the sliding friction stage. The electromagnetic radiation during briquette hammer fracturing is characterized by a frequency below 2000 Hz, an amplitude in the range from 0.05 to 0.6 mV, and a total energy on the order of ∼10−14–10−10 J. For coal masses with the same firmness, as the impact energy increases, the total energy of the electromagnetic radiation increases. For the same impact energy, as the firmness of the coal mass increases, the total energy of the electromagnetic radiation first increases and then decreases.
Natural deduction and semantic models of justification logic in the proof assistant Coq
Authors: Andrade Guzmán Jesús Mauricio , Hernández Quiroz Francisco
Published: March 2020

The purpose of this paper is to present a formalization of the language, semantics and axiomatization of justification logic in Coq. We present proofs in a natural deduction style derived from the axiomatic approach of justification logic. Additionally, we present possible world semantics in Coq based on Fitting models to formalize the semantic satisfaction of formulas. As an important result, with this implementation, it is possible to give a proof of soundness for $\mathsf{L}\mathsf{P}$ with respect to Fitting models.
On a Weak Conditional
Authors: Castiglioni José Luis , Ertola-Biraben Rodolfo C
Published: March 2020

It is well-known that adding to a lattice the usual relative meet complement is not conservative, in the sense that distributivity is implied. In this paper we consider a weak relative meet complement that does not have the mentioned effect. We mostly study the mentioned operation from an algebraic point of view. However, we also provide a Hilbert-style axiomatization for its corresponding assertional logic.
An axiomatic approach toCG′3 logic
Authors: Pérez-Gaspar Miguel , Hernández-Tello Alejandro , Arrazola Ramírez José , Osorio Galindo Mauricio
Published: March 2020

In memoriam José Arrazola Ramírez (1962–2018) The logic $\textbf{G}^{\prime}_3$ was introduced by Osorio et al. in 2008; it is a three-valued logic, closely related to the paraconsistent logic $\textbf{CG}^{\prime}_3$ introduced by Osorio et al. in 2014. The logic $\textbf{CG}^{\prime}_3$ is defined in terms of a multi-valued semantics and has the property that each theorem in $\textbf{G}^{\prime}_3$ is a theorem in $\textbf{CG}^{\prime}_3$. Kripke-type semantics has been given to $\textbf{CG}^{\prime}_3$ in two different ways by Borja et al. in 2016. In this work, we continue the study of $\textbf{CG}^{\prime}_3$, obtaining a Hilbert-type axiomatic system and proving a soundness and completeness theorem for this logic.
Still some way to go: Federal Ministry of Justice proposes to modernize the German Patents Act
Authors: Gärtner Anette
Published: March 2020

Although Germany is a leading venue for patent litigation, there is a need to update the law every now and then. Does the Bill, which is currently under discussion, meet the reasonable expectations of users of the system? The author applauds the proposal to make the “confidentiality club” available for patent infringement cases. The legal framework for enforcing injunctions, by contrast, requires additional attention. We are only half-way there.
Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype
Authors: Sarró Eduard , Durán Mónica , Rico Ana , Bou-Teen Diana , Fernández-Majada Vanesa , Croatt Anthony J , Nath Karl A , Salcedo Maria Teresa , Gundelach Justin H , Batlle Daniel , Bram Richard J , Meseguer Anna
Published: March 2020

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor β (TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail. This pro-epithelial action of CypA relies on its PPIase activity. By contrast, CypB emerges as an epithelial repressor, because CypB silencing promotes epithelial differentiation, prevents TGFβ-induced EMT, and induces tubular structures in 3D cultures. In addition, in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction, inflammatory and pro-fibrotic events were attenuated. CypB silencing/knockout leads to Slug, but not Snail, downregulation. CypB support of Slug expression depends on its endoplasmic reticulum location, where it interacts with calreticulin, a calcium-buffering chaperone related to Slug expression. As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation, we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.
Dynamically Efficient Royalties for Standard-Essential Patents
Authors: Neurohr Bertram
Published: March 2020

Some economists have argued that a reasonable royalty for a standard-essential patent should be based on the patent’s ex ante incremental value. Others have argued that a patent’s ex ante incremental value is insufficient, that a reasonable royalty is more akin to the prize in a winner-takes-all tournament, and that it should reflect the R&D costs associated with both the winning technology and unsuccessful alternative technologies. The results presented in this paper are favourable to the latter view, but with the additional qualification that a reasonable royalty ought to cover the costs of only those R&D efforts—successful or not—that are efficiency enhancing from an ex ante perspective. The notion of ex ante incremental value is core to identifying these efforts and hence to determining what the dynamically efficient outcome is. A reasonable royalty is one that induces this dynamically efficient outcome (i.e. a dynamically efficient level of R&D), balancing the costs incurred by innovators with the benefits that go to implementers and/or consumers. As such, a reasonable royalty is significantly higher than a technology’s ex ante incremental value. High ‘winner’ margins are offset by losses incurred by ‘losers’, leaving a significant proportion of the total net value generated by R&D to implementers and consumers.
A large anastomotic leakage after esophageal surgery treated with endoluminal vacuum-assisted closure: a case report
Authors: Mandarino Francesco Vito , Bonura Giuliano Francesco , Esposito Dario , Rosati Riccardo , Parise Paolo , Fanti Lorella
Published: March 2020

The treatment of anastomotic post-esophagectomy leaks and fistula is challenging. Endoluminal vacuum-assisted closure (EVAC) is an emerging technique that employs negative pressure wound therapy to treat anastomotic leaks endoscopically. Esosponge is specifically designed for esophageal EVAC therapy. We report on a 49-year-old woman who underwent a totally mini-invasive Ivor–Lewis esophagectomy and developed a giant postoperative leak with a complex pleural collection, but she was not fit for surgical re-intervention. The patient healed almost completely after 14 exchange sessions of Esosponge over 35 days.
The killer yeast Wickerhamomyces anomalus Cf20 exerts a broad anti-Candida activity through the production of killer toxins and volatile compounds
Authors: Fernández de Ullivarri Miguel , Bulacios Gabriela A , Navarro Silvia A , Lanza Lucía , Mendoza Lucia M , Chalón Miriam C
Published: March 2020

Candidiasis is a group of opportunistic infections caused by yeast of the genus Candida. The appearance of drug resistance and the adverse effects of current antifungal therapies require the search for new, more efficient therapeutic alternatives. Killer yeasts have aroused as suitable candidates for mining new antifungal compounds. Killer strains secrete antimicrobial proteins named killer toxins, with promissory antifungal activity. Here we found that the killer yeast Wickerhamomyces anomalus Cf20 and its cell-free supernatant (CFS) inhibited six pathogenic strains and one collection strain of Candida spp. The inhibition is mainly mediated by secreted killer toxins and, to a lesser extent, by volatile compounds such as acetic acid and ethyl acetate. A new large killer toxin (>180 kDa) was purified, which exerted 70–74% of the total CFS anti-Candida activity, and the previously described glucanase KTCf20 was inhibitory in a lesser extent as well. In addition, we demonstrated that Cf20 possesses the genes encoding for the β-1,3-glucanases WaExg1 and WaExg2, proteins with extensively studied antifungal activity, particularly WaExg2. Finally, the 10-fold concentrated CFS exerted a high candidacidal effect at 37°C, completely inhibiting the fungal growth, although the nonconcentrated CFS (RCF 1) had very limited fungistatic activity at this temperature. In conclusion, W. anomalus Cf20 produces different low and high molecular weight compounds with anti-Candida activity that could be used to design new therapies for candidiasis and as a source for novel antimicrobial compounds as well.
Deep fungal infections diagnosed by histology in Uganda: a 70-year retrospective study
Authors: Kwizera Richard , Bongomin Felix , Lukande Robert
Published: March 2020

Fungal infections cause substantial morbidity and mortality. However, the burden of deep fungal infections is not well described in Uganda. We aimed to estimate the burden and etiology of histologically diagnosed deep fungal infections in Uganda. We retrospectively reviewed histology reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 to identify any reports that had a fungal infection as the diagnosis. Over the study period, 697 cases of deep fungal infections were identified with an average incidence of 0.73/100,000 persons per decade. There was a general decline in the number of cases detected. Median age of the cases was 28 years (IQR: 11–40) and majority (59%) were male. The age group of 0–10 years were the most affected. The foot was the most affected part of the body (26%). Deep mycoses identified include eumycetoma (32%), subcutaneous phycomycosis (26%), histoplasmosis (9.2%), chromoblastomycosis (4.6%), aspergillosis (3.3%), cryptococcosis (3.3%), blastomycosis (1.6%), subcutaneous mycosis (1.4%), dermatomycosis (1.3%), coccidioidomycosis (0.6%), mucormycosis (0.6%), and sporotrichosis (0.1%). Histoplasma was the commonest causative agent (9.2%) followed by Aspergillus (3.4%) and Cryptococcus (3.3%), while 81% of the fungal pathogens were not identified to genus/species level. Only 31% of the cases were diagnosed clinically as deep fungal infections. There is a substantial burden of deep fungal infections caused by multiple fungal pathogens in Uganda. There is need to build local capacity for mycology so as to improve on the index of clinical suspicion and diagnostic capabilities.
The MAVERIC survey: a hidden pulsar and a black hole candidate in ATCA radio imaging of the globular cluster NGC 6397
Authors: Zhao Yue , Heinke Craig O , Tudor Vlad , Bahramian Arash , Miller-Jones James C A , Sivakoff Gregory R , Strader Jay , Chomiuk Laura , Shishkovsky Laura , Maccarone Thomas J , Pichardo Marcano Manuel , Gelfand Joseph D
Published: March 2020

Using a 16.2-h radio observation by the Australia Telescope Compact Array and archival Chandra data, we found >5σ radio counterparts to four known and three new X-ray sources within the half-light radius (rh) of the Galactic globular cluster NGC 6397. The previously suggested millisecond pulsar (MSP) candidate, U18, is a steep-spectrum (Sν ∝ να; $\alpha =-2.0^{+0.4}_{-0.5}$) radio source with a 5.5-GHz flux density of 54.7 ± 4.3 $\mu \mathrm{ Jy}$. We argue that U18 is most likely a ‘hidden’ MSP that is continuously hidden by plasma shocked at the collision between the winds from the pulsar and companion star. The non-detection of radio pulsations so far is probably the result of enhanced scattering in this shocked wind. On the other hand, we observed the 5.5-GHz flux of the known MSP PSR J1740−5340 (U12) to decrease by a factor of >2.8 during epochs of 1.4-GHz eclipse, indicating that the radio flux is absorbed in its shocked wind. If U18 is indeed a pulsar whose pulsations are scattered, we note the contrast with U12’s flux decreases in eclipse, which argues for two different eclipse mechanisms at the same radio frequency. In addition to U12 and U18, we also found radio associations for five other Chandra X-ray sources, four of which are likely background galaxies. The last, U97, which shows strong H α variability, is mysterious; it may be either a quiescent black hole low-mass X-ray binary or something more unusual.
Can assembly bias explain the lensing amplitude of the BOSS CMASS sample in a Planck cosmology?
Authors: Yuan Sihan , Eisenstein Daniel J , Leauthaud Alexie
Published: March 2020

In this paper, we investigate whether galaxy assembly bias can reconcile the 20–40 ${{\ \rm per\ cent}}$ disagreement between the observed galaxy projected clustering signal and the galaxy–galaxy lensing signal in the Baryon Oscillation Spectroscopic Survey CMASS galaxy sample. We use the suite of abacuscosmos lambda cold dark matter simulations at Planck best-fitting cosmology and two flexible implementations of extended halo occupation distribution (HOD) models that incorporate galaxy assembly bias to build forward models and produce joint fits of the observed galaxy clustering signal and the galaxy–galaxy lensing signal. We find that our models using the standard HODs without any assembly bias generalizations continue to show a 20–40 ${{\ \rm per\ cent}}$ overprediction of the observed galaxy–galaxy lensing signal. We find that our implementations of galaxy assembly bias do not reconcile the two measurements at Planck best-fitting cosmology. In fact, despite incorporating galaxy assembly bias, the satellite distribution parameter, and the satellite velocity bias parameter into our extended HOD model, our fits still strongly suggest a $\sim \! 34{{\ \rm per\ cent}}$ discrepancy between the observed projected clustering and galaxy–galaxy lensing measurements. It remains to be seen whether a combination of other galaxy assembly bias models, alternative cosmological parameters, or baryonic effects can explain the amplitude difference between the two signals.
Classical Nova Carinae 2018: discovery of circumbinary iron and oxygen
Authors: McLoughlin Dominic , Blundell Katherine M , Lee Steven
Published: March 2020

We present time-lapse spectroscopy of a classical nova explosion commencing 9 d after discovery. These data reveal the appearance of a transient feature in Fe ii and [O i]. We explore different models for this feature and conclude that it is best explained by a circumbinary disc shock-heated following the classical nova event. Circumbinary discs may play an important role in novae in accounting for the absorption systems known as transient heavy element absorption (THEA), the transfer of angular momentum, and the possible triggering of the nova event itself.
The STRong lensing Insights into the Dark Energy Survey (STRIDES) 2017/2018 follow-up campaign: discovery of 10 lensed quasars and 10 quasar pairs
Authors: Lemon C , Auger M W , McMahon R , Anguita T , Apostolovski Y , Chen G C-F , Fassnacht C D , Melo A D , Motta V , Shajib A , Treu T , Agnello A , Buckley-Geer E , Schechter P L , Birrer S , Collett T , Courbin F , Rusu C E , Abbott T M C , Allam S , Annis J , Avila S , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , De Vicente J , Desai S , Eifler T F , Flaugher B , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Honscheid K , James D J , Kim A , Krause E , Kuehn K , Kuropatkin N , Lahav O , Lima M , Lin H , Maia M A G , March M , Marshall J L , Menanteau F , Miquel R , Palmese A , Paz-Chinchón F , Plazas A A , Roodman A , Sanchez E , Schubnell M , Serrano S , Smith M , Soares-Santos M , Suchyta E , Tarle G , Walker A R
Published: March 2020

We report the results of the STRong lensing Insights into the Dark Energy Survey (STRIDES) follow-up campaign of the late 2017/early 2018 season. We obtained spectra of 65 lensed quasar candidates with ESO Faint Object Spectrograph and Camera 2 on the NTT and Echellette Spectrograph and Imager on Keck, confirming 10 new lensed quasars and 10 quasar pairs. Eight lensed quasars are doubly imaged with source redshifts between 0.99 and 2.90, one is triply imaged (DESJ0345−2545, z = 1.68), and one is quadruply imaged (quad: DESJ0053−2012, z = 3.8). Singular isothermal ellipsoid models for the doubles, based on high-resolution imaging from SAMI on Southern Astrophysical Research Telescope or Near InfraRed Camera 2 on Keck, give total magnifications between 3.2 and 5.6, and Einstein radii between 0.49 and 1.97 arcsec. After spectroscopic follow-up, we extract multi-epoch grizY photometry of confirmed lensed quasars and contaminant quasar + star pairs from DES data using parametric multiband modelling, and compare variability in each system’s components. By measuring the reduced χ2 associated with fitting all epochs to the same magnitude, we find a simple cut on the less variable component that retains all confirmed lensed quasars, while removing 94 per cent of contaminant systems. Based on our spectroscopic follow-up, this variability information improves selection of lensed quasars and quasar pairs from 34-45 per cent to 51–70 per cent, with most remaining contaminants being star-forming galaxies. Using mock lensed quasar light curves we demonstrate that selection based only on variability will over-represent the quad fraction by 10 per cent over a complete DES magnitude-limited sample, explained by the magnification bias and hence lower luminosity/more variable sources in quads.
Kin28 depletion increases association of TFIID subunits Taf1 and Taf4 with promoters in Saccharomyces cerevisiae
Authors: Knoll Elisabeth R , Zhu Z Iris , Sarkar Debasish , Landsman David , Morse Randall H
Published: March 2020

Transcription of eukaryotic mRNA-encoding genes by RNA polymerase II (Pol II) begins with assembly of the pre-initiation complex (PIC), comprising Pol II and the general transcription factors. Although the pathway of PIC assembly is well established, the mechanism of assembly and the dynamics of PIC components are not fully understood. For example, only recently has it been shown that in yeast, the Mediator complex normally occupies promoters only transiently, but shows increased association when Pol II promoter escape is inhibited. Here we show that two subunits of TFIID, Taf1 and Taf4, similarly show increased occupancy as measured by ChIP upon depletion or inactivation of Kin28. In contrast, TBP occupancy is unaffected by depletion of Kin28, thus revealing an uncoupling of Taf and TBP occupancy during the transcription cycle. Increased Taf1 occupancy upon Kin28 depletion is suppressed by depletion of TBP, while depletion of TBP in the presence of Kin28 has little effect on Taf1 occupancy. The increase in Taf occupancy upon depletion of Kin28 is more pronounced at TFIID-dominated promoters compared to SAGA-dominated promoters. Our results support the suggestion, based on recent structural studies, that TFIID may not remain bound to gene promoters through the transcription initiation cycle.
Development of a genetic toolset for the highly engineerable and metabolically versatile Acinetobacter baylyi ADP1
Authors: Biggs Bradley W , Bedore Stacy R , Arvay Erika , Huang Shu , Subramanian Harshith , McIntyre Emily A , Duscent-Maitland Chantel V , Neidle Ellen L , Tyo Keith E J
Published: March 2020

One primary objective of synthetic biology is to improve the sustainability of chemical manufacturing. Naturally occurring biological systems can utilize a variety of carbon sources, including waste streams that pose challenges to traditional chemical processing, such as lignin biomass, providing opportunity for remediation and valorization of these materials. Success, however, depends on identifying micro-organisms that are both metabolically versatile and engineerable. Identifying organisms with this combination of traits has been a historic hindrance. Here, we leverage the facile genetics of the metabolically versatile bacterium Acinetobacter baylyi ADP1 to create easy and rapid molecular cloning workflows, including a Cas9-based single-step marker-less and scar-less genomic integration method. In addition, we create a promoter library, ribosomal binding site (RBS) variants and test an unprecedented number of rationally integrated bacterial chromosomal protein expression sites and variants. At last, we demonstrate the utility of these tools by examining ADP1’s catabolic repression regulation, creating a strain with improved potential for lignin bioprocessing. Taken together, this work highlights ADP1 as an ideal host for a variety of sustainability and synthetic biology applications.
Frame-shifted proteins of a given gene retain the same function
Authors: Huang Xin , Chen Rong , Sun Meiling , Peng Yan , Pu Qinlin , Yuan Yi , Chen Gangyi , Dong Juan , Du Feng , Cui Xin , Tang Zhuo
Published: March 2020

Frameshift mutations are generally considered to be lethal because it could result in radical changes of the protein sequence behind. However, the protein of frameshift mutants of a type I toxin (ibsc) was found to be still toxic to bacteria, retaining the similar function as wild-type protein to arrest the cellular growth by impairing the membrane's integrity. Additionally, we have verified that this observation is not an individual event as the same phenomenon had been found in other toxins subsequently. After analyzing the coding sequence of these genes, we proposed a hypothesis to search this kind of hidden gene, through which a dihydrofolate reductase-encoding gene (dfrB3) was found out. Like the wild-type reductase, both +1 and –1 frame-shifted proteins of dfrB3 gene were also proved to catalyze the reduction of dihydrofolate to tetrahydrofolate by using NADPH.
Longitudinal evaluation of peripheral nerve sheath tumors in neurofibromatosis type 1: growth analysis of plexiform neurofibromas and distinct nodular lesions
Authors: Akshintala Srivandana , Baldwin Andrea , Liewehr David J , Goodwin Anne , Blakeley Jaishri O , Gross Andrea M , Steinberg Seth M , Dombi Eva , Widemann Brigitte C
Published: March 2020

Background

Understanding the natural history of non-malignant peripheral nerve sheath tumors (PNSTs) in neurofibromatosis type 1 (NF1) is critical to optimal clinical care and the development of meaningful clinical trials.

Methods

We longitudinally analyzed growth of plexiform neurofibromas (PNs) and of PNSTs with distinct nodular appearance (distinct nodular lesions [DNLs]) using volumetric MRI analysis in patients enrolled on a natural history study (NCT00924196).

Results

DNLs were observed in 58/122 (45.6%) patients (median 2 DNLs/patient). In DNLs that developed during follow-up, median age of development was 17 years. A moderate negative correlation was observed between the estimated PN growth rate and patients’ age at initial MRI (Spearman’s r [95% CI]: −0.60 [−0.73, −0.43], n = 70), whereas only a weak correlation was observed for DNLs (Spearman’s r [95% CI]: −0.25 [−0.47, 0.004]; n = 61). We observed a moderate negative correlation between tumor growth rate and baseline tumor volume for PNs and DNLs (Spearman’s r [95% CI]: −0.52 [−0.67, −0.32] and −0.61 [−0.75, −0.42], respectively). Spontaneous tumor volume reduction was observed in 10 PNs and 7 DNLs (median decrease per year, 3.6% and 7.3%, respectively).

Conclusion

We corroborate previously described findings that most rapidly growing PNs are observed in young children. DNLs tend to develop later in life and their growth is minimally age related. Distinct growth characteristics of PNs and DNLs suggest that these lesions have a different biology and may require different clinical management and clinical trial design. In a subset of PNs and DNLs, slow spontaneous regression in tumor volume was seen.
Optimal inflation, monetary integration, and asymmetric sticky prices
Authors: Paczos Wojtek
Published: March 2020

This article explores the optimal rate of trend inflation in open economies with and without a monetary union, accounting for empirically observed differences in the degree of price stickiness across countries. In a closed economy, the optimal inflation rate is negative to offset the markup caused by imperfect competition. In an open economy there is a ‘beggar-thy-neighbour’ incentive and the optimal inflation is positive. Monetary union is globally welfare improving because it removes this externality. In both setups, as price stickiness increases, the degree of price dispersion increases, and the optimal inflation rate tends towards zero. Gains from monetary integration are higher for economies with more flexible prices.
Initiation of Transdermal Fentanyl Among US Commercially Insured Patients Between 2007 and 2015
Authors: Costantino Ryan C , Gressler Laura E , Onukwugha Eberechukwu , McPherson Mary Lynn , Fudin Jeffrey , Villalonga-Olives Ester , Slejko Julia F
Published: March 2020

Introduction

This study examined patterns of initial transdermal fentanyl (TDF) claims among US commercially insured patients and explored the risk of 30-day hospitalization among patients with and without prior opioid exposure necessary to produce tolerance.

Design

A retrospective cohort study of initial outpatient TDF prescriptions.

Setting

A 10% random sample of commercially insured enrollees within the IQVIA Health Plan Claims Database (formerly known as PharMetrics Plus).

Subjects

Individuals with a claim for TDF between 2007 and 2015.

Methods

The primary exposure was a new transdermal fentanyl claim, and the primary outcome was guideline concordance based on time and dose exposure.

Results

Among the 24,770 patients in the cohort, 4,848 (20%) patients had sufficient time exposure to opioids before TDF. Among those with sufficient time exposure, 3,971 (82%) had adequate opioid exposure based on the US Food and Drug Administration (FDA) package insert dosing guidance. Overall, 3,971 of the 24,770 (16%) patients received guideline-consistent TDF. An exploratory analysis of 30-day hospitalization after a TDF claim did not detect a difference in odds between guideline-consistent or -inconsistent groups when adjusted for variables known to influence the risk of opioid-induced respiratory depression.

Conclusions

A majority of patients met FDA opioid dose thresholds for TDF but had insufficient time exposure based on package insert recommendations for tolerance. Exploratory analysis did not detect a difference in odds for all-cause hospitalization or respiratory-related 30-day hospitalization between guideline-consistent or -inconsistent TDF claims. Prescribers should continue to adhere to FDA TDF labeling, although certain aspects of the labeling should be reevaluated or clarified.
Reinforcement Effects between Digital Media Use and Political Participation: A Meta-Analysis of Repeated-Wave Panel Data
Authors: Oser Jennifer , Boulianne Shelley
Published: March 2020

As digital media use has rapidly increased in prevalence and diversified in form, scholars across the globe have focused extensive attention on how the use of digital media relates to political participation. To assess the results of this emerging body of research, we conduct the first meta-analysis of repeated-wave panel data studies on the relationship between digital media use and political participation. The findings, based on 38 survey-based, repeated-wave panel studies (279 coefficients) bring new evidence to bear on two questions central to this literature. First, the findings provide new insight into the classic mobilization versus reinforcement debate: contrary to common assumption, the findings support a reinforcement effect, whereby those who are already politically active are motivated to use digital media. Second, the results indicate that the relationship between digital media use and political participation is durable, as studies with a longer time lag were more likely to yield positive and significant effects. Taken together, this evidence in support of a durable reinforcement effect implies the potential for digital media use to contribute to increased inequality in political participation over time. In the concluding discussion, we outline directions for further theoretical inquiry and empirical research that leverage the value of repeated-wave panel studies to make causal inferences.
In Search of the Expressive Citizen
Authors: Lane Daniel S
Published: March 2020

Scholars have often used generational changes in citizenship norms to theorize new forms of youth political expression on social media. Public opinion data has been employed to demonstrate that young people’s perceptions of what it means to be a “good citizen” (i.e., injunctive citizenship norms) have shifted toward models of citizenship that value self-expression. Yet several fundamental assumptions of this dominant image of the young “expressive citizen” remain untested. Using data from a national survey of young Americans (ages 18–24) collected during the 2018 US midterm election, the present study examines: a) if youth indeed view expression as a relatively important part of being a good citizen; and b) if injunctive norms concerning political expression are positively associated with engagement in political expression on social media. Findings indicate that injunctive expressive norms are distinct, but rated as the least important of all injunctive norms. Further, injunctive expressive norms were only modestly associated with social media political expression and difficult to empirically distinguish from what respondents viewed as personally important (i.e., personal expressive norms). While these findings challenge the way past research has theorized and measured the normative role of political expression among young people, they also reveal promising future directions. Specifically, the finding that traditionally marginalized youth place more normative value on political self-expression suggests an important next step for studying the expressive citizen in the age of social media.
Crime is Terribly Revealing: Information Technology and Police Productivity
Authors: Mastrobuoni Giovanni
Published: March 2020

An increasing number of police departments use information technology (IT) to optimize patrolling strategies, yet little is known about its effectiveness in preventing crime. Based on quasi-random access to “predictive policing,” this study shows that IT improves police productivity as measured by crime clearance rates. Thanks to detailed information on individual incidents and offender-level identifiers it also shows that criminals strategies are predictable. Moreover, the introduction of predictive policing coincides with a large negative trend-discontinuity in crime rates. The benefit–cost ratio of this IT innovation appears to be large.