bluuebunny/crossref_metadata_2025 huggingface dataset:
Lint, a transmembrane serine protease, regulates growth and metabolism in Drosophila
Authors: Pathak Himani , Vijaykumar Maya Ananthakrishnan , Tanari Abdul Basith , Sarkar Sohela , Varghese Jishy
Published: March 2021

Insulin signaling in Drosophila has a significant role in regulating growth, metabolism, fecundity, stress response, and longevity. The molecular mechanism by which insulin signaling regulates these vital processes is dependent on the nutrient status and oxygen availability of the organism. In a genetic screen to identify novel genes that regulate Drosophila insulin signaling, we discovered lumens interrupted (lint), a gene that has previously been shown to act in tracheal development. The knockdown of lint gene expression using a Dilp2Gal4 driver which expresses in the neuronal insulin producing cells (IPCs), led to defects in systemic insulin signaling, metabolic status and growth. However, our analysis of lint knockdown phenotypes revealed that downregulation of lint in the trachea and not IPCs was responsible for the growth phenotypes, as the Gal4 driver is also expressed in the tracheal system. We found various tracheal terminal branch defects, including reduction in the length as well as number of branches in the lint knockdown background. Our study reveals that substantial effects of lint downregulation arose because of tracheal defects, which induced tissue hypoxia, altered systemic insulin/TOR signaling, and resulted in effects on developmental growth regulation.
A Biomarker-based Biological Age in UK Biobank: Composition and Prediction of Mortality and Hospital Admissions
Authors: Chan Mei Sum , Arnold Matthew , Offer Alison , Hammami Imen , Mafham Marion , Armitage Jane , Perera Rafael , Parish Sarah
Published: March 2021

Background

Chronological age is the strongest risk factor for most chronic diseases. Developing a biomarker-based age and understanding its most important contributing biomarkers may shed light on the effects of age on later-life health and inform opportunities for disease prevention.

Methods

A subpopulation of 141 254 individuals healthy at baseline were studied, from among 480 019 UK Biobank participants aged 40–70 recruited in 2006–2010, and followed up for 6–12 years via linked death and secondary care records. Principal components of 72 biomarkers measured at baseline were characterized and used to construct sex-specific composite biomarker ages using the Klemera Doubal method, which derived a weighted sum of biomarker principal components based on their linear associations with chronological age. Biomarker importance in the biomarker ages was assessed by the proportion of the variation in the biomarker ages that each explained. The proportions of the overall biomarker and chronological age effects on mortality and age-related hospital admissions explained by the biomarker ages were compared using likelihoods in Cox proportional hazard models.

Results

Reduced lung function, kidney function, reaction time, insulin-like growth factor 1, hand grip strength, and higher blood pressure were key contributors to the derived biomarker age in both men and women. The biomarker ages accounted for >65% and >84% of the apparent effect of age on mortality and hospital admissions for the healthy and whole populations, respectively, and significantly improved prediction of mortality (p < .001) and hospital admissions (p < 1 × 10−10) over chronological age alone.

Conclusions

This study suggests that a broader, multisystem approach to research and prevention of diseases of aging warrants consideration.
Measurement Invariance of Social Media Use in Younger and Older Adults and Links to Socioemotional Health
Authors: Sharifian Neika , Kraal A Zarina , Zaheed Afsara B , Sol Ketlyne , Morris Emily P , Zahodne Laura B
Published: March 2021

Background and Objectives

Social media use has been linked to socioemotional health; however, less is known regarding whether these associations are moderated by age. Additionally, as the use of social media in older adult populations is rapidly increasing, there is a greater need for the investigation of psychometric properties of social media usage scales before determining age differences in the impact of social media on socioemotional health outcomes.

Research Design and Methods

Using an online adult life-span sample (n = 592), the current cross-sectional study tested the measurement invariance of the general social media usage subscale of the Media and Technology Usage and Attitudes Scale across younger (aged 19–54) versus older (aged 55–81) adults and whether age moderated associations between social media use and socioemotional health (depressive symptoms, self-esteem, and envy).

Results

Confirmatory factor analyses revealed that posting-related and checking-related items were noninvariant across age groups. In multigroup structural equation models accounting for differential item functioning, higher social media use was associated with more depressive symptoms in younger adults, but not in older adults. While higher social media use was associated with higher envy in both age groups, this association was stronger in younger adults.

Discussion and Implications

Findings suggest younger adults may be more susceptible to the detrimental effects of social media use on socioemotional health. Future directions regarding the measurement of social media use and the salience of social media use across the life span are discussed.
Ap2s1 mutation causes hypercalcaemia in mice and impairs interaction between calcium-sensing receptor and adaptor protein-2
Authors: Hannan Fadil M , Stevenson Mark , Bayliss Asha L , Stokes Victoria J , Stewart Michelle , Kooblall Kreepa G , Gorvin Caroline M , Codner Gemma , Teboul Lydia , Wells Sara , Thakker Rajesh V
Published: March 2021

Adaptor protein 2 (AP2), a heterotetrameric complex comprising AP2α, AP2β2, AP2μ2 and AP2σ2 subunits, is ubiquitously expressed and involved in endocytosis and trafficking of membrane proteins, such as the calcium-sensing receptor (CaSR), a G-protein coupled receptor that signals via Gα11. Mutations of CaSR, Gα11 and AP2σ2, encoded by AP2S1, cause familial hypocalciuric hypercalcaemia types 1–3 (FHH1–3), respectively. FHH3 patients have heterozygous AP2S1 missense Arg15 mutations (p.Arg15Cys, p.Arg15His or p.Arg15Leu) with hypercalcaemia, which may be marked and symptomatic, and occasional hypophosphataemia and osteomalacia. To further characterize the phenotypic spectrum and calcitropic pathophysiology of FHH3, we used CRISPR/Cas9 genome editing to generate mice harboring the AP2S1 p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, and had marked hypercalcaemia, hypermagnesaemia, hypophosphataemia, and increases in alkaline phosphatase activity and fibroblast growth factor-23. Plasma 1,25-dihydroxyvitamin D was normal, and no alterations in bone mineral density or bone turnover were noted. Homozygous (Ap2s1L15/L15) mice invariably died perinatally. Co-immunoprecipitation studies showed that the AP2S1 p.Arg15Leu mutation impaired protein–protein interactions between AP2σ2 and the other AP2 subunits, and also with the CaSR. Cinacalcet, a CaSR positive allosteric modulator, decreased plasma calcium and parathyroid hormone concentrations in Ap2s1+/L15 mice, but had no effect on the diminished AP2σ2-CaSR interaction in vitro. Thus, our studies have established a mouse model that is representative for FHH3 in humans, and demonstrated that the AP2S1 p.Arg15Leu mutation causes a predominantly calcitropic phenotype, which can be ameliorated by treatment with cinacalcet.
The party scene: new directions for political party research in foreign policy analysis
Authors: Hofmann Stephanie C , Martill Benjamin
Published: March 2021

Research on political parties and foreign policy has grown in recent years in response to disciplinary and real-world changes. But party research still bears the imprint of earlier scepticism about the role of parties. The result is scholarship which is disaggregated, which avoids difficult cases for parties, and which has focused more on showing that parties matter relative to structural accounts of foreign policy-making. This article takes stock of recent research on political parties, party politics and their role in foreign policy-making. We argue that it is time for party research not only to embrace the question of whether parties matter but also how, when and where they matter. This requires a move away from most-likely cases and the realist foil towards an embrace of the complexity of party positions. Building on International Relations, comparative politics and foreign policy analysis scholarship, we suggest four avenues deserving of greater scholarly focus: 1) ideological multidimensionality; 2) parties as organizations and the role of entrepreneurs; 3) parties as transnational foreign policy actors; and 4) the interaction between parties and the changing global order. We propose how these literatures can help identify new research questions, contribute to theory development and help define scope conditions. This will hopefully help scholars establish benchmarks for judging the efficacy of parties in foreign policy-making.
Trade specialization and performance in global value chains
Authors: Bontadini Filippo
Published: March 2021

This article investigates whether trade specialization explains economies’ trade performance within the context of global value chains (GVCs). We consider trade specialization in natural resources (NR), high- and low-tech manufacturing (LTM and HTM) and business services, before and after the financial crisis. The aimed contribution of this article is to shed light on the effects of trade specialization as measured in domestic value added embodied in exports rather than gross exports. We add to the literature on GVCs by (i) studying the role of the domestic productive structure in countries’ trade specialization and performance, (ii) accounting for the rate of changes in trade specialization as affecting GVC performance. We employ Balassa indexes based on value added flows in a GMM dynamic panel framework. Our results suggest that trade specialization in LTM and NR relate to a decline in the growth of domestic value-added per capita exports relative to other countries. HTM and knowledge-intensive business services exhibit a positive effect during the crisis period. We discuss these findings in relation to the recent debates on the role of manufacturing and premature de-industrialization in developing countries.
Physicians’ perceptions of their knowledge and the preparedness of health facilities in Angola to diagnose and manage COVID-19
Authors: Arrais Margarete , Dias Welwitschia , Gama Jorge M R , Brito Miguel
Published: March 2021

Background

Healthcare professionals represent a vulnerable group in terms of responding to COVID-19. Knowledge can influence healthcare professionals through adoption of the correct attitudes and practices. The aim of this study was to evaluate, by a questionnaire, the perceptions of physicians about their level of knowledge as well as conditions in their workplaces for dealing with COVID-19.

Methods

A cross-sectional study of Angolan physicians took place from 11 May to 23 June 2020. A questionnaire was electronically shared across social media and via email.

Results

The sample consisted of 637 valid questionnaires; 53% of respondents were female, 41% were aged 31–40 y and 79% were from Luanda province. About 51% of physicians perceived that they had adequate knowledge about COVID-19 and 64% used personal protective equipment. These figures were higher among specialists from the province of Luanda. About 81% stated that their health units lacked the technical capacity to diagnose COVID-19. Only 35% of health units have chest tomography equipment; 44% are prepared for the care and/or isolation of patients. Only 33% of units are running intensive care units. The main concerns of physicians were training opportunities and limited access to personal protective equipment.

Conclusion

The results show that it is necessary to strengthen physicians’ knowledge about COVID-19, as well as to improve the conditions of the health units, so as to promote safe practices.
Retention of Human Body Fluids in Adults ofCalliphora vicina(Diptera: Calliphoridae)
Authors: Rivers David B , Hammerschmidt Claire , Carrigan Alexandra , Melvin Kayleen
Published: March 2021

Foraging by Calliphora vicina Robineau-Desvoidy often leads to a period of bubbling behavior, followed by either deposition of the regurgitate onto surfaces or reuptake of the bubble. Eventually, the partially or undigested food is passed in the excreta forming fecal or defecatory stains on surfaces in which deposition occurs. This study examined the digestive artifacts (i.e., regurgitate and defecatory stains) formed following consumption of human blood and semen by adult flies in an attempt to determine the length of time the meal was retained in the crop. The morphological appearance of either type of stain appeared consistent with the color of blood or semen for 10–20 d after feeding. When tested with ABA Hematrace immunochromatographic strip assays, blood was detectable in at least 33% of fly artifacts 25 d after the initial consumption of blood. Similarly, semen was detected in nearly 34% of digestive artifacts 30 d after feeding on human semen when using ABA p30 cards. Human body fluids were also detected in fly artifacts when using RSID lateral flow assays, but a much lower percentage of artifacts tested positive for blood (4.9%) and semen (4.6%) 25-d postfeeding in comparison to ABA strip assays. The difference between the types of lateral flow assays appeared to be due to extraction efficiencies of the buffers used for isolation of blood or semen from the fly artifacts. The implications of these observations in reference to seasonal adaptations and to bloodstain pattern analysis at crime scenes are discussed.
Dynamics of axially functionally graded conical pipes conveying fluid
Authors: Zhao Yuzhen , Hu Dike , Wu Song , Long Xinjun , Liu Yongshou
Published: March 2021

In this paper, the dynamics of axially functionally graded (AFG) conical pipes conveying fluid are analyzed. The materials are distributed along the conical pipe axis as a volume fraction function. Either the elastic modulus or the density of the AFG conical pipe is assumed to vary from the inlet to the outlet. The governing equation of the AFG conical pipe is derived using the Hamiltonian principle and solved by the differential quadrature method. The effects of the volume fraction index, volume fraction function type and reduction factor on the natural frequency and critical velocity are analyzed. It is found that for a power function volume fraction type, the natural frequency and critical velocity increase with increasing volume fraction index and clearly increase when the volume fraction index is within the range (0, 10). For an exponential function volume fraction type, the natural frequency and critical velocity change rapidly within the range (−10, 10), besides the above range the relationship between the natural frequency, critical velocity and volume fraction index is approximate of little change. The natural frequency and critical velocity decrease linearly with increasing reduction factor.
The spatially resolved gas and dust connection in neutral inflows and outflows in nearby AGN
Authors: Rupke David S N , Thomas Adam D , Dopita Michael A
Published: March 2021

Dusty, neutral outflows and inflows are a common feature of nearby star-forming galaxies. We characterize these flows in eight galaxies – mostly active galactic nuclei (AGN) – selected for their widespread Na i D signatures from the Siding Spring Southern Seyfert Spectroscopic Snapshot Survey (S7). This survey employs deep, wide field-of-view (FOV) integral field spectroscopy at moderate spectral resolution (R = 7000 at Na i D). We significantly expand the sample of sightlines in external galaxies in which the spatially resolved relationship has been studied between cool, neutral gas properties – N(Na i), Weq(Na i D) – and dust – E(B − V) from both stars and gas. Our sample shows strong, significant correlations of total Weq with E(B − V)⋆ and g − i colour within individual galaxies; correlations with E(B − V)gas are present but weaker. Regressions yield slope variations from galaxy to galaxy and intrinsic scatter ∼1 Å. The sample occupies regions in the space of N(Na i) and $W_\mathrm{eq}^\mathrm{abs}$ versus E(B − V)gas that are consistent with extrapolations from other studies to higher colour excess [E(B − V)gas ∼ 1]. For perhaps the first time in external galaxies, we detect inverse P Cygni profiles in the Na i D line, presumably due to inflowing gas. Via Doppler-shifted Na i D absorption and emission lines, we find ubiquitous flows that differ from stellar rotation by $\gtrsim$100 km s−1 or have $|v_{\mathrm{ abs}} - v_{\mathrm{ em}}|\gtrsim 100$ km s−1. Inflows and outflows extend towards the edge of the detected stellar disc/FOV, together subtend 10–40 per cent of the projected disc, and have similar mean N(Na i) and Weq(Na i D). Outflows are consistent with minor axis or jet-driven flows, while inflows tend towards the projected major axis. The inflows may result from non-axisymmetric potentials, tidal motions, or halo infall.
The non-linear infrared-radio correlation of low-z galaxies: implications for redshift evolution, a new radio SFR recipe, and how to minimize selection bias
Authors: Molnár Dániel Cs , Sargent Mark T , Leslie Sarah , Magnelli Benjamin , Schinnerer Eva , Zamorani Giovanni , Delhaize Jacinta , Smolčić Vernesa , Tisanić Krešimir , Vardoulaki Eleni
Published: March 2021

The infrared-radio correlation (IRRC) underpins many commonly used radio luminosity–star formation rate (SFR) calibrations. In preparation for the new generation of radio surveys, we revisit the IRRC of low-z galaxies by (a) drawing on the best currently available infrared (IR) and 1.4 GHz radio photometry, plus ancillary data over the widest possible area, and (b) carefully assessing potential systematics. We compile a catalogue of ∼9500, z < 0.2 galaxies and derive their 1.4 GHz radio (L1.4), total IR, and monochromatic IR luminosities in up to seven bands, allowing us to parametrize the wavelength dependence of monochromatic IRRCs from 22–500 µm. For the first time for low-z samples, we quantify how poorly matched IR and radio survey depths bias measured median IR/radio ratios, $\overline{q}_{\mathrm{TIR}}$, and discuss the level of biasing expected for low-z IRRC studies in ASKAP/MeerKAT fields. For our subset of ∼2000 high-confidence star-forming galaxies, we find a median $\overline{q}_{\mathrm{TIR}}$ of 2.54 (scatter: 0.17 dex). We show that $\overline{q}_{\mathrm{TIR}}$ correlates with L1.4, implying a non-linear IRRC with slope 1.11 ± 0.01. Our new L1.4–SFR calibration, which incorporates this non-linearity, reproduces SFRs from panchromatic SED fits substantially better than previous IRRC-based recipes. Finally, we match the evolutionary slope of recently measured $\overline{q}_{\mathrm{TIR}}$–redshift trends without having to invoke redshift evolution of the IRRC. In this framework, the redshift evolution of $\overline{q}_{\mathrm{TIR}}$ reported at GHz frequencies in the literature is the consequence of a partial, redshift-dependent sampling of a non-linear IRRC obeyed by low-z and distant galaxies.
Convective core entrainment in 1D main-sequence stellar models
Authors: Scott L J A , Hirschi R , Georgy C , Arnett W D , Meakin C , Kaiser E A , Ekström S , Yusof N
Published: March 2021

3D hydrodynamics models of deep stellar convection exhibit turbulent entrainment at the convective-radiative boundary which follows the entrainment law, varying with boundary penetrability. We implement the entrainment law in the 1D Geneva stellar evolution code. We then calculate models between 1.5 and 60 M⊙ at solar metallicity (Z = 0.014) and compare them to previous generations of models and observations on the main sequence. The boundary penetrability, quantified by the bulk Richardson number, RiB, varies with mass and to a smaller extent with time. The variation of RiB with mass is due to the mass dependence of typical convective velocities in the core and hence the luminosity of the star. The chemical gradient above the convective core dominates the variation of RiB with time. An entrainment law method can therefore explain the apparent mass dependence of convective boundary mixing through RiB. New models including entrainment can better reproduce the mass dependence of the main-sequence width using entrainment law parameters A ∼ 2 × 10−4 and n = 1. We compare these empirically constrained values to the results of 3D hydrodynamics simulations and discuss implications.
Segregated brain state during hypnosis
Authors: Tuominen Jarno , Kallio Sakari , Kaasinen Valtteri , Railo Henry
Published: March 2021

Can the brain be shifted into a different state using a simple social cue, as tests on highly hypnotizable subjects would suggest? Demonstrating an altered global brain state is difficult. Brain activation varies greatly during wakefulness and can be voluntarily influenced. We measured the complexity of electrophysiological response to transcranial magnetic stimulation in one ‘hypnotic virtuoso’. Such a measure produces a response arguably outside the subject’s voluntary control and has been proven adequate for discriminating conscious from unconscious brain states. We show that a single-word hypnotic induction robustly shifted global neural connectivity into a state where activity remained sustained but failed to ignite strong, coherent activity in frontoparietal cortices. Changes in perturbational complexity indicate a similar move towards a more segregated state. We interpret these findings to suggest a shift in the underlying state of the brain, likely moderating subsequent hypnotic responding.
Integrative molecular characterization of pediatric spinal ependymoma: the UK Children’s Cancer and Leukaemia Group study
Authors: Ahmad Omar , Chapman Rebecca , Storer Lisa C , Luo Li , Heath Paul R , Resar Linda , Cohen Kenneth J , Grundy Richard G , Lourdusamy Anbarasu
Published: March 2021

Background

Pediatric spinal ependymomas (SP-EPNs) are rare primary central nervous system tumors with heterogeneous clinical course. Considering that ependymomas in children are biologically distinct from their adult counterparts, this study aimed to define the molecular landscape of SP-EPNs in children.

Methods

In this retrospective study, we have collected tumor samples from 27 SP-EPN patients younger than 18 years and carried out the histological review, DNA methylation, and gene expression profiling.

Results

Unsupervised analyses with methylation profiles revealed 2 subgroups where all grade I tumors (n = 11) were in Group 1, but the grade II/III tumors split into 2 groups (n = 7 in Group 1 and n = 9 in Group 2). The Heidelberg classifier assigned Group 1 tumors as spinal myxopapillary ependymomas (SP-MPEs), 5 Group 2 tumors as SP-EPNs, and failed to classify 4 Group 2 tumors. Copy numbers derived from DNA methylation arrays revealed subgroup-specific genetic alterations and showed that SP-EPN tumors lack MYCN amplification. Gene expression profiling revealed distinct transcriptomic signatures, including overexpression of genes involved in oxidative phosphorylation in SP-MPEs that were validated by Western blot analysis. We discovered widespread decreases in DNA methylation at enhancer regions that are associated with the expression of oncogenic signaling pathways in SP-MPEs. Furthermore, transcription factor motifs for master regulators, including HNF1B, PAX3, and ZIC3, were significantly overrepresented in probes specific to distal regulatory regions in SP-MPEs.

Conclusion

Our findings show substantial heterogeneity in pediatric SP-EPN and uncover novel enhancers and transcriptional pathways specific to the SP-MPE subgroup, providing a foundation for future therapeutic strategies.
Combined 18F-FET PET and diffusion kurtosis MRI in posttreatment glioblastoma: differentiation of true progression from treatment-related changes
Authors: D’Amore Francesco , Grinberg Farida , Mauler Jörg , Galldiks Norbert , Blazhenets Ganna , Farrher Ezequiel , Filss Christian , Stoffels Gabriele , Mottaghy Felix M , Lohmann Philipp , Shah Nadim Jon , Langen Karl-Josef
Published: March 2021

Background

Radiological differentiation of tumor progression (TPR) from treatment-related changes (TRC) in pretreated glioblastoma is crucial. This study aimed to explore the diagnostic value of diffusion kurtosis MRI combined with information derived from O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) PET for the differentiation of TPR from TRC in patients with pretreated glioblastoma.

Methods

Thirty-two patients with histomolecularly defined and pretreated glioblastoma suspected of having TPR were included in this retrospective study. Twenty-one patients were included in the TPR group, and 11 patients in the TRC group, as assessed by neuropathology or clinicoradiological follow-up. Three-dimensional (3D) regions of interest were generated based on increased 18F-FET uptake using a tumor-to-brain ratio of 1.6. Furthermore, diffusion MRI kurtosis maps were obtained from the same regions of interest using co-registered 18F-FET PET images, and advanced histogram analysis of diffusion kurtosis map parameters was applied to generated 3D regions of interest. Diagnostic accuracy was analyzed by receiver operating characteristic curve analysis and combinations of PET and MRI parameters using multivariate logistic regression.

Results

Parameters derived from diffusion MRI kurtosis maps show high diagnostic accuracy, up to 88%, for differentiating between TPR and TRC. Logistic regression revealed that the highest diagnostic accuracy of 94% (area under the curve, 0.97; sensitivity, 94%; specificity, 91%) was achieved by combining the maximum tumor-to-brain ratio of 18F-FET uptake and diffusion MRI kurtosis metrics.

Conclusions

The combined use of 18F-FET PET and MRI diffusion kurtosis maps appears to be a promising approach to improve the differentiation of TPR from TRC in pretreated glioblastoma and warrants further investigation.
Fiscal policy uncertainty and its effects on the real economy: German evidence
Authors: Beckmann Joscha , Czudaj Robert L
Published: March 2021

This article introduces a new measure of fiscal policy uncertainty (FPU) based on the disagreement among professional forecasters. We analyse different patterns of this measure for the German economy and also use Italian data for comparison. Especially, we examine the impact of the introduction of the German ‘debt brake’ on FPU. Finally, we conduct an impulse response analysis to investigate the effect of FPU on the real economy and we provide robust evidence that FPU significantly decreases the growth rate of industrial production. The corresponding effect is robust to various sensitivity checks and exceeds the impact of a general measure of economic policy uncertainty. In general, the negative effect on the real economy might be explained by lower hiring and investment by firms, higher costs of financing due to risk premia and lower consumption spending as a result of precautionary savings.
Supplemental Nutrition Assistance Program Eligibility and HIV Incidence in the United States
Authors: Richterman Aaron , Block Jason P , Tsai Alexander C , Ivers Louise C
Published: March 2021

Background

The connection between food insecurity and HIV outcomes is well established. The Supplemental Nutrition Assistance Program (SNAP), the primary food safety net program in the United States, may have collateral impacts on HIV incidence. “Broad-based categorical eligibility” for SNAP is a policy that provides a mechanism for states to increase the income or asset limits for SNAP eligibility.

Methods

We estimated the association between the number of new HIV diagnoses in 2010–2014 for each state and (1) state income limits and (2) state asset limits for SNAP eligibility. We fitted multivariable negative binomial regression models with number of HIV diagnoses specified as the outcome; SNAP policies as the primary explanatory variable of interest; state and year fixed effects; and time-varying covariates related to the costs of food, health care, housing, employment, other SNAP policies, and Temporary Assistance for Needy Families spending.

Results

HIV diagnoses within states had a statistically significant association with state income limits for SNAP eligibility (incidence rate ratio [IRR], 0.94 per increase in the income limit by 35% of federal poverty level; 95% CI, 0.91–0.98), but no association with state asset limits (increased asset limit vs no change: IRR, 1.02; 95% CI, 0.94–1.10; eliminated asset limit vs no change: IRR, 1.04; 95% CI, 0.99–1.10).

Conclusions

State income limits for SNAP eligibility were inversely associated with the number of new HIV diagnoses for states between 2010 and 2014. Proposals to eliminate the use of broad-based categorical eligibility to increase the income limit for SNAP may undercut efforts to end the HIV epidemic in the United States.
Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score–Matched, Retrospective Cohort Analysis
Authors: Shah Niyati H , Shutt Kathleen A , Doi Yohei
Published: March 2021

Background

Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited.

Methods

We conducted a retrospective, propensity score–matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes.

Results

A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score–matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P < .0001).

Conclusions

Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score–matched EIE cohort.
Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice
Authors: Borghetti Alberto , Giacomelli Andrea , Borghi Vanni , Ciccullo Arturo , Dusina Alex , Fabbiani Massimiliano , Rusconi Stefano , Zazzi Maurizio , Mussini Cristina , Di Giambenedetto Simona
Published: March 2021

The TANGO trial demonstrated the efficacy of lamivudine plus dolutegravir in virologically suppressed patients without previous virological failures (VFs). In this dataset from clinical practice investigating the impact of past nucleoside reverse-transcriptase inhibitor resistance on this strategy, the combination of M184V/I plus at least 1 thymidine analog-associated mutation significantly increased the risk of VF.
Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections
Authors: Ramchandar Nanda , Coufal Nicole G , Warden Anna S , Briggs Benjamin , Schwarz Toni , Stinnett Rita , Xie Heng , Schlaberg Robert , Foley Jennifer , Clarke Christina , Waldeman Bryce , Enriquez Claudia , Osborne Stephanie , Arrieta Antonio , Salyakina Daria , Janvier Michelin , Sendi Prithvi , Totapally Balagangadhar R , Dimmock David , Farnaes Lauge
Published: March 2021

Background

Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections.

Methods

We conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis.

Results

We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours.

Conclusions

Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.
Detection of Environmental Spread of SARS-CoV-2 and Associated Patient Characteristics
Authors: Semelka Charles T , Ornelles David A , O’Connell Nathaniel S , Parsons Emma C , Blevins Maria W , Ivey Lauren E , Bischoff Werner E
Published: March 2021

Understanding transmission of severe acute respiratory syndrome coronavirus 2 informs infection prevention practices. Air sampling devices were placed in patient hospital rooms for consecutive collections with and without masks. With patient mask use, no virus was detected in the room. High viral load and fewer days from symptom onset were associated with viral particulate dispersion.
Circulating β-d-Glucan as a Marker of Subclinical Coronary Plaque in Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus
Authors: Isnard Stéphane , Fombuena Brandon , Sadouni Manel , Lin John , Richard Corentin , Routy Bertrand , Ouyang Jing , Ramendra Rayoun , Peng Xiaorong , Zhang Yonglong , Finkelman Malcolm , Tremblay-Sher Daniel , Tremblay Cecile , Chartrand-Lefebvre Carl , Durand Madeleine , Routy Jean-Pierre
Published: March 2021

Background

Despite antiretroviral therapy (ART), people with human immunodeficiency virus (PWH) have increased risk of inflammatory comorbidities, including cardiovascular diseases. Gut epithelial damage, and translocation of bacterial lipopolysaccharide (LPS) or fungal β-d-glucan (BDG) drive inflammation in ART-treated PWH. In this study, we investigated whether markers of gut damage and microbial translocation were associated with cardiovascular risk in asymptomatic ART-treated PWH.

Methods

We cross-sectionally analyzed plasma from 93 ART-treated PWH and 52 uninfected controls older than 40 years of age from the Canadian HIV and Aging Cohort. Participants were cardiovascular disease free and underwent a cardiac computed tomography (CT) to measure total coronary atherosclerotic plaque volume (TPV). Levels of bacterial LPS and gut damage markers REG3α and I-FABP were measured by enzyme-linked immunosorbent assay. Fungal BDG levels were analyzed using the Fungitell assay.

Results

β-d-glucan levels but not LPS were significantly elevated in ART-treated PWH with coronary artery plaque (P = .0007). Moreover, BDG but not LPS levels correlated with TPV (r = 0.26, P = .01). Intestinal fatty acid binding protein (I-FABP) but not REG3α levels correlated with TPV (r = 0.23, P = .03). However, BDG and LPS levels were not elevated in uninfected controls with plaque. In multivariable models, elevated BDG levels were independently associated with the presence of coronary atherosclerosis in PWH but not in uninfected controls.

Conclusions

Translocation of fungal BDG was associated with coronary atherosclerosis assessed by CT-scan imaging in ART-treated PWH, suggesting a human immunodeficiency virus-specific pathway leading to cardiovascular disease. Further investigation is needed to appraise causality of this association. Translocation of fungal products may represent a therapeutic target to prevent cardiovascular disease in ART-treated PWH.

Plasma levels of the fungal product β-D-Glucan, but not the bacterial product lipopolysaccharide, are associated with the presence and the size of subclinical coronary atherosclerosis plaque in people living with HIV taking antiretroviral therapy, independently of classical cardiovascular risk factors.
When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in Hematology Patients
Authors: Batchelor R , Thomas C , Gardiner B J , Lee S J , Fleming S , Wei A , Coutsouvelis J , Ananda-Rajah M
Published: March 2021

Background

Patients unable to take azoles are a neglected group lacking a standardized approach to antifungal prophylaxis. We evaluated the effectiveness and safety of intermittent liposomal amphotericin B (L-AMB) prophylaxis in a heterogenous group of hematology patients.

Methods

A retrospective cohort of all hematology patients who received a course of intravenous L-AMB, defined as 1 mg/kg thrice weekly from July 1, 2013 to June 30, 2018, were identified from pharmacy records. Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for premature discontinuation, and acute kidney injury.

Results

There were 198 patients who received 273 courses of L-AMB prophylaxis. Using a conservative definition, the BIFD rate was 9.6% (n = 19 of 198) occurring either during L-AMB prophylaxis or up to 7 days from cessation in patients who received a course. Probable/proven BIFD occurred in 13 patients (6.6%, 13 of 198), including molds in 54% (n = 7) and non-albicans Candidemia in 46% (n = 6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukemia (6.8%) followed by acute lymphoblastic leukemia (2.7%) and allogeneic stem cell transplantation (2.5%). The most common indication for L-AMB was chemotherapy, or anticancer drug-azole interactions (75% of courses) dominated by vincristine, or acute myeloid leukemia clinical trials, followed by gut absorption concerns (13%) and liver function abnormalities (8.8%). Acute kidney injury, using a modified international definition, complicated 27% of courses but was not clinically significant, accounting for only 3.3% (9 of 273) of discontinuations.

Conclusions

Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help researchers find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios in which azoles are unsuitable, especially as targeted anticancer drugs increase in use.
A case report of dyshidrotic bullous pemphigoid developing after partial anterior circulation ischaemic stroke
Authors: Fanelli D , Miller J , Setty R , Husain E , McNeil M
Published: March 2021

Dyshidrotic bullous pemphigoid is a rare form of bullous pemphigoid that affects predominantly a patient’s hands and feet. It has been associated in the literature with neurologic, psychiatric and cerebrovascular disorders. We present an interesting case of this rare skin condition developing in a patient following a diagnosis of partial anterior circulation stroke.
Cardiac arrest in anti-mitochondrial antibody associated inflammatory myopathy
Authors: Højgaard Pil , Witting Nanna , Rossing Kasper , Pecini Redi , Hartvig Lindkær Jensen Thomas , Hasbak Philip , Diederichsen Louise P
Published: March 2021

Insight into predictors of cardiac involvement in inflammatory myopathies is sparse. A negative prognostic role of anti-mitochondrial antibodies (AMA) has been noticed and is supported by the current case. We describe a male patient who at the age 40 suffered a cardiac arrest and over the following months experienced progressive heart failure, arrhythmias and proximal muscle weakness. Clinical, genetic and serologic testing and repeated imaging- and histopathological investigations resulted in a diagnosis of AMA-associated, necrotizing, inflammatory myositis with cardiac involvement. Besides a cardiac resynchronization therapy defibrillator, heart failure and antiarrhythmic drugs the patient received successive immunosuppressants, which improved skeletal muscle strength but not cardiac disease progression. At age 45 he died from end-stage heart failure. Clinicians must be aware of AMA-associated myositis as a cause of unclarified heart disease, even in patients with initially sparse extra-cardiac manifestations. Further knowledge of treatment strategies is highly needed for this disease entity.
Ischaemic stroke as the presenting feature of COVID-19: a series of three cases from Qatar
Authors: Iqbal Yousaf , Haddad Peter M , Latoo Javed , Alhatou Mohammed Ibrahim , Alabdulla Majid
Published: March 2021

Most cases of stroke associated with coronavirus disease 2019 (COVID-19) occur during the course of a characteristic COVID-19 respiratory illness. We report three patients where the presenting feature of COVID-19 was stroke. Two patients had no respiratory symptoms throughout their clinical course. In each case, COVID-19 was confirmed by a reverse transcription polymerase chain reaction (RT-PCR) test and the diagnosis of ischaemic stroke by brain imaging. The patients were relatively young (40, 45 and 50 years). None had a prior history of cerebrovascular events. Stroke risk factors were absent in one, limited to overweight and smoking in another but more prominent in the third patient. Two patients had large vessel occlusion and elevated D-dimer levels. Multiple infarcts were seen in two patients. Clinicians should consider the possibility of COVID-19 in patients presenting with stroke and conversely consider investigating for stroke if a patient with COVID-19, even if mildly ill, develops acute neurological symptoms.
The World Management Survey at 18: lessons and the way forward
Authors: Scur Daniela , Sadun Raffaella , Van Reenen John , Lemos Renata , Bloom Nicholas
Published: March 2021

Understanding how differences in management ‘best practices’ affect organizational outcomes has been a focus of both theoretical and empirical work in the fields of management, sociology, economics, and public policy. The World Management Survey (WMS) project was born almost two decades ago with the main goal of developing a new systematic measure of management practices being used in organizations. The WMS has contributed to a body of knowledge around how managerial structures, not just managerial talent, relate to organizational performance. Over 18 years of research, a set of consistent patterns have emerged and spurred new questions. We present a brief overview of what we have learned in terms of measuring and understanding management practices and condense the implications of these findings for policy. We end with an outline of what we see as the path forward for both research and policy implications of this research programme.
Breakthroughs in computational design methods open up new frontiers for de novo protein engineering
Authors: Meinen Ben A , Bahl Christopher D
Published: March 2021

Proteins catalyze the majority of chemical reactions in organisms, and harnessing this power has long been the focus of the protein engineering field. Computational protein design aims to create new proteins and functions in silico, and in doing so, accelerate the process, reduce costs and enable more sophisticated engineering goals to be accomplished. Challenges that very recently seemed impossible are now within reach thanks to several landmark advances in computational protein design methods. Here, we summarize these new methods, with a particular emphasis on de novo protein design advancements occurring within the past 5 years.
The role of pubertal status and sleep satisfaction in emotion reactivity and regulation in children and adolescents
Authors: Lustig Kari A , Cote Kimberly A , Willoughby Teena
Published: March 2021

Study Objectives

This study investigated the role of pubertal status and hormones in the association between sleep satisfaction and self-reported emotion functioning in 256 children and adolescents aged 8–15.

Methods

Self-report data was provided on sleep duration, sleep satisfaction, and emotion reactivity and regulation, and a saliva sample was obtained for hormone measures. A subset of children also wore an Actigraph watch to measure sleep for a week.

Results

Latent-class analysis revealed three classes of sleepers: Satisfied, Moderately Satisfied, and Dissatisfied. Dissatisfied sleepers reported more difficulties with emotion regulation and greater emotion reactivity than Satisfied sleepers. High difficulties with emotion regulation was associated with shorter objective sleep duration, and high emotion reactivity was associated with lower sleep efficiency. For girls, Dissatisfied sleepers reported being further through pubertal development than Satisfied sleepers. There were also significant correlations between pubertal development and shorter sleep duration and longer sleep latency in girls, and shorter and more irregular sleep in boys. Finally, pubertal development in girls was a significant moderator in the relationship between sleep satisfaction and difficulties with emotion regulation in Dissatisfied sleepers, such that being further through puberty and having unsatisfactory sleep resulted in the highest emotion regulation difficulties.

Conclusions

This study expands on previous literature by considering the role of sleep satisfaction and the interaction with puberty development on emotion function. Specifically, a role for pubertal development was identified in the association between unsatisfactory sleep and emotion regulation in girls.