bluuebunny/crossref_metadata_2025 huggingface dataset:
Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children
Authors: McFarland Elizabeth J , Karron Ruth A , Muresan Petronella , Cunningham Coleen K , Libous Jennifer , Perlowski Charlotte , Thumar Bhagvanji , Gnanashanmugam Devasena , Moye Jack , Schappell Elizabeth , Barr Emily , Rexroad Vivian , Fearn Laura , Spector Stephen A , Aziz Mariam , Cielo Mikhaela , Beneri Christy , Wiznia Andrew , Luongo Cindy , Collins Peter , Buchholz Ursula J
Published: November 2019

Background

The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children.

Methods

Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.

Results

Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.

Conclusions

LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
Gene cloning and characterization of thiourocanate hydratase from Burkholderia sp. HME13
Authors: Muramatsu Hisashi , Miyaoku Haruna , Kurita Syuya , Matsuo Hidenori , Kashiwagi Takehiro , Kim Chul-Sa , Hayashi Motoko , Yamamoto Hiroaki , Kato Shin-Ichiro , Nagata Shinji
Published: November 2019

A novel enzyme, thiourocanate hydratase, which catalyses the conversion of thiourocanic acid to 3-(5-oxo-2-thioxoimidazolidin-4-yl) propionic acid, was isolated from the ergothioneine-utilizing strain, Burkholderia sp. HME13. When the HME13 cells were cultured in medium containing ergothioneine as the sole nitrogen source, thiourocanate-metabolizing activity was detected in the crude extract from the cells. However, activity was not detected in the crude extract from HME13 cells that were cultured in Luria-Bertani medium. The gene encoding thiourocanate hydratase was cloned and expressed in Escherichia coli, and the recombinant enzyme was purified to homogeneity. The enzyme showed maximum activity at pH 7.5 and 55°C and was stable between pH 5.0 and 10.5, and at temperatures up to 45°C. The Km and Vmax values of thiourocanate hydratase towards thiourocanic acid were 30 μM and 7.1 μmol/min/mg, respectively. The enzyme was strongly inhibited by CuCl2 and HgCl2. The amino acid sequence of the enzyme showed 46% identity to urocanase from Pseudomonas putida, but thiourocanate hydratase had no urocanase activity.
Health and Reference Classes
Authors: Werkhoven Sander
Published: November 2019

In this article, I address two objections developed by Kingma against Boorse’s (1977) bio-statistical theory of health, the objections that choice of reference classes renders the theory both circular and problematically value-laden. These objections not only apply to the bio-statistical theory of health but also to other naturalistic theories, like the dispositional theory of health. I present three rejoinders. First, I argue that the circularity objection arises from excessive methodological demands. Second, I argue that naturalists can resist the normativist claim that health and pathology are differentiated on the basis of personal or cultural values. Finally, I show that it is possible to justify choices between rival theories of health without the interference of evaluative commitments. With these rejoinders, I conclude that the bio-statistical theory, as well as other naturalistic theories of health utilizing reference classes, is not undermined by Kingma’s arguments.
Whom You Don't Know, You Don't Trust: Vernacular Security, Distrust, and Its Exclusionary Effects in Post-Conflict Societies
Authors: Benzing Bettina
Published: November 2019

Arguments about the importance of vernacular security focus on its positive and inclusive potential for peacebuilding. Reflecting on the special constitutional and sociopolitical challenges post-conflict societies face in the aftermath of conflict, though, this article focuses on the way perceptions of security and security in the vernacular can exacerbate exclusionary effects in post-conflict societies. I discuss current approaches to security concepts dealing with social perceptions of (in)security and the linkages made in research between vernacular security and local peace. But I also highlight exclusionary structures in post-conflict settings, which are most often marked by distrustful social relations, as a byproduct of security measures. I argue, in contrast to current assumptions in research on security in the vernacular, that everyday measures not only have positive implications for peacebuilding but can also lead to social exclusion, fostering violence and hindering social equality, development, and peace.
Citrus PH4–Noemi regulatory complex is involved in proanthocyanidin biosynthesis via a positive feedback loop
Authors: Zhang Yin , Ye Junli , Liu Chaoyang , Xu Qiang , Long Lichang , Deng Xiuxin
Published: November 2019

Proanthocyanidins (PAs; or condensed tannins) are a major class of flavonoids that contribute to citrus fruit quality. However, the molecular mechanism responsible for PA biosynthesis and accumulation in citrus remains unclear. Here, we identify a PH4–Noemi regulatory complex that regulates proanthocyanidin biosynthesis in citrus. Overexpression of PH4 or Noemi in citrus calli activated the expression of PA biosynthetic genes and significantly increased the PA content. Interestingly, Noemi was also shown to be up-regulated in CsPH4-overexpressing lines compared with wild-type calli. Simultaneously, CsPH4 partially complemented the PA-deficient phenotype of the Arabidopsis tt2 mutant and promoted PA accumulation in the wild-type. Further analysis revealed that CsPH4 interacted with Noemi, and together these proteins synergistically activated the expression of PA biosynthetic genes by directly binding to the MYB-recognizing elements (MRE) of the promoters of these genes. Moreover, CsPH4 could directly bind to the promoter of Noemi and up-regulate the expression of this gene. These findings explain how the CsPH4–Noemi regulatory complex contributes to the activation of PA biosynthetic genes via a positive feedback loop and provide new insights into the molecular mechanisms underlying PA biosynthesis, which can be effectively employed for metabolic engineering to improve citrus fruit quality.
Seed comparative genomics in three coffee species identify desiccation tolerance mechanisms in intermediate seeds
Authors: Stavrinides Anna K , Dussert Stéphane , Combes Marie-Christine , Fock-Bastide Isabelle , Severac Dany , Minier Jérôme , Bastos-Siqueira Aldecinei , Demolombe Vincent , Hem Sonia , Lashermes Philippe , Joët Thierry
Published: November 2019

In contrast to desiccation-tolerant ‘orthodox’ seeds, so-called ‘intermediate’ seeds cannot survive complete drying and are short-lived. All species of the genus Coffea produce intermediate seeds, but they show a considerable variability in seed desiccation tolerance (DT), which may help to decipher the molecular basis of seed DT in plants. We performed a comparative transcriptome analysis of developing seeds in three coffee species with contrasting desiccation tolerance. Seeds of all species shared a major transcriptional switch during late maturation that governs a general slow-down of metabolism. However, numerous key stress-related genes, including those coding for the late embryogenesis abundant protein EM6 and the osmosensitive calcium channel ERD4, were up-regulated during DT acquisition in the two species with high seed DT, C. arabica and C. eugenioides. By contrast, we detected up-regulation of numerous genes involved in the metabolism, transport, and perception of auxin in C. canephora seeds with low DT. Moreover, species with high DT showed a stronger down-regulation of the mitochondrial machinery dedicated to the tricarboxylic acid cycle and oxidative phosphorylation. Accordingly, respiration measurements during seed dehydration demonstrated that intermediate seeds with the highest DT are better prepared to cease respiration and avoid oxidative stresses.
Combating stress: the interplay between hormone signaling and autophagy in plants
Authors: Liao Ching-Yi , Bassham Diane C
Published: November 2019

Autophagy is a conserved recycling process in which cellular components are delivered to and degraded in the vacuole/lysosome for reuse. In plants, it assists in responding to dynamic environmental conditions and maintaining metabolite homeostasis under normal or stress conditions. Under stress, autophagy is activated to remove damaged components and to recycle nutrients for survival, and the energy sensor kinases target of rapamycin (TOR) and SNF-related kinase 1 (SnRK1) are key to this activation. Here, we discuss accumulating evidence that hormone signaling plays critical roles in regulating autophagy and plant stress responses, although the molecular mechanisms by which this occurs are often not clear. Several hormones have been shown to regulate TOR activity during stress, in turn controlling autophagy. Hormone signaling can also regulate autophagy gene expression, while, reciprocally, autophagy can regulate hormone synthesis and signaling pathways. We highlight how the interplay between major energy sensors, plant hormones, and autophagy under abiotic and biotic stress conditions can assist in plant stress tolerance.
The buildup of strongly barred galaxies in the TNG100 simulation
Authors: Rosas-Guevara Yetli , Bonoli Silvia , Dotti Massimo , Zana Tommaso , Nelson Dylan , Pillepich Annalisa , Ho Luis C , Izquierdo-Villalba David , Hernquist Lars , Pakmor Rüediger
Published: November 2019

We analyse the properties of strongly barred disc galaxies using the TNG100 simulation, a cosmological hydrodynamical realisation of the IllustrisTNG suite. We identify 270 disc galaxies at z = 0 in the stellar mass range $M_{*}=10^{10.4-11}\rm M_{\odot}$, of which 40 per cent are barred. Of the detected bars, more than half are strong. We find that the fraction of barred galaxies increases with stellar mass, in agreement with observational results. Strongly barred galaxies exhibit, overall, lower gas-to-stellar mass ratios compared to unbarred galaxies. The majority of barred galaxies are quenched (sSFR ∼10−11.7yr−1), whereas unbarred galaxies continue to be active (sSFR ∼10−10.3yr−1) on the main sequence of star-forming galaxies. We explore the evolution of strongly barred and unbarred galaxies to investigate their formation and quenching histories. We find that strong bars form between 0.5 < z < 1.5, with more massive galaxies hosting older bars. Strong bars form in galaxies with an early-established prominent disc component, undergoing periods of enhanced star formation and black hole accretion, possibly assisted by cosmological inflows. Unbarred galaxies, on the other hand, assemble most of their mass and disc component at late times. The nuclear region of strongly barred galaxies quenches shortly after bar formation, while unbarred galaxies remain active across time. Our findings are indicative of bar quenching, possibly assisted by nuclear feedback processes. We conclude that the cosmological environment, together with small scale feedback processes, determine the chances of a galaxy to form a bar and to rapidly quench its central region.
DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts
Authors: Karagkouni Dimitra , Paraskevopoulou Maria D , Tastsoglou Spyros , Skoufos Giorgos , Karavangeli Anna , Pierros Vasilis , Zacharopoulou Elissavet , Hatzigeorgiou Artemis G
Published: November 2019

DIANA-LncBase v3.0 (www.microrna.gr/LncBase) is a reference repository with experimentally supported miRNA targets on non-coding transcripts. Its third version provides approximately half a million entries, corresponding to ∼240 000 unique tissue and cell type specific miRNA–lncRNA pairs. This compilation of interactions is derived from the manual curation of publications and the analysis of >300 high-throughput datasets. miRNA targets are supported by 14 experimental methodologies, applied to 243 distinct cell types and tissues in human and mouse. The largest part of the database is highly confident, AGO-CLIP-derived miRNA-binding events. LncBase v3.0 is the first relevant database to employ a robust CLIP-Seq-guided algorithm, microCLIP framework, to analyze 236 AGO-CLIP-Seq libraries and catalogue ∼370 000 miRNA binding events. The database was redesigned from the ground up, providing new functionalities. Known short variant information, on >67,000 experimentally supported target sites and lncRNA expression profiles in different cellular compartments are catered to users. Interactive visualization plots, portraying correlations of miRNA–lncRNA pairs, as well as lncRNA expression profiles in a wide range of cell types and tissues, are presented for the first time through a dedicated page. LncBase v3.0 constitutes a valuable asset for ncRNA research, providing new insights to the understanding of the still widely unexplored lncRNA functions.
Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases
Authors: Zheng Li , Meng Yuan , Campbell Judith L , Shen Binghui
Published: November 2019

DNA2 nuclease/helicase is a structure-specific nuclease, 5′-to-3′ helicase, and DNA-dependent ATPase. It is involved in multiple DNA metabolic pathways, including Okazaki fragment maturation, replication of ‘difficult-to-replicate’ DNA regions, end resection, stalled replication fork processing, and mitochondrial genome maintenance. The participation of DNA2 in these different pathways is regulated by its interactions with distinct groups of DNA replication and repair proteins and by post-translational modifications. These regulatory mechanisms induce its recruitment to specific DNA replication or repair complexes, such as DNA replication and end resection machinery, and stimulate its efficient cleavage of various structures, for example, to remove RNA primers or to produce 3′ overhangs at telomeres or double-strand breaks. Through these versatile activities at replication forks and DNA damage sites, DNA2 functions as both a tumor suppressor and promoter. In normal cells, it suppresses tumorigenesis by maintaining the genomic integrity. Thus, DNA2 mutations or functional deficiency may lead to cancer initiation. However, DNA2 may also function as a tumor promoter, supporting cancer cell survival by counteracting replication stress. Therefore, it may serve as an ideal target to sensitize advanced DNA2-overexpressing cancers to current chemo- and radiotherapy regimens.
Expanding the editable genome and CRISPR–Cas9 versatility using DNA cutting-free gene targeting based on in trans paired nicking
Authors: Chen Xiaoyu , Tasca Francesca , Wang Qian , Liu Jin , Janssen Josephine M , Brescia Marcella D , Bellin Milena , Szuhai Karoly , Kenrick Josefin , Frock Richard L , Gonçalves Manuel A F V
Published: November 2019

Genome editing typically involves recombination between donor nucleic acids and acceptor genomic sequences subjected to double-stranded DNA breaks (DSBs) made by programmable nucleases (e.g. CRISPR–Cas9). Yet, nucleases yield off-target mutations and, most pervasively, unpredictable target allele disruptions. Remarkably, to date, the untoward phenotypic consequences of disrupting allelic and non-allelic (e.g. pseudogene) sequences have received scant scrutiny and, crucially, remain to be addressed. Here, we demonstrate that gene-edited cells can lose fitness as a result of DSBs at allelic and non-allelic target sites and report that simultaneous single-stranded DNA break formation at donor and acceptor DNA by CRISPR–Cas9 nickases (in trans paired nicking) mostly overcomes such disruptive genotype-phenotype associations. Moreover, in trans paired nicking gene editing can efficiently and precisely add large DNA segments into essential and multiple-copy genomic sites. As shown herein by genotyping assays and high-throughput genome-wide sequencing of DNA translocations, this is achieved while circumventing most allelic and non-allelic mutations and chromosomal rearrangements characteristic of nuclease-dependent procedures. Our work demonstrates that in trans paired nicking retains target protein dosages in gene-edited cell populations and expands gene editing to chromosomal tracts previously not possible to modify seamlessly due to their recurrence in the genome or essentiality for cell function.
pathDIP 4: an extended pathway annotations and enrichment analysis resource for human, model organisms and domesticated species
Authors: Rahmati Sara , Abovsky Mark , Pastrello Chiara , Kotlyar Max , Lu Richard , Cumbaa Christian A , Rahman Proton , Chandran Vinod , Jurisica Igor
Published: November 2019

PathDIP was introduced to increase proteome coverage of literature-curated human pathway databases. PathDIP 4 now integrates 24 major databases. To further reduce the number of proteins with no curated pathway annotation, pathDIP integrates pathways with physical protein–protein interactions (PPIs) to predict significant physical associations between proteins and curated pathways. For human, it provides pathway annotations for 5366 pathway orphans. Integrated pathway annotation now includes six model organisms and ten domesticated animals. A total of 6401 core and ortholog pathways have been curated from the literature or by annotating orthologs of human proteins in the literature-curated pathways. Extended pathways are the result of combining these pathways with protein-pathway associations that are predicted using organism-specific PPIs. Extended pathways expand proteome coverage from 81 088 to 120 621 proteins, making pathDIP 4 the largest publicly available pathway database for these organisms and providing a necessary platform for comprehensive pathway-enrichment analysis. PathDIP 4 users can customize their search and analysis by selecting organism, identifier and subset of pathways. Enrichment results and detailed annotations for input list can be obtained in different formats and views. To support automated bioinformatics workflows, Java, R and Python APIs are available for batch pathway annotation and enrichment analysis. PathDIP 4 is publicly available at http://ophid.utoronto.ca/pathDIP.
CDD/SPARCLE: the conserved domain database in 2020
Authors: Lu Shennan , Wang Jiyao , Chitsaz Farideh , Derbyshire Myra K , Geer Renata C , Gonzales Noreen R , Gwadz Marc , Hurwitz David I , Marchler Gabriele H , Song James S , Thanki Narmada , Yamashita Roxanne A , Yang Mingzhang , Zhang Dachuan , Zheng Chanjuan , Lanczycki Christopher J , Marchler-Bauer Aron
Published: November 2019

As NLM’s Conserved Domain Database (CDD) enters its 20th year of operations as a publicly available resource, CDD curation staff continues to develop hierarchical classifications of widely distributed protein domain families, and to record conserved sites associated with molecular function, so that they can be mapped onto user queries in support of hypothesis-driven biomolecular research. CDD offers both an archive of pre-computed domain annotations as well as live search services for both single protein or nucleotide queries and larger sets of protein query sequences. CDD staff has continued to characterize protein families via conserved domain architectures and has built up a significant corpus of curated domain architectures in support of naming bacterial proteins in RefSeq. These architecture definitions are available via SPARCLE, the Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.
Opportunistic infections after conversion to belatacept in kidney transplantation
Authors: Bertrand Dominique , Chavarot Nathalie , Gatault Philippe , Garrouste Cyril , Bouvier Nicolas , Grall-Jezequel Anne , Jaureguy Maïté , Caillard Sophie , Lemoine Mathilde , Colosio Charlotte , Golbin Léonard , Rerolle Jean-Philippe , Thierry Antoine , Sayegh Johnny , Etienne Isabelle , Lebourg Ludivine , Sberro Rebecca , Guerrot Dominique
Published: November 2019

Background

Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported.

Methods

We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients.

Results

Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein–Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate <25/mL/min/1.73 m2 on the day of the switch and the use of immunosuppressive agents before transplantation were associated with the occurrence of OPI. We found a higher rate of infection-related hospitalization (24.1 versus 12.3/100 person-years, P = 0.0007) and also a higher rate of OPI (13.2 versus 6.7/100 person-years, P = 0.005) in the early conversion group (within 6 months).

Conclusions

The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case–control study.
Effects of Nicotine Metabolic Rate on Cigarette Reinforcement
Authors: Liakoni Evangelia , Nardone Natalie , St Helen Gideon , Dempsey Delia A , Tyndale Rachel F , Benowitz Neal L
Published: November 2019

Introduction

The rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking.

Aims and Methods

As part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers. After smoking a cigarette and measuring nicotine blood concentrations, participants smoked as desired over a 90-minute period. Analysis included time to first cigarette, total number of cigarettes, total number of puffs, and weight of tobacco consumed.

Results

Sixty-one (48%) participants were fast metabolizers and 66 (52%) slow metabolizers by NMR. No significant differences were found regarding the smoking topography variables by NMR. Normal metabolizers by genotype (n = 79) had a shorter time to first cigarette than reduced metabolizers (n = 39; p = .032). Blacks smoked fewer cigarettes (p = .008) and took fewer total puffs (p = .002) compared with Whites. Among Whites, fast metabolizers by NMR had a shorter time to first cigarette compared with slow metabolizers (p = .014). Among fast metabolizers, Whites had, compared with Blacks, shorter latency to first cigarette (p = .003) and higher number of total puffs (p = .014) and cigarettes smoked (p = .014). Baseline cigarettes per day and nicotine elimination half-life significantly predicted topography outcomes.

Conclusions

Saliva NMR did not predict cigarette reinforcement during a relatively brief period of ad libitum smoking. Differences were seen by race, with White fast metabolizers by NMR having shorter time to first cigarettes compared with slow metabolizers.

Implications

After a 90-minute period of nicotine abstinence, NMR was not significantly associated with smoking reinforcement. Slow and fast metabolizers had similar time to first cigarette, number of cigarettes smoked, total number of puffs, and tobacco consumed; however, within-race differences show that within Whites, fast metabolizers had a faster time to first cigarette than slow metabolizers.
Greater IL-6, D-dimer, and ICAM-1 Levels Are Associated With Lower Small HDL Particle Concentration in the Multicenter AIDS Cohort Study
Authors: Sarkar Sudipa , Haberlen Sabina , Whelton Seamus , Schneider Edward , Kingsley Lawrence , Palella Frank , Witt Mallory D , Kelesidis Theodoros , Rodriguez Annabelle , Post Wendy S , Brown Todd T
Published: November 2019

Background

Low HDL cholesterol (HDL-C) is common in people living with HIV infection, which is associated with inflammation, and correlates with greater cardiovascular disease (CVD) risk. HDL particles are subfractions of HDL, and in some general population studies, higher small HDL particle number (HDL-P) has been associated with lower CVD risk. The objective of this study was to determine whether HIV serostatus and systemic inflammation were associated with small HDL-P in the Multicenter AIDS Cohort Study (MACS).

Methods

The MACS is composed of HIV-infected and HIV-uninfected men. Separate linear regression analyses were conducted to evaluate the associations between outcomes (small HDL-P, large HDL-P, total HDL-P, and HDL size) and variables of interest (interleukin-6 (IL-6), D-dimer, and intercellular adhesion molecule-1 (ICAM-1) levels), with adjustment for other CVD risk factors.

Results

The study population included 553 HIV-infected (88.1% on current ART) and 319 HIV-uninfected men. The mean age was 52.7 years for HIV-infected men and 55.3 years for HIV-uninfected men. In separate models of the study population, higher log IL-6 was associated with lower total and small HDL-P (P < 0.01 for both), independent of HIV serostatus and CVD risk factors. Similar results were seen with ICAM-1. Positive HIV serostatus was associated with lower small and total HDL-P, adjusted for inflammatory markers.

Conclusions

Greater systemic inflammation and HIV infection were both associated with lower atheroprotective small HDL-P. This may be a potential mechanism contributing to increased cardiovascular risk among HIV-infected people.
Virological outcome measures during analytical treatment interruptions in chronic HIV-1 infected patients
Authors: Fehér Csaba , Leal Lorna , Plana Montserrat , Climent Nuria , Crespo Guardo Alberto , Martínez Esteban , Castro Pedro , Díaz-Brito Vicens , Mothe Beatriz , López Bernaldo De Quirós Juan Carlos , Gatell Josep María , Aloy Patrick , García Felipe
Published: November 2019

Background

Analytical treatment interruptions (ATI) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies.

Methods

A retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1 infected patients collected from 11 prospective studies. Quantitative [baseline VL, set point, delta set point, VL and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve], and temporal parameters [time to rebound (TtR), set point, peak, and certain absolute and relative VL thresholds] were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated.

Results

Set point was lower than baseline VL (median delta set point -0.26. p< 0.001). This difference was >1 log10 copies/mL in 13.9% of the cases. Median TtR was 2 weeks; no patients had undetectable VL at week 12. Median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions.

Conclusions

TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.
CBFs Function in Anthocyanin Biosynthesis by Interacting with MYB113 in Eggplant (Solanum melongena L.)
Authors: Zhou Lu , He Yongjun , Li Jing , Liu Yang , Chen Huoying
Published: November 2019

Eggplant is rich in anthocyanins. R2R3-MYB transcription factors play a key role in the anthocyanin pathway. Low temperature is vital abiotic stress that affects the anthocyanin biosynthesis in plants. CBFs (C-repeat binding factors) act as central regulators in cold response. In this study, we found that SmCBF1, SmCBF2 and SmCBF3, via their C-terminal, physically interacted with SmMYB113, a key regulator of anthocyanin biosynthesis in eggplant. SmCBF2 and SmCBF3 upregulated the expression of SmCHS and SmDFR via a SmMYB113-dependent pathway. In addition, the transient expression assays demonstrated that co-infiltrating SmCBFs and SmMYB113 significantly improved the contents of anthocyanin and the expression levels of anthocyanin structural genes in tobacco. When SmTT8, a bHLH partner of SmMYB113, coexpressed with SmCBFs and SmMYB113, the anthocyanin contents were significantly enhanced compared with SmCBFs and SmMYB113. Furthermore, overexpression of SmCBF2 and SmCBF3 could facilitate the anthocyanin accumulation under cold conditions in Arabidopsis. Taken together, these results shed light on the functions of SmCBFs and potential mechanisms of low-temperature-induced anthocyanin biosynthesis in eggplant.
The Importance of Climate Risks for Institutional Investors
Authors: Krueger Philipp , Sautner Zacharias , Starks Laura T
Published: November 2019

According to our survey about climate risk perceptions, institutional investors believe climate risks have financial implications for their portfolio firms and that these risks, particularly regulatory risks, already have begun to materialize. Many of the investors, especially the long-term, larger, and ESG-oriented ones, consider risk management and engagement, rather than divestment, to be the better approach for addressing climate risks. Although surveyed investors believe that some equity valuations do not fully reflect climate risks, their perceived overvaluations are not large.
A review of neck injury and protection in vehicle accidents
Authors: Li Fan , Liu Nian-song , Li Hong-geng , Zhang Biao , Tian Shi-wei , Tan Ming-gang , Sandoz Baptiste
Published: November 2019

Neck injury is one of the most common types of injury in vehicle accidents. The mechanisms of neck injury remain controversial due to the complex structure of the cervical spine and various impact conditions. The aim of the present study is to provide a summary of recent research on neck injury mechanisms, neck injury criteria and neck injury prevention measures. The main types of neck injury resulting from vehicle accidents, including whiplash injury, cervical bone fractures and spinal cord injury, are introduced. Neck injury mechanisms are summarized according to load directions, test or simulation methods, and thresholds by means of impact intensity, load intensity and stress/strain conditions. Neck injury criteria are introduced, including NIC, Nij, Nkm and LNL. Passive and active technologies for neck injury prevention are described and the challenge of neck injury prevention for future intelligent vehicles is discussed.
Factors Associated With Discharge Home Among Medical ICU Patients in an Early Mobilization Program
Authors: Kim Roger Y. , Murphy Terrence E. , Doyle Margaret , Pulaski Catherine , Singh Maura , Tsang Sui , Wicker Dawn , Pisani Margaret A. , Connors Geoffrey R. , Ferrante Lauren E.
Published: November 2019

Objectives:

One goal of early mobilization programs is to facilitate discharge home after an ICU hospitalization, but little is known about which factors are associated with this outcome. Our objective was to evaluate factors associated with discharge home among medical ICU patients in an early mobilization program who were admitted to the hospital from home.

Design:

Retrospective cohort study of medical ICU patients in an early mobilization program.

Setting:

Tertiary care center medical ICU.

Patients:

Medical ICU patients receiving early mobilization who were community-dwelling prior to admission.

Interventions:

None.

Measurements and Main Results:

A comprehensive set of baseline, ICU-related, and mobilization-related factors were tested for their association with discharge home using multivariable logistic regression. Among the analytic cohort (n = 183), the mean age was 61.9 years (sd 16.67 yr) and the mean Acute Physiology and Chronic Health Evaluation II score was 23.5 (sd 7.11). Overall, 65.0% of patients were discharged home after their critical illness. In multivariable analysis, each incremental increase in the maximum level of mobility achieved (range, 1–6) during the medical ICU stay was associated with nearly a 50% greater odds of discharge home (odds ratio, 1.46; 95% CI, 1.13–1.88), whereas increased age (odds ratio, 0.95; 95% CI, 0.93–0.98) and greater hospital length of stay (odds ratio, 0.94; 95% CI, 0.90–0.99) were associated with decreased odds of discharge home. Prehospital ambulatory status was not associated with discharge home.

Conclusions:

Among medical ICU patients who resided at home prior to their ICU admission, the maximum level of mobility achieved in the medical ICU was the factor most strongly associated with discharge back home. Identification of this factor upon ICU-to-ward transfer may help target mobilization plans on the ward to facilitate a goal of discharge home.
Development of a Framework to Describe Functions and Practice of Community Health Workers
Authors: Corder-Mabe Joan , Johnson Shirley , Mazmanian Paul E. , Smith Wally R.
Published: November 2019

There is evidence to support the effectiveness of community health workers (CHWs), as they practice in a wide range of health care settings; yet, the perceived value of CHWs suffers from a lack of uniform credentialing and from a dearth of billing and payment structures to recognize their individual work. In turn, credentialing and billing for the work of CHWs is hampered by widely variable regulation, conflicting job titles and position descriptions, and general confusion about CHW identity, sometimes complicated by service boundaries that overlap with those of other health care and social service occupations. This article presents evidence from a rapid review of the CHW literature from 2003 to 2018. It includes clinical trials, meta-analyses, and policy reports summarizing more than 200 CHW interventions intended to improve patient health status or care delivery. The evidence is used to identify CHW roles, responsibilities, behaviors, and competencies. Four categories of CHW practice are developed from the evidence: peer CHW, general CHW, clinical CHW, and health navigator. A framework is proposed to recognize unique CHW roles, promote and further integrate varied levels of CHW function into health care–related organizations, and to inform decisions regarding certification, education, and payment for CHW services in the United States.
Regional Variations in Postlens Tear Layer Thickness During Scleral Lens Wear
Authors: Vincent Stephen J. , Alonso-Caneiro David , Collins Michael J.
Published: November 2019

Objectives:

To quantify regional variations in the postlens tear layer (PLTL) thickness during scleral lens wear.

Methods:

Fifteen healthy adults (22±3 years) with normal corneae were fitted with a 16.5-mm-diameter rotationally symmetric scleral lens in one eye. The PLTL thickness was measured across the central 5 mm at 0, 15, 30, 45, 60, 90, 120, 240, and 480 min after lens insertion using a 12 radial line scan optical coherence tomography imaging protocol. Regional analyses were conducted by dividing the PLTL into 8 equal 45° segments.

Results:

A tilted optic zone was observed immediately after lens insertion with the greatest PLTL asymmetry between nasal and temporal regions (156±22 μm more clearance temporally) and superior nasal and inferotemporal regions (124±12 μm more clearance inferotemporally). The magnitude of lens settling observed in each region was associated with the initial PLTL (r=0.59–0.77, P≤0.02). The superior nasal PLTL furthest from the pupil center stabilized after 90 min compared with other regions which stabilized after 4 hr. On average, after 8 hr of lens wear, the PLTL decreased by 29% and PLTL asymmetries between opposing regions decreased by 30%.

Conclusions:

The PLTL was thickest temporally and thinnest nasally in healthy eyes fitted with rotationally symmetric scleral lenses, most likely because of regional differences in underlying scleral elevation, eyelid forces, and lens centration. Postlens tear layer asymmetries diminished with lens wear, and stabilization occurred more rapidly in regions with less corneal clearance immediately after lens insertion.
FemtoLASIK After Descemet Membrane Endothelial Keratoplasty
Authors: Fernández-Vega-Cueto Luis , Lisa Carlos , Naveiras Miguel , Madrid-Costa David , Alfonso José F.
Published: November 2019

Purpose:

To evaluate the efficacy and safety of femtosecond laser-assisted in situ keratomileusis (FemtoLASIK) to correct the residual refractive error after Descemet membrane endothelial keratoplasty (DMEK).

Methods:

This case series study included 7 eyes that underwent FemtoLASIK after a DMEK surgery. The refractive error, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, corneal topography (Sirius, CSO, Italy), and anterior segment optical coherence tomography (Visante, Carl Zeiss-Meditec AG, Jena, Germany) were registered at each postoperative follow-up visit.

Results:

All surgeries were uneventful, with no intraoperative or postoperative complications. The follow-up time after DMEK (before FemtoLASIK surgery) ranged from 18 to 36 months. The post-FemtoLASIK follow-up period ranged from 12 to 60 months. All cases experienced a significant improvement in UDVA after FemtoLASIK, all of them reaching a postoperative UDVA value ≥20/32. None of the eyes lost lines of CDVA, and 1 case showed a gain of lines of CDVA. In all cases, the refractive error, UDVA, and CDVA values remained stable at their respective postoperative follow-up visits. Furthermore, all topographic and pachymetric parameters were stable at the different postoperative follow-up visits.

Conclusions:

Our findings suggest that the residual refractive error after DMEK surgery can be safely and effectively treated with FemtoLASIK.
Corneal Collagen Cross-Linking Under General Anesthesia for Pediatric Patients With Keratoconus and Developmental Delay
Authors: Ahmad Tessnim R. , Pasricha Neel D. , Rose-Nussbaumer Jennifer , T. Oatts Julius , M. Schallhorn Julie , Indaram Maanasa
Published: November 2019

Purpose:

To report the clinical characteristics and outcomes of pediatric patients with keratoconus (KCN) who underwent corneal collagen cross-linking (CXL) under general anesthesia for developmental delay or inability to cooperate with topical anesthesia.

Methods:

In this retrospective case series, we reviewed the medical charts of pediatric patients with KCN who had CXL under general anesthesia from January 2018 to April 2019. Baseline disease characteristics of patients with and without developmental delay were compared using the Pearson χ2 test and the t test. Main outcomes were anesthesia or surgical complications and postoperative best corrected visual acuity (BCVA), keratometry (K) values, and caregiver report of eye-rubbing behavior.

Results:

Fourteen eyes of 9 patients were reviewed. All were habitual eye rubbers at baseline. Six (66.7%) were developmentally delayed. Compared with patients without developmental delay, developmentally delayed patients were diagnosed and treated at older ages (16.0 vs. 13.9 years), experienced longer delays from diagnosis to surgery (20.7 vs. 8.8 weeks), and had lower BCVA (20/70 vs. 20/40), higher steep K values (54.0 vs. 50.9), and a higher incidence of corneal scarring (75.0% vs. 33.3%) and monocular vision loss (50.0% vs. 0.0%) at baseline, although these differences were not statistically significant. No anesthesia or surgical complications occurred. BCVA and K values were stable at postoperative month 6, with no clinically or statistically significant change observed for either measure. Eight patients decreased or stopped eye rubbing.

Conclusions:

We demonstrate the efficacy and safety of CXL under general anesthesia in halting the progression of KCN for pediatric patients with developmental delay or an inability to cooperate with the procedure until topical anesthesia.
Central Venous Catheter Management in High-risk Children With Bloodstream Infections
Authors: Hecht Shaina M. , Ardura Monica I. , Yildiz Vedat O. , Ouellette Christopher P.
Published: November 2019

Background:

National guidelines recommend removal of central venous catheters (CVCs) for central line–associated bloodstream infections (CLABSIs) caused by Staphylococcus aureus, Pseudomonas aeruginosa, and fungi. Data regarding guideline compliance and rates of associated treatment failures in pediatric patients with attempted CVC salvage are limited.

Methods:

We performed a retrospective analysis of high-risk children (age ≤ 21 years) hospitalized from 1/2009 to 12/2015 with a long-term CVC and CLABSI due to S. aureus, Pseudomonas spp., and Candida spp. Enterococcus spp. was included given differing management recommendations between short and long-term CVCs. Compliance with national guideline recommendations, as well as treatment failures including infection relapse, recurrence, and death were evaluated in relation to CVC retention or removal. Multivariate logistic regression modeling was performed to account for confounders impacting treatment failure.

Results:

Fifty-three children had 108 CLABSI episodes requiring 84 hospitalizations. CVCs were removed in 36 (33%) CLABSI episodes per guideline recommendations. Optimal antimicrobial management, including targeted agent and adequate duration was provided in 54 (50%) of 106 treated episodes; no significant difference in treatment failure rates were noted compared with episodes with suboptimal management. The treatment failure rate was significantly higher in patients with CVC retention compared those with CVC removal within 7 days of the first positive blood culture (31% vs. 6%, P = 0.003).

Conclusions:

Despite pathogen-specific guideline recommendations for CVC removal, compliance with national guidelines was poor. CVC salvage was attempted in the majority of CLABSI episodes in our cohort and resulted in a significantly higher treatment failure rate.
Hand Cellulitis and Abscess From a Kinkajou Bite
Authors: Hadvani Teena , Dutta Ankhi
Published: November 2019

Medical literature on the microbiology of kinkajou bites is scarce. We present a patient presenting with hand cellulitis and abscess after a kinkajou bite that grew Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. We review the literature regarding microbiology and management of kinkajou bites.
Etiology and Outcome of Candidemia in Neonates and Children in Europe
Authors: Warris Adilia , Pana Zoi-Dorothea , Oletto Andrea , Lundin Rebecca , Castagnola Elio , Lehrnbecher Thomas , Groll Andreas H. , Roilides Emmanuel
Published: November 2019

Background:

Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.

Material and Methods:

All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients’ demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.

Results:

One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8–2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.

Conclusions:

This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.
Household air pollution in India and respiratory diseases: current status and future directions
Authors: Jindal Surinder K. , Aggarwal Ashutosh N. , Jindal Aditya
Published: November 2019

Purpose of review

Combustion of solid cooking fuels employed by more than 3 billion people globally, contributes to approximately one third of ambient air pollution. In the recent past, the issue has drawn global attention because of its threat to the health of rural communities, particularly women and children. This review is focused on the evidence from India on effects of household air pollution (HAP) on respiratory health and interventions to replace the solid fuels.

Recent findings

HAP exposure is a major risk factor for increased respiratory symptoms, respiratory infections, and chronic obstructive pulmonary disease. In most studies, the odds ratio for the risk of development of respiratory disorders is more than one in HAP exposed individuals. HAP is also associated with increased risk of tuberculosis, asthma, mortality from cardio-respiratory illnesses, and nonrespiratory problems such as adverse pregnancy outcomes, prematurity, and low birth weight.

Household air pollution is a common but preventable risk factor for respiratory diseases. Replacement of solid cooking fuels with clean fuels such as LPG gas as exemplified by the ‘Ujjwala’ program of India is likely to be most effective intervention to reduce the HAP related disease burden.