bluuebunny/crossref_metadata_2025 huggingface dataset:
Endovascular repair of ascending aortic diseases with custom-made endografts
Authors: Piffaretti Gabriele , Czerny Martin , Riambau Vicente , Gottardi Roman , Wolfgruber Thomas , Probst Chris , Matt Peter , Antonello Michele , Gerosa Gino , Hamady Mohamad , Fontana Federico , Ferrarese Sandro , Lomazzi Chiara , Grassi Viviana , Fernandez-Alonso Sebastian , Trimarchi Santi
Published: September 2020

OBJECTIVES

The aim of this article is to report the mid-term results of ascending thoracic endovascular aortic repair using a custom-made device (CMD).

METHODS

This was a retrospective study performed at tertiary centres. Nine patients considered unfit for open surgery received elective total endovascular repair of the ascending aorta with a Relay® (Terumo Aortic, Sunrise; FL, USA) CMD: pseudoaneurysn (n = 5), localized dissection (n =3) and contained rupture (n = 1).

RESULTS

Primary clinical success was achieved in all patients with no major complications and no early conversion to open surgery. All patients were discharged home and independent: median length of stay was 7 days (interquartile range, 6–18). No patient was lost to follow-up at a median 26 months (interquartile range, 12–36). Three patients died 2, 6 and 24 months after intervention; 1 was aorta related (late aorto-atrial fistula due to infection that required open surgery). At the last follow-up available, no endoleaks, migrations, fractures or ruptures were observed in the remaining 6 patients.

CONCLUSIONS

Ascending thoracic endovascular aortic repair with Terumo Aortic CMDs was technically feasible, effective and safe in very selected lesions. CMDs showed good ascending aorta conformability with different configurations and diameters, and satisfactory mid-term durability as shown by both structural integrity and aortic lesion exclusion.
Vector dynamics influence spatially imperfect genetic interventions against disease
Authors: Yuksel Mete K , Remien Christopher H , Karki Bandita , Bull James J , Krone Stephen M
Published: September 2020

Background and objectives

Genetic engineering and similar technologies offer promising new approaches to controlling human diseases by blocking transmission from vectors. However, in spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction. Here, we consider the sensitivity of this process to biological details: do simple generalities emerge that may facilitate interventions?

Methodology

We develop formal mathematical models of this process similar to standard Ross–Macdonald models, but (i) specifying spatial structure of two patches, with vector transmission blocked in one patch but not in the other, (ii) allowing temporary human movement (travel instead of migration) and (iii) considering two different modes of mosquito biting.

Results

We find that there is no invariant effect of disrupting spatial structure with travel. For both biting models, travel out of the unprotected patch has different consequences than travel by visitors into the patch, but the effects are reversed between the two biting models.

Conclusions and implications

Overall, the effect of human travel on the maintenance of vector-borne diseases in structured habitats must be considered in light of the actual biology of mosquito abundances, biting dynamics and human movement patterns.

Lay summary: Genetic interventions against pathogens transmitted by insect vectors are promising methods of controlling infectious diseases. These interventions may be imperfect, leaving pockets where the parasite persists. How will human movement between protected and unprotected areas affect persistence? Mathematical models developed here show that the answer is ecology-dependent, depending on vector biting behavior.
Evaluating spatial management options for tiger shark (Galeocerdo cuvier) conservation in US Atlantic Waters
Authors: Morgan Alexia , Calich Hannah , Sulikowski James , Hammerschlag Neil
Published: September 2020

There has been debate in the literature over the use and success of spatial management zones (i.e. marine protected areas and time/area closures) as policy tools for commercially exploited sharks. The tiger shark (Galeocerdo cuvier) is a highly migratory predator found worldwide in warm temperate and tropical seas, which is caught in multiple US fisheries. We used a spatially explicit modelling approach to investigate the impact of varying spatial management options in the Western North Atlantic Ocean on tiger shark biomass, catch, and distribution, and impacts to other species in the ecosystem. Results suggest that under current management scenarios, tiger shark biomass will increase over time. Model outputs indicate that protecting additional habitats will have relatively minimal impacts on tiger shark biomass, as would increasing or decreasing protections in areas not highly suitable for tiger sharks. However, increasing spatial management protections in highly suitable habitats is predicted to have a positive effect on their biomass. Results also predict possible spill-over effects from current spatial protections. Our results provide insights for evaluating differing management strategies on tiger shark abundance patterns and suggest that management zones may be an effective conservation tool for highly migratory species if highly suitable habitat is protected.
Per-partnership transmission probabilities for Chlamydia trachomatis infection: evidence synthesis of population-based survey data
Authors: Lewis Joanna , White Peter J , Price Malcolm J
Published: September 2020

Background

Chlamydia is the most commonly diagnosed sexually transmitted infection worldwide. Mathematical models used to plan and assess control measures rely on accurate estimates of chlamydia’s natural history, including the probability of transmission within a partnership. Several methods for estimating transmission probability have been proposed, but all have limitations.

Methods

We have developed a new model for estimating per-partnership chlamydia transmission probabilities from infected to uninfected individuals, using data from population-based surveys. We used data on sexual behaviour and prevalent chlamydia infection from the second UK National Study of Sexual Attitudes and Lifestyles (Natsal-2) and the US National Health and Nutrition Examination Surveys 2009–2014 (NHANES) for Bayesian inference of average transmission probabilities, across all new heterosexual partnerships reported. Posterior distributions were estimated by Markov chain Monte Carlo sampling using the Stan software.

Results

Posterior median male-to-female transmission probabilities per partnership were 32.1% [95% credible interval (CrI) 18.4–55.9%] (Natsal-2) and 34.9% (95%CrI 22.6–54.9%) (NHANES). Female-to-male transmission probabilities were 21.4% (95%CrI 5.1–67.0%) (Natsal-2) and 4.6% (95%CrI 1.0–13.1%) (NHANES). Posterior predictive checks indicated a well-specified model, although there was some discrepancy between reported and predicted numbers of partners, especially in women.

Conclusions

The model provides statistically rigorous estimates of per-partnership transmission probability, with associated uncertainty, which is crucial for modelling and understanding chlamydia epidemiology and control. Our estimates incorporate data from several sources, including population-based surveys, and use information contained in the correlation between number of partners and the probability of chlamydia infection. The evidence synthesis approach means that it is easy to include further data as it becomes available.
Ethnic-minority groups in England and Wales—factors associated with the size and timing of elevated COVID-19 mortality: a retrospective cohort study linking census and death records
Authors: Ayoubkhani Daniel , Nafilyan Vahé , White Chris , Goldblatt Peter , Gaughan Charlotte , Blackwell Louisa , Rogers Nicky , Banerjee Amitava , Khunti Kamlesh , Glickman Myer , Humberstone Ben , Diamond Ian
Published: September 2020

Background

We estimated population-level associations between ethnicity and coronavirus disease 2019 (COVID-19) mortality using a newly linked census-based data set and investigated how ethnicity-specific mortality risk evolved during the pandemic.

Methods

We conducted a retrospective cohort study of respondents to the 2011 Census of England and Wales in private households, linked to death registrations and adjusted for emigration (n = 47 872 412). The outcome of interest was death involving COVID-19 between 2 March 2020 and 15 May 2020. We estimated hazard ratios (HRs) for ethnic-minority groups compared with the White population, controlling for individual, household and area characteristics. HRs were estimated on the full outcome period and separately for pre- and post-lockdown periods.

Results

In age-adjusted models, people from all ethnic-minority groups were at elevated risk of COVID-19 mortality; the HRs for Black males and females were 3.13 (95% confidence interval: 2.93 to 3.34) and 2.40 (2.20 to 2.61), respectively. However, in fully adjusted models for females, the HRs were close to unity for all ethnic groups except Black [1.29 (1.18 to 1.42)]. For males, the mortality risk remained elevated for the Black [1.76 (1.63 to 1.90)], Bangladeshi/Pakistani [1.35 (1.21 to 1.49)] and Indian [1.30 (1.19 to 1.43)] groups. The HRs decreased after lockdown for all ethnic groups, particularly Black and Bangladeshi/Pakistani females.

Conclusion

Differences in COVID-19 mortality between ethnic groups were largely attenuated by geographical and socio-demographic factors, though some residual differences remained. Lockdown was associated with reductions in excess mortality risk in ethnic-minority populations, which has implications for a second wave of infection.
Effective Cylindrical Cell Decompositions for Restricted Sub-Pfaffian Sets
Authors: Binyamini Gal , Vorobjov Nicolai
Published: September 2020

The o-minimal structure generated by the restricted Pfaffian functions, known as restricted sub-Pfaffian sets, admits a natural measure of complexity in terms of a format${{\mathcal{F}}}$, recording information like the number of variables and quantifiers involved in the definition of the set, and a degree$D$, recording the degrees of the equations involved. Khovanskii and later Gabrielov and Vorobjov have established many effective estimates for the geometric complexity of sub-Pfaffian sets in terms of these parameters. It is often important in applications that these estimates are polynomial in $D$. Despite much research done in this area, it is still not known whether cell decomposition, the foundational operation of o-minimal geometry, preserves polynomial dependence on $D$. We slightly modify the usual notions of format and degree and prove that with these revised notions, this does in fact hold. As one consequence, we also obtain the first polynomial (in $D$) upper bounds for the sum of Betti numbers of sets defined using quantified formulas in the restricted sub-Pfaffian structure.
Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in a Rehabilitation Facility: Evolution of the Presence of Nasopharyngeal SARS-CoV-2 and Serological Antibody Responses
Authors: Harris Benjamin H L , Zuhair Mohamed , Di Giovannantonio Matteo , Rosadas Carolina , Khan Maryam , Short Charlotte-Eve , Thaventhiran Thilipan , Quinlan Rachael , Taylor Andrew , Calvez Ronan , Taylor Graham P , Tedder Richard S , McClure Myra O , Fertleman Michael
Published: September 2020

At the start of the UK coronavirus disease 2019 epidemic, this rare point prevalence study revealed that one-third of patients (15 of 45) in a London inpatient rehabilitation unit were found to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but asymptomatic. We report on 8 patients in detail, including their clinical stability, the evolution of their nasopharyngeal viral reverse-transcription polymerase chain reaction (RT-PCR) burden, and their antibody levels over time, revealing the infection dynamics by RT-PCR and serology during the acute phase. Notably, a novel serological test for antibodies against the receptor binding domain of SARS-CoV-2 showed that 100% of our asymptomatic cohort remained seropositive 3—6 weeks after diagnosis.
Epitope-Specific Antibody Responses to a Plasmodium falciparum Subunit Vaccine Target in a Malaria-Endemic Population
Authors: Friedman-Klabanoff DeAnna J , Travassos Mark A , Ifeonu Olukemi O , Agrawal Sonia , Ouattara Amed , Pike Andrew , Bailey Jason A , Adams Matthew , Coulibaly Drissa , Lyke Kirsten E , Laurens Matthew B , Takala-Harrison Shannon , Kouriba Bourema , Kone Abdoulaye K , Doumbo Ogobara K , Patel Jigar J , Thera Mahamadou A , Felgner Philip L , Tan John C , Plowe Christopher V , Berry Andrea A
Published: September 2020

Circumsporozoite protein (CSP) coats the Plasmodium falciparum sporozoite surface and is a major malaria subunit vaccine target. We measured epitope-specific reactivity to field-derived CSP haplotypes in serum samples from Malian adults and children on a custom peptide microarray. Compared to children, adults showed greater antibody responses and responses to more variants in regions proximal to and within the central repeat region. Children acquired short-lived immunity to an epitope proximal to the central repeat region but not to the central repeat region itself. This approach has the potential to differentiate immunodominant from protective epitope-specific responses when combined with longitudinal infection data.
DOCK8 controls survival of group 3 innate lymphoid cells in the gut through Cdc42 activation
Authors: Aihara Ryosuke , Kunimura Kazufumi , Watanabe Mayuki , Uruno Takehito , Yamane Nana , Sakurai Tetsuya , Sakata Daiji , Nishimura Fusanori , Fukui Yoshinori
Published: September 2020

Innate lymphoid cells (ILCs) are a family of developmentally related leukocytes that rapidly secrete polarized sets of cytokines to combat infection and promote tissue repair at mucosal barriers. Among them, group 3 ILCs (ILC3s) play an important role in maintenance of the gut homeostasis by producing IL-22, and their development and function critically depend on the transcription factor RORγt. Although recent evidence indicates that RORγt+ ILC3s are reduced in the gut in the absence of the Cdc42 activator DOCK8 (dedicator of cytokinesis 8), the underlying mechanism remains unclear. We found that genetic deletion of Dock8 in RORγt+-lineage cells markedly reduced ILC3s in the lamina propria of the small intestine. By analyzing BrdU incorporation, it was revealed that DOCK8 deficiency did not affect the cell proliferation. Furthermore, when lineage marker-negative (Lin–) α4β7+ CD127+ RORγt– fetal liver cells were cultured with OP9 stromal cells in the presence of stem cell factor (SCF) and IL-7 in vitro, RORγt+ ILC3s normally developed irrespective of DOCK8 expression. However, DOCK8-deficient ILC3s exhibited a severe defect in survival of ILC3s under the condition with or without IL-7. Similar defects were observed when we analyzed Dock8VAGR mice having mutations in the catalytic center of DOCK8, thereby failing to activate Cdc42. Thus, DOCK8 acts in cell-autonomous manner to control survival of ILC3s in the gut through Cdc42 activation.
Forum on Pedagogy: The Introductory Course in International Relations: Regional Variations
Authors: Frueh Jamie , Diehl Paul F , Li Xiaoting , Gokcek Gigi , Kalpakian Jack , Vlcek William , Bower Adam , Espinoza Raúl Salgado , Carranco Santiago , de Matos-Ala Jacqui , Behera Navnita Chadha , Acharya Amitav
Published: September 2020

This forum explores how societal contexts affect how instructors teach introductory undergraduate courses in international relations (IR), global politics, and international studies. Contributors teach at universities in China, Ecuador, India, Morocco, South Africa, the United Kingdom–Scotland, and the United States. Because instructors vary the structure, content, and pedagogical approaches in their courses (and perhaps most in their introductory courses) to account for their students’ backgrounds, conditions, and paradigms, the discipline can learn about contemporary global patterns by putting regionally diverse pedagogical approaches in conversation with each other. A concluding essay explores emergent patterns of a global IR and sets up points for further conversation. The authors hope sharing their pedagogical strategies will inspire instructors to devote the creativity necessary to improve how they teach introductory IR courses in their own societal contexts.
Double prenylation of SNARE protein Ykt6 is required for lysosomal hydrolase trafficking
Authors: Sakata Natsumi , Shirakawa Ryutaro , Goto Kota , Trinh Duc Anh , Horiuchi Hisanori
Published: September 2020

Ykt6 is an evolutionarily conserved SNARE protein regulating Golgi membrane fusion and other diverse membrane trafficking pathways. Unlike most SNARE proteins, Ykt6 lacks a transmembrane domain but instead has a tandem cysteine motif at the C-terminus. Recently, we have demonstrated that Ykt6 undergoes double prenylation at the C-terminal two cysteines first by farnesyltransferase and then by a newly identified protein prenyltransferase named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of a novel α subunit prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of Rab geranylgeranyltransferase. PTAR1 knockout (KO) cells, where Ykt6 is singly prenylated with a farnesyl moiety, exhibit structural and functional abnormalities in the Golgi apparatus with delayed intra-Golgi trafficking and impaired protein glycosylation. It remains unclear whether the second prenylation of Ykt6 is required for proper trafficking of lysosomal hydrolases from Golgi to lysosomes. Here, we show that lysosomal hydrolases, cathepsin D and β-hexosaminidase, were missorted at the trans-Golgi network and secreted into the extracellular space in PTAR1 KO cells. Moreover, maturation of these hydrolases was disturbed. LC3B, an autophagy marker, was accumulated in PTAR1 KO cells, suggesting defects in cellular degradation pathways. Thus, doubly prenylated Ykt6, but not singly prenylated Ykt6, is critical for the efficient sorting and trafficking of acid hydrolases to lysosomes.
The roles of nuclear myosin in the DNA damage response
Authors: Cook Alexander W , Toseland Christopher P
Published: September 2020

Myosin within the nucleus has often been overlooked due to their importance in cytoplasmic processes and a lack of investigation. However, more recently, it has been shown that their nuclear roles are just as fundamental to cell function and survival with roles in transcription, DNA damage and viral replication. Myosins can act as molecular transporters and anchors that rely on their actin binding and ATPase capabilities. Their roles within the DNA damage response can varies from a transcriptional response, moving chromatin and stabilizing chromosome contacts. This review aims to highlight their key roles in the DNA damage response and how they impact nuclear organization and transcription.
Quadruplex Negatio Invertit? The On-Line Processing of Depth Charge Sentences
Authors: Paape Dario , Vasishth Shravan , von der Malsburg Titus
Published: September 2020

So-called “depth charge” sentences (No head injury is too trivial to be ignored) are interpreted by the vast majority of speakers to mean the opposite of what their compositional semantics would dictate. The semantic inversion that is observed for sentences of this type is the strongest and most persistent linguistic illusion known to the field ( Wason & Reich, 1979). However, it has recently been argued that the preferred interpretation arises not because of a prevailing failure of the processing system, but rather because the non-compositional meaning is grammaticalized in the form of a stored construction ( Cook & Stevenson, 2010; Fortuin, 2014). In a series of five experiments, we investigate whether the depth charge effect is better explained by processing failure due to memory overload (the overloading hypothesis) or by the existence of an underlying grammaticalized construction with two available meanings (the ambiguity hypothesis). To our knowledge, our experiments are the first to explore the on-line processing profile of depth charge sentences. Overall, the data are consistent with specific variants of the ambiguity and overloading hypotheses while providing evidence against other variants. As an extension of the overloading hypothesis, we suggest two heuristic processes that may ultimately yield the incorrect reading when compositional processing is suspended for strategic reasons.
Multiwavelength power-spectrum analysis of NGC 5548
Authors: Panagiotou C , Papadakis I E , Kammoun E S , Dovčiak M
Published: September 2020

NGC 5548 was recently monitored intensively from NIR to X-rays as part of the STORM campaign. Its disc emission was found to lag behind the observed X-rays, while the measured time lag was increasing with wavelength. These results are consistent with the assumption that short-term variability in AGN emission is driven by the X-ray illumination of the accretion disc. In this work, we studied the power spectrum of UV/optical and X-ray emission of NGC 5548, using the data of the STORM campaign as well as previous Swift data, in order to investigate the relation between the UV/optical and X-ray variability and to examine its consistency with the above picture. We demonstrate that even the power spectrum results are compatible with a standard disc being illuminated by X-rays, with low accretion rates, but the details are not entirely consistent with the results from the modelling of the ‘τ versus λ’ relation. The differences indicate that the inner disc might be covered by a ‘warm corona’ which does not allow the detection of UV/optical emission from the inner disc. Finally, we found strong evidence that the UV emission of NGC 5548 is not stationary.
The MOSDEF-LRIS Survey: The connection between massive stars and ionized gas in individual galaxies at z ∼ 2
Authors: Topping Michael W , Shapley Alice E , Reddy Naveen A , Sanders Ryan L , Coil Alison L , Kriek Mariska , Mobasher Bahram , Siana Brian
Published: September 2020

We present constraints on the massive star and ionized gas properties for a sample of 62 star-forming galaxies at z ∼ 2.3. Using BPASS stellar population models, we fit the rest-UV spectra of galaxies in our sample to estimate age and stellar metallicity which, in turn, determine the ionizing spectrum. In addition to the median properties of well-defined subsets of our sample, we derive the ages and stellar metallicities for 30 high-SNR individual galaxies – the largest sample of individual galaxies at high redshift with such measurements. Most galaxies in this high-SNR subsample have stellar metallicities of 0.001 < Z* < 0.004. We then use Cloudy + BPASS photoionization models to match observed rest-optical line ratios and infer nebular properties. Our high-SNR subsample is characterized by a median ionization parameter and oxygen abundance, respectively, of log (U)med = −2.98 ± 0.25 and 12 + log (O/H)med = 8.48 ± 0.11. Accordingly, we find that all galaxies in our sample show evidence for α-enhancement. In addition, based on inferred log (U) and 12 + log (O/H) values, we find that the local relationship between ionization parameter and metallicity applies at z ∼ 2. Finally, we find that the high-redshift galaxies most offset from the local excitation sequence in the BPT diagram are the most α-enhanced. This trend suggests that α-enhancement resulting in a harder ionizing spectrum at fixed oxygen abundance is a significant driver of the high-redshift galaxy offset on the BPT diagram relative to local systems. The ubiquity of α-enhancement among z ∼ 2.3 star-forming galaxies indicates important differences between high-redshift and local galaxies that must be accounted for in order to derive physical properties at high redshift.
Probing the origin of low-frequency radio emission in PG quasars with the uGMRT – I
Authors: S Silpa , Kharb P , Ho L C , Ishwara-Chandra C H , Jarvis M E , Harrison C
Published: September 2020

We present the results from 685 MHz observations with the upgraded Giant Metrewave Radio Telescope (uGMRT) of 22 quasars belonging to the Palomar-Green (PG) quasar sample. Only four sources reveal extended radio structures on ∼10–30 kpc scales, while the rest are largely a combination of a radio core unresolved at the uGMRT resolution of ∼3–5 arcsec, surrounded by diffuse emission on few kpc to ∼10 kpc scales. A few sources reveal signatures of barely resolved jets and lobes in their spectral index images that are created using the 685 MHz uGMRT data and similar resolution GHz-frequency data from the Very Large Array. On the basis of their position on the radio–IR correlation as well as the spectral index images, we find that the radio emission in the two radio-loud (RL) quasars and nearly one-third of the radio-quiet (RQ) quasars is active galactic nucleus (AGN) dominated whereas the remaining sources appear to have significant contributions from stellar-related processes along with the AGN. While the two RL sources exhibit inverted spectral index in their cores, the RQ sources exhibit a range of spectral indices varying from flat to steep (−0.1 $\gtrsim $ αR  $\gtrsim $ −1.1) indicating the presence of unresolved jets/lobes or winds. Except for a significant correlation between the 685 MHz radio luminosity and the Eddington ratio, we do not find strong correlations between other 685 MHz radio properties and black hole (BH) properties in the RQ PG sources. This lack of correlations could be explained by the contribution of stellar-related emission, or radio emission from previous AGN activity episodes that may not be related to the current BH activity state.
Biased Mutation and Selection in RNA Viruses
Authors: Kustin Talia , Stern Adi
Published: September 2020

RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In −ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.
Ionotropic Receptors as a Driving Force behind Human Synapse Establishment
Authors: Viscardi Lucas Henriques , Imparato Danilo Oliveira , Bortolini Maria Cátira , Dalmolin Rodrigo Juliani Siqueira
Published: September 2020

The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human–Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human–Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.
Mechanisms of replication and repair in mitochondrial DNA deletion formation
Authors: Fontana Gabriele A , Gahlon Hailey L
Published: September 2020

Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.
ASHIC: hierarchical Bayesian modeling of diploid chromatin contacts and structures
Authors: Ye Tiantian , Ma Wenxiu
Published: September 2020

The recently developed Hi-C technique has been widely applied to map genome-wide chromatin interactions. However, current methods for analyzing diploid Hi-C data cannot fully distinguish between homologous chromosomes. Consequently, the existing diploid Hi-C analyses are based on sparse and inaccurate allele-specific contact matrices, which might lead to incorrect modeling of diploid genome architecture. Here we present ASHIC, a hierarchical Bayesian framework to model allele-specific chromatin organizations in diploid genomes. We developed two models under the Bayesian framework: the Poisson-multinomial (ASHIC-PM) model and the zero-inflated Poisson-multinomial (ASHIC-ZIPM) model. The proposed ASHIC methods impute allele-specific contact maps from diploid Hi-C data and simultaneously infer allelic 3D structures. Through simulation studies, we demonstrated that ASHIC methods outperformed existing approaches, especially under low coverage and low SNP density conditions. Additionally, in the analyses of diploid Hi-C datasets in mouse and human, our ASHIC-ZIPM method produced fine-resolution diploid chromatin maps and 3D structures and provided insights into the allelic chromatin organizations and functions. To summarize, our work provides a statistically rigorous framework for investigating fine-scale allele-specific chromatin conformations. The ASHIC software is publicly available at https://github.com/wmalab/ASHIC.
High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients
Authors: Sallustio Fabio , Curci Claudia , Chaoul Nada , Fontò Giulia , Lauriero Gabriella , Picerno Angela , Divella Chiara , Di Leo Vincenzo , De Angelis Maria , Ben Mkaddem Sanae , Macchia Luigi , Gallone Anna , Monteiro Renato C , Pesce Francesco , Gesualdo Loreto
Published: September 2020

Background

Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients.

Methods

We studied the intestinal–renal axis connections, analysing levels of BAFF, TNF ligand superfamily member 13 (APRIL) and intestinal-activated B cells in IgAN patients, healthy subjects (HSs) and patients with non-IgA glomerulonephritides.

Results

IgAN patients had increased serum levels of BAFF cytokine, correlating with higher amounts of five specific microbiota metabolites, and high APRIL cytokine serum levels. We also found that subjects with IgAN have a higher level of circulating gut-homing (CCR9+ β7 integrin+) regultory B cells, memory B cells and IgA+ memory B cells compared with HSs. Finally, we found that IgAN patients had high levels of both total plasmablasts (PBs) and intestinal-homing PBs. Interestingly, PBs significantly increased in IgAN but not in patients with other glomerulonephritides.

Conclusions

Our results demonstrate a significant difference in the amount of intestinal-activated B lymphocytes between IgAN patients and HSs, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in IgAN. The intestinal–renal axis plays a crucial role in IgAN and several factors may contribute to its complex pathogenesis and provide an important area of research for novel targeted therapies to modulate progression of the disease.
Long-lived tumor-associated macrophages in glioma
Authors: Georgieva Petya B , Mathivet Thomas , Alt Silvanus , Giese Wolfgang , Riva Matteo , Balcer Marly , Gerhardt Holger
Published: September 2020

Background

The tumor microenvironment plays a major tumor-supportive role in glioma. In particular, tumor-associated macrophages (TAMs), which can make up to one-third of the tumor mass, actively support tumor growth, invasion, and angiogenesis. Predominantly alternatively activated (M2-polarized) TAMs are found in late-stage glioma in both human and mouse tumors, as well as in relapse samples from patients. However, whether tumor-educated M2 TAMs can actively contribute to the emergence and growth of relapse is currently debated.

Methods

To investigate whether tumor-educated stromal cells remaining in the brain after surgical removal of the primary tumor can be long-lived and retain their tumor-supporting function, we developed a transplantation mouse model and performed lineage-tracing.

Results

We discovered that macrophages can survive transplantation and stay present in the tumor much longer than previously suggested, while sustaining an M2-polarized protumorigenic phenotype. Transplanted tumors showed a more aggressive growth and faster polarization of the TAMs toward an M2 phenotype compared with primary tumors, a process dependent on the presence of few cotransplanted macrophages.

Conclusions

Overall, we propose a new way for tumor-educated TAMs to contribute to glioma aggressiveness by long survival and stable protumorigenic features. These properties could have a relapse-supporting effect.
Evenness is important in assessing progress towards sustainable development goals
Authors: Liu Yali , Du Jianqing , Wang Yanfen , Cui Xiaoyong , Dong Jichang , Hao Yanbin , Xue Kai , Duan Hongbo , Xia Anquan , Hu Yi , Dong Zhi , Wu Bingfang , Zhao Xinquan , Fu Bojie
Published: September 2020

Sustainable development goals (SDGs) emphasize a holistic achievement instead of cherry-picking a few. However, no assessment has quantitatively considered the evenness among all 17 goals. Here, we propose a systematic method, which first integrates both the evenness and the overall status of all goals, to distinguish the ideal development pathways from the uneven ones and then revisit the development trajectory in China from 2000 to 2015. Our results suggest that, despite the remarkable progress, a bottleneck has occurred in China since 2013 due to the stagnant developments in some SDGs. However, many far-reaching policies in China have been targeting these deficiencies since then, providing a perspective on how a country approaches sustainable development by promoting evenness among all SDGs. Our results also indicate that regions with the slowest progress are the developed provinces, owing to the persistent uneven status of all goals. Our study demonstrates the importance of adopting evenness in assessing and guiding sustainable development.
Prognostic Role of Bacterial and Fungal Infections in Patients With Liver Cirrhosis With and Without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study
Authors: Bartoletti Michele , Baldassarre Maurizio , Domenicali Marco , Lewis Russell E , Giannella Maddalena , Antognoli Agnese , Rinaldi Matteo , Zaccherini Giacomo , Verucchi Gabriella , Marconi Lorenzo , Tamè Mariarosa , Berardi Sonia , Napoli Lucia , Siniscalchi Antonio , Fabbri Angela , Biselli Maurizio , Tufoni Manuel , Pavarin Raimondo M , Trevisani Franco , Viale Pierluigi , Bernardi Mauro , Caraceni Paolo
Published: September 2020

Background

Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors.

Methods

We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year.

Results

Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI.

Conclusions

This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF.
The Stressful Characteristics of Pain That Drive You NUTS: A Qualitative Exploration of a Stress Model to Understand the Chronic Pain Experience
Authors: Pagé M Gabrielle , Dassieu Lise , Develay Elise , Roy Mathieu , Vachon-Presseau Etienne , Lupien Sonia , Rainville, PhD Pierre
Published: September 2020

Objective

Despite decades of research on the identification of specific characteristics of situations that trigger a physiological stress response (novelty, unpredictability, threat to the ego, and sense of low control [NUTS]), no integrative research has examined the validity of this framework applied to pain experiences. This study aimed to 1) explore the stressful characteristics of pain among individuals living with chronic pain and 2) examine whether the NUTS framework comprehensively captures the stressful nature of pain.

Subjects

Participants were 41 adult participants living with chronic pain.

Methods

Interviews in six focus groups were conducted in French using a semistructured interview guide. Participants first discussed how pain is stressful. Then, they were introduced to the NUTS framework and commented on the extent to which it captured their experience. The verbatim transcriptions of interviews were reviewed using reflexive thematic analysis. Analyses were conducted in French; quotes and themes were translated into English by a professional translator.

Results

The pain-NUTS framework adequately captured participants’ experiences. Multiple aspects of pain (pain intensity fluctuations, pain flare-up duration, pain quality and location, functional limitations, diagnosis and treatment) were associated with one or more stress-inducing characteristics. In addition, a second layer of meaning emerged in the context of chronic pain that provided contextual information regarding when, how, and why pain became more or less stressful.

Conclusions

The NUTS characteristics seem to offer a comprehensive framework to understand how pain and its context of chronicity can be a source of stress. This study provides preliminary support for the pain-NUTS framework to allow the formal integration of pain and stress research.
Prior sleep problems and adverse post-traumatic neuropsychiatric sequelae of motor vehicle collision in the AURORA study
Authors: Neylan Thomas C , Kessler Ronald C , Ressler Kerry J , Clifford Gari , Beaudoin Francesca L , An Xinming , Stevens Jennifer S , Zeng Donglin , Linnstaedt Sarah D , Germine Laura T , Sheikh Sophia , Storrow Alan B , Punches Brittany E , Mohiuddin Kamran , Gentile Nina T , McGrath Meghan E , van Rooij Sanne J H , Haran John P , Peak David A , Domeier Robert M , Pearson Claire , Sanchez Leon D , Rathlev Niels K , Peacock William F , Bruce Steven E , Joormann Jutta , Barch Deanna M , Pizzagalli Diego A , Sheridan John F , Harte Steven E , Elliott James M , Hwang Irving , Petukhova Maria V , Sampson Nancy A , Koenen Karestan C , McLean Samuel A
Published: September 2020

Study Objectives

Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes.

Methods

A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were assessed retrospectively in the ED. The survey assessed acute stress disorder (ASD) and MDE at 2 weeks and at 8 weeks assessed PTSD and MDE (past 30 days). Control variables included demographics, MVC characteristics, and retrospective reports about PTSD and MDE in the 30 days before the MVC.

Results

Prevalence estimates were 41.0% for 2-week ASD, 42.0% for 8-week PTSD, 30.5% for 2-week MDE, and 27.2% for 8-week MDE. Pre-MVC nightmares and sleep stress reactivity predicted 8-week PTSD (mediated through 2-week ASD) and MDE (mediated through the transition between 2-week and 8-week MDE). Pre-MVC insomnia predicted 8-week PTSD (mediated through 2-week ASD). Estimates of population attributable risk suggest that blocking effects of sleep disturbance might reduce prevalence of 8-week PTSD and MDE by as much as one-third.

Conclusions

Targeting disturbed sleep in the immediate aftermath of MVC might be one effective way of reducing MVC-related PTSD and MDE.
The History of Botrytis Taxonomy, the Rise of Phylogenetics, and Implications for Species Recognition
Authors: Garfinkel Andrea R.
Published: September 2020

Botrytis is one of the oldest, most well studied, and most economically important fungal taxa. Nonetheless, many species in this genus have remained obscured for nearly 300 years because of the difficulty in distinguishing these species by conventional mycological methods. Aided by the use of phylogenetic tools, the genus is currently undergoing a taxonomic revolution. The number of putative species in the genus has nearly doubled over the last 10 years and more species are likely to be discovered in the future. The implementation of phylogenetic species recognition concepts in Botrytis is providing for more resolution on the relatedness among species than ever before, and this has helped to overcome issues in historical species recognition using morphology, sexual crosses, and pathogenicity tests. Meanwhile, the use of genetic tools is helping to reveal surprising insight into this archetypal necrotroph’s behavior, making these approaches increasingly important in species recognition and identification. As Botrytis taxonomy continues to evolve at a rapid pace, researchers should be encouraged to continue to employ the powerful tool of phylogenetics while considering how it fits into a larger framework of classical Botrytis species recognition. Starting points for discussion on how to move forward with Botrytis species recognition are included herein, with an emphasis on the implications and utility of new species descriptions.
Documentation of Hepatitis B Immunity in Nursing Students
Authors: Elting Julie Kientz
Published: September 2020

Because of the risk of occupational exposure, preparation for nursing student clinical placement includes documentation of the hepatitis B immunization series. Requiring a hepatitis B antibody titer is less common. Immunity from the hepatitis B vaccine decreases over time, particularly for those immunized as infants. A record review of one nursing program that required both immunization and an antibody titer found 86 percent of students immunized as infants had low antibody levels, requiring reimmunization following 2013 Centers for Disease Control and Prevention guidelines. Nursing education programs that do not require antibody titers should reevaluate their policies to protect their students.
Critical Thinking With Diverse Students: The Effects of a Concurrent RN-BSN Program and Nursing Residency
Authors: Wright Joyce
Published: September 2020

Critical thinking is an analytical attribute for nurses to make accurate clinical decisions. This study examined critical thinking progression though a concurrent RN-BSN program and nursing residency for a diverse cohort of associate degree graduates. A pretest/posttest design revealed improvement in scores; however, no statistical significance was established. There was a statistically significant (p = .015) reduction in scores for a bilingual subset group in the subcategories of Prioritization of Care and Ethical Dilemmas. Future research is warranted to assess critical thinking progression and critical thinking test construction with diverse students.