bluuebunny/crossref_metadata_2025 huggingface dataset:
Unplanned readmission and survival after video-assisted thoracic surgery and open thoracotomy in patients with non-small-cell lung cancer: a 12-month nationwide cohort study
Authors: Bouabdallah Ilies , Pauly Vanessa , Viprey Marie , Orleans Veronica , Fond Guillaume , Auquier Pascal , D'Journo Xavier Benoit , Boyer Laurent , Thomas Pascal Alexandre
Published: October 2020

OBJECTIVES

To compare outcomes at 12 months between video-assisted thoracic surgery (VATS) and open thoracotomy (OT) in patients with non-small-cell lung cancer (NSCLC) using real-world evidence.

METHODS

We did a nationwide propensity-matched cohort study. We included all patients who had a diagnosis of NSCLC and who benefitted from lobectomy between 1 January 2015 and 31 December 2017. We divided this population into 2 groups (VATS and OT) and matched them using propensity scores based on patients’ and hospitals’ characteristics. Unplanned readmission, mortality, complications, length of stay and hospitalization costs within 12 months of follow-up were compared between the 2 groups.

RESULTS

A total of 13 027 patients from 180 hospitals were included, split into 6231 VATS (47.8%) and 6796 OT (52.2%). After propensity score matching (5617 patients in each group), VATS was not associated with a lower risk of unplanned readmission compared with OT [20.7% vs 21.9%, hazard ratio 1.03 (0.95–1.12)] during the 12-months follow-up. Unplanned readmissions at 90 days were mainly due to pulmonary complications (particularly pleural effusion and pneumonia) and were associated with higher mortality at 12 months (13.4% vs 2.7%, P < 0.0001).

CONCLUSIONS

VATS and OT were both associated with high incidence of unplanned readmissions within 12 months, requiring a better identification of prognosticators of unplanned readmissions. Our study highlights the need to improve prevention, early diagnosis and treatment of pulmonary complications in patients with VATS and OT after discharge. These findings call for improving the dissemination of systematic perioperative care pathway including efficient pulmonary physiotherapy and rehabilitation.
The protective role of PHB and its degradation products against stress situations in bacteria
Authors: Müller-Santos Marcelo , Koskimäki Janne J , Alves Luis Paulo Silveira , de Souza Emanuel Maltempi , Jendrossek Dieter , Pirttilä Anna Maria
Published: October 2020

Many bacteria produce storage biopolymers that are mobilized under conditions of metabolic adaptation, for example, low nutrient availability and cellular stress. Polyhydroxyalkanoates are often found as carbon storage in Bacteria or Archaea, and of these polyhydroxybutyrate (PHB) is the most frequently occurring PHA type. Bacteria usually produce PHB upon availability of a carbon source and limitation of another essential nutrient. Therefore, it is widely believed that the function of PHB is to serve as a mobilizable carbon repository when bacteria face carbon limitation, supporting their survival. However, recent findings indicate that bacteria switch from PHB synthesis to mobilization under stress conditions such as thermal and oxidative shock. The mobilization products, 3-hydroxybutyrate and its oligomers, show a protective effect against protein aggregation and cellular damage caused by reactive oxygen species and heat shock. Thus, bacteria should have an environmental monitoring mechanism directly connected to the regulation of the PHB metabolism. Here, we review the current knowledge on PHB physiology together with a summary of recent findings on novel functions of PHB in stress resistance. Potential applications of these new functions are also presented.
Loving Others: The Impact of Compassionate Love on Later-Life Psychological Well-being
Authors: Kahana Eva , Bhatta Tirth R , Kahana Boaz , Lekhak Nirmala
Published: October 2020

Objectives

Existing scholarship in social gerontology has paid relatively little attention to broader loving emotions, such as compassionate and altruistic love, as potentially meaningful mechanisms for improving later-life psychological well-being outside a family framework.

Method

Drawing from a 3-wave longitudinal survey of community-dwelling older residents (n = 334) of Miami, Florida, we utilized generalized estimating equation models to examine the influence of changes in compassionate love (i.e., feeling love toward other persons and experiencing love from others) on depressive symptoms over time. We also explored cross-sectional relationship between compassionate love and positive and negative affects.

Results

An increase in the feeling of being loved (β = −0.77, p < .001) and feeling love for others (β = −0.78, p < .001) led to a decline in odds of reporting greater levels of depressive symptoms over time. The odds of reporting higher level of positive affect were significantly greater for older adults who reported feeling loved by others (β = .63, p < .001) and expressed love for other people (β = 0.43, p < .05). Older adults who felt loved and expressed love for other people, respectively, had 0.71 and 0.54-point lower ordered log odds of reporting higher negative affect than those who reported lower levels of love. The statistically significant impact of feeling loved on all well-being outcomes was maintained even after adjustment for altruistic attitudes and emotional support. Except for depressive symptoms, such adjustments explained the positive influence of love for others on well-being outcomes.

Discussion

Our findings underscore the powerful influence of both receiving and giving loving emotions for the maintenance of later-life psychological well-being.
Concordance between systematic reviews of randomized controlled trials in assisted reproduction: an overview
Authors: Mascarenhas Mariano , Kalampokas Theodoros , Sunkara Sesh Kamal , Kamath Mohan S
Published: October 2020

STUDY QUESTION

Are systematic reviews published within a 3-year period on interventions in ART concordant in their conclusions?

SUMMARY ANSWER

The majority of the systematic reviews published within a 3-year period in the field of assisted reproduction on the same topic had discordant conclusions.

WHAT IS KNOWN ALREADY

Systematic reviews and meta-analyses have now replaced individual randomized controlled trials (RCTs) at the top of the evidence pyramid. There has been a proliferation of systematic reviews and meta-analyses, many of which suffer from methodological issues and provide varying conclusions.

STUDY DESIGN, SIZE, DURATION

We assessed nine interventions in women undergoing ART with at least three systematic reviews each, published from January 2015 to December 2017.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The systematic reviews which included RCTs were considered eligible for inclusion. The primary outcome was extent of concordance between systematic reviews on the same topic. Secondary outcomes included assessment of quality of systematic reviews, differences in included studies in meta-analyses covering the same search period, selective reporting and reporting the quality of evidence.

MAIN RESULTS AND THE ROLE OF CHANCE

Concordant results and conclusions were found in only one topic, with reviews in the remaining eight topics displaying partial discordance. The AMSTAR grading for the majority of the non-Cochrane reviews was critically low whilst it was categorized as high for all of the Cochrane reviews. For three of the nine topics, none of the included systematic reviews assessed the quality of evidence. We were unable to assess selective reporting as most of the reviews did not have a pre-specified published protocol.

LIMITATIONS, REASONS FOR CAUTION

We were limited by the high proportion of reviews lacking a pre-specified protocol, which made it impossible to assess for selective reporting. Furthermore, many reviews did not specify primary and secondary outcomes which made it difficult to assess reporting bias. All the authors of this review were Cochrane review authors which may introduce some assessment bias. The categorization of the review’s conclusions as beneficial, harmful or neutral was subjective, depending on the tone and wording of the conclusion section of the review.

WIDER IMPLICATIONS OF THE FINDINGS

The majority of the systematic reviews published within a 3-year period on the same topic in the field of assisted reproduction revealed discordant conclusions and suffered from serious methodological issues, hindering the process of informed healthcare decision-making.

STUDY FUNDING/COMPETING INTEREST(S)

All the authors are Cochrane authors. M.S.K. is an editorial board member of Cochrane Gynaecology and Fertility group. No grant from funding agencies in the public, commercial or not-for-profit sectors was obtained.
Long-term exposure to iron and copper in fine particulate air pollution and their combined impact on reactive oxygen species concentration in lung fluid: a population-based cohort study of cardiovascular disease incidence and mortality in Toronto, Canada
Authors: Zhang Zilong , Weichenthal Scott , Kwong Jeffrey C , Burnett Richard T , Hatzopoulou Marianne , Jerrett Michael , Donkelaar Aaron van , Bai Li , Martin Randall V , Copes Ray , Lu Hong , Lakey Pascale , Shiraiwa Manabu , Chen Hong
Published: October 2020

Background

Exposure to fine particulate (PM2.5) air pollution is associated with increased cardiovascular disease (CVD), but less is known about its specific components, such as metals originating from non-tailpipe emissions. We investigated the associations of long-term exposure to metal components [iron (Fe) and copper (Cu)] in PM2.5 with CVD incidence.

Methods

We conducted a population-based cohort study in Toronto, Canada. Exposures to Fe and Cu in PM2.5 and their combined impact on the concentration of reactive oxygen species (ROS) in lung fluid were estimated using land use regression models. Incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and CVD death was ascertained using health administrative datasets. We used mixed-effects Cox regression models to examine the associations between the exposures and health outcomes. A series of sensitivity analyses were conducted, including indirect adjustment for individual-level cardiovascular risk factors (e.g. smoking), and adjustment for PM2.5 and nitrogen dioxide (NO2).

Results

In single-pollutant models, we found positive associations between the three exposures and all three outcomes, with the strongest associations detected for the estimated ROS. The associations of AMI and CHF were sensitive to indirect adjustment, but remained robust for CVD death in all sensitivity analyses. In multi-pollutant models, the associations of the three exposures generally remained unaltered. Interestingly, adjustment for ROS did not substantially change the associations between PM2.5 and CVD, but attenuated the associations of NO2.

Conclusions

Long-term exposure to Fe and Cu in PM2.5 and their combined impact on ROS were consistently associated with increased CVD death.
Orexin Modulation of VTA Dopamine Neuron Activity: Relevance to Schizophrenia
Authors: Perez Stephanie M , Lodge Daniel J
Published: October 2020

Background

The hippocampus is a region consistently implicated in schizophrenia and has been advanced as a therapeutic target for positive, negative, and cognitive deficits associated with the disease. Recently, we reported that the paraventricular nucleus of the thalamus (PVT) works in concert with the ventral hippocampus to regulate dopamine system function; however, the PVT has yet to be investigated as target for the treatment of the disease. Given the dense expression of orexin receptors in the thalamus, we believe these to be a possible target for pharmacological regulation of PVT activity.

Methods

Here we used the methylazoxymethanol acetate (MAM) rodent model, which displays pathological alterations consistent with schizophrenia to determine whether orexin receptor blockade can restore ventral tegmental area dopamine system function. We measured dopamine neuron population activity, using in vivo electrophysiology, following administration of the dual orexin antagonist, TCS 1102 (both intraperitoneal and intracranial into the PVT in MAM- and saline-treated rats), and orexin A and B peptides (intracranial into the PVT in naïve rats).

Results

Aberrant dopamine system function in MAM-treated rats was normalized by the systemic administration of TCS 1102. To investigate the potential site of action, the orexin peptides A and B were administered directly into the PVT, where they significantly increased ventral tegmental area dopamine neuron population activity in control rats. In addition, the direct administration of TCS 1102 into the PVT reproduced the beneficial effects seen with the systemic administration in MAM-treated rats.

Conclusion

Taken together, these data suggest the orexin system may represent a novel site of therapeutic intervention for psychosis via an action in the PVT.
Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Henss Lisa , Scholz Tatjana , von Rhein Christine , Wieters Imke , Borgans Frauke , Eberhardt Fabian J , Zacharowski Kai , Ciesek Sandra , Rohde Gernot , Vehreschild Maria , Stephan Christoph , Wolf Timo , Hofmann-Winkler Heike , Scheiblauer Heinrich , Schnierle Barbara S
Published: October 2020

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany.

Methods

SARS-CoV-2-specific–antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and human coronavirus NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors.

Results

The severity of COVID-19 increased with age, and male patients encountered more serious symptoms than female patients. Disease severity was correlated with the amount of SARS-CoV-2–specific immunoglobulin (Ig) G and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2–specific IgG antibodies decreased with time after polymerase chain reaction conformation of the infection, and antibodies directed against the nucleoprotein waned faster than spike protein-directed antibodies. In contrast, for the common flu coronavirus NL63, COVID-19 disease severity seemed to be correlated with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection.

Conclusion

The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.
Measures of electronic health record use in outpatient settings across vendors
Authors: Baxter Sally L , Apathy Nate C , Cross Dori A , Sinsky Christine , Hribar Michelle R
Published: October 2020

Electronic health record (EHR) log data capture clinical workflows and are a rich source of information to understand variation in practice patterns. Variation in how EHRs are used to document and support care delivery is associated with clinical and operational outcomes, including measures of provider well-being and burnout. Standardized measures that describe EHR use would facilitate generalizability and cross-institution, cross-vendor research. Here, we describe the current state of outpatient EHR use measures offered by various EHR vendors, guided by our prior conceptual work that proposed seven core measures to describe EHR use. We evaluate these measures and other reporting options provided by vendors for maturity and similarity to previously proposed standardized measures. Working toward improved standardization of EHR use measures can enable and accelerate high-impact research on physician burnout and job satisfaction as well as organizational efficiency and patient health.
The light and dark sides of nitric oxide: multifaceted roles of nitric oxide in plant responses to light
Authors: Lopes-Oliveira Patrícia Juliana , Oliveira Halley Caixeta , Kolbert Zsuzsanna , Freschi Luciano
Published: October 2020

Light drives photosynthesis and informs plants about their surroundings. Regarded as a multifunctional signaling molecule in plants, nitric oxide (NO) has been repeatedly demonstrated to interact with light signaling cascades to control plant growth, development and metabolism. During early plant development, light-triggered NO accumulation counteracts negative regulators of photomorphogenesis and modulates the abundance of, and sensitivity to, plant hormones to promote seed germination and de-etiolation. In photosynthetically active tissues, NO is generated at distinct rates under light or dark conditions and acts at multiple target sites within chloroplasts to regulate photosynthetic reactions. Moreover, changes in NO concentrations in response to light stress promote plant defenses against oxidative stress under high light or ultraviolet-B radiation. Here we review the literature on the interaction of NO with the complicated light and hormonal signaling cascades controlling plant photomorphogenesis and light stress responses, focusing on the recently identified molecular partners and action mechanisms of NO in these events. We also discuss the versatile role of NO in regulating both photosynthesis and light-dependent stomatal movements, two key determinants of plant carbon gain. The regulation of nitrate reductase (NR) by light is highlighted as vital to adjust NO production in plants living under natural light conditions.
The uncoupling of respiration in plant mitochondria: keeping reactive oxygen and nitrogen species under control
Authors: Popov Vasily N , Syromyatnikov Mikhail Y , Fernie Alisdair R , Chakraborty Subhra , Gupta Kapuganti Jagadis , Igamberdiev Abir U
Published: October 2020

Plant mitochondrial respiration involves the operation of various alternative pathways. These pathways participate, both directly and indirectly, in the maintenance of mitochondrial functions though they do not contribute to energy production, being uncoupled from the generation of an electrochemical gradient across the mitochondrial membrane and thus from ATP production. Recent findings suggest that uncoupled respiration is involved in reactive oxygen species (ROS) and nitric oxide (NO) scavenging, regulation, and homeostasis. Here we discuss specific roles and possible functions of uncoupled mitochondrial respiration in ROS and NO metabolism. The mechanisms of expression and regulation of the NDA-, NDB- and NDC-type non-coupled NADH and NADPH dehydrogenases, the alternative oxidase (AOX), and the uncoupling protein (UCP) are examined in relation to their involvement in the establishment of the stable far-from-equilibrium state of plant metabolism. The role of uncoupled respiration in controlling the levels of ROS and NO as well as inducing signaling events is considered. Secondary functions of uncoupled respiration include its role in protection from stress factors and roles in biosynthesis and catabolism. It is concluded that uncoupled mitochondrial respiration plays an important role in providing rapid adaptation of plants to changing environmental factors via regulation of ROS and NO.
Isoflavone malonyl-CoA acyltransferase GmMaT2 is involved in nodulation of soybean by modifying synthesis and secretion of isoflavones
Authors: Ahmad Muhammad Zulfiqar , Zhang Yanrui , Zeng Xiangsheng , Li Penghui , Wang Xiaobo , Benedito Vagner A , Zhao Jian
Published: October 2020

Malonyl-CoA:flavonoid acyltransferases (MaTs) modify isoflavones, but only a few have been characterized for activity and assigned to specific physiological processes. Legume roots exude isoflavone malonates into the rhizosphere, where they are hydrolyzed into isoflavone aglycones. Soybean GmMaT2 was highly expressed in seeds, root hairs, and nodules. GmMaT2 and GmMaT4 recombinant enzymes used isoflavone 7-O-glucosides as acceptors and malonyl-CoA as an acyl donor to generate isoflavone glucoside malonates. GmMaT2 had higher activity towards isoflavone glucosides than GmMaT4. Overexpression in hairy roots of GmMaT2 and GmMaT4 produced more malonyldaidzin, malonylgenistin, and malonylglycitin, and resulted in more nodules than control. However, only GmMaT2 knockdown (KD) hairy roots showed reduced levels of malonyldaidzin, malonylgenistin, and malonylglycitin, and, likewise, reduced nodule numbers. These were consistent with the up-regulation of only GmMaT2 by rhizobial infection, and higher expression levels of early nodulation genes in GmMaT2- and GmMaT4-overexpressing roots, but lower only in GmMaT2-KD roots compared with control roots. Higher malonyl isoflavonoid levels in transgenic hairy roots were associated with higher levels of isoflavones in root exudates and more nodules, and vice versa. We suggest that GmMaT2 participates in soybean nodulation by catalyzing isoflavone malonylation and affecting malonyl isoflavone secretion for activation of Nod factor and nodulation.
Correlations between triaxial shapes and formation history of dark matter haloes
Authors: Lau Erwin T , Hearin Andrew P , Nagai Daisuke , Cappelluti Nico
Published: October 2020

The shape of dark matter (DM) haloes plays a critical role in constraining cosmology with upcoming large-scale structure surveys. In this paper, we study the correlations between the triaxial shapes and formation histories in DM haloes in the MultiDark Planck 2 N-body cosmological simulation. We find that halo ellipticity is strongly correlated with halo properties that serve as proxies of halo formation history, such as halo concentration and the normalized peak-centroid offset. These correlations are nearly independent of the halo density peak height. We present a simple model for the correlation between halo ellipticity and concentration using conditional abundance matching, and provide fitting formulae for the multidimensional distributions of triaxial halo shape as a function of halo peak height. We apply our halo shape model to gauge the effects of halo ellipticity and orientation bias on the excess surface mass density profiles in cluster-sized haloes. Our model should be useful for exploring the impact of triaxial halo shape on cosmological constraints in upcoming weak lensing surveys of galaxy clusters.
Can jets make the radioactively powered emission from neutron star mergers bluer?
Authors: Nativi L , Bulla M , Rosswog S , Lundman C , Kowal G , Gizzi D , Lamb G P , Perego A
Published: October 2020

Neutron star mergers eject neutron-rich matter in which heavy elements are synthesized. The decay of these freshly synthesized elements powers electromagnetic transients (‘macronovae’ or ‘kilonovae’) whose luminosity and colour strongly depend on their nuclear composition. If the ejecta are very neutron-rich (electron fraction Ye < 0.25), they contain fair amounts of lanthanides and actinides that have large opacities and therefore efficiently trap the radiation inside the ejecta so that the emission peaks in the red part of the spectrum. Even small amounts of this high-opacity material can obscure emission from lower lying material and therefore act as a ‘lanthanide curtain’. Here, we investigate how a relativistic jet that punches through the ejecta can potentially push away a significant fraction of the high opacity material before the macronova begins to shine. We use the results of detailed neutrino-driven wind studies as initial conditions and explore with 3D special relativistic hydrodynamic simulations how jets are propagating through these winds. Subsequently, we perform Monte Carlo radiative transfer calculations to explore the resulting macronova emission. We find that the hole punched by the jet makes the macronova brighter and bluer for on-axis observers during the first few days of emission, and that more powerful jets have larger impacts on the macronova.
Two-component galaxy models with a central BH – II. The ellipsoidal case
Authors: Ciotti Luca , Mancino Antonio , Pellegrini Silvia , Ziaee Lorzad Azadeh
Published: October 2020

Recently, two-component spherical galaxy models have been presented, where the stellar profile is described by a Jaffe law, and the total density by another Jaffe law, or by an r−3 law at large radii. We extend these two families to their ellipsoidal axisymmetric counterparts: the JJe and J3e models. The total and stellar density distributions can have different flattenings and scale lengths, and the dark matter halo is defined by difference. First, the analytical conditions required to have a nowhere negative dark matter halo density are derived. The Jeans equations for the stellar component are then solved analytically, in the limit of small flattenings, also in the presence of a central BH. The azimuthal velocity dispersion anisotropy is described by the Satoh k-decomposition. Finally, we present the analytical formulae for velocity fields near the centre and at large radii, together with the various terms entering the virial theorem. The JJe and J3e models can be useful in a number of theoretical applications, e.g. to explore the role of the various parameters (flattening, relative scale lengths, mass ratios, rotational support) in determining the behaviour of the stellar kinematical fields before performing more time-expensive integrations with specific galaxy models, to test codes of stellar dynamics and in numerical simulations of gas flows in galaxies.
ROGER: Reconstructing orbits of galaxies in extreme regions using machine learning techniques
Authors: de los Rios Martín , Martínez Héctor J , Coenda Valeria , Muriel Hernán , Ruiz Andrés N , Vega-Martínez Cristian A , Cora Sofía A
Published: October 2020

We present the ROGER (Reconstructing Orbits of Galaxies in Extreme Regions) code, which uses three different machine learning techniques to classify galaxies in, and around, clusters, according to their projected phase-space position. We use a sample of 34 massive, M200 > 1015h−1M⊙, galaxy clusters in the MultiDark Planck 2 (MDLP2) simulation at redshift zero. We select all galaxies with stellar mass M⋆ ≥ 108.5h−1M⊙, as computed by the semi-analytic model of galaxy formation SAG, that are located in, and in the vicinity of, these clusters and classify them according to their orbits. We train ROGER to retrieve the original classification of the galaxies from their projected phase-space positions. For each galaxy, ROGER gives as output the probability of being a cluster galaxy, a galaxy that has recently fallen into a cluster, a backsplash galaxy, an infalling galaxy, or an interloper. We discuss the performance of the machine learning methods and potential uses of our code. Among the different methods explored, we find the K-Nearest Neighbours algorithm achieves the best performance.
The stochastic enrichment of Population II stars
Authors: Welsh Louise , Cooke Ryan , Fumagalli Michele
Published: October 2020

We investigate the intrinsic scatter in the chemical abundances of a sample of metal-poor ([Fe/H] < −2.5) Milky Way halo stars. We draw our sample from four historic surveys and focus our attention on the stellar Mg, Ca, Ni, and Fe abundances. Using these elements, we investigate the chemical enrichment of these metal-poor stars using a model of stochastic chemical enrichment. Assuming that these stars have been enriched by the first generation of massive metal-free stars, we consider the mass distribution of the enriching population alongside the stellar mixing and explosion energy of their supernovae. For our choice of stellar yields, our model suggests that the most metal-poor stars were enriched, on average, by $\hat{N}_{\star }=5^{+13}_{-3}~(1\sigma)$ Population III stars. This is comparable to the number of enriching stars inferred for the most metal-poor DLAs. Our analysis therefore suggests that some of the lowest mass structures at z ∼ 3 contain the chemical products from < 13(2σ) Population III enriched minihaloes. The inferred IMF is consistent with that of a Salpeter distribution and there is a preference towards ejecta from minimally mixed hypernovae. However, the estimated enrichment model is sensitive to small changes in the stellar sample. An offset of ∼ 0.1 dex in the [Mg/Ca] abundance is shown to be sensitive to the inferred number of enriching stars. We suggest that this method has the potential to constrain the multiplicity of the first generation of stars, but this will require: (1) a stellar sample whose systematic errors are well understood; and, (2) documented uncertainties associated with nucleosynthetic yields.
Optimal therapeutic targeting by HDAC inhibition in biopsy-derived treatment-naïve diffuse midline glioma models
Authors: Vitanza Nicholas A , Biery Matt C , Myers Carrie , Ferguson Eric , Zheng Ye , Girard Emily J , Przystal Justyna M , Park Giulia , Noll Alyssa , Pakiam Fiona , Winter Conrad A , Morris Shelli M , Sarthy Jay , Cole Bonnie L , Leary Sarah E S , Crane Courtney , Lieberman Nicole A P , Mueller Sabine , Nazarian Javad , Gottardo Raphael , Brusniak Mi-Youn , Mhyre Andrew J , Olson James M
Published: October 2020

Background

Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs), have a dismal prognosis, with less than 2% surviving 5 years postdiagnosis. The majority of DIPGs and all DMGs harbor mutations altering the epigenetic regulatory histone tail (H3 K27M). Investigations addressing DMG epigenetics have identified a few promising drugs, including the HDAC inhibitor (HDACi) panobinostat. Here, we use clinically relevant DMG models to identify and validate other effective HDACi and their biomarkers of response.

Methods

HDAC inhibitors were tested across biopsy-derived treatment-naïve in vitro and in vivo DMG models with biologically relevant radiation resistance. RNA sequencing was performed to define and compare drug efficacy and to map predictive biomarkers of response.

Results

Quisinostat and romidepsin showed efficacy with low nanomolar half-maximal inhibitory concentration (IC50) values (~50 and ~5 nM, respectively). Comparative transcriptome analyses across quisinostat, romidepsin, and panobinostat showed a greater degree of shared biological effects between quisinostat and panobinostat, and less overlap with romidepsin. However, some transcriptional changes were consistent across all 3 drugs at similar biologically effective doses, such as overexpression of troponin T1 slow skeletal type (TNNT1) and downregulation of collagen type 20 alpha 1 chain (COL20A1), identifying these as potential vulnerabilities or on-target biomarkers in DMG. Quisinostat and romidepsin significantly (P < 0.0001) inhibited in vivo tumor growth.

Conclusions

Our data highlight the utility of treatment-naïve biopsy-derived models; establishes quisinostat and romidepsin as effective in vivo; illuminates potential mechanisms and/or biomarkers of DMG cell lethality due to HDAC inhibition; and emphasizes the need for brain tumor–penetrant versions of potentially efficacious agents.
XND1 Regulates Secondary Wall Deposition in Xylem Vessels through the Inhibition of VND Functions
Authors: Zhong Ruiqin , Kandasamy Muthugapatti K , Ye Zheng-Hua
Published: October 2020

Secondary wall deposition in xylem vessels is activated by Vascular-Related NAC Domain proteins (VNDs) that belong to a group of secondary wall NAC (SWN) transcription factors. By contrast, Xylem NAC Domain1 (XND1) negatively regulates secondary wall deposition in xylem vessels when overexpressed. The mechanism by which XND1 exerts its functions remains elusive. We employed the promoter of the fiber-specific Secondary Wall-Associated NAC Domain1 (SND1) gene to ectopically express XND1 in fiber cells to investigate its mechanism of action on secondary wall deposition. Ectopic expression of XND1 in fiber cells severely diminished their secondary wall deposition and drastically reduced the expression of SWN-regulated downstream transcription factors and secondary wall biosynthetic genes but not that of the SWN genes themselves. Transactivation analyses revealed that XND1 specifically inhibited SWN-activated expression of these downstream genes but not their MYB46-activated expression. Both the NAC domain and the C-terminus of XND1 were required for its inhibitory function and its NAC domain interacted with the DNA-binding domains of SWNs. XND1 was shown to be localized in the cytoplasm and the nucleus and its co-expression with VND6 resulted in the cytoplasmic sequestration of VND6. Furthermore, the C-terminus of XND1 was indispensable for the XND1-mediated cytoplasmic retention of VND6 and its fusion to VND6 was able to direct VND6 to the cytoplasm and render it unable to activate the gene expression. Since the XND1 gene is specifically expressed in xylem cells, these results indicate that XND1 acts through inhibiting VND functions to negatively regulate secondary wall deposition in xylem vessels.
Potential efficacy of dendritic cell immunomodulation in the treatment of osteoarthritis
Authors: Alahdal Murad , Zhang Hui , Huang Rongxiang , Sun Wei , Deng Zhiqin , Duan Li , Ouyang Hongwei , Wang Daping
Published: October 2020

Dendritic cells (DCs) are a cluster of heterogeneous antigen-presenting cells that play a pivotal role in both innate and adaptive immune responses. Rare reports have discussed their role in OA immunopathogenesis. Recently, DCs derived from the synovial fluid of OA mice were shown to have increased expression of toll-like receptors. Moreover, from in vitro studies it was concluded that DCs derived from OA patients had secreted high levels of inflammatory cytokines. Likewise, a significant increase in CD123+BDCA-2 plasmacytoid DCs has been observed in the synovial fluid of OA patients. Furthermore, DCs have a peripheral tolerance potential and can become regulatory under specific circumstances. This could be exploited as a promising tool to eliminate immunoinflammatory manifestations in OA disease. In this review, the potential roles DCs could play in OA pathogenesis have been described. In addition, suggestions for the development of new immunotherapeutic strategies involving intra-articular injections of tolerogenic plasmacytoid DCs for treating OA inflammations have been made.
Day-to-day and longer-term longitudinal associations between physical activity, sedentary behavior, and sleep in children
Authors: Antczak Devan , Sanders Taren , del Pozo Cruz Borja , Parker Philip , Lonsdale Chris
Published: October 2020

Study Objectives

To determine the day-to-day and longer-term longitudinal associations between daytime physical activity and night-time sleep.

Methods

We used data from a 2-year longitudinal study which included three time points (i.e. baseline, year 1, and year 2). Participants were recruited from primary schools and included 1059 children (50% girls) with a mean age of 8.81-years-old (SD = 0.72) at baseline. Sleep variables included sleep duration, sleep efficiency, time in bed, sleep onset, and wake time. Physical activity variables included light, moderate, moderate-to-vigorous, and vigorous physical activity as well as sedentary time. We objectively assessed physical activity and sleep behaviors using the GENEActiv wrist-worn accelerometer over an 8-day period at each timepoint for a potential 21 190 observed days.

Results

We used fixed-effects multilevel models and parallel latent growth curve modeling to examine day-to-day and longer-term associations, respectively. Day-to-day, physical activity, and sleep variables were significantly, positively, and bidirectionally associated, except for sleep efficiency, which showed little association with physical activity. Longer-term, we found little association between physical activity and sleep variables.

Conclusions

Overall, our findings indicate that there is a day-to-day association between the amount of time spent being physically active and improved sleep. The lack of a longer-term association indicates that a focus on children’s daily behavior may be most appropriate to help children improve sleep and increase physical activity.
Genomic Profiling of Virulence in the Soybean Cyst Nematode Using Single-Nematode Sequencing
Authors: Ste-Croix Dave T. , St-Marseille Anne-Frédérique Gendron , Lord Etienne , Bélanger Richard R. , Brodeur Jacques , Mimee Benjamin
Published: October 2020

Soybean cyst nematode (SCN) is one of the most important diseases in soybean. Currently, the main management strategy relies on planting resistant cultivars. However, the overuse of a single resistance source has led to the selection of virulent SCN populations, although the mechanisms by which the nematode overcomes the resistance genes remain unknown. In this study, we used a nematode-adapted single-cell RNA-seq approach to identify SCN genes potentially involved in resistance breakdown in Peking and PI 88788 parental soybean lines. We established for the first time the full transcriptome of single SCN individuals allowing us to identify a list of putative virulence genes against both major SCN resistance sources. Our analysis identified 48 differentially expressed putative effectors (secreted proteins required for infection) alongside 40 effectors showing evidence of novel structural variants, and 11 effector genes containing phenotype-specific sequence polymorphisms. Additionally, a differential expression analysis revealed an interesting phenomenon of coexpressed gene regions with some containing putative effectors. The selection of virulent SCN individuals on Peking resulted in a profoundly altered transcriptome, especially for genes known to be involved in parasitism. Several sequence polymorphisms were also specific to these virulent nematodes and could potentially play a role in the acquisition of nematode virulence. On the other hand, the transcriptome of virulent individuals on PI 88788 was very similar to avirulent ones with the exception of a few genes, which suggest a distinct virulence strategy to Peking.
Detection of Nematophagous Fungi from Heterodera schachtii Females Using a Baiting Experiment with Soils Cropped to Brassica Species from California’s Central Coast
Authors: Chen Ying-Yu , Koike Steven T. , Logan Geoffrey D. , Drozd Christopher , De Oliveira Silva Juliana , Colindres Nicole B. , Peacock Beth B. , Smith Becker Jennifer , Loffredo Angelo , Wu Haiyan , Ruegger Paul M. , Becker J. Ole , Borneman James
Published: October 2020

Until the early 1990s, cyst nematodes were abundant pathogens in fields where hosts of Heterodera spp. were frequent members of crop rotations along California’s Central Coast. To mitigate damage caused by Heterodera schachtii and H. cruciferae, the soil fumigant 1,3-dichloropropene (1,3-D) was used by more than 43% of surveyed broccoli growers. Over the last few decades, use of 1,3-D and other nematicides has dramatically diminished, suggesting a decline in nematode disease pressure. The goal of this study was to examine the hypothesis that increased population densities of nematophagous fungi contribute to the low populations of Heterodera spp. in fields frequently cropped to their hosts. In 2016, soil samples were collected from 152 Brassica fields with a broad geographical distribution, from Santa Barbara County to Santa Cruz County. The average number of Heterodera cysts per 250 cm3 of soil ranged from 0.5 to 27.5, with 62% of the soils harboring no detectable cyst nematodes and only a few samples reaching a potentially damaging threshold level. A baiting experiment with H. schachtii and cabbage was performed in a greenhouse to detect nematophagous fungi associated with nematode females as their posterior end emerged and became exposed to the soil’s rhizosphere. An Illumina-based sequence analysis of these H. schachtii females identified several known nematophagous fungi, including members of the Hyalorbilia oviparasitica clade, Pochonia chlamydosporia, certain Fusarium spp., and others. These soils clearly harbor a diverse population of hyperparasitic fungi that could be biologically suppressing cyst nematodes below a damaging threshold.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Guiding Elements for Success in the Nurse Educator Role
Authors: Stanley Mary Jo , Martin Carolyn
Published: October 2020

As educators and administrators, we are challenged to find processes that support faculty entering educational roles whether in part-time, full-time, or tenured positions. This article focuses on guiding elements that bring about transition from the new or novice nurse instructor to the faculty role. Supporting elements for transition include mentoring, pedagogical instruction, and continued knowledge acquisition. Without formal role preparation, many nurse faculty experience conflict and ongoing deficits in the knowledge that is needed to be successful in an academic setting.
Contamination and Decontamination of Autologous Bone in the Operating Room: A Systematic Review
Authors: Mortazavi Seyed Mohammad Javad , Ghasemi Mohammad Ali , Khan Furqan Mohammed Yaseen , Zarei Mohammad , Shahabinezhad Ali
Published: October 2020

Objective:

To perform a systematic review of the literature to determine the rate of contamination of autologous bone fragments inadvertently dropped on the operating room floor, the microbial profile (contaminating organism), and the outcome of intraoperative decontamination techniques in terms of effectiveness and cellular toxicity.

Data Sources:

PubMed, Medline, and Embase were searched for English literature published from 1990 through 2020 using terms such as “bone graft contamination,” “dropped osteoarticular fragments,” “autogenous bone decontamination,” and similar interchangeable words.

Study Selection:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Inclusion criteria consisted of all studies on contamination of host bone fragments, means and/or rate of autologous bone contamination in operating rooms, microbial analysis of contaminated bone autograft, outcome of decontamination, and cellular viability after decontamination.

Data Extraction:

All potentially eligible studies underwent a full-text review and cross-referencing after title and abstract screening. Data on authors, publication year, study type, means and rate of contamination, microbial profile, decontamination technique, and effectiveness and cellular toxicity outcomes were extracted.

Data Synthesis:

Analysis and synthesis of data were performed on Microsoft Excel 2016.

Conclusion:

The rate of contamination for dropped osteoarticular or osteochondral host fragment approached 40%. Staphylococcus epidermidis was the most common organism contaminating the bone graft when dropped on the operating room floor. A 5-minute bath in 10% povidone-iodine solution followed by 1-minute bulb syringe lavage with normal saline has proved successful in decontamination and maintenance of cellular viability.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Timing and Management of Surgical Site Infections in Patients With Open Fracture Wounds: A Fluid Lavage of Open Wounds Cohort Secondary Analysis
Authors: Prada Carlos , Marcano-Fernández Francesc A. , Schemitsch Emil H. , Bzovsky Sofia , Jeray Kyle , Petrisor Brad , Bhandari Mohit , Sprague Sheila ,   on behalf of the FLOW Investigators
Published: October 2020

Background:

Many studies report on the incidence or prevalence of fracture-related surgical site infections (SSIs) after open fractures; however, few studies report on their timing and management outcomes. To address this gap, we used data from the Fluid Lavage of Open Wounds trial to determine timing of diagnosis, management, and resolution of SSIs.

Methods:

All participants included in this analysis had an SSI after an open fracture. Participants were assigned to a group based on the type of SSI as follows: (1) those who developed a superficial SSI and (2) those who had either a deep or organ/space SSI. Descriptive statistics characterized the type, timing, and management of each SSI.

Results:

Of the 2445 participants in the Fluid Lavage of Open Wounds trial, 325 (13.3%) had an SSI. Superficial SSIs were diagnosed significantly earlier [26.5 days, interquartile range (IQR) 12–48] than deep or organ/space SSIs (53 days, IQR 15–119). Of the 325 patients with SSIs, 174 required operative management and 151 were treated nonoperatively. For SSIs managed operatively, median time for infection resolution was 73 days (IQR 28–165), and on average, 1.73 surgeries (95% confidence interval 1.58–1.88) were needed during the 12 months follow-up. There were 24 cases whose SSIs were not resolved at the time of the final follow-up visit (12 months).

Conclusions:

Based on this study's findings and in contradistinction to the Centers for Disease Control and Prevention guidelines, after an open fracture, superficial SSIs were diagnosed at one month and deep/organ/space SSIs at 2 months. This information can allow for earlier infection detection. In addition, the knowledge that approximately 50% of the SSIs in our study required a reoperation and 3 months at a minimum to resolve will assist orthopaedic surgeons when counseling their patients.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Surgical Fixation of Quadrimalleolar Fractures of the Ankle
Authors: Rammelt Stefan , Bartoníček Jan , Kroker Livia , Neumann Annika Pauline
Published: October 2020

We present a technique of fixation of trimalleolar fractures with additional fracture of the anterior tibial tubercle (“quadrimalleolar”) or anterior fibular rim (“quadrimalleolar equivalent”). Twenty-four patients with a mean age of 60 years were treated with open reduction and internal fixation of all 4 malleoli. There were 17 quadrimalleolar and 6 quadrimalleolar equivalent fractures. One patient had both anterior tibial and fibular avulsion fracture in addition to a trimalleolar ankle fracture. Surgical approaches and internal fixation were tailored individually. Twenty patients were operated in the prone position with direct fixation of the posterior malleolus and 4 patients in the supine position with anterior to posterior screw fixation of the posterior malleolus. After fixation of al 4 malleoli, only 1 patient (4%) required a syndesmotic screw for residual syndesmotic instability on intraoperative testing. There were no infections and no wound healing problems. All patients went on to solid union. Nineteen patients (79%) were followed for a mean of 77 months (range, 15–156 months). The Foot Function Index averaged 15 (range, 50 to 0), the Olerud and Molander Score averaged 79 (range, 45–100), and the American Orthopaedic Foot and Ankle Society Ankle and Hindfoot Scale averaged 87 (range, 39–100). Fixation of the anterior and posterior tibial fragments increases syndesmotic stability by providing a bone-to-bone fixation. Anatomic reduction of the anterior and posterior tibial rim restores the physiological shape of the tibial incisura and therefore facilitates fibular reduction.