bluuebunny/crossref_metadata_2025 huggingface dataset:
A Repertory of Rearrangements and the Loss of an Inverted Repeat Region in Passiflora Chloroplast Genomes
Authors: Cauz-Santos Luiz Augusto , da Costa Zirlane Portugal , Callot Caroline , Cauet Stéphane , Zucchi Maria Imaculada , Bergès Hélène , van den Berg Cássio , Vieira Maria Lucia Carneiro
Published: July 2020

Chloroplast genomes (cpDNA) in angiosperms are usually highly conserved. Although rearrangements have been observed in some lineages, such as Passiflora, the mechanisms that lead to rearrangements are still poorly elucidated. In the present study, we obtained 20 new chloroplast genomes (18 species from the genus Passiflora, and Dilkea retusa and Mitostemma brevifilis from the family Passifloraceae) in order to investigate cpDNA evolutionary history in this group. Passiflora cpDNAs vary in size considerably, with ∼50 kb between shortest and longest. Large inverted repeat (IR) expansions were identified, and at the extreme opposite, the loss of an IR was detected for the first time in Passiflora, a rare event in angiosperms. The loss of an IR region was detected in Passiflora capsularis and Passiflora costaricensis, a species in which occasional biparental chloroplast inheritance has previously been reported. A repertory of rearrangements such as inversions and gene losses were detected, making Passiflora one of the few groups with complex chloroplast genome evolution. We also performed a phylogenomic study based on all the available cp genomes and our analysis implies that there is a need to reconsider the taxonomic classifications of some species in the group.
A New Look at Cohort Trend and Underlying Mechanisms in Cognitive Functioning
Authors: Zheng Hui
Published: July 2020

Objectives

The prevalence of dementia in the United States seems to have declined over the last few decades. We investigate trends and their underlying mechanisms in cognitive functioning (CF) across 7 decades of birth cohorts from the Greatest Generation to Baby Boomers.

Methods

Data come from 30,191 participants of the 1996–2014 Health and Retirement Study. CF is measured as a summary score on a 35-point cognitive battery of items. We use generalized linear models to examine the trends in CF and explanatory variables across birth cohorts. Then, Karlson–Holm–Breen decomposition method is used to evaluate the contribution of each explanatory variable to the trend of CF.

Results

CF has been improving from the Greatest Generation to Late Children of Depression and War Babies, but then significantly declines since the Early-Baby Boomers and continues into Mid-Baby Boomers. This pattern is observed universally across genders, race/ethnicities, education groups, occupations, income, and wealth quartiles. The worsening CF among Baby Boomers does not originate from childhood conditions, adult education, or occupation. It can be attributed to lower household wealth, lower likelihood of marriage, higher levels of loneliness, depression and psychiatric problems, and more cardiovascular risk factors (e.g., obesity, physical inactivity, hypertension, stroke, diabetes, and heart disease).

Discussion

The worsening CF among Baby Boomers may potentially reverse past favorable trends in dementia as they reach older ages and cognitive impairment becomes more common if no effective interventions and policy responses are in place.
Sensitivity of InSAR and teleseismic observations to earthquake rupture segmentation
Authors: Steinberg Andreas , Sudhaus Henriette , Heimann Sebastian , Krüger Frank
Published: July 2020

Earthquakes often rupture across more than one fault segment. If such rupture segmentation occurs on a significant scale, a simple point-source or one-fault model may not represent the rupture process well. As a consequence earthquake characteristics inferred, based on one-source assumptions, may become systematically wrong. This might have effects on follow-up analyses, for example regional stress field inversions and seismic hazard assessments. While rupture segmentation is evident for most Mw > 7 earthquakes, also smaller ones with 5.5 < Mw < 7 can be segmented. We investigate the sensitivity of globally available data sets to rupture segmentation and their resolution to reliably estimate the mechanisms in presence of segmentation. We focus on the sensitivity of InSAR (Interferometric Synthetic Aperture Radar) data in the static near-field and seismic waveforms in the far-field of the rupture and carry out non-linear and Bayesian optimizations of single-source and two-sources kinematic models (double-couple point sources and finite, rectangular sources) using InSAR and teleseismic waveforms separately. Our case studies comprises of four Mw 6–7 earthquakes: the 2009 L’Aquila and 2016 Amatrice (Italy) and the 2005 and 2008 Zhongba (Tibet) earthquakes. We contrast the data misfits of different source complexity by using the Akaike informational criterion (AIC). We find that the AIC method is well suited for data-driven inferences on significant rupture segmentation for the given data sets. This is based on our observation that an AIC-stated significant improvement of data fit for two-segment models over one-segment models correlates with significantly different mechanisms of the two source segments and their average compared to the single-segment mechanism. We attribute these modelled differences to a sufficient sensitivity of the data to resolve rupture segmentation. Our results show that near-field data are generally more sensitive to rupture segmentation of shallow earthquakes than far-field data but that also teleseismic data can resolve rupture segmentation in the studied magnitude range. We further conclude that a significant difference in the modelled source mechanisms for different segmentations shows that an appropriate choice of model segmentation matters for a robust estimation of source mechanisms. It reduces systematic biases and trade-off and thereby improves the knowledge on the rupture. Our study presents a strategy and method to detect significant rupture segmentation such that an appropriate model complexity can be used in the source mechanism inference. A similar, systematic investigation of earthquakes in the range of Mw 5.5–7 could provide important hazard-relevant statistics on rupture segmentation. In these cases single-source models introduce a systematic bias. Consideration of rupture segmentation therefore matters for a robust estimation of source mechanisms of the studied earthquakes.
Detachment in capillary adhesion: the relative roles of tilting and separation
Authors: Butler Matthew D , Vella Dominic
Published: July 2020

We study the dynamics of detachment in 2D capillary adhesion by considering a plate that is initially attached to a flat, rigid substrate via the surface tension of a bridging liquid droplet. In particular, we focus on the effect of allowing the plate to tilt freely during its subsequent motion. A linear stability analysis shows that small perturbations from equilibrium decouple into two modes: one in which the plate separates from the substrate, remaining parallel, and another in which it tilts, simultaneously causing the bridging droplet to migrate. If the initial tilt perturbation is of a similar magnitude to (or bigger than) the separation perturbation, then the presence of this second tilting mode can significantly alter the dynamics. Indeed, this tilting mechanism changes the ultimate fate of the plate: depending on the size of the plate and the initial perturbation, the plate may anomalously detach. We discuss this observation in relation to previous experiments on a 3D system that showed a qualitatively similar anomalous detachment.
Adaptive quarkonial domain decomposition methods for elliptic partial differential equations
Authors: Dahlke Stephan , Friedrich Ulrich , Keding Philipp , Sieber Alexander , Raasch Thorsten
Published: July 2020

This paper is concerned with new discretization methods for the numerical treatment of elliptic partial differential equations. We derive an adaptive approximation scheme that is based on frames of quarkonial type, which can be interpreted as a wavelet version of $hp$ finite element dictionaries. These new frames are constructed from a finite set of functions via translation, dilation and multiplication by monomials. By using nonoverlapping domain decomposition ideas, we establish quarkonial frames on domains that can be decomposed into the union of parametric images of unit cubes. We also show that these new representation systems are stable in a certain range of Sobolev spaces. The construction is performed in such a way that, similar to the wavelet setting, the frame elements, the so-called quarklets, possess a certain number of vanishing moments. This enables us to generalize the basic building blocks of adaptive wavelet algorithms to the quarklet case. The applicability of the new approach is demonstrated by numerical experiments for the Poisson equation on $L$-shaped domains.
Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections
Authors: Rijkers Ger , Murk Jean-Luc , Wintermans Bas , van Looy Bieke , van den Berge Marcel , Veenemans Jacobien , Stohr Joep , Reusken Chantal , van der Pol Pieter , Reimerink Johan
Published: July 2020

We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.
Peptidylarginine Deiminases 2 Mediates Caspase-1-Associated Lethality inPseudomonas aeruginosaPneumonia-Induced Sepsis
Authors: Wu Zhenyu , Tian Yuzi , Alam Hasan B , Li Patrick , Duan Xiuzhen , Williams Aaron M , Liu Baoling , Ma Jianjie , Li Yongqing
Published: July 2020

Background

Pseudomonas aeruginosa (PA) is a pathogenic bacterium that causes severe pneumonia in critically ill and immunocompromised patients. Peptidylarginine deiminase (PAD) 2, PAD4, and caspase-1 are important enzymes in mediating host response to infection. The goal of this study was to determine the interplay between PAD2, PAD4, and caspase-1 in PA pneumonia-induced sepsis.

Methods

Pneumonia was produced in wild-type, Pad2−/−, and Pad4−/− mice by intranasal inoculation of PA (2.5 × 106 colony-forming units per mouse), and survival (n = 15/group) was monitored for 10 days. Bone marrow-derived macrophages (BMDMs) were isolated for in vitro studies. Samples were collected at specific timepoints for Western blot, bacterial load determination, and flow cytometry analysis.

Results

Caspase-1-dependent inflammation was diminished in PA-inoculated Pad2−/− mice, contributing to reduced macrophage death and enhanced bacterial clearance. In addition, Pad2−/− mice exhibited improved survival and attenuated acute lung injury after PA infection. In contrast, Pad4−/− mice did not display diminished caspase-1 activation, altered bacterial loads, or improved survival.

Conclusions

Peptidylarginine deiminase 2 plays an essential role in the pathogenesis of pulmonary sepsis by mediating caspase-1 activation. This goes against previous findings of PAD4 in sepsis. Our study suggests that PAD2 is a potential therapeutic target of PA pneumonia-induced sepsis.
Drug interactions: a review of the unseen danger of experimental COVID-19 therapies
Authors: Hodge Daryl , Marra Fiona , Marzolini Catia , Boyle Alison , Gibbons Sara , Siccardi Marco , Burger David , Back David , Khoo Saye
Published: July 2020

As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.
Recommendations for patient similarity classes: results of the AMIA 2019 workshop on defining patient similarity
Authors: Seligson Nathan D , Warner Jeremy L , Dalton William S , Martin David , Miller Robert S , Patt Debra , Kehl Kenneth L , Palchuk Matvey B , Alterovitz Gil , Wiley Laura K , Huang Ming , Shen Feichen , Wang Yanshan , Nguyen Khoa A , Wong Anthony F , Meric-Bernstam Funda , Bernstam Elmer V , Chen James L
Published: July 2020

Defining patient-to-patient similarity is essential for the development of precision medicine in clinical care and research. Conceptually, the identification of similar patient cohorts appears straightforward; however, universally accepted definitions remain elusive. Simultaneously, an explosion of vendors and published algorithms have emerged and all provide varied levels of functionality in identifying patient similarity categories. To provide clarity and a common framework for patient similarity, a workshop at the American Medical Informatics Association 2019 Annual Meeting was convened. This workshop included invited discussants from academics, the biotechnology industry, the FDA, and private practice oncology groups. Drawing from a broad range of backgrounds, workshop participants were able to coalesce around 4 major patient similarity classes: (1) feature, (2) outcome, (3) exposure, and (4) mixed-class. This perspective expands into these 4 subtypes more critically and offers the medical informatics community a means of communicating their work on this important topic.
Low Doses of a Neonicotinoid Stimulate Reproduction in a Beneficial Predatory Insect
Authors: Rix R R , Cutler G C
Published: July 2020

Biological stimulation induced by low doses of toxicants or other stressors is known as hormesis. Hormetic stimulation of life history traits in insect pests can negatively impact agriculture, but stimulation of beneficial insects could be leveraged to enhance biological control agents. We examined whether low doses of imidacloprid could enhance oviposition, fecundity, fertility, and survival in the beneficial stink bug predator, Podisus maculiventris (Say) (Hemiptera: Pentatomidae), exposed at different life stages and across two generations. When treated as young adults, P. maculiventris fecundity was stimulated at 0.5 and 1.0 mg/liter imidacloprid (<2% of the field rate) without changes in time to oviposition, fertility, and survival. Nymphs exposed to 0.015 mg/liter imidacloprid (<1% of the field rate) also had stimulated reproduction without effects on oviposition, fertility, and survival, but treatment of nymphs at 0.15 and 1.5 mg/liter imidacloprid stimulated fecundity at the expense of fertility and survival. In another experiment we found reproductive stimulation can occur trans-generationally without major reduction in fertility or survival. Our results suggest biocontrol producers may be able to strategically apply low doses of stress to natural enemies during culturing without compromising fitness in subsequent generations.
Mesenteric inflammatory myofibroblastic tumor as a rare cause of small intestinal intussusception
Authors: Alabbas Zeina , Issa Mohsen , Omran Ammar , Issa Rana
Published: July 2020

Inflammatory myofibroblastic tumor (IMT) is an uncommon, usually benign, mesenchymal tumor. IMT affects people of all ages, but it more commonly occurs in children and adolescents. Also, it has the potential to arise in any part of the body, though, it frequently develops in the lungs and mesentery. In this report, we discuss a rare clinical manifestation of mesenteric IMT presented as intussusception of the small intestine in a 7-year-old child.
The transcription factor WRKY22 is required during cryo-stress acclimation in Arabidopsis shoot tips
Authors: Stock Johanna , Bräutigam Andrea , Melzer Michael , Bienert Gerd Patrick , Bunk Boyke , Nagel Manuela , Overmann Jörg , Keller E R Joachim , Mock Hans-Peter
Published: July 2020

Storage of meristematic tissue at ultra-low temperatures offers a mean to maintain valuable genetic resources from vegetatively reproduced plants. To reveal the biology underlying cryo-stress, shoot tips of the model plant Arabidopsis thaliana were subjected to a standard preservation procedure. A transcriptomic approach was taken to describe the subsequent cellular events which occurred. The cryoprotectant treatment induced the changes in the transcript levels of genes associated with RNA processing and primary metabolism. Explants of a mutant lacking a functional copy of the transcription factor WRKY22 were compromised for recovery. A number of putative downstream targets of WRKY22 were identified, some related to phytohormone-mediated defense, to the osmotic stress response, and to development. There were also alterations in the abundance of transcript produced by genes encoding photosynthesis-related proteins. The wrky22 mutant plants developed an open stomata phenotype in response to their exposure to the cryoprotectant solution. WRKY22 probably regulates a transcriptional network during cryo-stress, linking the explant’s defense and osmotic stress responses to changes in its primary metabolism. A model is proposed linking WRKY53 and WRKY70 downstream of the action of WRKY22.
GABA signaling in plants: targeting the missing pieces of the puzzle
Authors: Fromm Hillel
Published: July 2020

The adaptation of plants to unstable environments relies on their ability to sense their surroundings and to generate and transmit corresponding signals to different parts of the plant to evoke changes necessary for optimizing growth and defense. Plants, like animals, contain a huge repertoire of intra- and intercellular signals, including organic and inorganic molecules. The occurrence of neurotransmitter-like signaling molecules in plants has been an intriguing field of research. Among these, γ-aminobutyric acid (GABA) was discovered in plants over half a century ago, and studies of its roles as a primary metabolite have been well documented, particularly in the context of stress responses. In contrast, evidence of the potential mechanism by which GABA acts as a signaling molecule in plants has only recently been reported. In spite of this breakthrough, the roles of GABA as a signaling molecule in plants have yet to be established and several aspects of the complexity of the GABA signaling system remain obscure. This review summarizes the uncertainties in GABA signaling in plants and suggests research directions and technologies that would help in answering unsolved questions.
Evaluation of the Impact of Changing Quality Control Rules and Frequency on the Risk Management Index: Results from the Clinical Routine of a Medical Laboratory
Authors: Karnutsch Daniela , Occhipinti Francesca , Tumiatti Daniel , Mueller Thomas
Published: July 2020

Objective

The consideration of the principles of risk management in the analytical process is a current trend. The aim of this study was to evaluate whether the risk management index (RMI) for various laboratory parameters can be influenced by interventions that change the internal quality control (IQC) strategy.

Methods

We selected 10 laboratory parameters associated with cardiovascular disease for the study (myoglobin, N-terminal fragment of the pro B-type natriuretic polypeptide, cardiac troponin T, creatinine kinase, lactate dehydrogenase, glucose, triglycerides, total cholesterol, and low-density lipoprotein and high-density lipoprotein cholesterol). The study-specific interventions included changing the IQC rules and changing the IQC schedule. This was a one-armed intervention study in which changes in the RMI, a measure of patient harm risk, was recorded over time.

Results

Before the intervention, the mean RMI was 1.022 (95% confidence interval [CI], 0.269–1.776). After the intervention, the mean RMI was 0.934 (95% CI, 0.088–1.956). The RMI values before and after the intervention were not significantly different (P =.89).

Conclusion

The study-specific interventions did not lead to an improvement of the RMI in the clinical routines of a medical laboratory. There is a great need to further explore this subject area with interventional studies to clarify how the risk of unintended patient harm can be measurably improved.
Rapid Molecular Detection for Differentiation of Homozygous HbE and ß0-Thalassemia/HbE in Samples Related With HbE >80% and Variable HbF Levels
Authors: Tepakhan Wanicha , Jomoui Wittaya
Published: July 2020

Objective

To validate a novel rapid molecular testing method for differentiation of homozygous hemoglobin (Hb)E and HbE/β 0-thalassemia genotypes using multiplex melt curve combined with high-resolution melt (HRM) analysis in a single test tube.

Methods

All 10 genotypes contained (β N/β N; n = 95), (β N/β 3.5-kb; n = 71), (β N/β 45-kb; n = 28), (β N/β E; n = 10), (β E/β 3.5-kb; n = 6), (β E/β 45-kb; n = 4), (β E/β 41/42; n = 28), (β E/β 17; n = 9), (β E/β IVSI#1; n = 6), and (β E/β E; n = 76) were recruited for validation. A proposed strategy for rapid differentiation of β 0-thalassemia/HbE disease and homozygous Hb E in specimens with HbE greater than 80% and variable HbF levels was demonstrated.

Results

In the validation method, all genotypes showed 100% concordance, compared with the conventional reverse dot blot (RDB) and gap–polymerase chain reaction (PCR) methods.

Conclusions

Our newly developed method could be useful in routine laboratory settings. The method is rapid, simple, and cost effective; does not require a post-PCR step; and can be applied in routine settings.
Model of imbalanced kinetic Alfvén turbulence with energy exchange between dominant and subdominant components
Authors: Gogoberidze G , Voitenko Y M
Published: July 2020

Alfvénic turbulence in the fast solar wind is imbalanced: the energy of the (dominant) waves propagating outward from the Sun is much larger than energy of inward-propagating (subdominant) waves. At large scales Alfvén waves are non-dispersive and turbulence is driven by non-linear interactions of counter-propagating waves. Contrary to this, at kinetic scales Alfvén waves become dispersive and non-linear interactions become possible among co-propagating waves as well. The study of the transition between these two regimes of Alfvénic turbulence is important for understanding of complicated dynamics of imbalanced Alfvénic turbulence. In this paper, we present a semiphenomenological model of the imbalanced Alfvénic turbulence accounting for the energy exchange between the dominant and subdominant wave fractions. The energy transfer becomes non-negligible at sufficiently small yet still larger than the ion gyroradius scales and is driven by the non-linear beatings between dispersive dominant(subdominant) waves pumping energy into the subdominant(dominant) component. Our results demonstrate that the turbulence imbalance should decrease significantly in the weakly dispersive wavenumber range.
Clumpiness: time-domain classification of red giant evolutionary states
Authors: Kuszlewicz James S , Hekker Saskia , Bell Keaton J
Published: July 2020

Long, high-quality time-series data provided by previous space missions such as CoRoT and Kepler have made it possible to derive the evolutionary state of red giant stars, i.e. whether the stars are hydrogen-shell burning around an inert helium core or helium-core burning, from their individual oscillation modes. We utilize data from the Kepler mission to develop a tool to classify the evolutionary state for the large number of stars being observed in the current era of K2, TESS, and for the future PLATO mission. These missions provide new challenges for evolutionary state classification given the large number of stars being observed and the shorter observing duration of the data. We propose a new method, Clumpiness, based upon a supervised classification scheme that uses ‘summary statistics’ of the time series, combined with distance information from the Gaia mission to predict the evolutionary state. Applying this to red giants in the APOKASC catalogue, we obtain a classification accuracy of $\sim 91{{\ \rm per\ cent}}$ for the full 4 yr of Kepler data, for those stars that are either only hydrogen-shell burning or also helium-core burning. We also applied the method to shorter Kepler data sets, mimicking CoRoT, K2, and TESS achieving an accuracy $\gt 91{{\ \rm per\ cent}}$ even for the 27 d time series. This work paves the way towards fast, reliable classification of vast amounts of relatively short-time-span data with a few, well-engineered features.
Orbital period modulation in hot Jupiter systems
Authors: Lanza A F
Published: July 2020

We introduce a model for the orbital period modulation in systems with close-by giant planets based on a spin–orbit coupling that transfers angular momentum from the orbit to the rotation of the planet and vice versa. The coupling is produced by a permanent non-axisymmetric gravitational quadrupole moment assumed to be present in the solid core of the planet. We investigate two regimes of internal planetary rotation, that is, when the planet rotates rigidly and when the rotation of its deep interior is time-dependent as a consequence of a vacillating or intermittent convection in its outer shell. The model is applied to a sample of very hot Jupiters predicting maximum transit-time deviations from a constant-period ephemeris of approximately 50 s in the case of rigid rotation. The transit time variations of WASP-12, currently the only system showing evidence of a non-constant period, cannot be explained by assuming rigid rotation, but can be modelled in the time-dependent internal rotation regime, thus providing an alternative to their interpretation in terms of a tidal decay of the planet orbit.
Magnetic fields from cosmological bulk flows
Authors: Cembranos J A R , Maroto A L , Villarrubia-Rojo H
Published: July 2020

We explore the possibility that matter bulk flows could generate the required vorticity in the electron–proton–photon plasma to source cosmic magnetic fields through the Harrison mechanism. We analyse the coupled set of perturbed Maxwell and Boltzmann equations for a plasma in which the matter and radiation components exhibit relative bulk motions at the background level. These background bulk motions induce a relative velocity between the matter and cosmic microwave background rest frames at the present time, i.e. a bulk flow, with an amplitude β. We find that, to first order in cosmological perturbations, bulk flows with velocities compatible with current Planck limits (β < 8.5 × 10−4 at $95{{\ \rm per\ cent}}$ CL) could generate magnetic fields with an amplitude 10−21 G on 10 kpc comoving scales at the time of completed galaxy formation that could be sufficient to seed a galactic dynamo mechanism.
Can EDGES observation favour any dark matter model?
Authors: Rudakovskyi A , Savchenko D , Tsizh M
Published: July 2020

The recent detection of the 21-cm absorption signal by the EDGES collaboration has been widely used to constrain the basic properties of dark matter particles. However, extracting the parameters of the 21-cm absorption signal relies on a chosen parametrization of the foreground radio emission. Recently, the new parametrizations of the foreground and systematics have been proposed, showing significant deviations of the 21-cm signal parameters from those assumed by the original EDGES paper. In this paper, we consider this new uncertainty, comparing the observed signal with the predictions of several dark matter models, including the widely used cold dark matter model, 1–3 keV warm dark matter models, and 7 keV sterile neutrino (SN7) model, capable of producing the reported 3.5 keV line. We show that all these dark matter models cannot be statistically distinguished using the available EDGES data.
How eruptions of a small filament feed materials to a nearby larger-scaled filament
Authors: Wei H , Huang Z , Hou Z , Qi Y , Fu H , Li B , Xia L
Published: July 2020

As one of the most common features in the solar atmosphere, filaments are significant not only in solar physics but also in stellar and laboratory plasma physics. With the New Vacuum Solar Telescope and the Solar Dynamics Observatory, here we report on multi-wavelength observations of eruptions of a small (30 arcsec) filament (SF) and its consequences while interacting with ambient magnetic features including a large (300 arcsec) filament (LF). The eruptions of the SF drive a two-side-loop jet that is a result of magnetic reconnection between the SF threads and an overlying magnetic channel. As a consequence of the eruption, the heating in the footpoints of the SF destabilizes the barbs of the LF rooted nearby. Supersonic chromospheric plasma flows along the barbs of the LF are then observed in the H α passband and they apparently feed materials to the LF. We suggest that they are shock-driven plasma flows or chromospheric evaporations, which can both be the consequences of heating in the chromosphere by non-thermal particles generated in the magnetic reconnection associated with the two-side-loop jet. Our observations demonstrate that the destabilization in the vicinity of the footpoints of a barb can drive chromospheric plasma feeding to the filament.
GapR binds DNA through dynamic opening of its tetrameric interface
Authors: Huang Qian , Duan Bo , Dong Xianzhi , Fan Shilong , Xia Bin
Published: July 2020

GapR is a nucleoid-associated protein that is an essential regulator of chromosome replication in the cell cycle model Caulobacter crescentus. Here, we demonstrate that free GapR is a homotetramer, but not a dimer as previously reported (Guo et al., Cell 175: 583–597, 2018). We have determined the crystal structure of GapR in complex with a 10-bp A-tract DNA, which has an open tetrameric conformation, different from the closed clamp conformation in the previously reported crystal structure of GapR/DNA complex. The free GapR adopts multiple conformations in dynamic exchange equilibrium, with the major conformation resembling the closed tetrameric conformation, while the open tetrameric conformation is a representative of minor conformers. As it is impossible for the circular genomic DNA to get into the central DNA binding tunnel of the major conformation, we propose that GapR initially binds DNA through the open conformation, and then undergoes structural rearrangement to form the closed conformation which fully encircles the DNA. GapR prefers to bind DNA with 10-bp consecutive A/T base pairs nonselectively (Kd ∼12 nM), while it can also bind GC-rich DNA sequence with a reasonable affinity of about 120 nM. Besides, our results suggest that GapR binding results in widening the minor groove of AT-rich DNA, instead of overtwisting DNA.
A Novel RFXANK Mutation in a Chinese Child With MHC II Deficiency: Case Report and Literature Review
Authors: Cai Yu Qing , Zhang HangHu , Wang Xiang Zhi , Xu ChengYun , Chao Yun Qi , Shu YingYing , Tang Lan Fang
Published: July 2020

Major histocompatibility complex (MHC) II deficiency is a rare primary immunodeficiency disorder that is characterized by the deficiency of MHC class II molecules. The disease is caused by transcription factor mutations including class II transactivator (CIITA), regulatory factor X-5 (RFX5), RFX-associated protein (RFXAP), and RFXAP-containing ankyrin repeat (RFXANK), respectively. Mutations in the RFXANK gene account for >70% of all known patients worldwide. Herein, we reported a 10-month-old boy with MHC II deficiency caused by a novel mutation in the RFXANK gene (c.337 + 1G>C). The boy was admitted to the hospital due to pneumonia and diarrhea at 4 months of age. Genetic analysis revealed a novel homozygous mutation in the RFXANK gene, which derived from the c.337 + 1G>C heterozygous mutations in the RFXANK gene of his parents. The boy died 3 months after diagnosis. More than 200 cases have been reported, and a review of the literature revealed different mutation rates of 4 transcription factors in different countries or regions. This is the first case report of MHC II deficiency from East Asia. We also describe all gene mutations that cause MHC II deficiency and the epidemiology of MHC II deficiency with gene mutations in this paper.
The Risk of Being a Fallen Angel and the Corporate Dash for Cash in the Midst of COVID
Authors: Acharya Viral V , Steffen Sascha
Published: July 2020

Data on firm-loan-level daily credit line drawdowns in the United States expose a corporate “dash for cash” induced by the COVID-19 pandemic. In the first phase of the crisis, which was characterized by extreme precaution and heightened aggregate risk, all firms drew down bank credit lines and raised cash levels. In the second phase, which followed the adoption of stabilization policies, only the highest-rated firms switched to capital markets to raise cash. Consistent with the risk of becoming a fallen angel, the lowest-quality BBB-rated firms behaved more similarly to non-investment grade firms. The observed corporate behavior reveals the significant impact of credit risk on corporate cash holdings. (JEL G01, G14, G32, G35)

Received July 13, 2020; editorial decision July 17, 2020 by Editor Andrew Ellul
Distinguishing lupus lymphadenitis from Kikuchi disease based on clinicopathological features and C4d immunohistochemistry
Authors: Yu Shan-Chi , Chang Kung-Chao , Wang Hsuan , Li Meng-Fang , Yang Tsung-Lin , Chen Chun-Nan , Chen Chih-Jung , Chen Ko-Chin , Shen Chieh-Yu , Kuo Po-Yen , Lin Long-Wei , Lin Yueh-Min , Lin Wei-Chou
Published: July 2020

Objectives

Distinguishing Kikuchi disease (KD) from lupus lymphadenitis (LL) histologically is nearly impossible. We applied C4d immunohistochemical (IHC) stain to develop diagnostic tools.

Methods

We retrospectively investigated clinicopathological features and C4d IHC staining in an LL-enriched development cohort (19 LL and 81 KD specimens), proposed risk stratification criteria and trained machine learning models, and validated them in an external cohort (2 LL and 55 KD specimens).

Results

Clinically, we observed that LL was associated with an older average age (33 vs 25 years; P=0.005), higher proportion of biopsy sites other than the neck [4/19 (21%) vs 1/81 (1%); P=0.004], and higher proportion of generalized lymphadenopathy compared with KD [9/16 (56%) vs 7/31 (23%); P=0.028]. Histologically, LL involved a larger tissue area than KD did (P=0.006). LL specimens exhibited more frequent interfollicular pattern [5/19 (26%) vs 3/81 (4%); P=0.001] and plasma cell infiltrates (P=0.002), and less frequent histiocytic infiltrates in the necrotic area (P=0.030). Xanthomatous infiltrates were noted in 6/19 (32%) LL specimens. Immunohistochemically, C4d endothelial staining in the necrotic area [11/17 (65%) vs 2/62 (3%); P<10−7], and capillaries/venules [5/19 (26%) vs 7/81 (9%); P=0.048] and trabecular/hilar vessels [11/18 (61%) vs 8/81 (10%); P<10−4] in the viable area was more common in LL. During validation, both the risk stratification criteria and machine learning models were superior to conventional histological criteria.

Conclusions

Integrating clinicopathological and C4d findings could distinguish LL from KD.
Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A
Authors: Triantafyllias Konstantinos , Cavagna Lorenzo , Klonowski Anna , Drott Ulrich , Fiehn Christoph , Wendel Sarah , Bergner Raoul , de Blasi Michele , Voll Reinhard E , Baulmann Johannes , Konstantinides Stavros , Galle Peter R , Schwarting Andreas
Published: July 2020

Objectives

To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters.

Methods

SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices].

Results

We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P<0.001 and r = 0.664; P<0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039).

Conclusion

ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.
Identification of Flucloxacillin-Haptenated HLA-B*57:01 Ligands: Evidence of Antigen Processing and Presentation
Authors: Waddington James C , Meng Xiaoli , Illing Patricia T , Tailor Arun , Adair Kareena , Whitaker Paul , Hamlett Jane , Jenkins Rosalind E , Farrell John , Berry Neil , Purcell Anthony W , Naisbitt Dean J , Park Brian Kevin
Published: July 2020

Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of human leukocyte antigen (HLA)-B*57:01 increases susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the modification of peptides that are presented by the risk allele. In this study, the binding of flucloxacillin to immune cells was characterized and the nature of the peptides presented by HLA-B*57:01 was analyzed using mass spectrometric-based immunopeptidomics methods. Flucloxacillin modification of multiple proteins was observed, providing a potential source of neoantigens for HLA presentation. Of the peptides eluted from flucloxacillin-treated C1R-B*57:01 cells, 6 putative peptides were annotated as flucloxacillin-modified HLA-B*57:01 peptide ligands (data are available via ProteomeXchange with identifier PXD020137). To conclude, we have characterized naturally processed drug-haptenated HLA ligands presented on the surface of antigen presenting cells that may drive drug-specific CD8+ T-cell responses.
MAVRIC: A Multicenter Randomized Controlled Trial of Transabdominal vs Transvaginal Cervical Cerclage
Authors: Shennan Andrew , Chandiramani Manju , Bennett Phillip , David Anna L. , Girling Joanna , Ridout Alexandra , Seed Paul T. , Simpson Nigel , Thornton Steven , Tydeman Graham , Quenby Siobhan , Carter Jenny
Published: July 2020

(Abstracted from Am J Obstet Gynecol 2020;222:261.e1–261.e9)

Women who experience multiple late miscarriages or spontaneous preterm births may be candidates for vaginal cerclage. In women with a history of pregnancy loss with vaginal cerclage, observational studies have suggested that transabdominal cerclage (TAC) may be beneficial over high vaginal cerclage (HVC) and low vaginal cerclage (LVC).
Noninvasive Prenatal Detection of Hemoglobin Bart Hydrops Fetalis Via Maternal Plasma Dispensed With Parental Haplotyping Using the Semiconductor Sequencing Platform
Authors: Yang Jiexia , Peng Chun-fang , Qi Yiming , Rao Xing-qiang , Guo Fangfang , Hou Yaping , He Wei , Wu Jing , Chen Yang-yi , Zhao Xin , Wang Yu-nan , Peng Haishan , Wang Dongmei , Du Li , Luo Ming-yong , Huang Quan-fei , Liu Hai-liang , Yin Aihua
Published: July 2020

(Abstracted from Am J Obstet Gynecol 2020;222:185.e1–185.e17)

Hemoglobin Bart's hydrops fetalis syndrome (Hb Bart's) is a common inherited genetic disease in the south of China and Southeast Asia. Couples who are both carriers of the Southeast Asian type of α-thalassemia gene deletion have a 25% risk of having a pregnancy affected with Hb Bart's as a result of autosomal recessive inheritance.
Clinical Factors Affecting the Dose Conversion Ratio from Intravenous to Oral Tacrolimus Formulation among Pediatric Hematopoietic Stem Cell Transplantation Recipients
Authors: Kanamitsu Kiichiro , Yorifuji Takashi , Ishida Hisashi , Fujiwara Kaori , Washio Kana , Shimada Akira , Tsukahara Hirokazu
Published: July 2020

Background:

Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation.

Methods:

Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div).

Results:

The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137–0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062–0.133) and −0.0373 (95% CI, −0.072 to −0.002), respectively.

Conclusions:

After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5–6 and 3.5–4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration–time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4–5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.
Hysteroscopic Metroplasty for T-Shaped Uterus: A Systematic Review and Meta-analysis of Reproductive Outcomes
Authors: Garzon Simone , Laganà Antonio Simone , Di Spiezio Sardo Attilio , Alonso Pacheco Luis , Haimovich Sergio , Carugno Jose , Vitale Salvatore Giovanni , Casarin Jvan , Raffaelli Ricciarda , Andrisani Alessandra , Zizolfi Brunella , Cromi Antonella , Ghezzi Fabio , Franchi Massimo , Vitagliano Amerigo
Published: July 2020

Importance

To date, a comprehensive review on the safety and effectiveness of hysteroscopic metroplasty for T-shaped uterus is still missing.

Objective

To provide a robust synthesis of the available studies investigating reproductive outcomes after hysteroscopic metroplasty for T-shaped uterus.

Evidence Acquisition

We performed a systematic review and meta-analysis (CRD42019143291), using the proportion method with 95% confidence interval (CI). Statistical heterogeneity was assessed by Higgins test (I
2).

Results

We included 11 cohort studies embedding 937 women who underwent hysteroscopic metroplasty. After surgery, the pooled percentage of live birth was 44.54% (95% CI, 36.12%–53.12%; I
2 = 46.22%) and 56.88% (95% CI, 46.48%–66.98%; I
2 = 36.38%) in women with primary infertility and recurrent miscarriage, respectively. In women with recurrent miscarriage, the pooled proportion of miscarriage was 21.46% (95% CI, 15.09%–28.61%; I
2 = 30.18%). The pooled clinical pregnancy proportion in women with primary infertility was 57.19% (95% CI, 43.83%–70.03%; I
2 = 77.81%). The pooled rate of surgical complications was 0.65% (95% CI, 0.20%–1.33%; I
2 = 11.44%).

Conclusions

The hysteroscopic correction of T-shaped uteri was associated with high live birth rate and low miscarriage rate, both in case of primary infertility and recurrent miscarriage.

Relevance

Hysteroscopic metroplasty can be considered a safe and effective strategy to improve reproductive outcomes in case of T-shaped uterus.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the learner should be better able to identify and diagnose T-shaped uterus; explain the epidemiological data regarding reproductive outcomes in cases of untreated T-shaped uterus; and describe the technique and outcomes of hysteroscopic metroplasty for T-shaped uterus, both in case of primary infertility and recurrent miscarriage.
Accurate Diagnosis of Endometriosis Using Serum MicroRNAs
Authors: Moustafa Sarah , Burn Martina , Mamillapalli Ramanaiah , Nematian Sepide , Flores Valerie , Taylor Hugh S.
Published: July 2020

(Abstracted from Am J Obstet Gynecol 2020; doi: 10.1016/j.ajog.2020.02.050)

Endometriosis, a chronic inflammatory disorder causing pain and infertility, affects nearly 10% of reproductive age women. Despite its high prevalence, the average time from onset of symptoms to diagnosis is 5 to 10 years.